Bio

Bio


I received my PhD. in Mathematical Statistics in 1967. I joined the research community at the Stanford University School of Medicine, Division of Immunology & Rheumatology, in 1984 as head statistician directing the biostatistics consulting and analytic support of the Arthritis Rheumatism Aging Medical Information System (ARAMIS) and Multipurpose Arthritis Center (MAC) grant-related research programs. In 1993 I was appointed Associate Professor with a joint appointment in the Departments of Medicine and of Health Research & Policy, and am currently Professor of Biostatistics at Stanford University, emeritus since 2007. My contributions to the statistics literature span numerous fields, including methods of sample size estimation, efficiency and bias of estimators, research methods for kappa statistics, non-parametric classification methods and methods of assessing multi-parameter endpoints. I have over 200 peer-reviewed publications. I have been directly involved with the development of numerous criteria rules for classification of diseases and with establishing guidelines for clinical trial research and in proposing responder criteria for osteoarthritis drugs. Since 1987, I have been a consultant on an ad hoc basis to pharmaceutical and biotechnical firms, including both start-up and established companies. I have extensive experience with devices, drugs and biologics and have participated in all aspects of applying statistics to implement investigational plans; e.g.: for protocol development, design of trials, database design. I’ve been a member of the FDA Statistical Advisors Panel, the statistical member on numerous data safety monitoring boards, and frequently represent companies at meetings with the FDA

Academic Appointments


Publications

All Publications


  • Effects of Continuous Positive Airway Pressure on Neurocognitive Function in Obstructive Sleep Apnea Patients: The Apnea Positive Pressure Long-term Efficacy Study (APPLES) SLEEP Kushida, C. A., Nichols, D. A., Holmes, T. H., Quan, S. F., Walsh, J. K., Gottlieb, D. J., Simon, R. D., Guilleminault, C., White, D. P., Goodwin, J. L., Schweitzer, P. K., Leary, E. B., Hyde, P. R., Hirshkowitz, M., Green, S., McEvoy, L. K., Chan, C., Gevins, A., Kay, G. G., Bloch, D. A., Crabtree, T., Dement, W. C. 2012; 35 (12): 1593-U40

    Abstract

    To determine the neurocognitive effects of continuous positive airway pressure (CPAP) therapy on patients with obstructive sleep apnea (OSA).The Apnea Positive Pressure Long-term Efficacy Study (APPLES) was a 6-month, randomized, double-blind, 2-arm, sham-controlled, multicenter trial conducted at 5 U.S. university, hospital, or private practices. Of 1,516 participants enrolled, 1,105 were randomized, and 1,098 participants diagnosed with OSA contributed to the analysis of the primary outcome measures.Active or sham CPAP MEASUREMENTS: THREE NEUROCOGNITIVE VARIABLES, EACH REPRESENTING A NEUROCOGNITIVE DOMAIN: Pathfinder Number Test-Total Time (attention and psychomotor function [A/P]), Buschke Selective Reminding Test-Sum Recall (learning and memory [L/M]), and Sustained Working Memory Test-Overall Mid-Day Score (executive and frontal-lobe function [E/F])The primary neurocognitive analyses showed a difference between groups for only the E/F variable at the 2 month CPAP visit, but no difference at the 6 month CPAP visit or for the A/P or L/M variables at either the 2 or 6 month visits. When stratified by measures of OSA severity (AHI or oxygen saturation parameters), the primary E/F variable and one secondary E/F neurocognitive variable revealed transient differences between study arms for those with the most severe OSA. Participants in the active CPAP group had a significantly greater ability to remain awake whether measured subjectively by the Epworth Sleepiness Scale or objectively by the maintenance of wakefulness test.CPAP treatment improved both subjectively and objectively measured sleepiness, especially in individuals with severe OSA (AHI > 30). CPAP use resulted in mild, transient improvement in the most sensitive measures of executive and frontal-lobe function for those with severe disease, which suggests the existence of a complex OSA-neurocognitive relationship.Registered at clinicaltrials.gov. Identifier: NCT00051363. CITATION: Kushida CA; Nichols DA; Holmes TH; Quan SF; Walsh JK; Gottlieb DJ; Simon RD; Guilleminault C; White DP; Goodwin JL; Schweitzer PK; Leary EB; Hyde PR; Hirshkowitz M; Green S; McEvoy LK; Chan C; Gevins A; Kay GG; Bloch DA; Crabtree T; Demen WC. Effects of continuous positive airway pressure on neurocognitive function in obstructive sleep apnea patients: the Apnea Positive Pressure Long-term Efficacy Study (APPLES). SLEEP 2012;35(12):1593-1602.

    View details for DOI 10.5665/sleep.2226

    View details for Web of Science ID 000313000600005

    View details for PubMedID 23204602

  • Safety issues in the development of treatments for osteoarthritis: recommendations of the Safety Considerations Working Group OSTEOARTHRITIS AND CARTILAGE Strand, V., Bloch, D. A., Leff, R., Peloso, P. M., Simon, L. S. 2011; 19 (5): 493-499

    Abstract

    The symptomatic treatment of osteoarthritis (OA) remains to be improved, as many patients do not respond well to current palliative therapies and/or suffer unacceptable adverse events. Given the unmet need for innovative, effective and well-tolerated therapies, it is important to develop the means to estimate the ongoing safety profile of novel therapeutic agents over short- and longer term use.Methods are presented to estimate the number of serious adverse events (SAEs) of interest considered as "acceptable" per 1000 patient-years exposure and to estimate the numbers of patient-years needed in a randomized controlled trial (RCT) to meet objectives. As exposure is increased, more evidence is accrued that the overall risk is within study limits. It is equally important that requirements for delineating the safety of promising new therapies not create barriers that would preclude their development. Therefore, ongoing surveillance of occurrence of SAEs of interest during clinical development is proposed, for example after every incremental 500 patient-years exposure are accrued.This paper and others in this special issue focus on identification of safety signals for symptomatic treatments of OA. Much less information is available for agents aimed at slowing/preventing structural progression but it is expected that a higher risk profile might be considered acceptable in the context of more promising benefit.This paper provides a proposal and supporting data for a comprehensive approach for assessing ongoing safety during clinical development of both palliative and disease-modifying therapies for OA.

    View details for DOI 10.1016/j.joca.2011.02.019

    View details for Web of Science ID 000291378900004

    View details for PubMedID 21396471

  • Sham or Scam: A Critical Assessment of Recent Vertebroplasty Trials NEUROSURGERY Frankel, B., Bloch, D. A. 2010; 67 (2)
  • Plasma disc decompression compared with fluoroscopy-guided transforaminal epidural steroid injections for symptomatic contained lumbar disc herniation: a prospective, randomized, controlled trial Clinical article JOURNAL OF NEUROSURGERY-SPINE Gerszten, P. C., Smuck, M., Rathmell, J. P., Simopoulos, T. T., Bhagia, S. M., Mocek, C. K., Crabtree, T., Bloch, D. A. 2010; 12 (4): 357-371

    Abstract

    Patients with radiculopathy, with or without back pain, often do not respond to conservative care and may be considered for epidural steroid injection therapy or a disc decompression procedure. Plasma disc decompression (PDD) using the Coblation SpineWand device is a percutaneous, minimally invasive interventional procedure. The purpose of this study was to evaluate clinical outcomes with PDD as compared with standard care using fluoroscopy-guided transforaminal epidural steroid injection (TFESI) over the course of 2 years.This was a multicenter randomized controlled clinical study. Ninety patients (18-66 years old) who had sciatica (visual analog scale score > or = 50) associated with a single-level lumbar contained disc herniation were enrolled. In all cases, their condition was refractory to initial conservative care and 1 epidural steroid injection had failed. Participants were randomly assigned to receive either PDD (46 patients) or TFESI (44 patients, up to 2 injections).The patients in the PDD Group had significantly greater reduction in leg pain scores and significantly improved Oswestry Disability Index and 36-Item Short Form Health Survey ([SF-36], physical function, bodily pain, social function, and physical components summary) scores than those in the TFESI Group. During the 2-year follow-up, 25 (56%) of the patients in the PDD Group and 11 (28%) of those in the TFESI Group remained free from having a secondary procedure following the study procedure (log-rank p = 0.02). A significantly higher percentage of patients in the PDD Group showed minimum clinically important change in scores for leg and back pain and SF-36 scores that exceeded literature-based minimum clinically important changes. Procedure-related adverse events, including injection site pain, increased leg or back pain, weakness, and lightheadedness, were observed in 5 patients in the PDD Group (7 events) and 7 in the TFESI Group (14 events).In study patients who had radicular pain associated with a contained lumbar disc herniation, those patients treated with PDD had significantly reduced pain and better quality of life scores than those treated using repeated TFESI. In addition, significantly more PDD patients than TFESI patients avoided having to undergo a secondary procedure during the 2-year study follow-up.

    View details for DOI 10.3171/2009.10.SPINE09208

    View details for Web of Science ID 000275959900005

    View details for PubMedID 20201654

  • Performance goals and endpoint assessments for clinical trials of femoropopliteal bare nitinol stents in patients with symptomatic peripheral arterial disease CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS Rocha-Singh, K. J., Jaff, M. R., Crabtree, T. R., Bloch, D. A., Ansel, G. 2007; 69 (6): 910-919

    Abstract

    This analysis proposes safety and performance goals for prospective single-arm trials of bare nitinol stents to treat patients with debilitating claudication associated with femoropopliteal (FP) atherosclerotic lesions.To date there have been no analyses of clinical trials data to set efficacy and safety benchmarks for new bare nitinol stents in the treatment of claudication from FP disease. Industry has been reluctant to sponsor studies of nitinol stents due to logistical barriers.VIVA Physician's, Inc. (VPI) analyzed subject-level data from the PTA control arm of three randomized FDA device trials conducted by industry. Subjects with Rutherford category 2-4 claudication and FP lesion lengths 4-15 cm with 12 month duplex ultrasound (DUS) assessment were identified. These data were combined with the results of a survey of the medical literature (1990-2006) for similar subjects.Analysis of the industry derived control arm PTA data identified 116 patients (mean lesion length 8.7 cm) with a 12 month DUS defined FP patency of 28%. A similar cohort of 191 patients was identified from the medical literature in which the 12-month vessel patency equaled 37%; from these combined patient cohorts, expected vessel patency for PTA was estimated to equal 33%.Based on the PTA performance efficacy rate of 33% derived from industry clinical trial data and the medical literature, and the requirement that the bare nitinol stent 12-month efficacy performance goal be set to equal twice this rate, the patency efficacy goal equals 66%. Additional information is provided on safety and other reporting standards and stent integrity evaluation for bare metal stents.

    View details for DOI 10.1002/ccd.21104

    View details for Web of Science ID 000246259800025

    View details for PubMedID 17377972

  • A combined superiority and non-inferiority approach to multiple endpoints in clinical trials STATISTICS IN MEDICINE Bloch, D. A., Lai, T. L., Su, Z., Tubert-Bitter, P. 2007; 26 (6): 1193-1207

    Abstract

    Treatment comparisons in clinical trials often involve multiple endpoints. By making use of bootstrap tests, we develop a new non-parametric approach to multiple-endpoint testing that can be used to demonstrate non-inferiority of a new treatment for all endpoints and superiority for some endpoint when it is compared to an active control. It is shown that this approach does not incur a large multiplicity cost in sample size to achieve reasonable power and that it can incorporate complex dependencies in the multivariate distributions of all outcome variables for the two treatments via bootstrap resampling.

    View details for DOI 10.1002/sim.2611

    View details for Web of Science ID 000244903400002

    View details for PubMedID 16791905

  • Iliac fixation inhibits migration of both suprarenal and infrarenal aortic endografts JOURNAL OF VASCULAR SURGERY Benharash, P., Lee, J. T., Abilez, O. J., Crabtree, T., Bloch, D. A., Zarins, C. K. 2007; 45 (2): 250-257

    Abstract

    To evaluate the role of iliac fixation in preventing migration of suprarenal and infrarenal aortic endografts.Quantitative image analysis was performed in 92 patients with infrarenal aortic aneurysms (76 men and 16 women) treated with suprarenal (n = 36) or infrarenal (n = 56) aortic endografts from 2000 to 2004. The longitudinal centerline distance from the superior mesenteric artery to the top of the stent graft was measured on preoperative, postimplantation, and 1-year three-dimensional computed tomographic scans, with movement more than 5 mm considered to be significant. Aortic diameters were measured perpendicular to the centerline axis. Proximal and distal fixation lengths were defined as the lengths of stent-graft apposition to the aortic neck and the common iliac arteries, respectively.There were no significant differences in age, comorbidities, or preoperative aneurysm size (suprarenal, 6.0 cm; infrarenal, 5.7 cm) between the suprarenal and infrarenal groups. However, the suprarenal group had less favorable aortic necks with a shorter length (13 vs 25 mm; P < .0001), a larger diameter (27 vs 24 mm; P < .0001), and greater angulation (19 degrees vs 11 degrees ; P = .007) compared with the infrarenal group. The proximal aortic fixation length was greater in the suprarenal than in the infrarenal group (22 vs 16 mm; P < .0001), with the top of the device closer to the superior mesenteric artery (8 vs 21 mm; P < .0001) as a result of the 15-mm uncovered suprarenal stent. There was no difference in iliac fixation length between the suprarenal and infrarenal groups (26 vs 25 mm; P = .8). Longitudinal centerline stent graft movement at 1 year was similar in the suprarenal and infrarenal groups (4.3 +/- 4.4 mm vs 4.8 +/- 4.3 mm; P = .6). Patients with longitudinal centerline movement of more than 5 mm at 1 year or clinical evidence of migration at any time during the follow-up period comprised the respective migrator groups. Suprarenal migrators had a shorter iliac fixation length (17 vs 29 mm; P = .006) and a similar aortic fixation length (23 vs 22 mm; P > .999) compared with suprarenal nonmigrators. Infrarenal migrators had a shorter iliac fixation length (18 vs 30 mm; P < .0001) and a similar aortic fixation length (14 vs 17 mm; P = .1) compared with infrarenal nonmigrators. Nonmigrators had closer device proximity to the hypogastric arteries in both the suprarenal (7 vs 17 mm; P = .009) and infrarenal (8 vs 24 mm; P < .0001) groups. No migration occurred in either group in patients with good iliac fixation. Multivariate logistic regression analysis revealed that iliac fixation, as evidenced by iliac fixation length (P = .004) and the device to hypogastric artery distance (P = .002), was a significant independent predictor of migration, whereas suprarenal or infrarenal treatment was not a significant predictor of migration. During a clinical follow-up period of 45 +/- 22 months (range, 12-70 months), there have been no aneurysm ruptures, abdominal aortic aneurysm-related deaths, or surgical conversions in either group.Distal iliac fixation is important in preventing migration of both suprarenal and infrarenal aortic endografts that have longitudinal columnar support. Secure iliac fixation minimizes the risk of migration despite suboptimal proximal aortic neck anatomy. Extension of both iliac limbs to cover the entire common iliac artery to the iliac bifurcation seems to prevent endograft migration.

    View details for DOI 10.1016/j.jvs.2006.09.061

    View details for Web of Science ID 000243987200006

    View details for PubMedID 17263997

  • Effect of non-steroidal anti-inflammatory medications on the risk of amyotrophic lateral sclerosis AMYOTROPHIC LATERAL SCLEROSIS Popat, R. A., Tanner, C. M., Van Den Eeden, S. K., Bernstein, A. L., Bloch, D. A., Leimpeter, A., McGuire, V., Nelson, L. M. 2007; 8 (3): 157-163

    Abstract

    Inflammatory processes may be involved in the pathogenesis of amyotrophic lateral sclerosis (ALS). We examined the association of non-steroidal anti-inflammatory drugs (NSAIDs) with the risk of ALS in case-control study of incident cases (n = 111) conducted within the Kaiser Permanente Medical Care Program of Northern California during the years 1996-2000. Controls (n = 258) randomly selected from the same population were frequency matched by age and gender to the ALS cases. Information regarding use of NSAIDs (non-aspirin and aspirin) and three classes of 'control' medications was collected by in-person structured interview. Subjects who used medication at least twice a week for at least a month were classified as 'ever users'. Multivariable logistic regression models were adjusted for age, gender, history of osteoarthritis/rheumatoid arthritis and pain, and other medication use. Overall, there was no association between NSAID use and ALS; however, some sex differences were noted for non-aspirin NSAID use. Among men, non-aspirin NSAID use was associated with a two-fold increased risk of ALS (adjusted odds ratio (OR) 2.0, 95% confidence interval (CI) 1.0-3.9), whereas among women, non-aspirin NSAID use was not associated with increased ALS risk (adjusted OR 0.5, 95% CI 0.2-1.2). ALS risk was not associated with aspirin use or with 'control' medications. This study did not find any evidence to suggest that NSAID use reduces the risk of ALS. The observed sex differences with non-aspirin NSAID use could be due to chance or an unmeasured confounder.

    View details for DOI 10.1080/17482960601179456

    View details for Web of Science ID 000246949600004

    View details for PubMedID 17538777

  • Candidate early predictors for progression to joint damage in systemic juvenile idiopathic arthritis JOURNAL OF RHEUMATOLOGY Sandborg, C., Holmes, T. H., Lee, T., Biederman, K., Bloch, D. A., Emery, H., McCurdy, D., Mellins, E. D. 2006; 33 (11): 2322-2329

    Abstract

    To assess if joint damage at 2 years after diagnosis in patients with systemic juvenile idiopathic arthritis (SJIA) can be predicted by clinical or laboratory features assessed up to 3 or 6 months after diagnosis.Medical records from 70 children were retrospectively reviewed. The primary outcome measure was presence of joint damage at 2 years after diagnosis (JD2) as defined by presence of erosions or fusion in one or more joints. Potential predictor variables for JD2 in the first 3 and 6 months after diagnosis consisted of the highest observed white blood cell count, platelet count, erythrocyte sedimentation rate, active joint count, and presence of symptomatic pulmonary or cardiac disease or macrophage activation syndrome, and treatment data.The outcome of interest, JD2, was identified in 15/70 patients. Classification-tree analysis identified a pair of variables (highest observed platelet count and number of active joints) measured within the first 3 months after diagnosis that together predicted progression to JD2 with an estimated sensitivity of 87%, specificity of 82%, and positive predictive value of 57%. Multivariate logistic regression analyses at 3 months found that higher quantities of joints with active arthritis and early use of methotrexate (MTX) were factors significantly associated with increased odds of progression to JD2 (active joints odds ratio = 1.08, 95% CI 1.00-1.16, p = 0.04; MTX OR = 11.85, 95% CI 1.89-74.26, p = 0.01). Unsupervised cluster analysis identified 2 major phenotypes of patients at 3 months characterized by different ages at onset, acute phase markers, active joint counts, and presence of serositis. These phenotypes differed 3-fold in proportion of subjects progressing to JD2 (p < 0.05).By 3 months after diagnosis, a clinical phenotype based on active joint count and platelet count may be prognostic of an increased risk of progression to JD2. Use of corticosteroids did not appear to change the risk of joint damage. In contrast, the presence of serositis appeared to be associated with decreased risk of joint damage.

    View details for Web of Science ID 000242010700035

    View details for PubMedID 16960920

  • Fluoxetine and suicide rates: Suicide and the economy PLOS MEDICINE Camargo, C. A., Bloch, D. A. 2006; 3 (11): 2161-2164
  • Endovascular aneurysm repair at 5 years: does aneurysm diameter predict outcome? JOURNAL OF VASCULAR SURGERY Zarins, C. K., Crabtree, T., Bloch, D. A., Arko, F. R., Ouriel, K., White, R. A. 2006; 44 (5): 920-929

    Abstract

    The appropriate size threshold for endovascular repair of small abdominal aortic aneurysms (AAA) is unclear. We studied the outcome of endovascular aneurysm repair (EVAR) as a function of preoperative aneurysm diameter to determine the relationship between aneurysm size and long-term outcome of endovascular repair.We reviewed the results of 923 patients treated in a prospective, multicenter clinical trial of EVAR. Small aneurysms were defined according to two size thresholds of 5.5 cm and 5.0 cm. Two-way analysis was used to compare patients with small aneurysms (<5.5 cm, n = 441) to patients with large aneurysms (> or =5.5 cm, n = 482). An ordered three-way analysis was used to compare patients with small AAA (<5.0 cm, n = 145), medium AAA (5.0 to 5.9 cm, n = 461), and large AAA (> or =6.0 cm, n = 317). The primary outcome measures of rupture, AAA-related death, surgical conversion, secondary intervention, and survival were compared using Kaplan-Meier estimates at 5 years.Median aneurysm size was 5.5 cm. The two-way comparison showed that 5 years after EVAR, patients with small aneurysms (<5.5 cm) had a lower AAA-related death rate (1% vs 6%, P = .006), a higher survival rate (69% vs 57%, P = .0002), and a lower secondary intervention rate (25% vs 32%, P = .03) than patients with large aneurysms (> or =5.5 cm). Three-way analysis revealed that patients with small AAAs (<5.0 cm) were younger (P < .0001) and were more likely to have a family history of aneurysm (P < .05), prior coronary intervention (P = .003), and peripheral occlusive disease (P = .008) than patients with larger AAAs. Patients with smaller AAAs also had more favorable aortic neck anatomy (P < .004). Patients with large AAAs were older (P < .0001), had higher operative risk (P = .01), and were more likely to have chronic obstructive pulmonary disease (P = .005), obesity (P = .03), and congestive heart failure (P = .004). At 5 years, patients with small AAAs had better outcomes, with 100% freedom from rupture vs 97% for medium AAAs and 93% for large AAAs (P = .02), 99% freedom from AAA-related death vs 97% for medium AAAs and 92% for large AAAs (P = .02) and 98% freedom from conversion vs 92% for medium AAAs and 89% for large AAAs (P = .01). Survival was significantly improved in small (69%) and medium AAAs (68%) compared to large AAAs (51%, P < .0001). Multivariate Cox proportional hazards modeling revealed that aneurysm size was a significant independent predictor of rupture (P = .04; hazard ratio [HR], 2.195), AAA-related death (P = .03; HR, 2.007), surgical conversion (P = .007; HR, 1.827), and survival (P = .001; HR, 1.351). There were no significant differences in secondary intervention, endoleak, or migration rates between small, medium, and large AAAs.Preoperative aneurysm size is an important determinant of long-term outcome following endovascular repair. Patients with small AAAs (<5.0 cm) are more favorable candidates for EVAR and have the best long-term outcomes, with 99% freedom from AAA death at 5 years. Patients with large AAAs (> or =6.0 cm) have shorter life expectancy and have a higher risk of rupture, surgical conversion, and aneurysm-related death following EVAR compared to patients with smaller aneurysms. Nonetheless, 92% of patients with large AAAs are protected from AAA-related death at 5 years. Patients with AAAs of intermediate size (5 to 6 cm) represent most of the patients treated with EVAR and have a 97% freedom from AAA-related death at 5 years.

    View details for DOI 10.1016/j.jvs.2006.06.048

    View details for Web of Science ID 000241714300002

    View details for PubMedID 17098519

  • The Apnea Positive Pressure Long-term Efficacy Study (APPLES): rationale, design, methods, and procedures. Journal of clinical sleep medicine Kushida, C. A., Nichols, D. A., Quan, S. F., Goodwin, J. L., White, D. P., Gottlieb, D. J., Walsh, J. K., Schweitzer, P. K., Guilleminault, C., Simon, R. D., Leary, E. B., Hyde, P. R., Holmes, T. H., Bloch, D. A., Green, S., McEvoy, L. K., Gevins, A., Dement, W. C. 2006; 2 (3): 288-300

    Abstract

    To assess the size, time course, and durability of the effects of long-term continuous positive airway pressure (CPAP) therapy on neurocognitive function, mood, sleepiness, and quality of life in patients with obstructive sleep apnea.Randomized, double-blinded, 2-arm, sham-controlled, multicenter, long-term, intention-to-treat trial of CPAP therapy.Sleep clinics and laboratories at 5 university medical centers and community-based hospitals. Patients or Participants: Target enrollment is 1100 randomly assigned subjects across 5 clinical centers.Active versus sham (subtherapeutic) CPAP. Measurements and Results: A battery of conventional and novel tests designed to evaluate neurocognitive function, mood, sleepiness, and quality of life.The Apnea Positive Pressure Long-term Efficacy Study (APPLES) is designed to study obstructive sleep apnea and test the effects of CPAP through a comprehensive, controlled, and long-term trial in a large sample of subjects with obstructive sleep apnea.

    View details for PubMedID 17561541

  • Mature results from a randomized phase II trial of cisplatin plus 5-fluorouracil and radiotherapy with or without tirapazamine in patients with resectable stage IV head and neck squamous cell carcinomas CANCER Le, Q. T., Taira, A. I., Budenz, S., Dorie, M. J., Goffinet, D. R., Fee, W. E., Goode, R., Bloch, D., Koong, A., Brown, J. M., Pinto, H. A. 2006; 106 (9): 1940-1949

    Abstract

    The objective of this article was to report the results from a randomized trial that evaluated the efficacy and toxicity of adding tirapazamine (TPZ) to chemoradiotherapy in the treatment of patients with head and neck squamous cell carcinomas (HNSCC).Sixty-two patients with lymph node-positive, resectable, TNM Stage IV HNSCC were randomized to receive either 2 cycles of induction chemotherapy (TPZ, cisplatin, and 5-fluorouracil [5-FU]) followed by simultaneous chemoradiotherapy (TPZ, cisplatin, and 5-FU) or to receive the same regimen without TPZ. Patients who did not achieve a complete response at 50 Grays underwent surgical treatment. Stratification factors for randomization included tumor site, TNM stage, and median tumor oxygen tension. The primary endpoint was complete lymph node response.The addition of TPZ resulted in increased hematologic toxicity. There was 1 treatment-related death from induction chemotherapy. The complete clinical and pathologic response rate in the lymph nodes was 90% and 74% for the standard treatment arm and the TPZ arm, respectively (P = .08) and 89% and 90% at the primary site in the respective treatment arms (P = .71). The 5-year overall survival rate was 59%, the cause-specific survival rate was 68%, the rate of freedom from recurrence was 69%, and the locoregional control rate was 77% for the entire group. There was no difference with regard to any of the outcome parameters between the 2 treatment arms. The significant long-term toxicity rate also was found to be similar between the 2 arms.The addition of TPZ increased hematologic toxicity but did not improve outcomes in patients with resectable, Stage IV HNSCC using the protocol administered this small randomized study. The combination of induction and simultaneous chemoradiotherapy resulted in excellent survival in these patients.

    View details for DOI 10.1002/cncr.21785

    View details for Web of Science ID 000237187400010

    View details for PubMedID 16532436

  • Effect of reproductive factors and postmenopausal hormone use on the risk of amyotrophic lateral sclerosis NEUROEPIDEMIOLOGY Popat, R. A., Van Den Eeden, S. K., Tanner, C. M., Bernstein, A. L., Bloch, D. A., Leimpeter, A., McGuire, V., Nelson, L. M. 2006; 27 (3): 117-121

    Abstract

    To examine the associations of reproductive factors and postmenopausal hormone use with the risk of amyotrophic lateral sclerosis (ALS) among women.This case-control study was conducted within the Kaiser Permanente Medical Care Program (KPMCP) of Northern California during the years 1996-2000. Among the 193 postmenopausal women, 62 were incident ALS cases and 131 were controls randomly selected from KPMCP members and frequency matched by age and respondent type (self versus proxy) to the cases. Statistical analyses were carried out using logistic regression.Reproductive factors such as age at menarche, age at final menstrual period, parity, oral contraceptive use, and type of menopause (natural vs. hysterectomy with or without oophorectomy) were not associated with risk of ALS. Postmenopausal hormone use was positively, but not significantly, associated with the risk of ALS (adjusted OR 1.9, 95% CI 0.9-3.8).Reproductive factors were not associated with ALS risk. There is no evidence that suggests a protective effect of postmenopausal hormone use against the development of ALS. However, due to insufficient power, we cannot rule out a possible increase in ALS risk associated with postmenopausal hormone use.

    View details for DOI 10.1159/000095550

    View details for Web of Science ID 000241773900001

    View details for PubMedID 16946622

  • A comprehensive assessment of the safety of intravenous methamphetamine administration during treatment with selegiline PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR Newton, T. F., De la Garza, R., Fong, T., Chiang, N., Holmes, T. H., Bloch, D. A., Anderson, A., Elkashef, A. 2005; 82 (4): 704-711

    Abstract

    Selegiline (L-deprenyl) is a selective irreversible monoamine oxidase B inhibitor shown to be effective in the treatment of Parkinson's and Alzheimer's diseases. Recent evidence suggests that selegiline may also be useful in treating specific aspects of cocaine and nicotine dependence, generating interest in this compound for the treatment of methamphetamine addiction. To investigate this, we performed a randomized, single-blind, placebo-controlled study to evaluate the safety of selegiline treatment (as compared to placebo), concurrent with intravenous methamphetamine (15 or 30 mg). Secondary study objectives included determinations of plasma levels of selegiline and its metabolites, evaluating whether selegiline administration altered the pharmacokinetics of methamphetamine or its metabolites, and evaluating whether selegiline treatment alters the subjective responses to methamphetamine. Twenty-four methamphetamine-dependent participants were randomized to treatment, and 9 of these (N = 5 selegiline, N = 4 placebo) completed the entire protocol. The principal finding from this study was that intravenous administration of moderate doses of methamphetamine was safely tolerated during treatment with selegiline. No participants had electrocardiogram changes, and there were no meaningful differences in any laboratory values either between groups at screening or as a result of the study procedures. In general, adverse events were mild or moderate, and no subjects were discontinued due to adverse events or serious adverse events. Selegiline treatment did not enhance any of the cardiovascular changes (heart rate, blood pressure) produced by methamphetamine administration. Selegiline treatment slightly increased methamphetamine associated "bad effects" but did not alter any other subjective effects. The elimination half-life of methamphetamine was approximately 12 h, and selegiline did not alter clearance of methamphetamine. The available data suggest that selegiline is likely to be safe if used as a pharmacotherapy for methamphetamine dependence.

    View details for DOI 10.1016/j.pbb.2005.11.012

    View details for Web of Science ID 000235554000015

    View details for PubMedID 16413604

  • Protective conditioning for acute graft-versus-host disease NEW ENGLAND JOURNAL OF MEDICINE Lowsky, R., Takahashi, T., Liu, Y. P., Dejbakhsh-Jones, S., GRUMET, F. C., Shizuru, J. A., Laport, G. G., Stockerl-Goldstein, K. E., JOHNSTON, L. J., Hoppe, R. T., Bloch, D. A., Blume, K. G., Negrin, R. S., Strober, S. 2005; 353 (13): 1321-1331

    Abstract

    Conditioning with total lymphoid irradiation plus antithymocyte serum protects mice against acute graft-versus-host disease (GVHD) after hematopoietic-cell transplantation. We tested this strategy in humans.Thirty-seven patients with lymphoid malignant diseases or acute leukemia underwent an experimental conditioning regimen with 10 doses of total lymphoid irradiation (80 cGy each) plus antithymocyte globulin, followed by an infusion of HLA-matched peripheral-blood mononuclear cells from related or unrelated donors who received granulocyte colony-stimulating factor.Of the 37 transplant recipients, only 2 had acute GVHD after hematopoietic-cell transplantation. Potent antitumor effects in patients with lymphoid malignant diseases were shown by the change from partial to complete remission. In the transplant recipients who underwent conditioning with total lymphoid irradiation and antithymocyte globulin, the fraction of donor CD4+ T cells that produced interleukin-4 after in vitro stimulation increased by a factor of five, and the proliferative response to alloantigens in vitro was reduced, as compared with normal control subjects and control subjects who underwent conditioning with a single dose of total-body irradiation (200 cGy).A regimen of total lymphoid irradiation plus antithymocyte globulin decreases the incidence of acute GVHD and allows graft antitumor activity in patients with lymphoid malignant diseases or acute leukemia treated with hematopoietic-cell transplantation.

    View details for Web of Science ID 000232146200004

    View details for PubMedID 16192477

  • Effect of reproductive factors and postmenopausal hormone use on the risk of Parkinson disease NEUROLOGY Popat, R. A., Van Den Eeden, S. K., Tanner, C. M., McGuire, V., Bernstein, A. L., Bloch, D. A., Leimpeter, A., Nelson, L. M. 2005; 65 (3): 383-390

    Abstract

    Parkinson disease (PD) is less common in women possibly because of hormonal or reproductive influences. The objective of this study was to evaluate the associations of reproductive factors and postmenopausal hormone use with the risk of PD among postmenopausal women.Incident cases (n = 178) and randomly selected age-matched controls (n = 189) who were members of the Kaiser Permanente Medical Care Program (KPMCP) of Northern California participated in the study conducted during the years 1994 to 1995. Statistical analyses were carried out using logistic regression.The association of postmenopausal hormone use with PD risk depended on the type of menopause. Among women with history of a hysterectomy with or without an oophorectomy, estrogen use alone was associated with a 2.6-fold increased risk (adjusted odds ratio (OR) 2.6, 95% CI: 1.1 to 6.1) and significant trends in the risk of PD were observed with increasing duration of estrogen use, but disease risk was not influenced by recency of use. In contrast, among women with natural menopause, no increased risk of PD was observed with hormone use (estrogen alone or a combined estrogen-progestin regimen). Early age at final menstrual period (44 years or younger) was associated with reduction in risk (adjusted OR 0.5, 95% CI: 0.3 to 1.0). Age at menarche and parity were not associated with the risk of PD.Postmenopausal use of estrogen alone may increase the risk of Parkinson disease (PD) among women with a hysterectomy. Among women with natural menopause for whom the usual treatment is combined estrogen-progestin therapy, no increased risk of PD was observed.

    View details for Web of Science ID 000231067200010

    View details for PubMedID 16087902

  • Endovascular repair or surveillance of patients with small AAA EUROPEAN JOURNAL OF VASCULAR AND ENDOVASCULAR SURGERY Zarins, C. K., Crabtree, T., Arko, F. R., Heikkinen, M. A., Bloch, D. A., Ouriel, K., White, R. A. 2005; 29 (5): 496-503

    Abstract

    To compare the outcome of patients with small abdominal aortic aneurysms (AAA) treated in a prospective trial of endovascular aneurysm repair (EVAR) to patients randomized to the surveillance arm of the UK Small Aneurysm Trial.All patients with small AAA (< or = 5.5 cm diameter) treated with a stent graft (EVARsmall) in the multicenter AneuRx clinical trial from 1997 to 1999 were reviewed with follow up through 2003. A subgroup of patients (EVARmatch) who met the age (60-76 years) and aneurysm size (4.0-5.5 cm diameter) inclusion criteria of the UK Small Aneurysm Trial were compared to the published results of the surveillance patient cohort (UKsurveil) of the UK Small Aneurysm Trial (NEJM 346:1445, 2002). Endpoints of comparison were aneurysm rupture, fatal aneurysm rupture, operative mortality, aneurysm related death and overall mortality. The total patient years of follow-up for EVAR patients was 1369 years and for UK patients was 3048 years. Statistical comparisons of EVARmatch and UKsurveil patients were made for rates per 100 patient years of follow up (/100 years) to adjust for differences in follow-up time.The EVARsmall group of 478 patients comprised 40% of the total number of patients treated during the course of the AneuRx clinical trial. The EVARmatch group of 312 patients excluded 151 patients for age < 60 or > 76 years and 15 patients for AAA diameter < 4 cm. With the exception of age, there were no significant differences between EVARsmall and EVARmatch in pre-operative factors or post-operative outcomes. In comparison to the UKsurveil group of 527 patients, the EVARmatch group was slightly older (70 +/- 4 vs. 69 +/- 4 years, p = 0.009), had larger aneurysms (5.0 +/- 0.3 vs. 4.6 +/- 0.4 cm, p < 0.001), fewer women (7 vs. 18%, p < 0.001), and had a higher prevalence of diabetes and hypertension and a lower prevalence of smoking at baseline. Ruptures occurred in 1.6% of EVARmatch patients and 5.1% of UKsurveil patients; this difference was not significant when adjusted for the difference in length of follow up. Fatal aneurysm rupture rate, adjusted for follow up time, was four times higher in UKsurveil (0.8/100 patient years) than in EVARmatch (0.2/100 patient years, p < 0.001); this difference remained significant when adjusted for difference in gender mix. Elective operative mortality rate was significantly lower in EVARmatch (1.9%) than in UKsurveil (5.9%, p < 0.01). Aneurysm-related death rate was two times higher in UKsurveil (1.6/100 patient years) than in EVARmatch (0.8/100 patient years, p = 0.03). All-cause mortality rate was significantly higher in UKsurveil (8.3/100 patient years) than in EVARmatch (6.4/100 patient years, p = 0.02).It appears that endovascular repair of small abdominal aortic aneurysms (4.0-5.5 cm) significantly reduces the risk of fatal aneurysm rupture and aneurysm-related death and improves overall patient survival compared to an ultrasound surveillance strategy with selective open surgical repair.

    View details for DOI 10.1016/j.ejvs.2005.03.003

    View details for Web of Science ID 000228842700008

    View details for PubMedID 15966088

  • Meniscal tear and extrusion are strongly associated with progression of symptomatic knee osteoarthritis as assessed by quantitative magnetic resonance imaging ANNALS OF THE RHEUMATIC DISEASES Berthiaume, M. J., Raynauld, J. P., Martel-Pelletier, J., Labonte, F., Beaudoin, G., Bloch, D. A., Choquette, D., Haraoui, B., Altman, R. D., Hochberg, M., Meyer, J. M., Cline, G. A., Pelletier, J. P. 2005; 64 (4): 556-563

    Abstract

    The relation between knee meniscal structural damage and cartilage degradation is plausible but not yet clearly proven.To quantitate the cartilage volume changes in knee osteoarthritis using magnetic resonance imaging (MRI), and determine whether meniscal alteration predicts cartilage volume loss over time.32 patients meeting ACR criteria for symptomatic knee osteoarthritis were studied. MRI knee acquisitions were done every six months for two years. The cartilage volumes of different knee regions were measured. Three indices of structural change in the medial and lateral menisci were evaluated--degeneration, tear, and extrusion--using a semiquantitative scale.24 patients (75%) had mild to moderate or severe meniscal damage (tear or extrusion) at baseline. A highly significant difference in global cartilage volume loss was observed between severe medial meniscal tear and absence of tear (mean (SD), -10.1 (2.1)% v -5.1 (2.4)%, p = 0.002). An even greater difference was found between the medial meniscal changes and medial compartment cartilage volume loss (-14.3 (3.0)% in the presence of severe tear v -6.3 (2.7)% in the absence of tear; p<0.0001). Similarly, a major difference was found between the presence of a medial meniscal extrusion and loss of medial compartment cartilage volume (-15.4 (4.1)% in the presence of extrusion v -4.5 (1.7)% with no extrusion; p<0.001).Meniscal tear and extrusion appear to be associated with progression of symptomatic knee osteoarthritis.

    View details for DOI 10.1136/ard.2004.023796

    View details for Web of Science ID 000227950600009

    View details for PubMedID 15374855

  • Retrospective analyses of pooled data from CREST I and CREST II trials for treatment of cocaine dependence ADDICTION Elkashef, A., Holmes, T. H., Bloch, D. A., Shoptaw, S., Kampman, K., Reid, M. S., Somoza, E. R., Ciraulo, D., Rotrosen, J., Leiderman, D., Montgomery, A., Vocci, F. 2005; 100: 91-101

    Abstract

    To analyze pooled data from the Cocaine Rapid Evaluation Screening Trial (CREST). Pooling data from these small pilot trials into four major drug classes permitted data exploration for treatment and covariate effects with increased sample size.Small pilot trials were conducted to screen fifteen medications as prospective treatments for cocaine dependence. Studies included a flexible 2-week to 4-week screening/baseline period followed by an 8-week randomized treatment condition. Participants were randomized equally to one of up to three active medications or placebo.Five Medications Development Research Units at the five academic centers of University of Cincinnati, New York University, University of Pennsylvania, University of California Los Angeles and Boston University.The pooled data set consisted of 357 total subjects. Standardized inclusion and exclusion criteria were employed in subject selection to enhance consistency of cocaine-dependent study participants across all sites (see reports on individual trials in this supplement for details). All participants provided at least two urine samples that were positive for cocaine metabolite during a two-week period prior to being randomized.All subjects in these trials, those randomized to placebo and active medications, received active treatment in the form of evidence-based cognitive behavioral therapy.Quantitative urine benzoylecgonine (BE), self-report of cocaine use, and total Brief Substance Craving Scale (BSCS) scores were compared between each class of medication and its matched-placebo group.Regression analysis of pooled data did not identify any statistically significant differences between treatment and matched-placebo for any of the four classes. Exploration of the effects of baseline covariates indicated that gender and African American status were associated significantly with outcome. Female gender was consistently associated with poorer outcomes for medication and placebo groups, while the direction of association between African American status and outcome differed by treatment groups. Retention was also examined: dropout rates may have been somewhat higher for placebo than treatment groups during the early active-treatment period. Classification trees were used to identify characteristics of subjects who were abstinent for at least two weeks during the eight-week trial; only 4.0% of females while 17.9% of males achieved this criterion.Results presented here may prove useful for planning future clinical trials for therapies targeting cocaine dependence.

    View details for Web of Science ID 000227729200009

    View details for PubMedID 15730353

  • Cocaine Rapid Efficacy Screening Trial (CREST): a paradigm for the controlled evaluation of candidate medications for cocaine dependence ADDICTION Leiderman, D. B., Shoptaw, S., Montgomery, A., Bloch, D. A., Elkashef, A., LoCastro, J., Vocci, F. 2005; 100: 1-11

    Abstract

    Development of effective medications for the treatment of cocaine dependence remains a major priority for the National Institute on Drug Abuse (NIDA) at the National Institutes of Health. The Cocaine Rapid Efficacy Screening Trial (CREST) paradigm was developed by the Division of Treatment Research and Development (DT R&D) at NIDA with the goal of enhancing pilot clinical trial validity when systematically assessing a range of medications and drug classes for potential utility in treatment of cocaine dependence.CREST utilizes a randomized, controlled, parallel group, blinded methodology for comparing one or more marketed medications against a standard, pharmaceutical grade placebo. The trial design is comprised of a flexible 24-week screening/baseline period followed by randomization to an 8-week treatment period.Standard measures of outcomes for the CREST included urinary benzoylecgonine (primary metabolite of cocaine), retention, cocaine craving, depression, clinical global impression and HIV-risk behaviors. In order to facilitate comparisons of data from the CREST studies across sites, drug classes and time, standardized procedures, measures and psychosocial counseling were used.A total of 19 medications were evaluated in out-patient treatment research clinics in Boston, Cincinnati, Los Angeles, New York and Philadelphia.Findings supported decisions to move forward three medications (cabergoline, reserpine, tiagabine) using full-scale, adequately powered, randomized placebo-controlled trial designs. Lessons learned from the CREST experience continue to shape cocaine pharmacotherapy trial design and execution.

    View details for Web of Science ID 000227729200001

    View details for PubMedID 15773068

  • A medication screening trial evaluation of reserpine, gabapentin and lamotrigine pharmacotherapy of cocaine dependence ADDICTION Berger, S. P., Winhusen, T. M., Somoza, E. C., Harrer, J. M., Mezinskis, J. P., Leiderman, D. B., Montgomery, M. A., Goldsmith, R. J., Bloch, D. A., Singal, B. M., Elkashef, A. 2005; 100: 58-67

    Abstract

    To conduct a preliminary evaluation of the safety and efficacy of reserpine, gabapentin or lamotrigine versus an unmatched placebo control as a treatment for cocaine dependence.A 10-week out-patient study using the Cocaine Rapid Efficacy and Safety Trial (CREST) study design.The study was conducted at the Cincinnati Medication Development Research Unit (MDRU).Participants met Diagnostic and Statistical Manual version IV (DSM-IV) criteria for cocaine dependence. Sixty participants were enrolled, with 50 participants completing the final study measures.The targeted daily doses of medication were reserpine 0.5 mg, gabapentin 1800 mg and lamotrigine 150 mg. All participants received 1 hour of manualized individual cognitive behavioral therapy on a weekly basis.Primary outcome measures of efficacy included urine benzoylecgonine (BE) level, Cocaine Clinical Global Impression scale--observer and self-report of cocaine use. Safety measures included adverse events, electrocardiograms (ECGs), vital signs and laboratory tests.Subjective measures of cocaine dependence indicated significant improvement for all study groups. Urine BE results indicated a significant improvement for the reserpine group (P < 0.05) and non-significant changes for the other study groups. No pattern of physical or laboratory abnormalities attributable to treatment with any of the medications was identified. There were three serious adverse events reported, none of which were related to study procedures. The medications appeared to be tolerated well.The present findings suggest that reserpine may be worthy of further study as a cocaine dependence treatment.

    View details for Web of Science ID 000227729200006

    View details for PubMedID 15730350

  • A placebo-controlled screening trial of tiagabine, sertraline and donepezil as cocaine dependence treatments ADDICTION Winhusen, T. M., Somoza, E. C., Harrer, J. M., Mezinskis, J. P., Montgomery, M. A., Goldsmith, R. J., Coleman, F. S., Bloch, D. A., Leiderman, D. B., Singal, B. M., Berger, P., Elkashef, A. 2005; 100: 68-77

    Abstract

    To conduct a preliminary evaluation of the safety and efficacy of tiagabine, sertraline or donepezil versus an unmatched placebo control as a treatment for cocaine dependence.A 10-week out-patient study was conducted using the Cocaine Rapid Efficacy and Safety Trial (CREST) study design.This study was conducted at the Cincinnati Medication Development Research Unit (MDRU) and at an affiliated site in Dayton, Ohio.Participants met Diagnostic and Statistical Manual version IV (DSM-IV) criteria for cocaine dependence. Sixty-seven participants were enrolled with 55 completing final study measures.The targeted daily doses of medication were tiagabine 20 mg, sertraline 100 mg and donepezil 10 mg. All participants received 1 hour of manualized individual cognitive behavioral therapy on a weekly basis.Primary outcome measures of efficacy included urine benzoylecgonine (BE) level, Cocaine Clinical Global Impression Scale-Observer and self-report of cocaine use. Safety measures included adverse events, ECGs, vital signs and laboratory tests.Subjective measures of cocaine dependence indicated significant improvement for all study groups. Generalized estimating equations analysis indicated that the tiagabine group showed a trend toward a significant decrease in urine BE level from baseline to weeks 5-8 (P = 0.10) and non-significant changes for the other study groups. No pattern of physical or laboratory abnormalities attributable to treatment with any of the medications was identified. There were three serious adverse events reported, none of which were related to study procedures.The present findings suggest that tiagabine may be worthy of further study as a cocaine dependence treatment.

    View details for Web of Science ID 000227729200007

    View details for PubMedID 15730351

  • Cocaine Rapid Efficacy Screening Trials (CREST): lessons learned ADDICTION Kampman, K. M., Leiderman, D., Holmes, T., LoCastro, J., Bloch, D. A., Reid, M. S., Shoptaw, S., Montgomery, M. A., Winhusen, T. M., Somoza, E. C., Ciraulo, D. A., Elkashef, A., Vocci, F. 2005; 100: 102-110

    Abstract

    The Cocaine Rapid Efficacy Screening Trials (CREST) were designed by the National Institute on Drug Abuse Division of Treatment Research and Development (NIDA, DT R&D) to rapidly screen a number of medications potentially useful for the treatment of cocaine dependence.Each CREST trial was designed to compare several medications in a single trial against an unmatched placebo. The placebo group was included in each trial to avoid the nearly universal positive response to medications seen in open-label trials. In addition, a common set of procedures and outcome measures were employed throughout to increase comparability of results obtained from different trials and from different times.In all, 18 medications were screened in seven different trials, conducted in four different sites throughout the United States involving 398 cocaine-dependent patients.Three medications were found to be promising enough to include in subsequent larger trials. Common statistical procedures for evaluating medications were developed to facilitate comparisons across sites and across time. A portion of the data were pooled and analyzed, which yielded some useful insights into cocaine dependence and its treatment. Finally, a review of individual trials together with the pooled analysis revealed several potential improvements for future screening trials.Overall, the CREST trials proved to be useful for rapidly screening medications for treatment of cocaine dependence, but several modifications in design should be made before this framework is applied further.

    View details for Web of Science ID 000227729200010

    View details for PubMedID 15730354

  • Efficacy screening trials of paroxetine, pentoxifylline, riluzole, pramipexole and venlafaxine in cocaine dependence ADDICTION Ciraulo, D. A., Sarid-Segal, O., Knapp, C. M., Ciraulo, A. M., LoCastro, J., Bloch, D. A., Montgomery, M. A., Leiderman, D. B., Elkashef, A. 2005; 100: 12-22

    Abstract

    The two studies presented here were conducted to assess the efficacy of paroxetine, pentoxifylline, riluzole, venlafaxine and pramipexole as medications for the treatment of cocaine dependence.A multi-arm, modified blinded, placebo-controlled design was used.The studies were conducted at the Boston VA Healthcare System and the Boston University School of Medicine Medication Development Research Unit (MDRU).Participants met criteria for cocaine dependence during a 2-week screening period.Following random assignment to one of the treatment groups, subjects received active medication or placebo for 8 weeks in combination with cognitive behavioral counseling. In the first study the efficacy of the antidepressant paroxetine (20 mg daily), the phosphodiesterase inhibitor pentoxifylline (1200 mg daily) and the glutamate release inhibitor riluzole (100 mg daily) was assessed. The antidepressant venlafaxine (150 mg daily) and the dopamine agonist pramipexole (1.5 mg daily) were evaluated in the second study.Urine benzoylecgonine (BE) concentrations, self-report of cocaine use and global impression scores served as primary outcome measures. Secondary measures included assessments of cocaine craving and psychiatric functioning. Adverse events were monitored during the treatment period.None of the active medications produced greater reductions in urine BE concentrations over the treatment period than did placebo. There were trends for BE levels to become reduced in the pentoxifylline group during the first 4 weeks of treatment and for Addiction Severity Index (ASI) drug composite scores to be lower in the pentoxyfylline group at end-point compared to the placebo group. Significant within-group reductions in reported cocaine use and craving were found for all treatment groups, but none of the active medications were superior to placebo on these measures. The accuracy of self-reported cocaine use declined over the study period. Overall, the active medications were well tolerated.This study does not support the use of paroxetine, pentoxifylline, riluzole, venlafaxine or pramipexole for the treatment of cocaine dependence. However, these results need to be interpreted with caution because of the small size and lack of homogeneity of the experimental groups.

    View details for Web of Science ID 000227729200002

    View details for PubMedID 15730346

  • A nonparametric comparison of the effectiveness of treatments: A multivariate toxicity-penalized approach JOURNAL OF BIOPHARMACEUTICAL STATISTICS Tubert-Bitter, P., Letierce, A., Bloch, D. A., Kramar, A. 2005; 15 (1): 129-142

    Abstract

    In cancer clinical trials, the amount of treatment dose actually received by a patient may be limited by severe toxicity or lack of efficacy. A nonparametric approach is proposed for comparing the effectiveness of treatments based on the bivariate relationship defined by the doses at which efficacy and toxicity are observed to occur. Simulation studies are used to contrast the performance of the new procedure with the usual method of comparing percentages of patients who have effective results. Data from a randomized clinical trial of patients with metastatic nonseminomatous germ cell tumors are used to illustrate the method.

    View details for DOI 10.1081/BIP-200040851

    View details for Web of Science ID 000236207800010

    View details for PubMedID 15702609

  • Quantitative air-trapping analysis in children with mild cystic fibrosis lung disease PEDIATRIC PULMONOLOGY Bonnel, A. S., Song, S. M., Kesavarju, K., Newaskar, M., Paxton, C. J., Bloch, D. A., Moss, R. B., Robinson, T. E. 2004; 38 (5): 396-405

    Abstract

    The purpose of this study was to compare quantitative computed tomography air trapping (AT) and pulmonary function measurements between subjects with mild cystic fibrosis lung disease (MCF; forced expiratory volume in 1 sec (FEV1) > 70% predicted) and normal age-matched controls. Quantitative AT measurements at different levels of expiration were evaluated. Ten subjects from the MCF group and 10 normal subjects underwent inspiratory and expiratory spirometer-triggered chest high-resolution computed tomography (HRCT) and pulmonary function tests. Six matched CT images were obtained at full inflation and at a lung volume near residual volume (nRV). Quantitative measurements of AT were determined by evaluating expiratory CT lung density and by the percent of segmented lung which demonstrated AT on expiratory scans. Percent AT was evaluated for all lung slices combined (global AT), and also by regional assessment. Additional comparisons of lung density and percent air trapping were made in 10 CF subjects with three matched axial HRCT images at lung volumes corresponding to full inflation, near functional residual capacity (nFRC), and nRV. All measurements of expiratory lung density in CF subjects were significantly lower and % AT significantly higher than normal controls. Significant correlations for all subjects were observed between % global AT and RV/TLC as well as forced expiratory flow between 25-75% of forced vital capacity (FEF(25-75)) % predicted. Pulmonary density measurements and % AT better discriminated differences between groups than PFTs. Measurements made on expiratory scans near FRC showed significantly higher values for AT than those made near RV.

    View details for DOI 10.1002/ppul.20091

    View details for Web of Science ID 000224625500004

    View details for PubMedID 15390349

  • Misperceptions regarding the long-term safety of the AneuRx stent graft JOURNAL OF VASCULAR SURGERY Zarins, C. K., Bloch, D. A. 2004; 40 (3): 594-595

    View details for DOI 10.1016/j.jvs.2004.07.016

    View details for Web of Science ID 000227388200040

    View details for PubMedID 15337899

  • A two-year evaluation of disease progression by quantitative magnetic resonance imaging in a large primary osteoarthritic patient population. Raynauld, J. P., Martel-Pelletier, J., Berthiaume, M. J., Beaudoin, G., Labonte, F., Bloch, D. A., Choquette, C., Haraoui, B., Altman, R. D., Hochberg, M., Beary, J., Cline, G., Meyer, J., Valent, D., Pelletier, J. P. WILEY-BLACKWELL. 2004: S349-S349
  • Explant analysis of AneuRx stent grafts: Relationship between structural findings and clinical outcome JOURNAL OF VASCULAR SURGERY Zarins, C. K., Arko, F. R., Crabtree, T., Bloch, D. A., Ouriel, K., Allen, R. C., White, R. A. 2004; 40 (1): 1-11

    Abstract

    We reviewed the structural findings of explanted AneuRx stent grafts used to treat abdominal aortic aneurysms, and relate the findings to clinical outcome measures.We reviewed data for all bifurcated AneuRx stent grafts explanted at surgery or autopsy and returned to the manufacturer from the US clinical trial and worldwide experience of more than 33,000 implants from 1996 to 2003. Devices implanted for more than 1 month with structural analysis are included in this article. Explant results were analyzed in relation to cause of explantation and pre-explant evidence of endoleak, enlargement, or device migration.One hundred twenty explanted stent grafts, including 37 from the US clinical trial, were analyzed. Mean implant duration was 22 +/- 13 months (range, 1-61 months). Structural abnormalities included stent fatigue fractures, fabric abrasion holes, and suture breaks. The mean number of nitinol stent strut fractures per explanted device was 3 +/- 4, which represents less than 0.2% of the total number of stent struts in each device. The mean number of fabric holes per explanted device was 2 +/- 3, with a median hole size of 0.5 mm(2). Suture breaks were seen in most explanted devices, but composed less than 1.5% of the total number of sutures per device. "For cause" explants (n = 104) had a 10-month longer implant duration (P =.007) compared with "incidental" explants (n = 16). "For cause" explants had more fractures (3 +/- 5; P =.005) and fabric holes (2 +/- 3; P =.008) per device compared with "incidental" explants, but these differences were not significant (P =.3) when adjusted for duration of device implantation. Among clinical trial explants the number of fabric holes in grafts in patients with endoleak (2 +/- 3 per device) was no different from those without endoleak (3 +/- 4 per device; P = NS). The number of fatigue fractures or fabric holes was no different in grafts in clinical trial patients with pre-explant aneurysm enlargement compared with those without enlargement. Pre-explant stent-graft migration was associated with a greater number of stent strut fractures (5 +/- 7 per device; P =.04) and fabric holes (3 +/- 3 per bifurcation; P =.03) compared with explants without migration. Serial imaging studies revealed inadequate proximal, distal, or junctional device fixation as the probable cause of rupture or need for conversion to open surgery in 86% of "for cause" explants. Structural device abnormalities were usually remote from fixation sites, and no causal relationship between device findings and clinical outcome could be established.Nitinol stent fatigue fractures, fabric holes, and suture breaks found in explanted AneuRx stent grafts do not appear to be related to clinical outcome measures. Longer term studies are needed to confirm these observations.

    View details for DOI 10.1016/j.jvs.2004.03.008

    View details for Web of Science ID 000222522300001

    View details for PubMedID 15218454

  • A two-year evaluation of disease progression by quantitative magnetic resonance imaging in a large primary osteoarthritic patient population Raynauld, J. P., Martel-Pelletier, J., Berthiaume, M., Beaudoin, G., Labonte, F., Bloch, D., Choquette, D., Haraoui, B., Altman, R., Hochberg, M., Beary, J., Cline, G., Meyer, J., Valent, D., Pelletier, J. P. BMJ PUBLISHING GROUP. 2004: 71-71
  • Quantitative magnetic resonance imaging evaluation of knee osteoarthritis progression over two years and correlation with clinical symptoms and radiologic changes ARTHRITIS AND RHEUMATISM Raynauld, J. P., Martel-Pelletier, J., Berthiaume, M. J., Labonte, F., Beaudoin, G., de Guise, J. A., Bloch, D. A., Choquette, D., Haraoui, B., Altman, R. D., Hochberg, M. C., Meyer, J. M., Cline, G. A., Pelletier, J. P. 2004; 50 (2): 476-487

    Abstract

    To evaluate the change in osteoarthritic (OA) knee cartilage volume over a two-year period with the use of magnetic resonance imaging (MRI) and to correlate the MRI changes with radiologic changes.Thirty-two patients with symptomatic knee OA underwent MRI of the knee at baseline and at 6, 12, 18, and 24 months. Loss of cartilage volumes were computed and contrasted with changes in clinical variables for OA and with standardized semiflexed knee radiographs at baseline at 1 and 2 years.Progression of cartilage loss at all followup points was statistically significant (P < 0.0001), with a mean +/- SD of 3.8 +/- 5.1% for global cartilage loss and 4.3 +/- 6.5% for medial compartment cartilage loss at 6 months, 3.6 +/- 5.1% and 4.2 +/- 7.5% at 12 months, and 6.1 +/- 7.2% and 7.6 +/- 8.6% at 24 months. Discriminant function analysis identified 2 groups of patients, those who progressed slowly (<2% of global cartilage loss; n = 21) and those who progressed rapidly (>15% of global cartilage loss; n = 11) over the 2 years of study. At baseline, there was a greater proportion of women (P = 0.001), a lower range of motion (P = 0.01), a greater circumference and higher level of pain (P = 0.05) and stiffness in the study knee, and a higher body mass index in the fast progressor group compared with the slow progressor group. No statistical correlation between loss of cartilage volume and radiographic changes was seen.Quantitative MRI can measure the progression of knee OA precisely and can help to identify patients with rapidly progressing disease. These findings indicate that MRI could be helpful in assessing the effects of treatment with structure-modifying agents in OA.

    View details for DOI 10.1002/art.20000

    View details for Web of Science ID 000188978800018

    View details for PubMedID 14872490

  • Aneurysm enlargement following endovascular aneurysm repair: AneuRx clinical trial JOURNAL OF VASCULAR SURGERY Zarins, C. K., Bloch, D. A., Crabtree, T., Matsumoto, A. H., White, R. A., Fogarty, T. J. 2004; 39 (1): 109-117

    Abstract

    The purpose of this study was to determine the incidence and significance of aneurysm enlargement, with or without treatment, in relation to the primary end points of rupture, surgical conversion, aneurysm-related death, and survival following endovascular repair.Aneurysm (AAA) size changes and clinical outcome of all patients treated from 1997 through 1998 during the Phase II AneuRx multicenter clinical trial of endovascular AAA repair were reviewed. Aneurysm dimensions and the presence or absence of endoleak were determined by an independent core laboratory, with enlargement or shrinkage defined as a diameter change of 5 mm or more compared with baseline.Among 383 patients (89% men, 11% women, age 73 +/- 9 years), with a mean device implant time of 36 +/- 11 months (median = 39 months), aneurysm diameter decreased from 5.7 +/- 1.0 at baseline to 5.2 +/- 1.0 at 3 years (P =.0001). A total of 46 patients (12%) experienced AAA enlargement, 199 patients (52%) had no change in AAA diameter, and 138 patients (36%) had a decrease in AAA diameter of 5 mm or more. Significant risk factors for enlargement included age (enlargement patients were 4 years older on average than patients with aneurysms that decreased in size; P =.002) and the presence of an endoleak (P <.001). Among patients with endoleak at any time, 17% had aneurysm enlargement, whereas only 2% of patients without endoleak had aneurysm enlargement (P <.001). Patients with enlargement were more likely to undergo secondary endovascular procedures and surgical conversions (P <.001). Twenty patients (43%) with enlargement underwent treatment, and 26 patients were untreated. There were two deaths following elective surgical conversion and one death in a patient with untreated enlargement and a type I endoleak. Three aneurysms ruptured: one with enlargement, one with no change, and one with a decrease in aneurysm size; all three aneurysms were larger than 6.5 cm. Kaplan-Meier analysis showed that freedom from rupture at 3 years was 98% with enlargement, 99% with no change, and 99% with decrease in AAA size (log-rank test, not significant). Freedom from AAA death at 3 years was 93% in patients with enlargement, 99% in no increase, and 99% in decrease (P =.005). Survival at 3 years was 86% with increase, 82% with no change, and 93% with decrease (P =.02).Aneurysm enlargement following endovascular repair was not associated with an increased risk of aneurysm rupture or decrease in patient survival during a 3-year observation period. Aneurysm size rather than enlargement may be a more meaningful predictor of rupture. Close follow-up and a high re-intervention rate (43%) may account for the low risk of rupture in patients with enlargement. The long-term significance of aneurysm enlargement following endovascular repair remains to be determined.

    View details for DOI 10.1016/j.jvs.2003.08.002

    View details for Web of Science ID 000187840600026

    View details for PubMedID 14718827

  • Stent graft migration after endovascular aneurysm repair: Importance of proximal fixation JOURNAL OF VASCULAR SURGERY Zarins, C. K., Bloch, D. A., Crabtree, T., Matsumoto, A. H., White, R. A., Fogarty, T. J. 2003; 38 (6): 1264-1272

    Abstract

    We reviewed the incidence of stent-graft migration after endovascular aneurysm repair in a prospective multicenter trial and identified factors that may predispose to such migration.All patients who received treatment during the course of the multicenter AneuRx clinical trial were reviewed for evidence of stent-graft migration over 5 years, from 1996 to 2001. Post-deployment distance from the renal arteries to the proximal end of the stent graft and the proximal fixation length (length of the infrarenal neck covered by the stent graft) were determined in patients for whom pre-procedure and post-procedure computed tomography scans were measured in an independent core laboratory.Stent-graft migration was reported in 94 of 1119 patients, with mean time after device implantation of 30 +/- 11 months. Freedom from migration was 98.6% at 1 year, 93.4% at 2 years, and 81.2% at 3 years (Kaplan-Meier method). Subset (n = 387) analysis revealed that initial device deployment was lower in 47 patients with migration, as evidenced by a greater renal artery to stent-graft distance (1.1 +/- 0.7 cm), compared with 340 patients without migration (0.8 +/- 0.6 cm; P =.006) on post-implantation computed tomography scan. Proximal fixation length was shorter in patients with migration (1.6 +/- 1.4 cm) compared with patients without migration (2.3 +/- 1.4 cm; P =.005). There was significant variation in migration rate among clinical sites (P <.001), ranging from 0% to 30% (median, 8%), with a greater than twofold difference in migration rate between the lowest quartile (6%) and the highest quartile (15%) clinical sites. Univariate and multivariate analysis revealed that renal artery to stent-graft distance (P =.001) and proximal fixation length (P =.005) were significant predictors of migration, and that each millimeter increase in distance below the renal arteries increased risk for subsequent migration by 5.8% and each millimeter increase in proximal fixation length decreased risk for migration by 2.5%. Pre-implantation aortic neck length, neck diameter, degree of device oversizing, correct versus incorrect oversizing, device type (stiff vs flexible), placement of proximal extender cuffs at the original procedure, and post-procedure endoleak were not significant predictors of migration. Migration was treated with placement of extender modules in 23 patients and surgical conversion in 7 patients; 64 patients (68%) with migration have required no treatment.Stent-graft migration among patients treated in the AneuRx clinical trial appears to be largely related to low initial deployment of the device, below the renal arteries, and short proximal fixation length. Significant variation in migration rate among clinical sites highlights the importance of the technical aspects of stent-graft deployment. Advances in intraoperative imaging and deployment techniques that have been made since completion of the clinical trial facilitate precision of device placement below the renal arteries and should increase proximal fixation length. Whether this, together with increased iliac fixation length, will result in lower risk for migration remains to be determined in long-term follow-up studies.

    View details for DOI 10.1016/S0741-5214(03)00946-7

    View details for Web of Science ID 000186955400028

    View details for PubMedID 14681625

  • Composite spirometric-computed tomography outcome measure in early cystic fibrosis lung disease AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE Robinson, T. E., Leung, A. N., Northway, W. H., Blankenberg, F. G., Chan, F. P., Bloch, D. A., Holmes, T. H., Moss, R. B. 2003; 168 (5): 588-593

    Abstract

    With the advent of therapies aimed at young patients with cystic fibrosis, who have mildly reduced pulmonary function, the need for improved outcome measures that discriminate treatment effects has become important. Pulmonary function measurements or chest high-resolution computed tomography (HRCT) scores have been separately used to assess interventions. We evaluated these modalities separately and together during a treatment study to develop a more sensitive outcome measure. In a 1-year trial, 25 children randomized either to daily Pulmozyme or to normal saline aerosol were evaluated at randomization and at 3 and 12 months. Outcome variables were pulmonary function test (PFT) results, a global HRCT score, and a composite score incorporating PFTs and HRCT scoring. Regression analyses with generalized estimating equations permitted estimation of the difference in treatment effect between groups over time for each outcome. The largest difference in treatment effects observed at 12 months, measured by the percentage change from baseline, were with the composite total and maximal CT/PFT scores (35.4 and 30.4%), compared with mean forced expiratory flow during the middle half of the FVC (FEF25-75%) (13.0%) and total and maximal global HRCT scores (6.2%, 7.2%). The composite total and maximal CT/PFT scores were the most sensitive outcome measures for discriminating a treatment effect in children with cystic fibrosis with normal or mildly reduced pulmonary function during a 1-year trial of Pulmozyme.

    View details for DOI 10.1164/rccm.200209-1093OC

    View details for Web of Science ID 000185039000015

    View details for PubMedID 12746252

  • Meniscal damage is strongly associated with the progression of knee osteoarthritis as assessed by a quantification imaging system using magnetic resonance imaging. Pelletier, J. P., Raynauld, J. P., Beaudoin, G., Berthiaume, M. J., DeGuise, J., Bloch, D., Altman, R., Hochberg, M., Cline, G., Meyer, J., Martel-Pelletier, J. WILEY-BLACKWELL. 2003: S453-S453
  • Meniscal damage is strongly associated with the progression of knee osteoarthritis as assessed by a quantification imaging system using the magnetic resonance imaging Raynauld, J. P., Pelletier, J. P., Beaudoin, G., Berthiaume, M. J., DeGuise, J., Bloch, D. A., Altman, R. D., Hochberg, M. C., Cline, G., Meyer, J. M., Martel-Pelletier, J. BMJ PUBLISHING GROUP. 2003: 327-327
  • Incidence of Parkinson's disease: Variation by age, gender, and Race/Ethnicity AMERICAN JOURNAL OF EPIDEMIOLOGY Van den Eeden, S. K., Tanner, C. M., Bernstein, A. L., Fross, R. D., Leimpeter, A., Bloch, D. A., Nelson, L. M. 2003; 157 (11): 1015-1022

    Abstract

    The goal of this study was to estimate the incidence of Parkinson's disease by age, gender, and ethnicity. Newly diagnosed Parkinson's disease cases in 1994-1995 were identified among members of the Kaiser Permanente Medical Care Program of Northern California, a large health maintenance organization. Each case met modified standardized criteria/Hughes diagnostic criteria as applied by a movement disorder specialist. Incidence rates per 100,000 person-years were calculated using the Kaiser Permanente membership information as the denominator and adjusted for age and/or gender using the direct method of standardization. A total of 588 newly diagnosed (incident) cases of Parkinson's disease were identified, which gave an overall annualized age- and gender-adjusted incidence rate of 13.4 per 100,000 (95% confidence interval (CI): 11.4, 15.5). The incidence rapidly increased over the age of 60 years, with only 4% of the cases being under the age of 50 years. The rate for men (19.0 per 100,000, 95% CI: 16.1, 21.8) was 91% higher than that for women (9.9 per 100,000, 95% CI: 7.6, 12.2). The age- and gender-adjusted rate per 100,000 was highest among Hispanics (16.6, 95% CI: 12.0, 21.3), followed by non-Hispanic Whites (13.6, 95% CI: 11.5, 15.7), Asians (11.3, 95% CI: 7.2, 15.3), and Blacks (10.2, 95% CI: 6.4, 14.0). These data suggest that the incidence of Parkinson's disease varies by race/ethnicity.

    View details for DOI 10.1093/aie/kwg068

    View details for Web of Science ID 000183420800010

    View details for PubMedID 12777365

  • Comparison of the comet assay and the oxygen microelectrode for measuring tumor oxygenation in head-and-neck cancer patients INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Le, Q. T., Kovacs, M. S., Dorie, M. J., Koong, A., Terris, D. J., Pinto, H. A., Goffinet, D. R., Nowels, K., Bloch, D., Brown, J. M. 2003; 56 (2): 375-383

    Abstract

    To compare the Eppendorf PO2 histograph and the alkaline comet assay as methods of measuring tumor hypoxia in patients with head-and-neck squamous cell carcinomas.As part of a larger clinical trial, 65 patients with head-and-neck squamous cell carcinoma nodal metastasis underwent tumor oxygenation measurements with Eppendorf PO2 histographs and comet assays, performed on fine-needle aspirates at 1 and 2 min after 5 Gy. Fifty-four patients had sufficient tumor cells for comet analysis at 1 min and 26 at both 1 and 2 min. Individual cells were examined for DNA single-strand breaks by alkaline gel electrophoresis, and the distribution of values was quantified using median tail moment (MTM). Nonirradiated tumor cells from pretreatment fine-needle aspirates received 5 Gy in vitro to establish the oxygenated response.There was a significant correlation between the 1- and 2-min MTM (slope = 0.77 +/- 0.03). There was no relationship between DNA damage in tumor cells irradiated in vitro and in vivo. No correlation was found between Eppendorf PO2 measurements and comet MTM. There was a statistically significant correlation between the treatment response in the node studied and comet MTMs, whereas no correlation was observed between treatment response and Eppendorf measurements.Comet assays are reproducible, as shown by biopsies at 1 and 2 min. Intertumor variation in the MTM is not a result of intrinsic radiosensitivity but of tumor hypoxia. There was no correlation between Eppendorf PO2 measurements and comet MTM. Comet assays were better than Eppendorf in predicting treatment response as an end point for short-term outcome. Longer follow-up is needed to determine the role of the comet assay as a predictor for locoregional tumor control and survivals.

    View details for DOI 10.1016/S0360-3016(02)04503-0

    View details for Web of Science ID 000182861500010

    View details for PubMedID 12738312

  • Reliability of a quantification imaging system using magnetic resonance images to measure cartilage thickness and volume in human normal and osteoarthritic knees OSTEOARTHRITIS AND CARTILAGE Raynauld, J. P., Kauffmann, C., Beaudoin, G., Berthiaume, M. J., de Guise, J. A., Bloch, D. A., Camacho, F., Godbout, B., Altman, R. D., Hochberg, M., Meyer, J. M., Cline, G., Pelletier, J. P., Martel-Pelletier, J. 2003; 11 (5): 351-360

    Abstract

    The aim of this study was to evaluate the reliability of a software tool that assesses knee cartilage volumes using magnetic resonance (MR) images. The objectives were to assess measurement reliability by: (1) determining the differences between readings of the same image made by the same reader 2 weeks apart (test-retest reliability), (2) determining the differences between the readings of the same image made by different readers (between-reader agreement), and (3) determining the differences between the cartilage volume readings obtained from two MR images of the same knee image acquired a few hours apart (patient positioning reliability).Forty-eight MR examinations of the knee from normal subjects, patients with different stages of symptomatic knee osteoarthritis (OA), and a subset of duplicate images were independently and blindly quantified by three readers using the imaging system. The following cartilage areas were analyzed to compute volumes: global cartilage, medial and lateral compartments, and medial and lateral femoral condyles.Between-reader agreement of measurements was excellent, as shown by intra-class correlation (ICC) coefficients ranging from 0.958 to 0.997 for global cartilage (P<0.0001), 0.974 to 0.998 for the compartments (P<0.0001), and 0.943 to 0.999 for the condyles(P<0.0001). Test-retest reliability of within-reader data was also excellent, with Pearson correlation coefficients ranging from 0.978 to 0.999 (P<0.0001). Patient positioning reliability was also excellent, with Pearson correlation coefficients ranging from 0.978 to 0.999 (P<0.0001).The results of this study establish the reliability of this MR imaging system. Test-retest reliability, between-reader agreement, and patient positioning reliability were all extremely high. This study represents a first step in the overall validation of an imaging system designed to follow progression of human knee OA.

    View details for DOI 10.1016/S1063-4584(03)00029-3

    View details for Web of Science ID 000183091100006

    View details for PubMedID 12744941

  • Modulation of bone ingrowth and tissue differentiation by local infusion of interleukin-10 in the presence of ultra-high molecular weight polyethylene (UHMWPE) wear particles JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A Goodman, S., Trindade, M., Ma, T., Lee, M., Wang, N., Ikenou, T., Matsuura, I., Miyanishi, K., Fox, N., Regula, D., Genovese, M., Klein, J., Bloch, D., Smith, R. L. 2003; 65A (1): 43-50

    Abstract

    Interleukin-10 (IL-10) is a cytokine that plays a major role in suppressing the inflammatory response, particularly cell-mediated immunity that is characteristic of the TH1 response. The purpose of this study was to determine whether local infusion of IL-10 could mitigate the suppression of bone ingrowth associated with polyethylene wear particles. Drug test chambers were implanted in the proximal tibia of 20 mature New Zealand White rabbits. The DTC provided a continuous 1 x 1 x 5-mm canal for tissue ingrowth. After a 6-week period for osseointegration, the DTC was then connected to an osmotic diffusion pump. IL-10 at doses of 0.1-100 ng/mL (0.25 microL/h) was infused with or without ultra-high molecular weight polyethylene particles (0.5 +/- 0.2 microm diameter, 10(12) particles/mL) present in the chamber for a 3- or 6-week period. The tissue in the chamber was harvested after each treatment; sections were stained with hematoxylin and eosin for morphometric analysis. Osteoclast-like cells were identified by immunohistochemical staining using a monoclonal antibody directed against the alpha chain of the vitronectin receptor, CD51. Osteoblasts were identified using alkaline phosphatase staining. In dose-response studies, infusion of 1 ng/mL IL-10 yielded the greatest bone ingrowth in the presence of particles. The addition of polyethylene particles evoked a marked foreign body reaction and fibrosis; bone ingrowth was significantly suppressed (p = 0.0003). Bone ingrowth was increased by over 48% with infusion of IL-10 for the final 3 weeks of a 6-week ultra-high molecular weight polyethylene particle exposure compared with particles alone (p = 0.027). IL-10 is a cytokine that plays a major role in suppressing the inflammatory response, especially cell-mediated immunity that is characteristic of the TH1 response. Local infusion of immune-modulating cytokines such as IL-10 may prove to be useful in abating particle-induced periprosthetic osteolysis.

    View details for DOI 10.1002/jbm.a.10279

    View details for Web of Science ID 000182453600007

  • Meniscal damage is strongly associated with the progression of knee osteoarthritis as assessed by a quantification imaging system using the magnetic resonance imaging Pelletier, J. P., Raynauld, J. P., Beaudoin, G., Berthiaume, M. J., de Guise, J. A., Bloch, D. A., Altman, R. D., Hochberg, M., Cline, G., Meyer, J., Martel-Pelletier, J. SPRINGER LONDON LTD. 2003: S10-S11
  • Unexpectedly high prevalence of posttransplant anemia in pediatric and young adult renal transplant recipients AMERICAN JOURNAL OF KIDNEY DISEASES Yorgin, P. D., Belson, A., Sanchez, J., Al Uzri, A. Y., Sarwal, M., Bloch, D. A., Oehlert, J., Salvatierra, O., Alexander, S. R. 2002; 40 (6): 1306-1318

    Abstract

    Although posttransplant anemia (PTA) is recognized as a common problem in adult renal transplant recipients, few pediatric studies have been published.In this retrospective cohort study of 162 pediatric renal transplant recipients treated at Stanford University, the authors sought to determine the prevalence, severity, and the predictive factors of PTA. Anemia was defined as a hematocrit (HCT) level greater than 2 SD below published means for age or as erythropoietin dependency to maintain a normal HCT.Sixty-seven percent of pediatric renal transplant recipients were anemic at the time of transplantation. The prevalence of anemia increased to 84.3% in the first month posttransplant. From 6 months to 60 months posttransplant, the prevalence of anemia remained high at 64.2% to 82.2%. Only 4 patients (2.5%) were never anemic. Iron depletion was detected in 19 of 26 and 23 of 23 anemic patients 12 and 60 months posttransplant, respectively. Serum erythropoietin levels were low relative to hematocrit levels in 38 of 56 anemic patients. Logistic regression at 3 months posttransplant showed that discharge hematocrit level (P < 0.0001), calcium (P = 0.0004), and cyclosporine dose (P = 0.0002) correlated with anemia. Creatinine clearance (P = 0.002) and white blood cell count (P = 0.004) correlated with anemia at 12 months posttransplant, but only creatinine clearance (P = 0.011) correlated with anemia 60 months posttransplant.Nearly all pediatric renal transplant recipients experience PTA. However, few children less than 2 years of age were anemic during the first year posttransplant. Antirejection therapy, bone disease, iron depletion, and creatinine clearance appear to play pivotal roles in the development of PTA in children.

    View details for DOI 10.1053/ajkd.2002.36910

    View details for Web of Science ID 000179581900025

    View details for PubMedID 12460052

  • Assessment of low-flow CSF drainage as a treatment for AD - Results of a randomized pilot study NEUROLOGY Silverberg, G. D., Levinthal, E., SULLIVAN, E. V., Bloch, D. A., Chang, S. D., Leverenz, J., Flitman, S., Winn, R., Marciano, F., Saul, T., Huhn, S., Mayo, M., McGuire, D. 2002; 59 (8): 1139-1145

    Abstract

    This prospective, randomized, controlled study was designed to investigate the safety, feasibility, and preliminary efficacy of long-term CSF drainage via a low-flow ventriculoperitoneal shunt in subjects suffering from AD.Twenty-nine subjects selected for probable AD (National Institute of Neurological and Communicative Diseases and Stroke-Alzheimer's Disease and Related Dementias Association criteria) were screened to exclude normal pressure hydrocephalus or other etiologies of dementia and randomized to treatment (shunt) or no treatment groups. The study endpoint was the comparison of group performance on psychometric testing at quarterly intervals for 1 year. Shunted subjects had CSF withdrawn for MAP-tau and Abeta((1-42)) assays at the same time intervals.There was no mortality from the surgical procedure, and no patient sustained a subdural hematoma. Five notable postoperative adverse events, which resolved without permanent neurologic deficit, were reported in the shunt group. Group mean Mattis Dementia Rating Scale total scores showed little change over the year in the shunt-treatment group, in contrast to a decline in the control group (p = 0.06). Mini-Mental State Examination mean scores supported a trend in favor of shunt treatment (p = 0.1). There was a concomitant decrease in ventricular CSF concentrations of AD biomarkers MAP-tau and Abeta((1-42)).The surgical procedure and the device are reasonably safe. Adverse events were consistent with shunt procedures for hydrocephalus in this older population. The endpoint data show a trend in favor of the treated group. A larger, randomized, double-blinded, controlled, clinical trial is underway.

    View details for Web of Science ID 000178726700007

    View details for PubMedID 12391340

  • A two-year study in osteoarthritis patients following the progression of the disease by magnetic resonance imaging using a novel quantification Imaging system. Raynauld, J. P., Pelletier, J. P., Beaudoin, G., Berthiaume, M. J., de Guise, J. A., Bloch, D. A., Altman, R. D., Hochberg, M., Cline, G., Buckland-Wright, C., Meyer, J., Martel-Pelletier, J. WILEY-BLACKWELL. 2002: S150-S150
  • Risk estimation for classification trees JOURNAL OF COMPUTATIONAL AND GRAPHICAL STATISTICS Bloch, D. A., Olshen, R. A., Walker, M. G. 2002; 11 (2): 263-288
  • Lifestyle habits and compression of morbidity JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES Hubert, H. B., Bloch, D. A., Oehlert, J. W., Fries, J. F. 2002; 57 (6): M347-M351

    Abstract

    There has been much debate regarding the degree to which healthy lifestyles can increase longevity and whether added years will be offset by increased morbidity at older ages. This study was designed to test the compression of morbidity hypothesis, proposing that healthy lifestyles can reduce and compress disability into a shorter period toward the end of life.Functional status in 418 deceased members of an aging cohort was observed between 1986 and 1998 in relationship to lifestyle-related risk factors, including cigarette smoking, physical inactivity, and under- or overweight. Three risk groups were created based on the number of these factors at study entry. Disability scores prior to death were modeled for each risk group to compare levels and rates of change, as well as to determine if and when acceleration in functional decline occurred.The risk-factor-free group showed average disability scores near zero 10-12 years before death, rising slowly over time, without evidence of accelerated functional decline. In contrast, those with two or more factors maintained a greater level of disability throughout follow-up and experienced an increase in the rate of decline 1.5 years prior to death. For those at moderate risk, the rate of decline increased significantly only in the last 3 months of life. Other differences between groups provided no alternative explanations for the findings.These results make a compelling argument for the reduction and postponement of disability with healthier lifestyles as proposed by the compression of morbidity hypothesis.

    View details for Web of Science ID 000175979900007

    View details for PubMedID 12023263

  • Long-term followup of patients treated with total lymphoid irradiation for lupus nephritis ARTHRITIS AND RHEUMATISM Genovese, M. C., Uhrin, Z., Bloch, D. A., Oehlert, J., Sibley, R. K., Myers, B., Strober, S. 2002; 46 (4): 1014-1018

    Abstract

    To describe the long-term survival, renal condition, and morbidity outcomes in patients who received total lymphoid irradiation (TLI) for the treatment of lupus nephritis.Twenty-one patients with biopsy-proven, diffuse membranoproliferative glomerulonephritis and significant proteinuria of >2.5 grams/day received TLI from 1980 to 1987 at Stanford University Medical Center. All patients had previously failed to respond to treatment with high-dose corticosteroids or therapy with corticosteroids plus immunosuppressive agents (azathioprine, cyclophosphamide, or chlorambucil).The mean duration of followup since TLI was 10.7 years. Fifteen of 21 patients (71%) remained alive at the time of this assessment. Nine of the 21 patients (43%) survived without developing end-stage renal disease (ESRD). The probability of long-term survival without ESRD and without need for additional immunosuppressive agents after TLI was 19% (4 of 21). Factors predicting renal failure at the time of TLI included elevated creatinine levels, increased interstitial fibrosis on renal biopsy, and increased fractional excretion of immunoglobulin and albumin. Malignancies were found in 4 patients, and opportunistic infections occurred in 7 patients.Overall, patients with lupus nephritis treated with TLI do not appear to have better 10-year survival with lower incidence of ESRD compared with patients in published series treated with conventional immunosuppressive therapies. However, in this series of patients, treatment with conventional immunosuppressive therapies had been unsuccessful and given the limited number of adverse events and the efficacy seen in some patients, TLI appears to be a reasonable therapeutic option for the treatment of severe lupus nephritis among patients who fail to respond under standard cytotoxic regimens.

    View details for Web of Science ID 000174946500022

    View details for PubMedID 11953979

  • Fetal ear length measurement: a useful predictor of aneuploidy? ULTRASOUND IN OBSTETRICS & GYNECOLOGY Chitkara, U., Lee, L., Oehlert, J. W., Bloch, D. A., Holbrook, R. H., El-Sayed, Y. Y., Druzin, M. L. 2002; 19 (2): 131-135

    Abstract

    To determine the usefulness of short ear length (EL) measurement in the prenatal detection of fetuses with chromosomal abnormalities.Fetal EL measurements, routine biometry and complete anatomic survey for fetal abnormalities were prospectively performed by antenatal sonography.One thousand eight hundred and forty-eight patients with singleton pregnancies undergoing genetic amniocentesis in the second or third trimester.Complete data for EL, biometry and anatomic survey for major structural abnormalities and minor sonographic markers of chromosomal abnormality were available in 1311 fetuses. Of these, 48 (3.7%) had an abnormal karyotype and 1263 (96.3%) had a normal karyotype. Using an EL measurement of < or = 10th percentile for corresponding gestational age in normal fetuses as abnormal cut-off values, detection rates for chromosomal abnormalities by short EL were determined.Among the 48 abnormal karyotypes, 34 were considered significant, and 11 of these 34 (32.4%) fetuses had short EL. In 14 cases, the karyotypic abnormality was considered non-significant and fetal EL was normal in all cases. Of the 34 fetuses with significant chromosomal abnormalities, six (17.6%) on antenatal sonography had no detectable abnormal findings, other than short EL. An increased biparietal diameter (BPD)/EL ratio of > or = 4.0 was also noted in fetuses with an abnormal karyotype, but the sensitivity and predictive value of increased BPD/EL ratio alone or increased BPD/EL ratio in combination with short EL was no better than the sensitivity and predictive value of short EL alone. A combination of short EL and abnormal ultrasound, however, gave a much higher positive predictive value (46%) for significant chromosomal abnormalities.Our findings suggest that in women at high risk for fetal chromosomal abnormality, a short fetal EL measurement on prenatal ultrasound, either alone or in combination with other sonographically detectable structural abnormalities, may be a useful parameter in predicting fetal aneuploidy.

    View details for Web of Science ID 000174123500004

    View details for PubMedID 11876803

  • Postural balance in children with cerebral palsy DEVELOPMENTAL MEDICINE AND CHILD NEUROLOGY Rose, J., Wolff, D. R., Jones, V. K., Bloch, D. A., Oehlert, J. W., Gamble, J. G. 2002; 44 (1): 58-63

    Abstract

    Postural control deficits have been suggested to be a major component of gait disorders in cerebral palsy (CP). Standing balance was investigated in 23 ambulatory children and adolescents with spastic diplegic CP, ages 5 to 18 years, and compared with values of 92 children without disability, ages 5 to 18 years, while they stood on a force plate with eyes open or eyes closed. The measurements included center of pressure calculations of path length per second, average radial displacement, mean frequency of sway, and Brownian random motion measures of the short-term diffusion coefficient, and the long-term scaling exponent. In the majority of children with CP (14 of 23) all standing balance values were normal. However, approximately one-third of the children with CP (eight of 23) had abnormal values in at least two of the six center of pressure measures. Thus, mean values for path length, average radial displacement, and diffusion coefficient were higher for participants with CP compared with control individuals with eyes open and closed (p<0.05). Mean values for frequency of sway and the long-term scaling exponent were lower for participants with CP compared with control participants (p<0.05). Increased average radial displacement was the most common (nine of 23) postural control deficit. There was no increase in abnormal values with eyes closed compared with eyes open for participants with CP, indicating that most participants with CP had normal dependence on visual feedback to maintain balance. Identification of those children with impaired standing balance can delineate factors that contribute to the patient's gait disorder and help to guide treatment.

    View details for Web of Science ID 000173138000009

    View details for PubMedID 11811652

  • One-sided tests in clinical trials with multiple endpoints BIOMETRICS Bloch, D. A., Lai, T. L., Tubert-Bitter, P. 2001; 57 (4): 1039-1047

    Abstract

    Treatment comparisons in clinical trials often involve several endpoints. For example, one might wish to demonstrate that a new treatment is superior to the current standard for some components of the multivariate response vector and is not inferior, modulo biologically unimportant difference to the standard treatment for all other components. We introduce a new approach to multiple-endpoint testing that incorporates the essential univariate and multivariate features of the treatment effects. This approach is compared with existing methods in a simulation study and applied to data on rheumatoid arthritis patients receiving one of two treatments.

    View details for Web of Science ID 000174956800006

    View details for PubMedID 11764242

  • Spirometer-triggered high-resolution computed tomography and pulmonary function measurements during an acute exacerbation in patients with cystic fibrosis JOURNAL OF PEDIATRICS Robinson, T. E., Leung, A. N., Northway, W. H., Blankenberg, F. G., Bloch, D. A., Oehlert, J. W., Al-Dabbagh, H., Hubli, S., Moss, R. B. 2001; 138 (4): 553-559

    Abstract

    To evaluate a high-resolution computed tomography (HRCT) scoring system, clinical parameters, and pulmonary function measurements in patients with cystic fibrosis (CF) before and after therapy for a pulmonary exacerbation.Patients (n = 17) were evaluated by spirometer-triggered HRCT imaging, clinical parameters, and pulmonary function tests (PFTs) before and after treatment. HRCT scans were reviewed by 3 radiologists using a modified Bhalla scoring system.Bronchiectasis, bronchial wall thickening, and air trapping were identified in all subjects on initial evaluation. The initial total HRCT score correlated significantly with the Brasfield score (r = -.91, P <.001) and several PFT measures. After treatment, there were improvements in the acute change clinical score (ACCS) (P <.001), most pulmonary function measurements, and total HRCT score (P <.05). Bronchiectasis, bronchial wall thickening, and air trapping did not significantly change. Mucus plugging subcomponent HRCT score, slow vital capacity (SVC), forced expiratory volume in 1 second (FEV(1)), and forced vital capacity (FVC) (percent predicted) and reversible and total HRCT scores were most sensitive to change by effect size analysis.Improvements occurred with treatment in total and reversible HRCT scores, PFTs, and ACCS. Total and reversible HRCT scores and percent predicted SVC, FEV1, and FVC were the most sensitive to change. The greatest change was seen in the mucus plugging subcomponent HRCT score.

    View details for Web of Science ID 000168175400024

    View details for PubMedID 11295720

  • The AneuRx stent graft: Four-year results and worldwide experience 2000 JOURNAL OF VASCULAR SURGERY Zarins, C. K., White, R. A., Moll, F. L., Crabtree, T., Bloch, D. A., Hodgson, K. J., Fillinger, M. F., Fogarty, T. J. 2001; 33 (2): S135-S145

    Abstract

    The objective was to review the current results of endovascular abdominal aortic aneurysm repair with the AneuRx stent graft and to determine the effectiveness of the device in achieving the primary objective of preventing aneurysm rupture.The outcome of all patients treated during the past 4 years in the U.S. AneuRx clinical trial was determined, and the worldwide clinical experience was reviewed.A total of 1192 patients were treated with the AneuRx stent graft during all phases of the U.S. Clinical Trial from June 1996 to November 1999, with follow-up extending to June 2000. Ten (0.8%) patients have had aneurysm rupture, with most ruptures (n = 6) occurring in 174 (3.4%) patients treated with an early stiff bifurcation stent graft design used in phase I and in the initial stages of phase II. Since the current, flexible, segmented bifurcation stent graft design was introduced, four (0.4%) ruptures have occurred among 1018 patients treated. Of these, one was during implantation, two were placed too far below the renal arteries, and one patient refused treatment of a type I endoleak. Kaplan-Meier analysis of all 1192 patients treated with the AneuRx stent graft including both stent graft designs revealed the patient survival rate to be 93% at 1 year, 88% at 2 years, and 86% at 3 years, freedom from conversion to open repair to be 98% at 1 year, 97% at 2 years, and 93% at 3 years, and freedom from secondary procedure to be 94% at 1 year, 92% at 2 years, and 88% at 3 years. Freedom from aneurysm rupture with the commercially available segmented bifurcation stent graft was 99.7% at 1 year, 99.5% at 2 years, and 99.5% at 3 years. The presence or absence of endoleak on contrast computed tomography scanning after stent graft placement was not found to be a significant predictor of long-term outcome measures. Worldwide experience with the AneuRx device now approaches 10,000 patients.Endovascular management of abdominal aortic aneurysms with the AneuRx stent graft has markedly reduced the risk of aneurysm rupture while eliminating the need for open aneurysm surgery in 98% of patients at 1 year and 93% of patients at 3 years. The device was effective in preventing aneurysm rupture in 99.5% of patients over a 3-year period. The overall patient survival rate was 93% at 1 year and 86% at 3 years.

    View details for Web of Science ID 000167332500020

    View details for PubMedID 11174825

  • Reliability of proxy-reported and self-reported household appliance use EPIDEMIOLOGY Mills, K. M., Kheifets, L. I., Nelson, L. M., Bloch, D. A., Takemoto-Hambleton, R., Kelsey, J. L. 2000; 11 (5): 581-588

    Abstract

    Exposure assessment presents a major challenge for studies evaluating the association between household exposure to electric and magnetic fields and adverse health outcomes, especially the reliance on proxy respondents when study subjects themselves have died. We evaluated the reliability of proxy- and self-reported household appliance exposure. We recruited 92 healthy couples through either random-digit dialing or newspaper advertisements. Trained interviewers administered questionnaires to each member of a couple independently to assess the reliability of proxy-reported household appliance use. Eighty-five couples completed a second interview 2 months later to assess the reliability of self-reported appliance use. Reliability of proxy-reported appliance exposure was good when we inquired about having any exposure to each of the eight indicator appliances during the past year (range of kappa coefficients = 0.63-0.85; median = 0.76) but was lower with increased time to recall or increased detail. Reliability of self respondents reporting 2 months apart was excellent (range of kappa coefficients = 0.75-0.94; median = 0.87) for having any exposure to the eight indicator appliances during the past year, but reliability was again lower with increased detail. When we used self reports at the first interview as the standard, little systematic over- or underreporting occurred for proxy respondents or for self respondents reporting 2 months later. Because this study did not include cases of specific disease, these findings of no systematic differences in reporting do not refer to case or control status. In summary, reliability of self respondents' reports of appliance use is very good for recent time periods and good for broad aspects of exposure in distant time periods. Proxy respondents can provide information regarding broad aspects of appliance exposure in the past year, but detailed aspects of exposure or exposure in more distant time periods is not reliable.

    View details for Web of Science ID 000088854500015

    View details for PubMedID 10955412

  • Ultrasonographic ear length measurement in normal second-and third-trimester fetuses AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY Chitkara, U., Lee, L., El-Sayed, Y. Y., Holbrook, R. H., Bloch, D. K., Oehlert, J. W., Druzin, M. L. 2000; 183 (1): 230-234

    Abstract

    We sought to develop a nomogram for fetal ear length measurements from a large population of healthy second- and third-trimester fetuses and to investigate the correlation of fetal ear length with other standard fetal biometry measurements, as follows: biparietal diameter, head circumference, abdominal circumference, femur length, and humerus length.Ear length measurement was obtained prospectively in 4240 singleton fetuses between 15 and 40 weeks' gestational age. Either complete data for normal karyotype on amniocentesis or normal infant examination at birth or both were available in 2583 cases. These constituted the final study population.A nomogram was developed by linearly regressing ear length on gestational age (Ear length [in millimeters] = 1.076 x Gestational age [in weeks] - 7. 308). There was a high correlation between ear length and gestational age (r = 0.96; P =.0001).The results of this study provide normative data on growth of fetal ear length from 15 to 40 weeks' gestation. Good correlation was also observed between ear length and other fetal biometric measurements (biparietal diameter, head circumference, abdominal circumference, femur length, and humerus length).

    View details for Web of Science ID 000088565500039

    View details for PubMedID 10920337

  • DNA damage measured by the comet assay in head and neck cancer patients treated with tirapazamine. Neoplasia Dorie, M. J., Kovacs, M. S., Gabalski, E. C., Adam, M., Le, Q. T., Bloch, D. A., Pinto, H. A., Terris, D. J., Brown, J. M. 1999; 1 (5): 461-467

    Abstract

    Tirapazamine (TPZ) [3-amino-1,2,4-benzotriazine 1,4-dioxide, SR4233, WIN 59075, and Tirazone] is a novel anticancer drug that is selectively activated by the low oxygen environment in solid tumors. By killing the radioresistant hypoxic cells, TPZ potentiates the antitumor efficacy of fractionated irradiation of transplanted tumors in mice. As this cell kill is closely correlated with TPZ-induced DNA damage, we investigated whether human head and neck cancers would show DNA damage similar to that seen in mouse tumors following TPZ administration. TPZ-induced DNA damage in both transplanted tumors in mice and in neck nodes of 13 patients with head and neck cancer was assessed using the alkaline comet assay on cells obtained from fine-needle aspirates. The oxygen levels of the patients' tumors were also measured using a polarographic oxygen electrode. Cells from the patients' tumors showed DNA damage immediately following TPZ administration that was comparable to, or greater than, that seen with transplanted mouse tumors. The heterogeneity of DNA damage in the patients' tumors was greater than that of individual mouse tumors and correlated with tumor hypoxia. The similarity of TPZ-induced DNA damage in human and rodent tumors suggests that tirapazamine should be effective when added to radiotherapy or to cisplatin-based chemotherapy in head and neck cancers.

    View details for PubMedID 10933062

  • Falls in older Mexican-American women JOURNAL OF THE AMERICAN GERIATRICS SOCIETY Schwartz, A. V., Villa, M. L., Prill, M., Kelsey, J. A., Galinus, J. A., Delay, R. R., Nevitt, M. C., Bloch, D. A., Marcus, R., Kelsey, J. L. 1999; 47 (11): 1371-1378

    Abstract

    To determine the frequency of falls and identify risk factors for falls among older Mexican-American women.A prospective cohort study with an average follow-up of 2.7 years.A clinical center at the Palo Alto Veterans Affairs Medical Center, California.152 community-dwelling Mexican-American Caucasian women aged 59 years or older.Falls and injurious falls, as determined by monthly telephone interviews.The rate of falls was 508 per 1000 person-years (95% confidence interval (CI), 440-577). Injurious falls requiring medical attention occurred at a rate of 79 per 1000 person-years (95% CI, 52-107). Factors that were associated independently with an increased risk of falling were older age, a history of arthritis or rheumatism, a history of high thyroid, having fainted at least once in the year before baseline, current use of psychotropic medications, and walking fewer than 5 blocks a day. Those persons with an average time for the chair stand test had a lower risk of falling than those with the slowest times or the fastest times.The frequency of falls and injurious falls in this cohort of 152 relatively acculturated, healthy, older Mexican-American women was similar or slightly higher than previously reported rates for non-Hispanic Caucasian(s). Many of the factors associated with falls in this study were similar to those reported for non-Hispanic Caucasian women, suggesting that fall prevention measures tested mainly among non-Hispanic Caucasian women would also be appropriate for Mexican-American women.

    View details for Web of Science ID 000083515800018

    View details for PubMedID 10573450

  • Children's symptoms in the wake of Challenger: A field study of distant-traumatic effects and an outline of related conditions AMERICAN JOURNAL OF PSYCHIATRY Terr, L. C., Bloch, D. A., Michel, B. A., Shi, H., Reinhardt, J. A., Metayer, S. 1999; 156 (10): 1536-1544

    Abstract

    The Challenger space shuttle explosion in January 1986 offered an opportunity to determine what, if any, symptoms of posttraumatic stress disorder (PTSD) and bereavement normal latency-age children and adolescents would develop after a distant, horrifying event.With a structured interview, the authors assessed the symptoms of 153 randomly selected children from Concord, N.H., and Porterville, Calif. Responses were statistically compared between East Coast children, who saw the event on television and who generally cared more about the teacher aboard Challenger, and West Coast children, who heard about it first; between latency-age children and adolescents; and between children seen 5-7 weeks later and those same children seen 14 months later.More than 60% of the subjects feared at least one stimulus related to Challenger within the first 5-7 weeks of the explosion. The East Coast and latency-age groups appeared significantly more symptomatic than did the West Coast and adolescent groups. Over the 14-month study period, most symptoms dramatically faded. However, adolescents' diminished expectations for the future in general increased, and latency-age children's changed approach to space careers held relatively steady. Three East Coast latency-age children met the DSM-III-R symptom requirements for PTSD in 1986; no children met these in 1987.Children's symptomatic patterns after Challenger relate to the patterns for PTSD listed in diagnostic manuals and to three symptoms not in the DSM-IV list. To the authors, distant traumas appear to be one of a newly defined spectrum of trauma-related conditions that include relatively evanescent symptoms and a few longer-lasting ones. These symptoms may affect large numbers of normal children.

    View details for Web of Science ID 000082896500011

    View details for PubMedID 10518163

  • Capturing the patient's view of change as a clinical outcome measure JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Fischer, D., Stewart, A. L., Bloch, D. A., Lorig, K., Laurent, D., Holman, H. 1999; 282 (12): 1157-1162

    Abstract

    Measurement of change in patients' health status is central to both clinical trials and clinical practice. Trials commonly use serial measurements by the patients at 2 points in time while clinicians use the patient's retrospective assessment of change made at 1 point in time. How well these measures correlate is not known.To compare the 2 methods in measurement of changes in pain and disability.Longitudinal survey of patients starting new therapy for chronic arthritis in 1994 and 1995. Surveys were completed at baseline (before intervention) and at 6 weeks and 4 months.Community health education program and university medical and orthopedic services.A total of 202 patients undertaking self-management education (n = 140), therapy with prednisone or methotrexate (n = 34), or arthroplasty of the knee or hip (n = 28).Concordance between serial (visual analog scale for pain and Health Assessment Questionnaire for disability) and retrospective (7-point Likert scale) measures, sensitivities of these measures, and their correlation with patients' satisfaction with the change (7-point Likert scale).When change was small (education group), serial measures correlated poorly with retrospective assessments (eg, r=0.13-0.21 at 6 weeks). With greater change, correlations improved (eg, r = 0.45-0.71 at 6 weeks). Average agreement between all pairs of assessments was 29%. Significant lack of concordance was confirmed in all 12 comparisons by McNemar tests (P = .02 to <.001) and by t tests (P = .03 to <.001). Retrospective measures were more sensitive to change than serial measures and correlated more strongly with patients' satisfaction with change.The 2 methods for measuring health status change did not give concordant results. Including patient retrospective assessments in clinical trials might increase the comprehensiveness of information gained and its accord with clinical practice.

    View details for Web of Science ID 000082596200031

    View details for PubMedID 10501119

  • Plans, designs, and analyses for clinical trials of anti-cocaine medications: Where we are today JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY Lavori, P. W., Bloch, D. A., Bridge, P. T., Leiderman, D. B., LoCastro, J. S., Somoza, E. 1999; 19 (3): 246-256

    Abstract

    Increased interest in addiction psychopharmacology has raised unique methodologic issues in the design, conduct, and analysis of outcomes in clinical trials of therapeutic agents for drug dependence. This article summarizes issues raised at a meeting in Palo Alto, California, on November 4, 1996, that was sponsored by the Medication Development Division of the National Institute on Drug Abuse and the Department of Veterans Affairs Cooperative Studies Program to discuss the methodologic issues in clinical trials of cocaine pharmacotherapy.

    View details for Web of Science ID 000080345000007

    View details for PubMedID 10350031

  • Patient preferences in coronary revascularization AMERICAN HEART JOURNAL Hornberger, J., Bloch, D. K., Hlatky, M. A., BAUMGARTNER, W. 1999; 137 (6): 1153-1162

    Abstract

    This study was performed to assess patient preferences for consequences of 3 coronary revascularization procedures: angioplasty, conventional coronary bypass surgery, and minimally invasive coronary bypass surgery.A nationwide sample of 3 types of respondents was recruited: respondents with no heart disease (n = 89), respondents with heart disease who had not undergone cardiac surgery (n = 97), and respondents with heart disease who had undergone cardiac surgery (n = 118).Sixty-two percent ranked the risk of repeat revascularization as the most important concern, followed by postprocedure pain (22%), time to recovery of physical functioning (8%), time in hospital (4%), and body appearance (4%). Respondents preferred angioplasty to conventional and minimally invasive cardiac surgery if the 3-year risk of repeat revascularization with angioplasty were to decline to less than 28% and 21%, respectively.These data suggest that patient preference should influence individual and policy recommendations when choosing among coronary revascularization procedures.

    View details for Web of Science ID 000080715600033

    View details for PubMedID 10347345

  • Analysis of radiographic measurements as prognostic indicators of treatment success in patients with developmental dysplasia of the hip JOURNAL OF PEDIATRIC ORTHOPAEDICS-PART B Rosen, A., Gamble, J. G., Vallier, H., Bloch, D., Smith, L., Rinsky, L. A. 1999; 8 (2): 118-121

    Abstract

    Measurements were taken and statistically analyzed from the initial radiographs, the 1-year follow-up radiographs, and the most recent radiographs of 81 patients (103 hips) to determine which measurements could predict the success of treatment. The average follow-up was 49 months (range, 12-139 months), and the average age of the patients at the last follow-up was 65 months (range, 15-190 months). Analysis of the data showed that the measurement with statistically significant predictive value was the Tonnis grade of dislocation determined from the initial radiograph. A single unit increase in the Tonnis grade was associated with a doubling of the odds of failure in patients treated with a Pavlik harness (P < 0.04, odds ratio = 2.2) or a closed reduction (odds ratio = 2.0).

    View details for Web of Science ID 000081887100011

    View details for PubMedID 10218173

  • Tissue oxygen distribution in head and neck cancer patients HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK Adam, M. F., Gabalski, E. C., Bloch, D. A., Oehlert, J. W., Brown, J. M., Elsaid, A. A., Pinto, H. A., Terris, D. J. 1999; 21 (2): 146-153

    Abstract

    The importance of hypoxia in limiting the sensitivity of tumor cells to ionizing radiation has long been known.We evaluated the tissue oxygenation status with a polarographic needle electrode system in 37 patients with malignancies of the head and neck and correlated the pO2 of 25 patients with treatment outcome.Sixteen tumors contained areas of severe hypoxia, defined by pO2 values below 2.5 mm Hg. Tumor oxygenation parameters were not correlated with hemoglobin, age, and history of tobacco use. There were no subcutaneous PO2 values below 10 mm Hg (ie, no areas of moderate or severe hypoxia), whereas this degree of hypoxia was commonly found in the tumors. Though not statistically significant, hypoxic tumors showed trends for poorer treatment outcome.Our data demonstrate a great interindividual variability in the oxygenation of head and neck cancers and appears unassociated with clinical parameters. The method is capable of identifying patients with poorly oxygenated tumors, thereby providing important information for selecting patients who might need customized therapy designed to kill hypoxic tumor cells. Hypoxic tumors show a consistent trend for poor treatment outcome.

    View details for Web of Science ID 000078724600008

    View details for PubMedID 10091983

  • An intervention to increase patients' trust in their physicians ACADEMIC MEDICINE Thom, D. H., Bloch, D. A., Segal, E. S. 1999; 74 (2): 195-198

    Abstract

    To investigate the effect of a one-day workshop in which physicians were taught trust-building behaviors on their patients' levels of trust and on outcomes of care.In 1994, the study recruited 20 community-based family physicians and enrolled 412 consecutive adult patients from those physicians' practices. Ten of the physicians (the intervention group) were randomly assigned to receive a one-day training course in building and maintaining patients' trust. Outcomes were patients' trust in their physicians, patients' and physicians' satisfaction with the office visit, continuity in the patient-physician relationship, patients' adherence to their treatment plans, and the numbers of diagnostic tests and referrals.Physicians and patients in the intervention and control groups were similar in demographic and other data. There was no significant difference in any outcome. Although their overall ratings were not statistically significantly different, the patients of physicians in the intervention group reported more positive physician behaviors than did the patients of physicians in the control group.The trust-building workshop had no measurable effect on patients' trust or on outcomes hypothesized to be related to trust.

    View details for Web of Science ID 000078705800028

    View details for PubMedID 10065061

  • Pretreatment and midtreatment measurement of oxygen tension levels in head and neck cancers LARYNGOSCOPE Gabalski, E. C., Adam, M., PINTO, H., Brown, J. M., Bloch, D. A., Terris, D. J. 1998; 108 (12): 1856-1860

    Abstract

    Considerable evidence exists to suggest that tumor hypoxia results in radioresistance. Historically, it has been difficult to assess tumor oxygen tension levels reliably. These levels can now be assessed in head and neck malignancies using the Eppendorf pO2 histograph, which uses a fine-needle electrode and a computerized micromanipulator. This technology was used to compare the pretreatment tumor oxygen tension level in lymph node metastases of patients with head and neck cancer to measurements taken during nonsurgical treatment after a partial response had been achieved.Prospective study.Oxygen tension levels were measured in the cervical lymph nodes of 10 patients with biopsy-proven head and neck squamous cell carcinoma and cervical metastases who were being treated with nonsurgical management. These levels were obtained using the Eppendorf pO2 histograph system. Measurements were taken before the start of treatment and were repeated when the size of the cervical metastatic node had decreased by 50%. Normal subcutaneous tissue was measured during the same session. The mean and median pO2 levels, as well as the percentage of measurements with pO2 less than 5 mm Hg were determined.A mean of 72.6 measurements per session was taken from each lymph node. The median tumor pO2 measurement fell from a mean (+/-SD) of 13.9+/-8.0 mm Hg to 7.3+/-9.9 mm Hg. Even more dramatic, however, was the substantial increase in the percentage of values less than 5 mm Hg, a rise from 29% to 52%.While there is variability both in the pretreatment oxygenation of head and neck cervical metastases and in the change in tumor oxygen tension during treatment, there appears to be a decrease in the overall oxygenation of the tumors. The dramatic increase in very low oxygen measurements may reflect selective survival of radioresistant or chemoresistant hypoxic tumor cells. Cells at the very low level would be expected to be radiobiologically hypoxic (resistant to radiation-induced cell kill).

    View details for Web of Science ID 000077386900017

    View details for PubMedID 9851504

  • Donor blood monocytes but not T or B cells facilitate long-term allograft survival after total lymphoid irradiation TRANSPLANTATION Hayamizu, K., Zeng, D., Huie, P., Garcia-Ojeda, M. E., Bloch, D. A., Fong, L., Engleman, E. G., Sibley, R. K., Strober, S. 1998; 66 (5): 585-593

    Abstract

    Previous studies showed that a combination of posttransplant total lymphoid irradiation (TLI), rabbit antithymocyte globulin (ATG), and a single donor blood transfusion induced tolerance to ACI heart allografts in Lewis rats. All three modalities were required to achieve tolerance. The objective of the current study was to determine the subset(s) of cells in the donor blood that facilitated long-term allograft survival.Lewis hosts received TLI, ATG, and donor cell infusion after heart transplantation. Graft survival, mixed leukocyte reaction (MLR), and intragraft cytokine mRNA were studied.The intravenous injection of 25 x 10(6) ACI peripheral blood mononuclear cells (PBMC) significantly prolonged graft survival as compared with that of Lewis hosts given TLI and ATG alone. Injection of highly enriched blood T cells or splenic B cells adjusted for the number contained in 25 x 10(6) PBMC failed to induce significant graft prolongation. Unexpectedly, depletion of monocytes (CD11b+ cells) from PBMC resulted in the loss of graft prolongation activity. Enriched populations of monocytes obtained by plastic adherence were more efficient in prolonging graft survival than PBMC on a per cell basis. Hosts with long-term grafts (>100-day survival) showed evidence of immune deviation, because the MLR to ACI stimulator cells was vigorous, but secretion of interferon-gamma in the MLR was markedly reduced. In situ hybridization studies of long-term grafts showed markedly reduced levels of interferon-gamma mRNA as compared with rejecting grafts.Infusion of donor monocytes facilitated graft prolongation via immune deviation.

    View details for Web of Science ID 000075996500006

    View details for PubMedID 9753336

  • Patient retrospective evaluation of change: An appropriate outcome measure for clinical trials? Fischer, D., Stewart, A. L., Bloch, D. A., Lorig, K., Laurent, D., Holman, H. R. WILEY-BLACKWELL. 1998: S229-S229
  • Prediction of postoperative knee flexion in Insall-Burstein II total knee arthroplasty CLINICAL ORTHOPAEDICS AND RELATED RESEARCH Schurman, D. J., Matityahu, A., Goodman, S. B., Maloney, W., Woolson, S., Shi, H., Bloch, D. A. 1998: 175-184

    Abstract

    Postoperative knee flexion in patients undergoing Insall-Burstein-II total knee arthroplasty at 2 years was evaluated regarding two basic questions: what groups of patients gain or lose the most flexion and what groups of patients have the best or worst postoperative flexion. Thirteen preoperative variables (maximum flexion, flexion arc, tibiofemoral angle, quadriceps strength, extensor lag, Knee Society score, Knee Society patient assessment, gender, age, height, weight, diagnosis, and surgeon) and four postoperative variable (leg length change, tibiofemoral angle, distance from patella to the joint line, and the tibial prosthesis anteroposterior translation on a lateral radiograph) were used in an attempt to explain postoperative flexion. The analysis was performed on 164 consecutive Insall-Burstein-II total knees in which the data were gathered prospectively on a time oriented medical record database. A regression tree analysis was used to identify several groups of patients, characterized by preoperative factor values, who had markedly above average performance on postoperative flexion. The preoperative factors identified include preoperative flexion, flexion arc, tibiofemoral angle, extensor lag, diagnosis, and age. The only postoperative variable of significance was tibiofemoral angle. Among the potential determinants of postoperative flexion that failed to appear predictive were the Knee Society scores and surgeon. Preoperative flexion is known to be a critical determinant of postoperative flexion in total knee replacement. However, in the current study, preoperative flexion accounted for only half of the difference between the best (122 degrees) and the worst (88 degrees) group, as determined with regression tree analysis.

    View details for Web of Science ID 000075541700020

    View details for PubMedID 9728172

  • Postural balance measurements for children and adolescents JOURNAL OF ORTHOPAEDIC RESEARCH Wolff, D. R., Rose, J., Jones, V. K., Bloch, D. A., Oehlert, J. W., Gamble, J. G. 1998; 16 (2): 271-275

    Abstract

    Measurements of standing balance were determined for 92 children and adolescents, 5-18 years old, while they stood on a force plate with eyes open or eyes closed. The measurements included center-of-pressure calculations for path length per second, average radial displacement, anterior-posterior and mediolateral amplitudes, area per second, mean frequency of sway, Brownian random motion measure of short-term diffusion coefficient, and long-term scaling exponent. All balance parameters improved from youngest to oldest subjects, and the parameters improved when measured with the subjects' eyes open compared with closed. The mean values for data from three trials varied by only 5% when compared with the mean values from 10 trials. Data from this study suggest that force-plate center-of-pressure data can be used to determine differences in standing balance between children and adolescents of different ages and those with movement and balance abnormalities.

    View details for Web of Science ID 000073905500014

    View details for PubMedID 9621902

  • Recursive partitioning for the identification of disease risk subgroups: A case-control study of subarachnoid hemorrhage JOURNAL OF CLINICAL EPIDEMIOLOGY Nelson, L. M., Bloch, D. A., Longstreth, W. T., Shi, H. 1998; 51 (3): 199-209

    Abstract

    Recursive partitioning is a nonparametric technique that produces a classification tree in which subjects are assigned to mutually exclusive subsets according to a set of predictor variables. We examined the utility of recursive partitioning as a supplement to logistic regression for the multivariable analysis of data from case-control studies, demonstrating the technique using data from women enrolled in a population-based study of subarachnoid hemorrhage. The classification tree produced by recursive partitioning consisted of three main risk subgroups: (1) elderly women who had long-standing hypertension and who were not smokers, (2) middle-aged women who were cigarette smokers and frequent binge drinkers, and (3) women in whom risk variables indicate relative estrogen deficiency (i.e., postmenopausal status, no recent exposure to hormone replacement therapy, cigarette smoking). As a supplemental method, recursive partitioning not only identifies subgroups with varying risks, but also may uncover interactions between variables that may be overlooked in the traditional application of logistic regression to case-control data.

    View details for Web of Science ID 000072147700004

    View details for PubMedID 9495685

  • The relationship of running to osteoarthritis of the knee and hip and bone mineral density of the lumbar spine: A 9 year longitudinal study JOURNAL OF RHEUMATOLOGY Lane, N. E., Oehlert, J. W., Bloch, D. A., Fries, J. F. 1998; 25 (2): 334-341

    Abstract

    To determine the associations between running and radiographic hip osteoarthritis (OA), the progression of radiographic knee OA, and changes in bone mineral density (BMD) after 9 year followup in 28 members of a running club now aged 60-77 years and 27 nonrunner controls.Running subjects and nonrunning controls were matched for age (+/- 2 years), years of education, and occupation. All subjects underwent rheumatologic examination, completed annual questionnaires, and had radiographs taken of the knees in 1984, 1986, 1989, and 1993 and of the hips in 1993. BMD of the first lumbar spine vertebrae was obtained in 36 subjects by quantitative computed tomography (QCT) in 1984, 1986, 1989, and 1993. In 1993, knee radiographs were assessed in pairs (1984 and 1993), and hip radiographs were scored by 2 readers individually without knowledge of running status.Nine year radiographic results for both runners and nonrunners for the knees showed significant within-group progression of both osteophytes and total knee radiographic scores (p = 0.01 for runners and p = 0.05 for nonrunners) and joint space narrowing in nonrunners (p = 0.01). Runners tended to have higher radiographic scores, but no significant differences in between-group differences were seen in 1984 or 1993. Radiographic OA of the hip was not different between the groups. QCT of the first lumbar vertebrae for BMD in 1984, 1986, 1989, and 1993 was greater in runners than nonrunners (p = 0.01), but rates of change in QCT values were similar between the 2 groups (p < 0.001).The presence of radiographic hip OA and the progression of radiographic knee OA was similar for older runners and nonrunners. Lumbar spine BMD remained higher in runners, but changes in lumbar BMD were similar for runners and nonrunners over a 9 year period.

    View details for Web of Science ID 000071729900027

    View details for PubMedID 9489830

  • Functional indices for sciatic, peroneal, and posterior tibial nerve lesions in the mouse MICROSURGERY Inserra, M. M., Bloch, D. A., Terris, D. J. 1998; 18 (2): 119-124

    Abstract

    The sciatic functional index previously described in rats has proven to be a reliable index of functional recovery following sciatic nerve injury and repair. A similar functional assay of sciatic, peroneal, and posterior tibial nerve lesions was developed in a mouse model. Forty-eight C57/BL6 mice were randomly divided into 4 groups: sham surgery, sciatic nerve transection, peroneal nerve transection, and posterior tibial nerve transection. Preoperative and postoperative (48 hours) walking tracks were obtained. The pawprints were analyzed in a blinded fashion for measurements of print length (PL), toe spread (TS), intermediate toe spread (IT), and the orthogonal distance from the toe of one paw to the hind pad of the opposite paw (TOF). Multiple linear regression analysis was performed using these measurements to determine their significance and appropriate weighted contribution to the index formula for each nerve lesion. For the sciatic functional index, changes in the PL (P = 0.0092) and TS (P = 0.0008) were significant, resulting in an R2 value of 0.88. For the peroneal functional index, only TS (P < 0.0001) was significant with R2 = 0.83. For the posterior tibial index, only PL (P < 0.0001) was significant with R2 = 0.89. Formulas for a sciatic, peroneal, and posterior tibial functional index were created based on the coefficients derived from the multiple linear regression analysis. The indices that were developed will allow investigators to assess functional recovery following specific nerve lesions in mice.

    View details for Web of Science ID 000074631400010

    View details for PubMedID 9674927

  • Running and osteoarthritis of the knee: A 12 year longitudinal study. Lane, N. E., Oehlert, J., Ward, M., Genovese, M., Bloch, D., Fries, J. F. WILEY-BLACKWELL. 1997: 1242-1242
  • Children's thinking in the wake of Challenger AMERICAN JOURNAL OF PSYCHIATRY Terr, L. C., Bloch, D. A., Michel, B. A., Shi, H., Reinhardt, J. A., Metayer, S. A. 1997; 154 (6): 744-751

    Abstract

    The Challenger spacecraft explosion in 1986 offered an opportunity to study the thinking of normal children after a sudden and distant disaster, differences in thinking among children of different levels of emotional concern and different ages, and changes in their thinking over time.The authors studied six thinking patterns known to characterize childhood posttraumatic stress disorder and four additional hypothesized patterns in 153 randomly selected children of Concord, N.H. (who watched the explosion on television) and Porterville, Calif. (who heard about it later). They compared the structured-interview responses of the more involved (East Coast) and less involved (West Coast) children, of the latency-age children and the adolescents, and of the children initially (5-7 weeks after the explosion) and 14 months later.The children exhibited the 10 predictable thinking patterns. They initially defended themselves, denying the reality of the explosion. They later fantasized about it. They tried to cope by seeking additional information on their own, at home, and at school. Most children talked about Challenger, but a minority of the latency-age youngsters avoided related talk and thoughts. The adolescents experienced more paranormal thinking, philosophical changes, and negative attitudes. Over the year, omens, paranormal experiences, and Challenger-based fantasies tended to disappear, but negative views about institutions and the world's future held steady or increased.The children's thinking followed predictable patterns. A higher degree of emotional involvement (East Coast children) was strongly linked to these thinking patterns, as was being an adolescent. Distant disasters appear to set up commonalities of thought that might come to characterize certain generations of children.

    View details for Web of Science ID A1997XA58700005

    View details for PubMedID 9167500

  • Identifying hospitalized older patients at varying risk for physical performance decline: A new approach Winograd, C. H., Lindenberger, E. C., Chavez, C. M., MAURICIO, M. P., Shi, H., Bloch, D. A. WILLIAMS & WILKINS. 1997: 604-609

    Abstract

    A classification tree analysis identifies patient groups at varying risk for decline in physical performance 1 year after hospitalization.Prospective cohort study.Tertiary care VAMC.A total of 507 acutely ill hospitalized male veterans aged 65 years and older.Eighteen admission characteristics were considered as potential predictors: demographic data, medical diagnoses, functional status (e.g., ADL and IADL), geriatric conditions (e.g., incontinence, vision impairment, weight change), mental status, depression, and physical functioning (measured by self-report (MOS-PFR) and the Physical Performance and Mobility Examination (PPME)). Outcome measure was change in PPME status at 12-months post-admission.Patients with the greatest risk for decline had both high baseline physical performance (PPME > or = 9) and at least moderate self-report limitations on physical functioning (MOS-PFR < or = 36, mean = 30.8). Patients with the lowest risk of decline had impaired baseline physical performance (PPME < or = 8) but fewer self-report limitations on physical functioning (MOS-PFR > or = 31, mean = 37.4) and two or less geriatric conditions.The predictive role of self-report functioning suggests that perception of the impact of health on one's own physical functioning is associated with future performance. The number of geriatric conditions is also an important predictor of physical performance change. By identifying patient risk groups based on geriatric conditions, physical performance, and self-report physical functioning, future targeting strategies may improve physical performance outcomes for hospitalized older adults.

    View details for Web of Science ID A1997WZ00900011

    View details for PubMedID 9158583

  • Analysis of estrogen receptor messenger RNA in breast carcinomas from archival specimens is predictive of tumor biology AMERICAN JOURNAL OF PATHOLOGY Carmeci, C., DECONINCK, E. C., Lawton, T., Bloch, D. A., Weigel, R. J. 1997; 150 (5): 1563-1570

    Abstract

    As the size of breast tumors continues to decrease, it has become more difficult to obtain adequate tumor tissue for molecular studies. We have used the estrogen receptor (ER) gene as a model to study the ability to perform a quantitative analysis of ER mRNA extracted from archival breast carcinoma specimens using reverse transcriptase polymerase chain reaction. Based upon ER mRNA abundance, tumors were characterized as having low, medium, or high ER mRNA expression. These data were compared with ER and progesterone receptor (PR) status determined by enzyme immunoassay, tumor histology, and Bloom-Richardson grade. Comparing the low and high ER mRNA groups, there were statistically significant differences in ER-positive status (10% versus 95%; P = 0.0001), PR-positive status (10% versus 90%; P = 0.0001), and tumor grade (2.67 +/- 0.12 versus 2.09 +/- 0.14; P = 0.0025). Of the 28 tumors in the high ER mRNA group, 5 (18%) were invasive lobular carcinomas whereas all 24 tumors with low ER mRNA were invasive ductal carcinomas. These data demonstrate that archival breast tumor specimens can be characterized for ER mRNA abundance. In addition, we conclude that the mechanisms regulating ER gene transcription influence the phenotype of breast carcinomas. These results also suggest that this technique can be designed to provide a quantitative analysis of gene expression for any gene of interest utilizing archival tumor specimens.

    View details for Web of Science ID A1997WX14100007

    View details for PubMedID 9137083

  • The relationship of clinical knowledge to months of clinical training among medical students ACADEMIC MEDICINE Vosti, K. L., Bloch, D. A., Jacobs, C. D. 1997; 72 (4): 305-307

    Abstract

    To assess the correlation of the number of months of clinical training with clinical knowledge, as measured by the United States Medical Licensing Examination (USMLE) Step 2.The total number of months of clinical training and percentile scores on USMLE Step 2 were determined for 217 Stanford. University School of Medicine graduates from 1992 through 1994. Percentile scores on each subsection of the Medical College Admission Test (MCAT) and the National Board of Medical Examiners Part 1 or USMLE Step 1 (Part 1/Step 1) for the graduates were also determined. For some analyses the graduates were separated into three groups according to the duration of clinical training. The Pearson product-moment correlation coefficient was used to quantify and define the significance of correlations. The Jorickheere-Terpstra nonparametric test was used to assess trends across the three groups. A multiple linear regression model was used to test the effects of confounding variables.The total numbers of clerkship months ranged from 12 to 23; the median was 18. A highly significant correlation was found between increasing months of clinical training and increasing scores on Step 2 (p = .002); a weaker significant correlation was found with scores on Part 1/Step 1 (p = .03). The correlation for Step 2 scores did not diminish appreciably (p = .004) when scores for Part 1/Step 1 and each MCAT subsection were introduced into the regression model.A highly significant correlation was found between the amount of clinical training and the acquisition and utilization of clinical knowledge. In the current climate of concerns about the rising costs of medical education, the impulse to solve these concerns by decreasing the amount of medical students' clinical training should be approached with caution.

    View details for Web of Science ID A1997WV34100023

    View details for PubMedID 9125948

  • Comparing two diagnostic tests against the same ''gold standard'' in the same sample BIOMETRICS Bloch, D. A. 1997; 53 (1): 73-85

    Abstract

    Methods are proposed for comparing two diagnostic tests for the same data where a threshold for positive for each test is specified. One method contrasts the diagnostic tests' estimated risks. A second method compares the two tests' kappa coefficients. When thresholds for positive test results are specified a priori, maximum likelihood estimators and their asymptotic variances are derived and test statistics are presented for both case-control and naturalistic methods of sampling. The bootstrap is proposed as a method to assess differences in risk estimators when thresholds for positive test results are chosen by scanning the data. Examples are given to illustrate the methods.

    View details for Web of Science ID A1997WN18000007

    View details for PubMedID 9147604

  • Optimization of thoracic spiral CT: Effects of iodinated contrast medium concentration RADIOLOGY Rubin, G. D., Lane, M. J., Bloch, D. A., Leung, A. N., Stark, P. 1996; 201 (3): 785-791

    Abstract

    To determine the effect of varying iodine concentration on arterial enhancement and perivenous artifact during thoracic spiral computed tomographic (CT) scanning.One hundred thirty-eight outpatients received 15.0 g (n = 76) or 22.5 g (n = 62) of iodine (300 mg/mL iodine) while undergoing thoracic spiral CT. Patients received either undiluted contrast medium, 1:1 normal saline dilution, or 3:1 normal saline dilution. Contrast medium was injected at a flow rate determined to deliver the entire iodine dose within 40 seconds. Attenuation was measured within arteries and veins. Three blinded thoracic radiologists independently graded perivenous artifact and arterial enhancement.Perivenous artifacts were statistically significantly reduced with successive iodine dilution (P < .002). Arterial enhancement was statistically significantly better with 15.0 g of iodine diluted 1:1 when compared with the same iodine dose undiluted or diluted 3:1 (P < .01). Arterial enhancement achieved with 15.0 g of iodine diluted 1:1 was not statistically significantly lower than that achieved with 22.5 g of iodine diluted 1:1 (P > .31); however, venous artifact was greater with 22.5 g of iodine (P < .004).Reduced iodine concentration appears to diminish perivenous artifact and to result in improved arterial enhancement during thoracic spiral CT.

    View details for Web of Science ID A1996VU50000033

    View details for PubMedID 8939232

  • Effects of growth hormone and estrogen on T lymphocytes in older women JOURNAL OF THE AMERICAN GERIATRICS SOCIETY Bonello, R. S., Marcus, R., Bloch, D., Strober, S. 1996; 44 (9): 1038-1042

    Abstract

    To assess the effect on peripheral blood T lymphocytes of recombinant human growth hormone administered to healthy older women.Prospective, open study.Veterans Administration clinical research unit and community surrounding Palo Alto, California.Thirty-three women were recruited in two age groups: 20 to 40 years (n = 13) and 70 years or older (n = 24). Subjects were healthy, community-dwelling volunteers.Recombinant human growth hormone at a dose of 0.025 mg/kg body weight/day was administered to the older subjects by daily subcutaneous injection over a 6-month study period.Mean percentage and number of peripheral blood CD45RA + ("naive") T cells, mean counts per minute (CPM) of [3H]-thymidine incorporation following stimulation of peripheral blood mononuclear cells with phytohemaglutinin (T cell proliferation).Before therapy, mean percentage and number of peripheral blood CD45RA + T cells and T cell proliferative responses were significantly reduced in older compared with younger women. The fraction of older women with CD45RA + T cell levels or T cell proliferative responses in the young range was significantly decreased in those who were receiving estrogen (1/10) compared with those who were not (9/14). After treatment with growth hormone, there were no significant changes in the mean CD45RA + T cell levels or proliferative responses of the older women.The results suggest that T cell changes associated with the age-related decline in secretion of growth hormone cannot be reversed by growth hormone therapy during the eighth decade.

    View details for Web of Science ID A1996VF44000003

    View details for PubMedID 8790227

  • Identifying hospitalized older adults at varying risk for functional status decline Lindenberger, E. C., Winograd, C. H., Bloch, D. A., Shi, H. BLACKWELL SCIENCE INC. 1996: P61-P61
  • Eliminating language barriers for non-English-speaking patients MEDICAL CARE Hornberger, J. C., GIBSON, C. D., Wood, W., Dequeldre, C., CORSO, I., PALLA, B., Bloch, D. A. 1996; 34 (8): 845-856

    Abstract

    More than 31 million persons living in the United States do not speak English, therefore language discordance between the clinician and patient may hinder delivery of cost-effective medical care. A new language service was developed in which interpreters are trained in the skills of simultaneous interpretation commonly used at international conferences. The interpreters are linked from a remote site to headsets worn by the clinician and patient through standard communication wires. The service is called "remote-simultaneous interpretation," to contrast it with a traditional method of an interpreter being physically present at the interview and interpreting consecutively "proximate-consecutive interpretation." The aim of this study is to assess in a randomized protocol the quality of communication, interpretation, and level of patient, interpreter, and physician satisfaction with these two language services.The first postpartum visit with each of 49 mothers and their new born babies was assigned randomly to proximate-consecutive interpretation (control) or to remote-simultaneous interpretation (experimental). Main outcome measures included (1) the number of physician and mother utterances in the visit, (2) the quality of the interpretation, and (3) physician, interpreter, and mother preferences between the two services.The remote-simultaneous interpreter service averaged 8.3 (10%) more physician utterances (95% confidence interval [CI] 4.3, 12.4) and 9.1 (28%) more mother utterances (95% CI 6.1, 12.1). On average, there were 2.8 (12%) fewer inaccuracies of physician utterances in experimental visits compared with control visits (95% CI -5.9, 0.4) and 3.0 (13%) fewer inaccuracies of mother utterances in experimental visits compared with control visits (95% CI -5.4, -0.6). Mothers and physicians significantly preferred the remote-simultaneous service to proximate-consecutive interpretation service. Interpreters stated that they thought mothers and physicians better understood each other using the remote-simultaneous service, although the interpreters preferred to work with the proximate-consecutive service.Using remote-simultaneous interpretation to improve the quality of communication in discordant-language encounters promises to enhance delivery of medical care for the millions of non-English-speaking patients in the United States.

    View details for Web of Science ID A1996VB19300011

    View details for PubMedID 8709665

  • Geriatric targeting criteria as predictors of survival and health care utilization JOURNAL OF THE AMERICAN GERIATRICS SOCIETY Satish, S., Winograd, C. H., Chavez, C., Bloch, D. A. 1996; 44 (8): 914-921

    Abstract

    To assess the utility of geriatric targeting criteria in predicting survival and health care utilization in a cohort of hospitalized older veterans.A prospective cohort study assessing geriatric targeting criteria, e.g., polypharmacy, falls, or confusion, with respect to adverse outcomes at 12 months.A Tertiary Care VA Medical Center.507 acutely hospitalized male veterans aged 65 years or more.Survival status, nursing home placement, and total hospital days during 12 months following hospital admission.Patients who had a higher number of targeting criteria at admission showed a significantly increasing trend toward death (P < or = .001), nursing home placement (P < or = .01), and longer hospital stays (P < or = .01) at 12 months. In univariate analyses, weight loss (relative hazard 3.8, 95% CI 2.4, 5.9), appetite loss (relative hazard 3.3, 95% CI 1.9, 5.8), depression (relative hazard 2.5, 95% CI 1.4, 4.5), falls (relative hazard 2.2, 95% CI 1.2, 4.1), confusion (relative hazard 2.2, 95% CI 1.2, 4.0), and socioeconomic problems (relative hazard 1.6, 95% CI 1.0, 2.5) predicted death. Polypharmacy (OR 3.4, 95% CI 1.3, 8.8), confusion (OR 4.4, 95% CI 1.5, 13.0), and prolonged bedrest (OR 7.6, 95% CI 1.5, 39.3) predicted nursing home placement. Confusion (Beta 12.0, 95% CI 2.9, 21.3), falls (Beta 14.2, 95% CI 4.2, 24.3), and prolonged bedrest (Beta 22.4, 95% CI 3.9, 41.0) predicted total hospital days. In multivariate analyses, weight loss, depression, and socioeconomic problems predicted death; confusion and polypharmacy predicted nursing home placements; and falls predicted total hospital days.This prospective cohort study of hospitalized older veterans demonstrated geriatric targeting criteria as predictors of adverse hospital outcomes. Our findings suggest screening acutely hospitalized patients using chart abstracted geriatric targeting criteria is useful in identifying patients at risk for adverse outcomes of hospitalization.

    View details for Web of Science ID A1996VA56300004

    View details for PubMedID 8708300

  • An index for assessing blindness in a multi-centre clinical trial: Disulfiram for alcohol cessation - A VA Cooperative Study STATISTICS IN MEDICINE James, K. E., Bloch, D. A., Lee, K. K., Kraemer, H. C., Fuller, R. K. 1996; 15 (13): 1421-1434

    Abstract

    This paper considers an index to assess the success of blinding with application to a clinical trial of disulfiram. The index increases as the success of blinding increases, accounts for uncertain responses, and is scaled to an interval of 0.0 to 1.0, 0.0 being complete lack of blinding and 1.0 being complete blinding.

    View details for Web of Science ID A1996UX57400009

    View details for PubMedID 8841652

  • Comparing health care expenditures between systemic lupus erythematosus patients in Stanford and Montreal ARTHRITIS AND RHEUMATISM Gironimi, G., Clarke, A. E., Hamilton, V. H., Danoff, D. S., Bloch, D. A., Fries, J. F., Esdaile, J. M. 1996; 39 (6): 979-987
  • Children's memories in the wake of Challenger AMERICAN JOURNAL OF PSYCHIATRY Terr, L. C., Bloch, D. A., Michel, B. A., Shi, H., Reinhardt, J. A., Metayer, S. 1996; 153 (5): 618-625

    Abstract

    The Challenger spacecraft explosion of Jan. 28, 1986, offered an opportunity to study the memories of normal latency and adolescent children of different emotional involvements following one sudden and distant disaster. How would children of various levels of concern express their memories? And if studied over time, how would these narratives change? Would there be developmental differences? And would there be false details of memory?The authors set out to compare the memories of 153 children from Concord, N.H. (who watched the explosion on television), and Porterville, Calif. (who heard about it). The structured-interview responses of involved and less involved children; latency-age versus adolescent children; and those seen initially (5-7 weeks after the explosion) versus those same children seen later (at 14 months) were statistically compared.The vast majority of children's memories of Challenger were clear, consistent, and detailed, with highlighting of personal placement, who else was there, and personal occurrences linked to the event. Those children who were less emotionally involved demonstrated significantly less clarity, consistency, and correct ordering of sequences and were less likely to remember personal placement, other people who were there, and related personal incidents. About 30% of all children in this study misunderstood something about Challenger and incorporated these misunderstandings into their memories as false details. Latency-age children continued to harbor false details for 14 months, as opposed to the adolescents.Childhood memories of the Challenger space shuttle explosion appeared predictable, were related to patterns of memory that have been observed following single, unrepeated traumas, and reflected age and stage differences.

    View details for Web of Science ID A1996UH92100005

    View details for PubMedID 8615406

  • Lymphoma and luekemia in rheumatoid arthritis: are they associated with azathioprine, cyclophosphamide, or methotrexate? Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases WILLIAMS, C. A., Bloch, D. A., Sibley, J., Haga, M., Wolfe, F., Raynauld, J. P., Singh, G., Hickey, A. R., Fries, J. F. 1996; 2 (2): 64-72

    Abstract

    Incident cases of lymphoma and leukemia in a cohort of 3824 rheumatoid arthritis (RA) patients from the Arthritis, Rheumatism and Aging Medical Information System (ARAMIS) database were identified, and the use of azathioprine, cyclophosphamide, and methotrexate was compared in a matched case-control study. Controls were matched on age, sex, year of study entry, disease duration, center, and years of follow-up. Twenty-four cases of lymphoma and 10 cases of leukemia were identified: 21% of patients with cancer versus 9% of controls had taken azathioprine [McNemar statistic 1.50 (p = 0.22), odds ratio 5.0 (95% confidence interval 0.6,236.5)]. Equal numbers of cases and controls (6% each) had taken cyclophosphamide and 18% of cases and 12% of controls had taken methotrexate [McNemar statistic 0.13 (p = 0.72), odds ratio 1.7 (0.3, 10.7)]. Results suggest but do not prove that RA patients taking azathioprine and methotrexate may have an increased risk of developing lymphoma. However, even if this increased risk can be confirmed, it accounts for only a small proportion of the greatly increased incidence of these malignancies in RA.

    View details for PubMedID 19078032

  • Trends in asthma therapy in the United States: 1965-1992 ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY Terr, A. I., Bloch, D. A. 1996; 76 (3): 273-281

    Abstract

    Many recent studies indicate an increasing morbidity and mortality of asthma in the past two decades. This study uses data from the National Disease and Therapeutic Index (NDTI) to document and analyze trends in drug therapy for asthma in the United States from 1965 through 1992.The NDTI maintains a continuous rotating national sampling of approximately 1% of US physicians in office-based practice proportionately representative of practicing generalists and specialists who report issuance of drugs in treatment by diagnosis for all patient encounters for a period of two days every 3 months. Annual summaries of five demographic categories and 14 drug categories, characterizing the asthma patient-physician encounters as percent of visits for the 28-year period of 1965 through 1992 are analyzed and characterized.Physician visits for asthma treatment have shifted somewhat from generalists to specialists in internal medicine and pediatrics. Allergists treat a significant proportion of the asthmatic population. Most patients are seen in the office. There has been no significant change in rates of inpatient visits. Age distribution of the population of patient visits for asthma has been stable, but there is a steady drop in ratio of males to females. Since the mid-1970s, inhaled adrenergic bronchodilator prescriptions have been issued at a markedly increasing rate. Concurrently, issuance of xanthines and oral adrenergic drugs also rose dramatically but then decreased beginning in the mid-1980s. Corticosteroids are used in 15% to 20% of visits, but only recently has the inhaled route of administration shown prominence. Allergen immunotherapy for asthma has decreased more than 10-fold. Cromolyn is prescribed infrequently.Major changes have occurred in drug treatment by physicians for asthma in the US since 1965. Bronchodilating drugs predominate, and they are being prescribed in more effective forms at a generally increasing rate. Corticosteroid use has increased at a slower rate and in smaller proportion of patient-visits, while allergen immunotherapy has dramatically declined. The male-to-female ratio of asthmatic patients who visit doctors for treatment appears to be decreasing.

    View details for Web of Science ID A1996UA05500014

    View details for PubMedID 8634884

  • LYMPHOMA AND LEUKEMIA IN RHEUMATOID-ARTHRITIS - A MATCHED CASE-CONTROL STUDY IN THE ARAMIS (ARTHRITIS, RHEUMATISM AND AGING MEDICAL INFORMATION-SYSTEM) POPULATION WILLIAMS, C. A., Bloch, D. A., Sibley, J., Haga, M., Wolfe, F., Raynauld, J. P., Singh, G., Hickey, A. R., Fries, J. F. WILEY-BLACKWELL. 1995: 311-311
  • A LONGITUDINAL-STUDY OF FUNCTIONAL DISABILITY IN A NATIONAL COHORT OF PATIENTS WITH POLYMYOSITIS DERMATOMYOSITIS ARTHRITIS AND RHEUMATISM Clarke, A. E., Bloch, D. A., Medsger, T. A., Oddis, C. V. 1995; 38 (9): 1218-1224

    Abstract

    To analyze changes in functional status and the factors contributing to disability in a national inception cohort of 257 patients with polymyositis/dermatomyositis (PM/DM).Data were gathered from patients' self-reports on questionnaires: one concerning disease- and treatment-related complications, and the other concerning disability, as reflected by a disability index (DI) derived from the Health Assessment Questionnaire (HAQ).Based on certain characteristics that differentiated disability patterns, 3 groups of patients were identified. Group 1 patients (n = 153) were < or = 60 years old and never had avascular necrosis (AVN) or a vertebral compression fracture (CF), Group 2 patients were > 60 and never had AVN or a vertebral CF, and Group 3 patients reported AVN or a vertebral CF irrespective of age. As measured by the HAQ DI, disability increased very gradually over time in Group 1 patients and more rapidly in Group 2 and Group 3 patients. The increase in disability in patients experiencing AVN was greater than that in patients with similar pre-AVN disease characteristics who did not develop AVN (P = 0.003).In this prospective study of disease course and iatrogenic factors related to functional disability in PM/DM, the HAQ DI increased with disease duration. Corticosteroid-related morbidity, as reflected by the development of AVN or CF, significantly contributed to patient-reported functional disability.

    View details for Web of Science ID A1995RW60300006

    View details for PubMedID 7575715

  • PREDICTORS OF ONE-YEAR PHYSICAL PERFORMANCE CHANGE IN OLDER HOSPITALIZED ADULTS Lindenberger, E. C., Winograd, C. H., MAURICIO, M. P., Chavez, C. M., Shi, H., Bloch, D. A. WILEY-BLACKWELL. 1995: SA58-SA58
  • THE NATURAL-HISTORY OF FUNCTIONAL STATUS IN HOSPITALIZED OLDER ADULTS MAURICIO, M. P., Winograd, C. H., Chavez, C. M., Bloch, D. A., Shi, H. WILEY-BLACKWELL. 1995: SA51-SA51
  • COMPARING THE BIVARIATE EFFECTS OF TOXICITY AND EFFICACY OF TREATMENTS TUBERTBITTER, P., Bloch, D. A., Raynauld, J. P. JOHN WILEY & SONS LTD. 1995: 1129-1141

    Abstract

    Medical studies often involve comparing the toxicity and efficacy of drugs. Separately evaluating toxicity and efficacy, the usual practice, does not correspond to how doctors manage patients and does not use the information provided in their bivariate relationship. This paper presents methods for analysing the bivariate data. One method is based on assessing the benefit for patient values to lie in different regions of the toxicity-efficacy plane. A second method includes patient thresholds for tolerating drugs. We propose dividing the toxicity-efficacy plane into regions where patients are likely to tolerate the drug. Several statistics are defined on these regions for measuring the toxic-therapeutic relationship, and the bootstrap is proposed for estimating their variances. We illustrate with treatment information available on rheumatoid arthritis patients.

    View details for Web of Science ID A1995RC52800031

    View details for PubMedID 7569504

  • DISCORDANT EFFECTS OF DIETARY L-ARGININE ON VASCULAR STRUCTURE AND REACTIVITY IN HYPERCHOLESTEROLEMIC RABBITS JOURNAL OF CARDIOVASCULAR PHARMACOLOGY Singer, A. H., Tsao, P. S., Wang, B. Y., Bloch, D. A., Cooke, J. P. 1995; 25 (5): 710-716

    Abstract

    We investigated the effect of dietary supplementation of L-arginine (L-Arg), the precursor of endothelial nitric oxide (NO), on endothelium-dependent and endothelium-independent vascular responses, as well as vascular structure, in the abdominal aorta of hypercholesterolemic rabbits. Rabbits were fed (a) normal rabbit chow, (b) 1% cholesterol diet, or (c) 1% cholesterol diet supplemented with 2.25% L-Arg HCl in drinking water. After 10 weeks, the abdominal aorta was harvested for study of vascular reactivity and histomorphometry. L-Arg did not affect serum cholesterol levels. Histomorphometric analysis demonstrated an eightfold reduction in intimal thickening in the abdominal aorta of the arginine-supplemented hypercholesterolemic rabbits. By contrast, the effects on vascular reactivity were subtle. Contraction to norepinephrine (NE) was not altered by hypercholesterolemia or L-Arg. Contraction to acetylcholine (ACh) was increased in hypercholesterolemic animals; this was normalized by dietary arginine supplementation. Relaxation to nitroglycerin (NTG) was not altered by hypercholesterolemia but was attenuated in the arginine-supplemented rabbits. Endothelium-dependent relaxation to ACh was impaired in both hypercholesterolemic groups. Dietary L-Arg has a dramatic antiatherogenic effect in hypercholesterolemic rabbits. This effect is associated with rather slight changes in vascular reactivity that are suggestive of a slight increase in NO elaboration by the endothelium. The discordance between the effects of dietary arginine on vascular structure and reactivity suggests that the antiatherogenic effects of the NO precursor may not be mediated entirely by its effect on the endothelium.

    View details for Web of Science ID A1995QV17000005

    View details for PubMedID 7630149

  • ASSESSMENT OF LIVING RENAL DONORS WITH SPIRAL CT RADIOLOGY Rubin, G. D., Alfrey, E. J., Dake, M. D., Semba, C. P., Sommer, F. G., Kuo, P. C., Dafoe, D. C., WASKERWITZ, J. A., Bloch, D. A., Jeffrey, R. B. 1995; 195 (2): 457-462

    Abstract

    To determine whether spiral computed tomography (CT) can be used to evaluate potential living renal donors.Twelve potential living renal donors underwent spiral CT and conventional arteriography. CT angiography was performed with 30-second spiral acquisition during injection of 150 mL of nonionic iodinated contrast material into an antecubital vein at 5 mL/sec. Five minutes after injection, a frontal abdominal scout projection was obtained to assess the renal collecting system. Results of blinded interpretations of axial CT angiograms, three-dimensional CT angiograms, and conventional arteriograms were correlated with intraoperative findings in 11 cases.Axial and three-dimensional CT angiography were 100% sensitive for identifying seven accessory renal arteries and 14% and 93% sensitive for identifying five prehilar renal artery branches. Renal venous anomalies were confirmed in three patients at surgery. Operative management changed in four of 11 patients who underwent donor nephrectomy.Spiral CT holds promise as a single examination for anatomic assessment of living renal donors.

    View details for Web of Science ID A1995QU71700028

    View details for PubMedID 7724766

  • MINIMUM DATA NEEDED ON PATIENT PREFERENCES FOR ACCURATE, EFFICIENT MEDICAL DECISION-MAKING MEDICAL CARE Hornberger, J. C., Habraken, H., Bloch, D. A. 1995; 33 (3): 297-310

    Abstract

    Involving patients in their health care decisions improves patient satisfaction and outcomes, but can be costly because of the materials and time needed to discuss the many issues that constitute a medical problem. The authors present a framework for identifying the minimum data needed on patient preferences for accurate medical decision making. The method is illustrated for the decision of whether patients with end-stage renal disease should undergo short or long hemodialysis treatments. The value of health states to patients was modeled as a function of six outcomes: survival, uremic symptoms, hospital days per year, the inconvenience associated with long dialysis treatment duration, presence of hypotension during dialysis, and presence of other symptoms during dialysis. The relative importance of each outcome was characterized in a value function by weights referred to as preference-scaling factors. These factors were varied at random over a uniform distribution to simulate different patterns of patient preferences on the six outcomes. The decision model's recommendation was recorded for each simulation. Classification and regression-tree (CART) and stepwise logistic regression analyses were applied to these recommendations to determine the scaling-factor levels that predict short or long treatments. Knowledge of scaling factors on only the inconvenience of long dialysis treatment duration, the worst alive state of health on hemodialysis, and presence of hypotension identified the correct treatment in more than 97% of simulations. Fifty-five patients undergoing hemodialysis were then surveyed for their scaling factors on the six dimensions of well-being. When patients' scaling factors were applied to the predictive rule generated by CART using simulated scaling factors, more than 94% of treatment decisions were classified correctly--sensitivity and specificity of predicting long dialysis were 89% and 100%, respectively. These statistical techniques applied to results of a decision model help identify the minimum data needed on patient preferences to involve patients in efficient and accurate decisions about their health care.

    View details for Web of Science ID A1995QK26300008

    View details for PubMedID 7861831

  • PHYSICAL-DISABILITY IN OLDER RUNNERS - PREVALENCE, RISK-FACTORS, AND PROGRESSION WITH AGE JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES Ward, M. M., Hubert, H. B., Shi, H., Bloch, D. A. 1995; 50 (2): M70-M77

    Abstract

    Concern exists that certain types of exercise, particularly vigorous activity, may increase physical disability among older individuals. We investigated the prevalence of, and risk factors for, physical disability in active older persons (runners), and examined factors influencing the progression of physical disability with age.Physical disability, measured using the Health Assessment Questionnaire Disability Index, was assessed prospectively in 454 runners, age 50 or greater, over five to seven years by annual mailed questionnaires. Baseline sociodemographic, clinical, and life-style characteristics associated with the presence of any disability over the course of the study were determined and contrasted with those in 292 older non-runners who had been similarly followed.Two hundred twenty-two runners (49%) reported some physical disability during the study. The presence of arthritis symptoms at baseline was the most important risk factor for physical disability; older age, greater body mass index, strenuous work-related physical activity, and the use of more medications were also associated with a greater likelihood of physical disability. Among the non-runners, 224 (77%) reported some physical disability, and the presence of arthritis symptoms was also the most important risk factor for physical disability in this group. Age-related changes in physical disability differed between those with and without arthritis symptoms in both the runner and non-runner groups.The presence of arthritis symptoms was an important risk factor for physical disability among both older runners and non-runners, and also identified subgroups of individuals with different progressions of disability with age.

    View details for Web of Science ID A1995RY60100009

    View details for PubMedID 7874592

  • DECREASING COSTS AND IMPROVING OUTCOMES IN SYSTEMIC LUPUS-ERYTHEMATOSUS - USING REGRESSION TREES TO DEVELOP HEALTH-POLICY JOURNAL OF RHEUMATOLOGY Clarke, A. E., Bloch, D. A., Danoff, D. S., Esdaile, J. M. 1994; 21 (12): 2246-2253

    Abstract

    To characterize patients with systemic lupus erythematosus (SLE) who are expected to experience the highest direct and indirect monetary costs and greatest diminished productivity so that we may intervene to reduce costs and improve outcomes.We assessed demographics and health status in January, 1990 and costs incurred in the last 6 months of 1990 in January, 1991 in 151 patients with SLE enrolled in the Montreal General Hospital Lupus Registry. We used regression trees to separate low from high cost patients.Patients with poor physical or poor psychological functioning incur the highest direct costs (3-fold and 1.6-fold the group mean, respectively); those with the poorest psychological functioning incur the highest indirect costs (2-fold the group average); and those with the most intense pain experience the greatest impairment in productivity (3-fold the group average).Targeting patients with poor physical and psychological functioning and substantial pain with appropriate interventions may improve their outcomes and reduce disease costs. Targeting patients expected to have low costs with preventative interventions may delay worse outcomes and reduce future costs.

    View details for Web of Science ID A1994PX44600015

    View details for PubMedID 7699625

  • DEVELOPMENT OF A PHYSICAL PERFORMANCE AND MOBILITY EXAMINATION JOURNAL OF THE AMERICAN GERIATRICS SOCIETY Winograd, C. H., LEMSKY, C. M., Nevitt, M. C., NORDSTROM, T. M., Stewart, A. L., Miller, C. J., Bloch, D. A. 1994; 42 (7): 743-749

    Abstract

    To develop and validate the Physical Performance and Mobility Examination (PPME), an observer-administered, performance-based instrument assessing 6 domains of physical functioning and mobility for hospitalized elderly.Development of a pass-fail and 3-level scoring system and training manuals for the PPME instrument for use in both clinical and research settings. Two patient samples were used to assess construct validity and interrater reliability of the PPME. A third sample was selected to assess the test-retest reliability of the instrument.(1) 146 subjects > or = 65 years of age with impaired mobility admitted to Medical Units of Stanford University Hospital. (2) 352 subjects > or = 65 admitted to acute Medical and Surgical Services of the Palo Alto VA Medical Center. Patient samples were obtained during hospitalization and followed until 3 months post-discharge. To study test-retest reliability, 50 additional patients, whose clinical condition was stable, were selected from both settings.An expert panel selected 6 mobility tasks integral to daily life: bed mobility, transfer skills, multiple stands from chair, standing balance, step-up, and ambulation. Tasks were piloted with frail hospitalized subjects for appropriateness and safety. Test-retest and interrater reliability and construct validity were evaluated. Construct validity was tested using the Folstein Mini-Mental State Examination, Activities of Daily Living (ADL), Instrumental Activities of Daily Living (IADL), Geriatric Depression Scale, and modified Medical Outcomes Study Measure of Physical Functioning (MOS-PFR). Two scoring schema were developed for each task: (1) dichotomous pass-fail and (2) 3-level high pass, low pass, and fail. A summary scale was developed for each method of scoring.High interrater reliability and intrarater reliability were demonstrated for individual tasks. The mean percent agreement (interrater) for each pass/fail task ranged from 96 to 100% and from 90 to 100% for the 3 pairs of raters for each task using the 3-level scoring. Kappas for individual pairs of raters ranged from .80 to 1.0 for pass-fail scoring and from .75 to 1.0 for 3-level scoring (all P < 0.01). Intraclass correlation coefficients for 3-level scoring by pairs of raters ranged from .66 to 1.0. For summary scales, the mean intraclass correlation was .99 for both scoring schema. Test-retest reliability for summary scales using kappa coefficients was .99 for both pass-fail and 3-level scoring, and .99 and .98, respectively, using Pearson Product Moment Correlation. Correlations of PPME with other instruments (construct validity) suggest that the PPME adds a unique dimension of mobility beyond that measured by self-reported ADLS and physical functioning, and it is not greatly influenced by mood or mental status (r = 0.70 (ADL), r = 0.43 (IADL), r = 0.36 (MMSE), r = 0.71 (MOS-PFR), r = 0.23 (GDS)). The 3-level summary scale was sensitive to the variability in the patient population and exhibited neither ceiling nor floor effects.The PPME is a reliable and valid performance-based instrument measuring physical functioning and mobility in hospitalized and frail elderly.

    View details for Web of Science ID A1994NW33900010

    View details for PubMedID 8014350

  • APPLICATION OF NEURAL NETWORKS TO THE CLASSIFICATION OF GIANT-CELL ARTERITIS ARTHRITIS AND RHEUMATISM Astion, M. L., Wener, M. H., Thomas, R. G., Hunder, G. G., Bloch, D. A. 1994; 37 (5): 760-770

    Abstract

    Neural networks are a group of computer-based pattern recognition methods that have recently been applied to clinical diagnosis and classification. In this study, we applied one type of neural network, the backpropagation network, to the diagnostic classification of giant cell arteritis (GCA).The analysis was performed on the 807 cases in the vasculitis database of the American College of Rheumatology. Classification was based on the 8 clinical criteria previously used for classification of this data set: 1) age > or = 50 years, 2) new localized headache, 3) temporal artery tenderness or decrease in temporal artery pulse, 4) polymyalgia rheumatica, 5) abnormal result on artery biopsy, 6) erythrocyte sedimentation rate > or = 50 mm/hour, 7) scalp tenderness or nodules, and 8) claudication of the jaw, of the tongue, or on swallowing. To avoid overtraining, network training was terminated when the generalization error reached a minimum. True cross-validation classification rates were obtained.Neural networks correctly classified 94.4% of the GCA cases (n = 214) and 91.9% of the other vasculitis cases (n = 593). In comparison, classification trees correctly classified 91.6% of the GCA cases and 93.4% of the other vasculitis cases. Neural nets and classification trees were compared by receiver operating characteristic (ROC) analysis. The ROC curves for the two methods crossed, indicating that the better classification method depended on the choice of decision threshold. At a decision threshold that gave equal costs to percentage increases in false-positive and false-negative results, the methods were not significantly different in their performance (P = 0.45).Neural networks are a potentially useful method for developing diagnostic classification rules from clinical data.

    View details for Web of Science ID A1994NK47700022

    View details for PubMedID 8185705

  • THE MORTALITY OF RHEUMATOID-ARTHRITIS ARTHRITIS AND RHEUMATISM Wolfe, F., MITCHELL, D. M., Sibley, J. T., Fries, J. F., Bloch, D. A., WILLIAMS, C. A., SPITZ, P. W., Haga, M., KLEINHEKSEL, S. M., CATHEY, M. A. 1994; 37 (4): 481-494

    Abstract

    To determine the risk and causes of death and to quantify mortality predictors in patients with rheumatoid arthritis (RA).RA patients (n = 3,501) from 4 centers (Saskatoon n = 905, Wichita n = 1,405, Stanford n = 886, and Santa Clara n = 305) were followed for up to 35 years; 922 patients died.The overall standardized mortality ratio (SMR) was 2.26 (Saskatoon 2.24, Wichita 1.98, Stanford 3.08, Santa Clara 2.18) and increased with time. Mortality was strikingly increased for specific causes: infection, lymphoproliferative malignancy, gastroenterologic, and RA. In addition, as an effect of the SMR of 2.26, the expected number of deaths was increased nonspecifically across all causes (except cancer), with a large excess of deaths attributable to cardiovascular and cerebrovascular diseases. Independent predictors of mortality included age, education, male sex, function, rheumatoid factor, nodules, erythrocyte sedimentation rate, joint count, and prednisone use.Mortality rates are increased at least 2-fold in RA, and are linked to clinical severity.

    View details for Web of Science ID A1994NF04400007

    View details for PubMedID 8147925

  • THE IMPACT OF DISEASE-ACTIVITY, TREATMENT AND DISEASE SEVERITY ON SHORT-TERM COSTS OF SYSTEMIC LUPUS-ERYTHEMATOSUS JOURNAL OF RHEUMATOLOGY Lacaille, D., Clarke, A. E., Bloch, D. A., Danoff, D., Esdaile, J. M. 1994; 21 (3): 448-453

    Abstract

    To assess the impact of disease activity, current treatment, and global disease severity (or damage) on short-term direct and indirect costs of systemic lupus erythematosus (SLE).150 patients were evaluated twice, one year apart. Disease activity was assessed by the SLE disease activity index, and ordinal scales were used to evaluate treatment (prednisone = 0, 1 to 20 mg/day, > 20 mg/day, and use of immunosuppressive agents) and global disease severity [renal severity = 0 to 3, central nervous system (CNS) severity = 0 to 2, hematologic severity = 0 to 1]. Costs were assessed with the economic portion of the Health Assessment Questionnaire adapted for Canada.Global disease severity was significantly correlated with both direct (p = 0.0001) and indirect (p = 0.02) costs, and current treatment with indirect costs (p = 0.002). The renal and CNS subscales of the global severity measure predicted direct costs (p < 0.01) and the CNS subscale predicted indirect costs (p = 0.002). Stepwise multivariable models selected the global severity index (p = 0.004) as a predictor of direct costs, and either the treatment index (p = 0.02) or the global severity index (p = 0.02) as a predictor of indirect costs.The global disease severity index, particularly the subscales involving the renal and CNS organ systems, and the treatment index are predictors of the short-term costs of SLE.

    View details for Web of Science ID A1994MZ50500013

    View details for PubMedID 8006887

  • A REEVALUATION OF ASPIRIN THERAPY IN RHEUMATOID-ARTHRITIS ARCHIVES OF INTERNAL MEDICINE Fries, J. F., Ramey, D. R., Singh, G., MORFELD, D., Bloch, D. A., Raynauld, J. P. 1993; 153 (21): 2465-2471

    Abstract

    Aspirin therapy has been largely superseded by prescription nonsteroidal anti-inflammatory drug (NSAID) therapy in rheumatoid arthritis, in part because of premarketing studies suggesting lesser toxic effects for NSAIDs than for aspirin. This study evaluates these toxic effects in a postmarketing population of patients with rheumatoid arthritis.We studied 1521 consecutive courses of aspirin and 4860 courses of NSAIDs in patients with rheumatoid arthritis from eight Arthritis, Rheumatism, and Aging Medical Information System Post-marketing Surveillance Centers. Toxicity index scores were generated from symptoms, laboratory abnormalities, and hospitalizations, weighted for variable severity and severity of side effect.The toxicity index was only 1.37 (SE = 0.10) for aspirin and 1.87 to 2.90 for selected nonsalicylate NSAIDs. These differences were consistent across centers and remained after statistical adjustment for differing patient characteristics. There was a different toxicity with different aspirin preparations, with a score for plain aspirin of 1.36 (SE = 0.23), for buffered aspirin of 1.10 (0.20), and for enteric-coated aspirin preparations of 0.92 (0.14). Most important, there were strong dose effects, with a score of 0.73 (0.09) for 651 to 2600 mg daily, 1.08 (0.17) for 2601 to 3900 mg, and 1.91 (0.38) for more than 3900 mg. The average aspirin dose taken was only 2665 mg/d, approximately eight "tablets," compared with 3600 to 4800 mg/d used in the 16 pivotal premarketing studies reviewed. Average NSAID doses were, on the other hand, lower in premarketing trials (eg, naproxen 500 mg/d vs 773 mg/d in the Arthritis, Rheumatism, and Aging Medical System clinical practices).Aspirin therapy, in doses commonly employed in practice, has an excellent safety profile in rheumatoid arthritis, and it is the least costly NSAID. The safety advantage is explained primarily by a dose effect and secondarily by possible differences between formulations. Newer management strategies for rheumatoid arthritis emphasize NSAID use as symptomatic therapy and use of disease-modifying anti-rheumatic drug therapy for anti-inflammatory objectives. Thus, the original recommendation for "anti-inflammatory" doses of aspirin now is less easily justified. Aspirin therapy merits reconsideration as adjunctive therapy for the management of rheumatoid arthritis.

    View details for Web of Science ID A1993ME65900008

    View details for PubMedID 8215751

  • A CANADIAN STUDY OF THE TOTAL MEDICAL COSTS FOR PATIENTS WITH SYSTEMIC LUPUS-ERYTHEMATOSUS AND THE PREDICTORS OF COSTS ARTHRITIS AND RHEUMATISM Clarke, A. E., Esdaile, J. M., Bloch, D. A., Lacaille, D., Danoff, D. S., Fries, J. F. 1993; 36 (11): 1548-1559

    Abstract

    We conducted a cost identification analysis on 164 consecutive patients with systemic lupus erythematosus (SLE) who entered the Montreal General Hospital Lupus Registry between January 1977 and January 1990, compared their costs to the population of Quebec, and determined the predictors of cost.In January 1990 and 1991, participants completed questionnaires on health services utilization and on employment history over the preceding 6 months, as well as on functional, psychological, and social well-being. The societal burden of SLE was determined in terms of direct costs (all resources consumed in patient care) and indirect costs (wages lost due to lack of work force participation because of morbidity).The mean total annual cost for 1989, as assessed in January 1990 and expressed in 1990 Canadian dollars, was $13,094. Although only 44% of the patients were fully employed, indirect costs were responsible for 54% of this total ($7,071). Ambulatory costs, primarily diagnostic procedures, medications, and visits to health care professionals, comprised 55% of direct costs ($3,331). The results of the 1990 cost determination were similar. On average, hospitalizations among SLE patients were 4 times more frequent than among the general population of Quebec (matched for age and sex), and the number of ambulatory visits to physicians was double that for the average resident of Quebec. Higher 1989 values of creatinine and a poorer level of physical functioning were the best predictors of higher 1990 direct costs (R2 = 0.29). A poorer SLE well-being score, a combination of education and employment status, and a weaker level of social support were the best predictors of higher indirect costs (R2 = 0.29).The direct and indirect costs for patients with SLE are substantial, and their respective predictors are distinct. Direct costs arise from organic complications which induce functional disability. Predictors of indirect costs are potentially amenable to psychological or social interventions and may be more easily modified than the determinants of direct costs, thereby improving patient outcome while simultaneously reducing disease costs.

    View details for Web of Science ID A1993MF62700008

    View details for PubMedID 8240431

  • THE RELATIVE TOXICITY OF ALTERNATIVE THERAPIES FOR RHEUMATOID-ARTHRITIS - IMPLICATIONS FOR THE THERAPEUTIC PROGRESSION SEMINARS IN ARTHRITIS AND RHEUMATISM Fries, J. F., WILLIAMS, C. A., Ramey, D. R., Bloch, D. A. 1993; 23 (2): 68-73

    Abstract

    The traditional pyramid for the therapeutic progression in rheumatoid arthritis (RA) is based on assumptions that RA is a mild disease, that nonsteroidal antiinflammatory drugs (NSAIDs) have low toxicity, and that disease-modifying antirheumatic drugs (DMARDs) are extremely toxic. This article reviews data from ARAMIS (Arthritis, Rheumatism, and Aging Medical Information System), casting strong doubt on these assumptions. NSAIDs result in 1.3% excess gastrointestinal hospitalizations per year. Mortality rates in RA are far above those expected from age- and sex-matched populations. Individual NSAIDs show widely different overall quantitative toxicity indices, as do individual DMARDs. However, the ranges of toxicity of the two classes of drugs show nearly complete overlap. It is suggested that the new therapeutic progression in RA should emphasize initial use of DMARDs, beginning with the least toxic.

    View details for Web of Science ID A1993MF17600010

    View details for PubMedID 8278821

  • FRACTURES IN RHEUMATOID-ARTHRITIS - AN EVALUATION OF ASSOCIATED RISK-FACTORS JOURNAL OF RHEUMATOLOGY Michel, B. A., Bloch, D. A., Wolfe, F., Fries, J. F. 1993; 20 (10): 1666-1669

    Abstract

    Our purpose was to identify factors indicative of a high fracture risk during the disease course of rheumatoid arthritis (RA).In 1110 patients (879 women and 231 men) with RA from five Arthritis, Rheumatism and Aging Medical Information System centers, information from history, clinical and laboratory examination, outcome assessment, and therapy was evaluated for association with the 226 first fractures having occurred during the years from 1975 to 1988.The mean age of the patients was 54 years, the mean time of observation was 8 years. Multivariate analyses identified the following factors to be associated with fracturing: years taking prednisone, previous diagnosis of osteoporosis, disability, age, lack of physical activity, female sex, disease duration, impaired grip strength, and low body mass.We conclude that patients with RA at greatest risk for fracturing are easily identified by using a few clinical variables. These findings support encouragement of active lifestyle habits and avoidance of longterm administration of corticosteroids in patients with RA.

    View details for Web of Science ID A1993MG97800007

    View details for PubMedID 8295176

  • SEASONAL-VARIATION IN THE ONSET OF WEGENERS GRANULOMATOSIS, POLYARTERITIS-NODOSA AND GIANT-CELL ARTERITIS JOURNAL OF RHEUMATOLOGY Raynauld, J. P., Bloch, D. A., Fries, J. F. 1993; 20 (9): 1524-1526

    Abstract

    The hypothesis of a seasonal pattern in the onset of symptoms for some vasculitides has been raised in previous small studies.Using the data collected by the American College of Rheumatology (ACR) Subcommittee on Classification of Vasculitis, we specifically tested for a higher proportion of onset of symptoms in winter, lower in summer, and intermediate for the other seasons for polyarteritis nodosa (PAN) and Wegener's granulomatosis. We also tested for a higher proportion of onset of symptoms in the spring-summer months for giant cell arteritis (GCA).The results of our study support the hypothesis of a seasonal trend for the onset of symptoms of Wegener's granulomatosis (p = 0.04) as described previously. No seasonal pattern was found for the other vasculitides studied (PAN and GCA).

    View details for Web of Science ID A1993MJ67800013

    View details for PubMedID 7909333

  • OVERTRAINING IN NEURAL NETWORKS THAT INTERPRET CLINICAL-DATA CLINICAL CHEMISTRY Astion, M. L., Wener, M. H., Thomas, R. G., Hunder, G. G., Bloch, D. A. 1993; 39 (9): 1998-2004

    Abstract

    Backpropagation neural networks are a computer-based pattern-recognition method that has been applied to the interpretation of clinical data. Unlike rule-based pattern recognition, backpropagation networks learn by being repetitively trained with examples of the patterns to be differentiated. We describe and analyze the phenomenon of overtraining in backpropagation networks. Overtraining refers to the reduction in generalization ability that can occur as networks are trained. The clinical application we used was the differentiation of giant cell arteritis (GCA) from other forms of vasculitis (OTH) based on results for 807 patients (593 OTH, 214 GCA) and eight clinical predictor variables. The 807 cases were randomly assigned to either a training set with 404 cases or to a cross-validation set with the remaining 403 cases. The cross-validation set was used to monitor generalization during training. Results were obtained for eight networks, each derived from a different random assignment of the 807 cases. Training error monotonically decreased during training. In contrast, the cross-validation error usually reached a minimum early in training while the training error was still decreasing. Training beyond the minimum cross-validation error was associated with an increased cross-validation error. The shape of the cross-validation error curve and the point during training corresponding to the minimum cross-validation error varied with the composition of the data sets and the training conditions. The study indicates that training error is not a reliable indicator of a network's ability to generalize. To find the point during training when a network generalizes best, one must monitor cross-validation error separately.

    View details for Web of Science ID A1993LX46500049

    View details for PubMedID 8375090

  • THE RELATIONSHIP BETWEEN SPINAL AND PERIPHERAL OSTEOARTHRITIS AND BONE-DENSITY MEASUREMENTS JOURNAL OF RHEUMATOLOGY BELMONTESERRANO, M. A., Bloch, D. A., Lane, N. E., Michel, B. E., Fries, J. F. 1993; 20 (6): 1005-1013

    Abstract

    To determine the influence of osteoarthritis (OA) on bone density measurements and whether OA at one site is associated with OA at other sites.Nonrandomized, cross sectional observational study; secondary analysis of a general population database. Sixty-four subjects derived from a longitudinal study of long distance runners and community controls had a complete peripheral radiographic evaluation for osteoarthritic changes in hands, knees, and lumbar spine. Forty-four of these were studied in 1984 with quantitative computed tomography (QCT) of L1, and 54 were studied in 1988 with 153-Gd dual photon absorptiometry (DPA) in the spine and total body. Thirty-four subjects had all measurements done.Total body and lumbar spine DPA were positively correlated with radiological scores of OA in the spine and knees, with coefficients ranging between 0.467 to 0.530 (p < 0.001 in all cases). This correlation was principally associated with spinal spurs and knee sclerosis. Results of stepwise multiple linear regression modeling for QCT included age, spine sclerosis, knee sclerosis and knee spurs as the main predictors of bone mineral density (BMD). For DPA measurements, spine spur score was a useful regressor for all the models. Altogether, the percentage of variance accounted for by individual radiological OA variables was 27.4% for lumbar QCT, 27.3% for lumbar BMD, 7.3% for total spine BMD, and 45.2% for total body BMD. OA scores at different sites were not correlated, although repeated assessment at the same site showed very close correlation.All methods used to determine BMD showed a highly significant positive correlation between lumbar and knee radiological OA and bone mineral content both in the spine and the total body. Thus, our results support the hypothesis that OA is negatively correlated with osteopenia. OA, as seen in this population, was not a generalized condition, but rather, was site specific.

    View details for Web of Science ID A1993LH11200019

    View details for PubMedID 8350306

  • 2-YEAR RESULTS OF A RANDOMIZED CONTROLLED TRIAL OF A HEALTH PROMOTION PROGRAM IN A RETIREE POPULATION - THE BANK-OF-AMERICA STUDY AMERICAN JOURNAL OF MEDICINE Fries, J. F., Bloch, D. A., Harrington, H., Richardson, N., Beck, R. 1993; 94 (5): 455-462

    Abstract

    To evaluate the effectiveness of a health promotion program in a retiree population in terms of health risk reduction and reduction in medical costs.Randomized controlled trial.Bank of America retirees (n = 4,712), divided into 33 retiree club regions, were randomized into 3 groups and followed for 24 months by patient report and claims experience. Group 1, the intervention group, received a low-cost ($30/year), individualized, serially reinforcing health promotion program including risk appraisal, recommendation letters, and self-management materials, delivered entirely through the mail. Group 2 received risk appraisals only, without feedback, for the first 12 months and subsequently the full intervention for the second 12 months. Group 3 was followed with claims data only. Participation rates of 57% at 1 year and 47% at 2 years were achieved.Overall health risk scores improved by 12% at 12 months compared with control (p < 0.001) and by 23% (from baseline) at 24 months (p < 0.001). Individual health habit changes were favorable for all parameters studied, and were highly statistically significant for most variables. Similar health risk reductions were seen in age groups of 55 to 65 years, 65 to 75 years, and over 75. Cost reduction differences were more than 20% by self-report (p < 0.01) and 10% by claims experience (p = 0.02) at 12 months. For the randomized controlled period of the first 12 months, reductions averaged $164 in the intervention group contrasted with an average increase of $15 in the combined control groups.Risk reduction programs directed at retiree populations can improve health risk status and can reduce costs.

    View details for Web of Science ID A1993LC87400002

    View details for PubMedID 8498389

  • THE RELATIVE TOXICITY OF DISEASE-MODIFYING ANTIRHEUMATIC DRUGS ARTHRITIS AND RHEUMATISM Fries, J. F., WILLIAMS, C. A., Ramey, D., Bloch, D. A. 1993; 36 (3): 297-306

    Abstract

    To compare the toxicities of commonly employed disease-modifying antirheumatic drugs (DMARDs) in rheumatoid arthritis (RA).Toxicity Index scores, computed from symptoms, laboratory abnormalities, and hospitalizations attributable to DMARD therapy, were assessed in 2,747 patients with RA receiving 3,053 courses of 6 DMARDs and 1,309 courses of prednisone over 7,278 patient-years. Results were adjusted for severity of illness and other covariates.Least toxic was hydroxychloroquine (mean +/- SEM score 1.38 +/- 0.15), followed by intramuscular gold (2.27 +/- 0.17) and the closely grouped D-penicillamine (3.38 +/- 0.36), methotrexate (3.82 +/- 0.35), and azathioprine (3.92 +/- 0.39). Auranofin (5.25 +/- 0.32) was most toxic, but this toxicity resulted from a high frequency of minor complications. Hospitalizations because of auranofin or hydroxychloroquine therapy were not noted. Prednisone (3.83 +/- 0.39) was of comparable toxicity, although it is likely that not all events of prednisone toxicity were captured. For reference, the toxicity of methotrexate and azathioprine was similar to that of the most toxic nonsteroidal antiinflammatory drugs (NSAIDs) (indomethacin 3.99, tolmetin sodium 3.96, and meclofenamate 3.86). Hydroxychloroquine showed less toxicity than the most commonly used prescription NSAIDs.There are substantial differences in toxicity among DMARDs and less important differences in toxicity between specific DMARDs and specific NSAIDs.

    View details for Web of Science ID A1993KR79800002

    View details for PubMedID 8452574

  • THE RISK OF OSTEOARTHRITIS WITH RUNNING AND AGING - A 5-YEAR LONGITUDINAL-STUDY JOURNAL OF RHEUMATOLOGY Lane, N. E., Michel, B., BJORKENGREN, A., Oehlert, J., Shi, H., Bloch, D. A., Fries, J. F. 1993; 20 (3): 461-468

    Abstract

    Our purpose was to determine the 5-year longitudinal effects of running and aging on the development of radiographic and clinical osteoarthritis (OA) of the knees, hands and lumbar spine. Thirty-five running subjects and 38 controls, with a mean age of 63 years, were matched for age (+/- 2 years), years of education, and occupation; 33 matched pairs were constructed. All subjects underwent rheumatologic examination, completed questionnaires, and had radiographs taken of the hands, lateral lumbar spine, and knees in 1984 and in 1989. Five year radiographic results for both the runner and control groups showed OA progression for the knees, hands, and lumbar spine. In 1989, 10 (13%) of the 73 subjects fit American College of Rheumatology (ACR) criteria for clinical OA of the hand, and 9 subjects (12%) fit ACR criteria for OA of the knee. In summary, running did not accelerate the development of radiographic or clinical OA of the knees, but with aging, 13% of all subjects developed OA of the hands and 12% of all subjects developed OA of the knees.

    View details for Web of Science ID A1993KU05800010

    View details for PubMedID 8478853

  • RISK-FACTORS FOR PHYSICAL-DISABILITY IN AN AGING COHORT - THE NHANES-I EPIDEMIOLOGIC FOLLOW-UP-STUDY JOURNAL OF RHEUMATOLOGY Hubert, H. B., Bloch, D. A., Fries, J. F. 1993; 20 (3): 480-488

    Abstract

    Successful improvement in health in our increasingly aged population will depend in substantial part on reduction of age specific disability levels. In turn, the epidemiologic model suggests that this requires identification of risk factors, development of intervention models, and testing of these models. We attempted to identify risk factors for physical disability among 4,428 50-77-year-olds using baseline data collected in the first National Health and Nutrition Examination Survey (NHANES I) (1971-1975) linked to disability data collected 10 years later in the NHANES I Epidemiologic Followup Study. Results of forward stepwise linear regression analysis showed that the major characteristics contributing to greater disability (explaining at least 1% of the variability in scores) were older age at baseline, less nonrecreational activity, arthritis history, less education, female sex, and greater body mass index at age 40. Other factors associated with greater disability included a history of asthma, cardiovascular disease, abnormal urine test, less recreational activity, higher sedimentation rate, rheumatic fever history, lower caloric intake, positive musculoskeletal findings, histories of polio and allergies, lower family income, elevated blood pressure, lower serum albumin, history of tuberculosis, glucose in the urine, and histories of hip or spine fracture, chronic pulmonary disease, and kidney disease.

    View details for Web of Science ID A1993KU05800013

    View details for PubMedID 8478855

  • PREDICTORS OF SURVIVAL IN HOSPITALIZED OLDER VETERANS Winograd, C. H., Bloch, D. A., Chavez, C. M., Shi, H., LEMSKY, C. M. SLACK INC. 1993: A10-A10
  • PREDICTORS OF HEALTH-CARE UTILIZATION Winograd, C. H., LEMSKY, C. M., Bloch, D. A., Chavez, C. M., Shi, H. SLACK INC. 1993: A104-A104
  • IMPACT OF RUNNING ON LUMBAR BONE-DENSITY - A 5-YEAR LONGITUDINAL-STUDY JOURNAL OF RHEUMATOLOGY Michel, B. A., Lane, N. E., BJORKENGREN, A., Bloch, D. A., Fries, J. F. 1992; 19 (11): 1759-1763

    Abstract

    Our study was designed to examine associations of longterm physical impact (running) with changes in lumbar bone mineralization. Study subjects were a volunteer sample of 14 members of a running club now aged 55 to 77 years and 14 matched controls undergoing computerized scans of the first lumbar vertebra both at baseline and after 5 years. Separate analyses included data from 23 runners available over the entire 5-year period. A decrease in bone mineral density (BMD) over time was statistically significant in both runners and controls. Among runners bone loss was most pronounced in those decreasing their running habits substantially. At the 5-year mark, runners maintained greater BMD. A highly significant correlation was found between change in lumbar BMD and average time spent running (min/week) over the 5-year period. Furthermore, changes in BMD were positively correlated with changes in run min/week. We conclude that regular running appears to reduce age related bone loss both in women and men over 50 years of age. However, substantial decreases in physical weight bearing activity are associated with important bone loss in the lumbar spine.

    View details for Web of Science ID A1992JY69000022

    View details for PubMedID 1491398

  • THE COMPARATIVE TOXICITY OF NONSTEROIDAL ANTIINFLAMMATORY DRUGS (NSAIDS) IN RHEUMATOID-ARTHRITIS (RA) - 1992 Fries, J. F., Singh, G., Ramey, D. R., MORFELD, D., WILLIAMS, C. A., Bloch, D. A. WILEY-LISS. 1992: S236-S236
  • A STUDY TO ASSESS RADIOGRAPHIC LUMBAR-DISK DEGENERATION Lane, N. E., Michel, B. A., BJORKENGREN, A., Shi, H., Bloch, D. A., Fries, J. F. WILEY-LISS. 1992: S295-S295
  • HYPERSENSITIVITY VASCULITIS AND HENOCH-SCHONLEIN PURPURA - A COMPARISON BETWEEN THE 2 DISORDERS JOURNAL OF RHEUMATOLOGY Michel, B. A., Hunder, G. G., Bloch, D. A., Calabrese, L. H. 1992; 19 (5): 721-728

    Abstract

    Leukocytoclastic vasculitis of small vessels and predominant involvement of the skin are common features of both hypersensitivity vasculitis (HV) and Henoch-Schönlein purpura. In a study comparing 93 patients with HV and 85 patients with Henoch-Schönlein purpura we found major differences with respect to frequencies and type of organ involvement (gastrointestinal tract, kidneys, skin and joints) which were present in both younger and older patients when analyzed separately. To investigate which clinical criteria best differentiate between these 2 vasculitides, 2 methodologies were employed. A rule requiring 3 or more criteria to be present from a list of 6 yielded 87.1% of correctly classified Henoch-Schönlein purpura cases; and 2 or fewer criteria from the same list of 6 correctly classified 74.2% of HV cases. A classification tree was associated with respective values of 83.5 and 84.9%. The results indicate that HV and Henoch-Schönlein purpura are similar but separable clinical syndromes.

    View details for Web of Science ID A1992HW15600012

    View details for PubMedID 1613701

  • THE RELATIVE TOXICITY OF NONSTEROIDAL ANTIINFLAMMATORY DRUGS (NSAIDS) RHEUMATOLOGY, STATE OF THE ART Fries, J. F., WILLIAMS, C. A., Bloch, D. A. 1992; 984: 322-324
  • THE RELATIVE TOXICITY OF NONSTEROIDAL ANTIINFLAMMATORY DRUGS ARTHRITIS AND RHEUMATISM Fries, J. F., WILLIAMS, C. A., Bloch, D. A. 1991; 34 (11): 1353-1360

    Abstract

    Toxicity Index scores were computed from symptoms, laboratory abnormalities, and hospitalizations attributed to nonsteroidal antiinflammatory drug (NSAID) therapy in 2,747 patients with rheumatoid arthritis receiving 5,642 courses of 11 NSAIDs over 8,481 patient-years. Substantial differences in overall toxicity were found, the differences between drugs often being clinically significant (2-3 times as toxic) and highly statistically significant. The results strengthened after adjustment for differing patient characteristics, held generally across multiple ARAMIS (Arthritis, Rheumatism, and Aging Medical Information System) data bank centers, and persisted after use of different techniques for the weighting of side effects. The most toxic side effects were experienced by patients taking indomethacin (mean +/- SEM score 3.99 +/- 0.58), tolmetin sodium (3.96 +/- 0.74), and meclofenamate sodium (3.86 +/- 0.66). Least toxic were coated or buffered aspirin (1.19 +/- 0.10), salsalate (1.28 +/- 0.34), and ibuprofen (1.94 +/- 0.43). The most toxic drugs were generally taken in the lowest relative doses. There are statistical differences in overall toxicity between different NSAIDs as used in rheumatoid arthritis, and these differences are both clinically and statistically significant.

    View details for Web of Science ID A1991GN25900002

    View details for PubMedID 1953813

  • EFFECT OF CHANGES IN WEIGHT-BEARING EXERCISE ON LUMBAR BONE MASS AFTER AGE 50 ANNALS OF MEDICINE Michel, B. A., Lane, N. E., Bloch, D. A., Jones, H. H., Fries, J. F. 1991; 23 (4): 397-401

    Abstract

    This two year longitudinal study of 40 healthy subjects over age fifty (27 exercisers, 13 non-exercisers) was designed to evaluate the impact of weight-bearing exercise on lumbar bone mineral density as assessed by quantitative computed tomography. In both males and females exercising at moderate levels, a high correlation was found between changes in exercise and changes in bone density (r = 0.78 and 0.91, respectively P less than 0.002). For extreme levels of exercise (greater than 300 min/week in females over age fifty, and greater than 200 min/week in males over age seventy) bone density was low, confirming earlier cross-sectional results. Subjects without change in their exercise levels and non-exercisers lost similar amounts of bone. Increasing body mass index was identified as a protective factor with regard to lumbar bone loss. We conclude that in exercisers continuation of weight-bearing exercise is mandatory to prevent excessive bone loss. Extreme levels of exercise may be detrimental to bone density in subjects over age fifty years.

    View details for Web of Science ID A1991GL13600010

    View details for PubMedID 1930935

  • NONSTEROIDAL ANTIINFLAMMATORY DRUG-ASSOCIATED GASTROPATHY - INCIDENCE AND RISK FACTOR MODELS AMERICAN JOURNAL OF MEDICINE Fries, J. F., WILLIAMS, C. A., Bloch, D. A., Michel, B. A. 1991; 91 (3): 213-222

    Abstract

    The most prevalent serious drug toxicity in the United States is increasingly recognized as gastrointestinal (GI) pathology associated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs). The incidence of serious GI events (hospitalization or death) associated with NSAID use was therefore prospectively analyzed in patients with rheumatoid arthritis (RA) and patients with osteoarthritis.The study consisted of 2,747 patients with RA and 1,091 patients with osteoarthritis. The yearly hospitalization incidence during NSAID treatment was 1.58% in RA patients and was similar in all five populations studied. The hazard ratio of patients taking NSAIDs to those not taking NSAIDs was 5.2. The incidence in osteoarthritis may be less. The risk of GI-related death in RA patients was 0.19% per year with NSAIDs. Multivariate analyses assessing risk factors for serious GI events were performed in the 1,694 (98 with an event) RA patients taking NSAIDs at the predictive visit. The main risk factors were higher age, use of prednisone, previous NSAID GI side effects, prior GI hospitalization, level of disability, and NSAID dose. A rule is presented that allows estimation of the risk for the individual patient with RA.Knowledge of the risk factors for NSAID-associated gastropathy and their inter-relationships provides a tool for identification of the patient at high risk and for initiation of appropriate therapeutic action.

    View details for Web of Science ID A1991GG13000002

    View details for PubMedID 1892140

  • THE PROGRESSION OF EROSION AND JOINT SPACE NARROWING SCORES IN RHEUMATOID-ARTHRITIS DURING THE 1ST 25 YEARS OF DISEASE ARTHRITIS AND RHEUMATISM Sharp, J. T., Wolfe, F., MITCHELL, D. M., Bloch, D. A. 1991; 34 (6): 660-668

    Abstract

    Erosions and cartilage destruction are nearly universal features in peripheral joints that have been chronically affected by rheumatoid arthritis. Scoring methods to measure the extent of these abnormalities in hands and wrists have been developed and have been thoroughly tested in several studies to establish their reproducibility. In this study, we utilized one of these scoring methods to examine the progression of radiologic damage as related to duration of disease. Two hundred ninety-two patients from 3 different participating centers in the Arthritis, Rheumatism, and Aging Medical Information System were included. Six hundred fifty films of the hands and wrists, obtained from 210 patients, were scored for erosions and joint space narrowing. The average annual rate of progression of the total radiologic score, which sums erosion and joint space abnormalities and has a maximum possible score of 314, was approximately 4 units per year over the first 25 years after onset; this progression was more rapid in the earlier years of disease and slightly slower in the later years. Data were insufficient to accurately determine the progression rate in disease of more than 25 years duration.

    View details for Web of Science ID A1991FR47300004

    View details for PubMedID 2053913

  • PREDICTORS OF FRACTURES IN EARLY RHEUMATOID-ARTHRITIS JOURNAL OF RHEUMATOLOGY Michel, B. A., Bloch, D. A., Fries, J. F. 1991; 18 (6): 804-808

    Abstract

    Three hundred ninety-five patients with rheumatoid arthritis (mean age 49 years) were followed for an average of 6.7 years, and their baseline variables from the initial visit were examined for prediction of time to first fracture. Multivariate analyses identified use of corticosteroids in women and prior diagnosis of osteoporosis as important risk factors. Among patients taking 5 mg or more of prednisone, female sex strongly predicted fractures: the 5-year probability of having a fracture was 34%. Low risk groups were nonosteoporotic and consisted of men and patients taking less than 5 mg prednisone.

    View details for Web of Science ID A1991FU45400005

    View details for PubMedID 1895260

  • PREDICTORS OF SURVIVAL IN SYSTEMIC-SCLEROSIS (SCLERODERMA) ARTHRITIS AND RHEUMATISM Altman, R. D., Medsger, T. A., Bloch, D. A., Michel, B. A. 1991; 34 (4): 403-413

    Abstract

    We conducted followup of 264 patients with definite systemic sclerosis (SSc) who were entered into the multicenter Scleroderma Criteria Cooperative Study (SCCS) during 1973-1977. At the end of the study (average 5.2 years of followup), 38% were known to be alive, 50% were dead (68% of these deaths definitely related to SSc), and 12% were lost to followup. Survival analyses of 484 demographic, clinical, and laboratory items recorded at entry into the SCCS (within 2 years of physician diagnosis of SSc) were performed. Survival declined linearly, and the cumulative survival rate was less than 80% at 2 years, 50% at 8.5 years, and 30% at 12 years after entry. Analysis using combinations of entry variables identifying organ system involvement confirmed that renal, cardiac, pulmonary, and gastrointestinal involvement in SSc predicted reduced survival; however, data on organ system involvement at study entry could not be used to consistently predict which organ system would ultimately be involved as the primary cause of death. By survival tree analysis, the individual entry variables best predicting reduced survival included older age (greater than 64 years), reduced renal function (blood urea nitrogen greater than 16 mg/dl), anemia (hemoglobin less than or equal to 11 gm/dl), reduced pulmonary diffusing capacity for carbon monoxide (less than or equal to 50% of predicted), reduced total serum protein level (less than or equal to 6 gm/dl), and reduced pulmonary reserve (forced vital capacity less than 80% with hemoglobin greater than 14 gm/dl or forced vital capacity less than 65% with hemoglobin less than or equal to 14 gm/dl). Cox proportional hazards model analysis confirmed these results. Different combinations of variables led to markedly different survival rates. The poorest prospects for survival were in patients with SSc who were less than or equal to 64 years old with a hemoglobin level less than or equal to 11 gm/dl, and in those greater than 64 years old with a blood urea nitrogen level greater than 16 mg/dl. These results may be useful in predicting individual patients at risk for shortened survival.

    View details for Web of Science ID A1991FF99400004

    View details for PubMedID 1901491

  • TOXICITY PROFILES OF DISEASE MODIFYING ANTIRHEUMATIC DRUGS IN RHEUMATOID-ARTHRITIS JOURNAL OF RHEUMATOLOGY Singh, G., Fries, J. F., WILLIAMS, C. A., Zatarain, E., Spitz, P., Bloch, D. A. 1991; 18 (2): 188-194

    Abstract

    The toxicity profiles of 7 disease modifying antirheumatic drugs (DMARD) (hydroxychloroquine, intramuscular (im) gold, D-penicillamine, oral gold, methotrexate (MTX), azathioprine and cyclophosphamide) were evaluated in 2,479 patients with rheumatoid arthritis consecutively enrolled at 5 centers in the Arthritis, Rheumatism and Aging Medical Information System (ARAMIS) program. Incidence rates for side effects are reported as events/1000 patient-years. Our descriptive study revealed an individual profile of prevalent toxicities for each drug. Oral gold was characterized by substantial lower gastrointestinal (GI) toxicity (diarrhea 391 events/1000 patient-years, loose bowel movement 148, lower abdominal pain 76), MTX by hepatotoxicity (47) while D-penicillamine had the only clinically significant incidence of altered taste (40). MTX users reported the most mucosal ulcers (87), followed by oral gold (76), im gold (55) and D-penicillamine (38). Rash was frequently seen with gold compounds and D-penicillamine, while upper GI toxicity was common with immunosuppressive agents. Cyclophosphamide had 48% discontinuations within 6 months. MTX had the lowest discontinuation rate in the first 6 months, but then showed little difference from im gold. A preliminary similarity index was developed to compare the toxicity profiles of various DMARD. Close similarities were found between toxicity profiles of im gold and D-penicillamine, and between azathioprine and MTX. Oral gold had a unique toxicity pattern. Knowledge of these different toxicity patterns can enable more appropriate selection of agents for particular patients.

    View details for Web of Science ID A1991EZ83100008

    View details for PubMedID 1673721

  • STATISTICAL APPROACHES TO CLASSIFICATION - METHODS FOR DEVELOPING CLASSIFICATION AND OTHER CRITERIA RULES ARTHRITIS AND RHEUMATISM Bloch, D. A., Moses, L. E., Michel, B. A. 1990; 33 (8): 1137-1144

    View details for Web of Science ID A1990DV71700012

    View details for PubMedID 2202313

  • THE AMERICAN-COLLEGE-OF-RHEUMATOLOGY 1990 CRITERIA FOR THE CLASSIFICATION OF VASCULITIS - SUMMARY ARTHRITIS AND RHEUMATISM Fries, J. F., Hunder, G. G., Bloch, D. A., Michel, B. A., Arend, W. P., Calabrese, L. H., Fauci, A. S., Leavitt, R. Y., Lie, J. T., LIGHTFOOT, R. W., Masi, A. T., MCSHANE, D. J., Mills, J. A., Stevens, M. B., Wallace, S. L., Zvaifler, N. J. 1990; 33 (8): 1135-1136

    View details for Web of Science ID A1990DV71700011

    View details for PubMedID 2202312

  • THE AMERICAN-COLLEGE-OF-RHEUMATOLOGY 1990 CRITERIA FOR THE CLASSIFICATION OF VASCULITIS - PATIENTS AND METHODS ARTHRITIS AND RHEUMATISM Bloch, D. A., Michel, B. A., Hunder, G. G., MCSHANE, D. J., Arend, W. P., Calabrese, L. H., Edworthy, S. M., Fauci, A. S., Fries, J. F., Leavitt, R. Y., Lie, J. T., LIGHTFOOT, R. W., Masi, A. T., Mills, J. A., Stevens, M. B., Wallace, S. L., Zvaifler, N. J. 1990; 33 (8): 1068-1073

    Abstract

    The American College of Rheumatology Subcommittee on Classification of Vasculitis of the Diagnostic and Therapeutic Criteria Committee developed classification criteria for 7 forms of vasculitis: polyarteritis nodosa, Churg-Strauss syndrome, Wegener's granulomatosis, hypersensitivity vasculitis, Henoch-Schönlein purpura, giant cell (temporal) arteritis, and Takayasu arteritis. The data collection methods, quality control, and analytic procedures used to derive the classification rules are discussed herein.

    View details for Web of Science ID A1990DV71700002

    View details for PubMedID 2202306

  • THE AMERICAN-COLLEGE-OF-RHEUMATOLOGY 1990 CRITERIA FOR THE CLASSIFICATION OF CHURG-STRAUSS-SYNDROME (ALLERGIC GRANULOMATOSIS AND ANGIITIS) ARTHRITIS AND RHEUMATISM Masi, A. T., Hunder, G. G., Lie, J. T., Michel, B. A., Bloch, D. A., Arend, W. P., Calabrese, L. H., Edworthy, S. M., Fauci, A. S., Leavitt, R. Y., LIGHTFOOT, R. W., MCSHANE, D. J., Mills, J. A., Stevens, M. B., Wallace, S. L., Zvaifler, N. J. 1990; 33 (8): 1094-1100

    Abstract

    Criteria for the classification of Churg-Strauss syndrome (CSS) were developed by comparing 20 patients who had this diagnosis with 787 control patients with other forms of vasculitis. For the traditional format classification, 6 criteria were selected: asthma, eosinophilia greater than 10% on differential white blood cell count, mononeuropathy (including multiplex) or polyneuropathy, non-fixed pulmonary infiltrates on roentgenography, paranasal sinus abnormality, and biopsy containing a blood vessel with extravascular eosinophils. The presence of 4 or more of these 6 criteria yielded a sensitivity of 85% and a specificity of 99.7%. A classification tree was also constructed with 3 selected criteria: asthma, eosinophilia greater than 10% on differential white blood cell count, and history of documented allergy other than asthma or drug sensitivity. If a subject has eosinophilia and a documented history of either asthma or allergy, then that subject is classified as having CSS. For the tree classification, the sensitivity was 95% and the specificity was 99.2%. Advantages of the traditional format compared with the classification tree format, when applied to patients with systemic vasculitis, and their comparison with earlier work on CSS are discussed.

    View details for Web of Science ID A1990DV71700005

    View details for PubMedID 2202307

  • THE AMERICAN-COLLEGE-OF-RHEUMATOLOGY 1990 CRITERIA FOR THE CLASSIFICATION OF GIANT-CELL ARTERITIS ARTHRITIS AND RHEUMATISM Hunder, G. G., Bloch, D. A., Michel, B. A., Stevens, M. B., Arend, W. P., Calabrese, L. H., Edworthy, S. M., Fauci, A. S., Leavitt, R. Y., Lie, J. T., LIGHTFOOT, R. W., Masi, A. T., MCSHANE, D. J., Mills, J. A., Wallace, S. L., Zvaifler, N. J. 1990; 33 (8): 1122-1128

    Abstract

    Criteria for the classification of giant cell (temporal) arteritis were developed by comparing 214 patients who had this disease with 593 patients with other forms of vasculitis. For the traditional format classification, 5 criteria were selected: age greater than or equal to 50 years at disease onset, new onset of localized headache, temporal artery tenderness or decreased temporal artery pulse, elevated erythrocyte sedimentation rate (Westergren) greater than or equal to 50 mm/hour, and biopsy sample including an artery, showing necrotizing arteritis, characterized by a predominance of mononuclear cell infiltrates or a granulomatous process with multinucleated giant cells. The presence of 3 or more of these 5 criteria was associated with a sensitivity of 93.5% and a specificity of 91.2%. A classification tree was also constructed using 6 criteria. These criteria were the same as for the traditional format, except that elevated erythrocyte sedimentation rate was excluded, and 2 other variables were included: scalp tenderness and claudication of the jaw or tongue or on deglutition. The classification tree was associated with a sensitivity of 95.3% and specificity of 90.7%.

    View details for Web of Science ID A1990DV71700009

    View details for PubMedID 2202311

  • THE AMERICAN-COLLEGE-OF-RHEUMATOLOGY 1990 CRITERIA FOR THE CLASSIFICATION OF HENOCH-SCHONLEIN PURPURA ARTHRITIS AND RHEUMATISM Mills, J. A., Michel, B. A., Bloch, D. A., Calabrese, L. H., Hunder, G. G., Arend, W. P., Edworthy, S. M., Fauci, A. S., Leavitt, R. Y., Lie, J. T., LIGHTFOOT, R. W., Masi, A. T., MCSHANE, D. J., Stevens, M. B., Wallace, S. L., Zvaifler, N. J. 1990; 33 (8): 1114-1121

    Abstract

    Criteria for identifying Henoch-Schönlein Purpura (HSP) and distinguishing HSP from other forms of systemic arteritis were developed by comparing the manifestations in 85 patients who had HSP with those of 722 control patients with other forms of vasculitis. By the traditional format of choosing different combinations of candidate criteria and comparing the combinations for their ability to separate HSP cases from controls, 4 criteria were identified: age less than or equal to 20 years at disease onset, palpable purpura, acute abdominal pain, and biopsy showing granulocytes in the walls of small arterioles or venules. The presence of any 2 or more of these criteria distinguish HSP from other forms of vasculitis with a sensitivity of 87.1% and a specificity of 87.7%. The criteria selected by a classification tree method were similar: palpable purpura, age less than or equal to 20 years at disease onset, biopsy showing granulocytes around arterioles or venules, and gastrointestinal bleeding. These were able to distinguish HSP from other forms of vasculitis with a sensitivity of 89.4% and a specificity of 88.1%.

    View details for Web of Science ID A1990DV71700008

    View details for PubMedID 2202310

  • THE AMERICAN-COLLEGE-OF-RHEUMATOLOGY 1990 CRITERIA FOR THE CLASSIFICATION OF HYPERSENSITIVITY VASCULITIS ARTHRITIS AND RHEUMATISM Calabrese, L. H., Michel, B. A., Bloch, D. A., Arend, W. P., Edworthy, S. M., Fauci, A. S., Fries, J. F., Hunder, G. G., Leavitt, R. Y., Lie, J. T., LIGHTFOOT, R. W., Masi, A. T., MCSHANE, D. J., Mills, J. A., Stevens, M. B., Wallace, S. L., Zvaifler, N. J. 1990; 33 (8): 1108-1113

    Abstract

    Criteria for the classification of hypersensitivity vasculitis were developed by comparing 93 patients who had this disease with 714 control patients with other forms of vasculitis. For the traditional format classification, 5 criteria were selected: age greater than 16 at disease onset, history of taking a medication at onset that may have been a precipitating factor, the presence of palpable purpura, the presence of maculopapular rash, and a biopsy demonstrating granulocytes around an arteriole or venule. The presence of 3 or more of these 5 criteria was associated with a sensitivity of 71.0% and a specificity of 83.9%. A classification tree was also constructed. The criteria appearing in the tree structure were the same as for the traditional format, except there were 2 pathology criteria: one required the presence of granulocytes in the wall of an arteriole or venule, and the other required the presence of eosinophils in the inflammatory exudate. The classification tree was associated with a sensitivity of 78.5% and a specificity of 78.7%.

    View details for Web of Science ID A1990DV71700007

    View details for PubMedID 2202309

  • THE AMERICAN-COLLEGE-OF-RHEUMATOLOGY 1990 CRITERIA FOR THE CLASSIFICATION OF TAKAYASU ARTERITIS ARTHRITIS AND RHEUMATISM Arend, W. P., Michel, B. A., Bloch, D. A., Hunder, G. G., Calabrese, L. H., Edworthy, S. M., Fauci, A. S., Leavitt, R. Y., Lie, J. T., LIGHTFOOT, R. W., Masi, A. T., MCSHANE, D. J., Mills, J. A., Stevens, M. B., Wallace, S. L., Zvaifler, N. J. 1990; 33 (8): 1129-1134

    Abstract

    Criteria for the classification of Takayasu arteritis were developed by comparing 63 patients who had this disease with 744 control patients with other forms of vasculitis. Six criteria were selected for the traditional format classification: onset at age less than or equal to 40 years, claudication of an extremity, decreased brachial artery pulse, greater than 10 mm Hg difference in systolic blood pressure between arms, a bruit over the subclavian arteries or the aorta, and arteriographic evidence of narrowing or occlusion of the entire aorta, its primary branches, or large arteries in the proximal upper or lower extremities. The presence of 3 or more of these 6 criteria demonstrated a sensitivity of 90.5% and a specificity of 97.8%. A classification tree also was constructed with 5 of these 6 criteria, omitting claudication of an extremity. The classification tree demonstrated a sensitivity of 92.1% and a specificity of 97.0%.

    View details for Web of Science ID A1990DV71700010

    View details for PubMedID 1975175

  • THE AMERICAN-COLLEGE-OF-RHEUMATOLOGY 1990 CRITERIA FOR THE CLASSIFICATION OF WEGENER GRANULOMATOSIS ARTHRITIS AND RHEUMATISM Leavitt, R. Y., Fauci, A. S., Bloch, D. A., Michel, B. A., Hunder, G. G., Arend, W. P., Calabrese, L. H., Fries, J. F., Lie, J. T., LIGHTFOOT, R. W., Masi, A. T., MCSHANE, D. J., Mills, J. A., Stevens, M. B., Wallace, S. L., Zvaifler, N. J. 1990; 33 (8): 1101-1107

    Abstract

    Criteria for the classification of Wegener's granulomatosis (WG) were developed by comparing 85 patients who had this disease with 722 control patients with other forms of vasculitis. For the traditional format classification, 4 criteria were selected: abnormal urinary sediment (red cell casts or greater than 5 red blood cells per high power field), abnormal findings on chest radiograph (nodules, cavities, or fixed infiltrates), oral ulcers or nasal discharge, and granulomatous inflammation on biopsy. The presence of 2 or more of these 4 criteria was associated with a sensitivity of 88.2% and a specificity of 92.0%. A classification tree was also constructed with 5 criteria being selected. These criteria were the same as for the traditional format, but included hemoptysis. The classification tree was associated with a sensitivity of 87.1% and a specificity of 93.6%. We describe criteria which distinguish patients with WG from patients with other forms of vasculitis with a high level of sensitivity and specificity. This distinction is important because WG requires cyclophosphamide therapy, whereas many other forms of vasculitis can be treated with corticosteroids alone.

    View details for Web of Science ID A1990DV71700006

    View details for PubMedID 2202308

  • THE AMERICAN-COLLEGE-OF-RHEUMATOLOGY 1990 CRITERIA FOR THE CLASSIFICATION OF POLYARTERITIS-NODOSA ARTHRITIS AND RHEUMATISM LIGHTFOOT, R. W., Michel, B. A., Bloch, D. A., Hunder, G. G., Zvaifler, N. J., MCSHANE, D. J., Arend, W. P., Calabrese, L. H., Leavitt, R. Y., Lie, J. T., Masi, A. T., Mills, J. A., Stevens, M. B., Wallace, S. L. 1990; 33 (8): 1088-1093

    Abstract

    Criteria for the classification of polyarteritis nodosa were developed by comparing 118 patients who had this disease with 689 control patients who had other forms of vasculitis. For the traditional format classification, 10 criteria were selected: weight loss greater than or equal to 4 kg, livedo reticularis, testicular pain or tenderness, myalgias, mononeuropathy or polyneuropathy, diastolic blood pressure greater than 90 mm Hg, elevated blood urea nitrogen or serum creatinine levels, presence of hepatitis B reactants in serum, arteriographic abnormality, and presence of granulocyte or mixed leukocyte infiltrate in an arterial wall on biopsy. The presence of 3 or more of these 10 criteria was associated with a sensitivity of 82.2% and specificity of 86.6%. A classification tree was also constructed, with 6 criteria being selected. Three of these, angiographic abnormality, biopsy-proven granulocyte or mixed leukocyte infiltrate in arterial wall, and neuropathy, were criteria used in the traditional format. The other 3 criteria used in the tree format included the patient's sex, weight loss greater than 6.5 kg, and elevated serum aspartate aminotransferase or alanine aminotransferase levels above the range of normal. The classification tree yielded a sensitivity of 87.3% and a specificity of 89.3%.

    View details for Web of Science ID A1990DV71700004

    View details for PubMedID 1975174

  • THE INFLUENCE OF CONTINUOUS PASSIVE MOTION ON OUTCOME IN TOTAL KNEE ARTHROPLASTY CLINICAL ORTHOPAEDICS AND RELATED RESEARCH Maloney, W. J., Schurman, D. J., HANGEN, D., Goodman, S. B., Edworthy, S., Bloch, D. A. 1990: 162-168

    Abstract

    All primary condylar total knee replacement arthroplasties (TKAs) performed from 1977 to 1984 at the authors' institution were divided into two groups based on the use of continuous passive motion (CPM) in the immediate postoperative period. The control group consisted of 73 patients who were treated with 95 TKAs without postoperative CPM. The average age was 65.4 years. The study group consisted of 38 patients who had 51 TKAs in which CPM was used postoperatively. The mean patient age was 62.8 years. The most common diagnoses in both groups were osteoarthritis and rheumatoid arthritis. Range of motion (ROM) was recorded preoperatively, at discharge, at three months, one year, two years, and at the last follow-up visit. There were no statistically significant differences in the ROM between the two groups at any of these time periods. At two years, the mean flexion and extension in the study group were 99 degrees and -4 degrees, respectively, compared to 103 degrees and -5 degrees in the control group. The average hospital stay was 11.2 days in the study group, whereas it was 15.1 days in control group. In the control group, there was one superficial infection, no deep infections, and four pulmonary emboli compared with three superficial infections, two deep infections, and no pulmonary emboli in the study group. There was no difference in the transfusion requirements between the two groups. CPM is advocated by the authors to help achieve discharge ROM earlier, but the protocol has been changed to begin CPM on the second postoperative day to allow the wound to stabilize.

    View details for Web of Science ID A1990DM91300023

    View details for PubMedID 2364605

  • RUNNING, OSTEOARTHRITIS, AND BONE-DENSITY - INITIAL 2-YEAR LONGITUDINAL-STUDY AMERICAN JOURNAL OF MEDICINE Lane, N. E., Bloch, D. A., Hubert, H. B., Jones, H., SIMPSON, U., Fries, J. F. 1990; 88 (5): 452-459

    Abstract

    The purpose of this study was to present the 2-year follow-up results examining associations of repetitive long-term physical impact (running) with osteoarthritis and osteoporosis in 34 members of a running club now aged 52 to 74 years and 34 matched control subjects.Roentgenograms of the hands, lateral lumbar spine, and knees were assessed in pairs (1984 and 1986) without knowledge of running status. Computerized scans of the first lumbar vertebrae were obtained to quantify bone mineral.A decrease in bone density over the 2-year period was statistically significant for nearly all subjects, especially for runners who decreased their running habits. At the 2-year follow-up, runners maintained greater bone density. Progression of the roentgenographic scores for osteoarthritis demonstrated a statistically significant increase in almost all groups in this normative population over the 2-year period. Female runners had more spur formation in the weight-bearing knee roentgenograms than did control subjects.With the possible exception of spur formation in women, running did not appear to influence the development of radiologic osteoarthritis in the populations studied.

    View details for Web of Science ID A1990DC71600002

    View details for PubMedID 2337104

  • PLAIN RADIOGRAPHS CAN BE USEFUL IN ESTIMATING LUMBAR BONE-DENSITY JOURNAL OF RHEUMATOLOGY Michel, B. A., Lane, N. E., Jones, H. H., Fries, J. F., Bloch, D. A. 1990; 17 (4): 528-531

    Abstract

    On standard lateral roentgenograms of the lumbar spine, a decrease in bone density is said to be detectable only after a bone loss of about 40%. To evaluate this view, we compared findings on plain films with bone mineral content of L1 determined by quantitative computed tomography in 80 healthy subjects with a mean age of 60 years. The highest correlations with bone mineral content were found for the criteria "vertebral density versus soft tissue" (r = 0.5, p less than 0.0001), the "amount of trabeculations" (r = 0.49, p less than 0.0001), and for the "overall" estimate of osteopenia in the vertebra (r = 0.55, p less than 0.0001). Surprisingly, these three radiographic criteria proved to be most helpful in subjects with bone mineral content above 110 mg/cm3 (nonosteoporotic range). We conclude that lateral radiographs of the lumbar spine can provide a rough estimate of bone density in nonosteoporotic subjects which may be helpful in determining when further analysis with more precise methods is appropriate.

    View details for Web of Science ID A1990DC41300019

    View details for PubMedID 2189996

  • A NOTE ON CASE CONTROL SAMPLING TO ESTIMATE KAPPA COEFFICIENTS BIOMETRICS Kraemer, H. C., Bloch, D. A. 1990; 46 (1): 49-59

    Abstract

    The feasibility and cost-effectiveness of estimation of kappa using a case-control method of sampling, proposed by Jannarone, Macera, and Garrison (1987, Biometrics 43, 433-437), is provided support. However, in this article unrealistic assumptions in their presentation are identified and more general results for more realistic settings are provided.

    View details for Web of Science ID A1990DA02200004

    View details for PubMedID 2112410

  • Identification of patients at risk for gastropathy associated with NSAID use. journal of rheumatology. Supplement Fries, J. F., Miller, S. R., SPITZ, P. W., WILLIAMS, C. A., Hubert, H. B., Bloch, D. A. 1990; 20: 12-19

    Abstract

    It is suggested that gastropathy associated with nonsteroidal antiinflammatory drugs (NSAID) is the most frequent and, in aggregate, the most severe drug side effect in the United States. This work is based on a consecutive series of 2,400 patients with rheumatoid arthritis (RA) followed prospectively for an average of 3.5 years by the American Rheumatism Association Medical Information System. We present a preliminary exploration of the magnitude of the problem, the population at risk and the patients within that population who are at particularly high risk. Patients on NSAID had a hazard ratio for gastrointestinal (GI) hospitalization that was 6.45 times that of patients not on NSAID. Characteristically, patients at high risk for GI hospitalization and GI death are older, have had previous upper abdominal pain, have previously stopped NSAID due to GI side effects and have previously used antacids or histamine2-receptor antagonists for GI side effects. These patients also frequently take corticosteroids. Patients attributing relatively minor symptoms to NSAID tend to be younger and female. Our preliminary analysis is univariate; since these variables are interdependent, firm conclusions regarding the relative importance of these risk factors require development of multivariate risk factor models. The syndrome of NSAID-associated gastropathy can be estimated to account for at least 2,600 deaths and 20,000 hospitalizations each year in patients with RA alone.

    View details for PubMedID 2325051

  • IDENTIFICATION OF PATIENTS AT RISK FOR GASTROPATHY ASSOCIATED WITH NSAID USE JOURNAL OF RHEUMATOLOGY Fries, J. F., Miller, S. R., SPITZ, P. W., WILLIAMS, C. A., Hubert, H. B., Bloch, D. A. 1990; 17: 12-19
  • A TOXICITY INDEX FOR COMPARISON OF SIDE-EFFECTS AMONG DIFFERENT DRUGS ARTHRITIS AND RHEUMATISM Fries, J. F., SPITZ, P. W., WILLIAMS, C. A., Bloch, D. A., Singh, G., Hubert, H. B. 1990; 33 (1): 121-130

    View details for Web of Science ID A1990CL04700017

    View details for PubMedID 2302262

  • EMPIRICAL-COMPARISON OF APPROACHES TO FORMING STRATA - USING CLASSIFICATION TREES TO ADJUST FOR COVARIATES JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION Bloch, D. A., Segal, M. R. 1989; 84 (408): 897-905
  • WEIGHT-BEARING EXERCISE, OVER-EXERCISE, AND LUMBAR BONE-DENSITY OVER AGE 50 YEARS ARCHIVES OF INTERNAL MEDICINE Michel, B. A., Bloch, D. A., Fries, J. F. 1989; 149 (10): 2325-2329

    Abstract

    This cross-sectional study of 78 healthy subjects older than age 50 years was designed to examine the association between weight-bearing exercise and lumbar bone mineral content as assessed by quantitative computed tomography. In women, a strong correlation existed between bone density and the amount of exercise for up to 300 min/wk. However, 5 of 28 women exercising 300 min/wk or more had surprisingly low bone density, not explained by other factors. In 50 men, we also found a strong positive correlation between exercise and bone density for those up to age 65 years. Over age 65, 3 men had low bone density despite extremely vigorous exercise. We conclude that moderate weight-bearing exercise may increase lumbar bone density, but we raise the hypothesis that extremely vigorous exercise actually may be detrimental to bone density in individuals after age 50.

    View details for Web of Science ID A1989AU93500026

    View details for PubMedID 2802897

  • PREDISPOSING FACTORS IN POLYMYOSITIS-DERMATOMYOSITIS - RESULTS OF A NATIONWIDE SURVEY JOURNAL OF RHEUMATOLOGY LYON, M. G., Bloch, D. A., HOLLAK, B., Fries, J. F. 1989; 16 (9): 1218-1224

    Abstract

    Utilizing case-control methods, we surveyed 322 persons who experienced the onset of polymyositis-dermatomyositis (PM-DM) during calendar years 1985 and 1986, in an effort both to test specific hypotheses, and to generate new hypotheses regarding antecedent risk associations for the disease. Data obtained by recall of events during the 12 months before disease onset in cases, and an identical time period in sex matched sibling controls, suggest that important questions for further study include the roles of antecedent heavy muscular exertion and emotional stress as risk factors for PM-DM. Furthermore, it appears that vaccinations, toxic exposures and symptoms of allergic phenomena, throat infection, and upper respiratory infection are either neutral or are negatively associated with risk of PM-DM, findings which also raise important new etiologic questions, or perhaps lay old ones to rest. Malignancy was infrequently noted.

    View details for Web of Science ID A1989AV08900011

    View details for PubMedID 2810279

  • THE NATURAL-HISTORY OF ANKYLOSING-SPONDYLITIS - IS THE DISEASE REALLY CHANGING JOURNAL OF RHEUMATOLOGY Fries, J. F., Singh, G., Bloch, D. A., Calin, A. 1989; 16 (7): 860-863

    View details for Web of Science ID A1989AK77000002

    View details for PubMedID 2788741

  • OSTEO-ARTHRITIS IN THE HAND - A COMPARISON OF HANDEDNESS AND HAND USE JOURNAL OF RHEUMATOLOGY Lane, N. E., Bloch, D. A., Jones, H. H., SIMPSON, U., Fries, J. F. 1989; 16 (5): 637-642

    Abstract

    Osteoarthritis (OA) of the hand has been suggested to be the result of "wear" and "tear." If so, OA should develop more frequently in the dominant hand. We compared dominant with nondominant hands of 134 consecutive community subjects aged 53-75 by questionnaire, radiographs of hands, and rheumatologic evaluation. Mean age was 60 years, 93% were right handed, and 95% were in occupations classified as nonphysical. Subjects estimated dominant hand use of 2-10 times the amount of the nondominant hand. OA was found in 133 of 134 subjects. No radiologic or clinical differences were found between the dominant and nondominant hands. Twenty-six subjects who self-reported heavier lifetime hand use had somewhat greater clinical and hand radiographic OA scores than the 36 subjects reporting lighter hand use (43.5 vs 34.5) (p less than 0.01). In our study population, OA was not more prevalent in the dominant hand.

    View details for Web of Science ID A1989AA47100017

    View details for PubMedID 2754667

  • CONVENTIONAL CEMENTED TOTAL HIP-ARTHROPLASTY - ASSESSMENT OF CLINICAL FACTORS ASSOCIATED WITH REVISION FOR MECHANICAL FAILURE CLINICAL ORTHOPAEDICS AND RELATED RESEARCH Schurman, D. J., Bloch, D. A., Segal, M. R., Tanner, C. M. 1989: 173-180

    Abstract

    This study investigates risk factors associated with mechanical loosening of cemented total hip arthroplasties. Mechanical failure was evaluated using survivorship analysis on all arthroplasties performed at the authors' institution by the Orthopedic Service from March 1971 until September 1983. Failure was defined as the necessity for replacement of one or more components for any reason other than infection. The failure rate was approximately 1.7% per year and, at 12 years, 20% of the hips had failed. Variables evaluated as potential risk factors for arthroplasty revision included weight, gender, age, surgeon, preoperative functional status, prosthetic type, and diagnosis. A Cox proportional hazard analysis indicated that weight (p less than 0.015) and age (p = 0.087) are important determinants of hip failure. The use of regression trees identified subsets of patients at differing risks for failure. Patients who weighed less than 75.22 kg had the best outcome with a 90% survival to 12 years. Patients weighing more than 75.22 kg are at varying risk depending on their age. These data define a subset of special-risk patients not previously described. Patients weighing more than 75.22 kg who were older than 75.4 years had a revision rate of 73% by eight years.

    View details for Web of Science ID A1989T494800022

    View details for PubMedID 2917432

  • 2X2 KAPPA-COEFFICIENTS - MEASURES OF AGREEMENT OR ASSOCIATION BIOMETRICS Bloch, D. A., Kraemer, H. C. 1989; 45 (1): 269-287

    Abstract

    Two general but different contexts in which kappa might be used are defined: agreement and association. Two models, one for agreement and one for utility of association, are defined yielding different kappa coefficients and different sampling theory. Asymptotic results are derived for both models. Small-sample evaluations are presented for the model for agreement.

    View details for Web of Science ID A1989U124500023

    View details for PubMedID 2655731

  • TOWARD AN EPIDEMIOLOGY OF GASTROPATHY ASSOCIATED WITH NONSTEROIDAL ANTIINFLAMMATORY DRUG-USE GASTROENTEROLOGY Fries, J. F., Miller, S. R., SPITZ, P. W., WILLIAMS, C. A., Hubert, H. B., Bloch, D. A. 1989; 96 (2): 647-655

    Abstract

    The thesis of this paper is that gastropathy associated with nonsteroidal antiinflammatory drugs (NSAIDs) is the most frequent and, in aggregate, the most severe drug side effect in the United States. This work is based on a consecutive series of 2400 patients with rheumatoid arthritis followed prospectively for an average of 3.5 yr by ARAMIS, the American Rheumatism Association Medical Information System. We present a preliminary exploration of the magnitude of the problem, the population at risk, and the patients within that population who are at particularly high risk. Patients on NSAIDs had a hazard ratio for gastrointestinal (GI) hospitalization that was 6.45 times that of patients not on NSAIDs. Characteristically, high-risk patients for GI hospitalization and GI death are older, have had previous upper abdominal pain, have previously stopped NSAIDs for GI side effects, and have previously used antacids or H2-receptor antagonists for GI side effects. They also are frequently on corticosteroids. In contrast, patients attributing relatively minor symptoms to the drug tend to be younger and more frequently female. Our preliminary analysis is univariate and, as these variables are interdependent, firm conclusions regarding the relative importance of these risk factors will require reevaluating our data base as it is expanded using multivariate analysis. The syndrome of NSAID-associated gastropathy can be estimated to account for at least 2600 deaths and 20,000 hospitalizations each year in patients with rheumatoid arthritis alone.

    View details for Web of Science ID A1989T033900012

    View details for PubMedID 2909442

  • A STATE MODEL OF RENAL-FUNCTION IN SYSTEMIC LUPUS-ERYTHEMATOSUS - ITS VALUE IN THE PREDICTION OF OUTCOME IN 292 PATIENTS JOURNAL OF RHEUMATOLOGY Edworthy, S. M., Bloch, D. A., MCSHANE, D. J., Segal, M. R., Fries, J. F. 1989; 16 (1): 29-35

    Abstract

    We defined a clinical staging of renal function in systemic lupus erythematosus (SLE) which uses inexpensive outpatient measures to serially stage patient status and then analyzed the disease course of 292 patients followed since 1968. The 4 mutually exclusive states used were (1) normal (creatinine less than 1.2 mg/dl and protein less than 2+ on dipstick); (2) proteinuria alone (creatinine less than 1.2 mg/dl and protein greater than or equal to 2+ on dipstick); (3) moderate filtration dysfunction (creatinine greater than or equal to 1.2 mg/dl and less than 4.0 mg/dl); and (4) severe azotemia (creatinine greater than or equal to 4.0 mg/dl). Duration in each state and subsequent transitions were incorporated in an assessment of outcome. Prognostic variables were found which predicted different outcomes within each of the 4 states. This stratification, based on renal function over time, provides a useful analytical tool for comparing subsets of patients with lupus. We found that serum complement (C3) predicted progression in state 1 and 2 as well as potential responders to therapy in state 3. No improvement was noted for patients in state 4.

    View details for Web of Science ID A1989T170100007

    View details for PubMedID 2716006

  • ANALYSIS OF THE 1982 ARA LUPUS CRITERIA DATA SET BY RECURSIVE PARTITIONING METHODOLOGY - NEW INSIGHTS INTO THE RELATIVE MERIT OF INDIVIDUAL CRITERIA JOURNAL OF RHEUMATOLOGY Edworthy, S. M., Zatarain, E., MCSHANE, D. J., Bloch, D. A. 1988; 15 (10): 1493-1498

    Abstract

    The 339 cases of systemic lupus erythematosus (SLE) and controls used in 1982 to develop the current ARA rules for classifying this disease were further analyzed using recursive partitioning methodology. The method identified 9 subgroups of cases and controls. It allowed correct classification of 97% of cases and 95% of controls while using only 6 criteria instead of 11. Antibodies to DNA were found to be the overall best discriminator. The largest subgroup (116 cases/4 controls) was made up of patients with both anti-DNA and fluorescent antinuclear antibody (FANA). Presence of malar rash was helpful in distinguishing SLE cases among patients who were anti-DNA negative. Low and high FANA values, in combination with other variables, helped to identify 3 SLE subgroups. Unlike the 1982 criteria, which did not include serum complement, the classification tree also identified subgroups of patients in which complement was either the best or the 2nd best discriminator. Recursive partitioning methodology thus gives important insights into how the criteria interact and the relative importance of specific variables for classification purposes.

    View details for Web of Science ID A1988Q842800008

    View details for PubMedID 3060613

  • POSTMARKETING SURVEILLANCE IN RHEUMATOLOGY - ANALYSIS OF PURPURA AND UPPER ABDOMINAL-PAIN JOURNAL OF RHEUMATOLOGY Fries, J. F., Bloch, D. A., Segal, M. R., SPITZ, P. W., Williams, C., Lane, N. E. 1988; 15 (2): 348-355

    Abstract

    A system of postmarketing surveillance of antirheumatic drugs employing prospective protocol based consecutive patient cohorts is described, together with use of recursive partitioning techniques for statistical adjustment for potentially confounding variables. An analysis of 2 side effects (purpura and upper abdominal pain) is presented. Purpura was found to be associated with age, sex, disease duration, and amount of disability. The combination of aspirin and prednisone was associated with the highest prevalence of purpura. Upper abdominal pain also varied across drug classes. Within the nonsteroidal antiinflammatory drug category, there were clinically important differences in the relative prevalence of upper gastrointestinal pain between specific drugs.

    View details for Web of Science ID A1988M422500031

    View details for PubMedID 3361544

  • NONOPTIMALLY WEIGHTED LEAST-SQUARES AMERICAN STATISTICIAN Bloch, D. A., Moses, L. E. 1988; 42 (1): 50-53
  • KAPPA-COEFFICIENTS IN EPIDEMIOLOGY - AN APPRAISAL OF A REAPPRAISAL JOURNAL OF CLINICAL EPIDEMIOLOGY Kraemer, H. C., Bloch, D. A. 1988; 41 (10): 959-968

    Abstract

    While we agree with the general message of the Thompson and Walter paper on the use and value of kappa, the mathematical bases of these conclusions, their equations, tables, and figures are based on mathematical assumptions so limiting that their application to real data is questionable. As a result, several of their specific conclusions are misleading. Some of the same results are here obtained without the limiting restrictions. From these results, the value of kappa as a measure of reliability, validity and (possibly) of general 2 x 2 association is demonstrated.

    View details for Web of Science ID A1988R350200003

    View details for PubMedID 3193139

  • RADIOGRAPHIC ASSESSMENT OF PROGRESSION IN OSTEOARTHRITIS ARTHRITIS AND RHEUMATISM Altman, R. D., Fries, J. F., Bloch, D. A., Carstens, J., Cooke, D., Genant, H., GOFTON, P., Groth, H., MCSHANE, D. J., Murphy, W. A., Sharp, J. T., Spitz, P., WILLIAMS, C. A., Wolfe, F. 1987; 30 (11): 1214-1225

    Abstract

    We evaluated methods of grading radiologic progression of osteoarthritis (OA). Sets of radiographs were assessed separately by 8 readers who were blinded to the time sequence. Included were radiographs of patients with OA of the hands (24 pairs), hips (40 pairs), and knees (32 pairs). Most films were taken 12-60 months apart. The relative contribution of individual joints (such as particular interphalangeal joints), of observations (such as narrowing or spurs), and of a single joint compartment (such as the medial or lateral compartment of the knee) toward evidence of OA progression was evaluated, as well as the reliability and concordance of scoring, and the sensitivity in detecting change. In assessing OA of the hand, the greatest sensitivity was achieved by reading a single posteroanterior bilateral hand radiograph for narrowing, spurs, and erosions, and scoring 10 joints (second and third distal interphalangeal, second and third proximal interphalangeal, and trapeziometacarpal joints, bilaterally), using a scale of 0-3. In OA of the hip, a single anteroposterior radiograph assessed for joint space narrowing and cyst formation yielded the greatest sensitivity. In OA of the knee, an anteroposterior radiograph, with weight-bearing, assessed for narrowing, spurs, and sclerosis in both the medial and lateral compartments yielded the greatest sensitivity. These techniques will be useful to the investigator in designing experimental studies and to the clinician in determining the rate of disease progression in an individual patient.

    View details for Web of Science ID A1987L238800003

    View details for PubMedID 3689459

  • DISABILITY IN RHEUMATOID-ARTHRITIS - COMPARISON OF PROGNOSTIC FACTORS ACROSS 3 POPULATIONS JOURNAL OF RHEUMATOLOGY Sherrer, Y. S., Bloch, D. A., MITCHELL, D. M., Roth, S. H., Wolfe, F., Fries, J. F. 1987; 14 (4): 705-709

    Abstract

    We previously identified variables that predict functional disability in rheumatoid arthritis (RA). Because of potential instabilities in the statistical model, we sought to determine whether these predictors were consistent across populations: 2,448 consecutive patients with (RA) were followed prospectively at ARAMIS centers in Phoenix, AZ, Wichita, KS, and Saskatoon, SK. Average followup was 1.7 years in Phoenix, 3.4 years in Wichita, and 12 years in Saskatoon. Twenty-four potentially predictive variables were analyzed by stepwise linear regression. Common predictors were age, sex, and duration of illness, suggesting that these variables are important predictors of disease regardless of the population being studied. In addition, the initial level of disability and radiographic variables are good predictors of disability. Elevated erythrocyte sedimentation rate and latex titers also were associated with future functional disability but do not have a linear relationship and predict less well.

    View details for Web of Science ID A1987K037600012

    View details for PubMedID 3668976

  • AGING, LONG-DISTANCE RUNNING, AND THE DEVELOPMENT OF MUSCULOSKELETAL DISABILITY - A CONTROLLED-STUDY AMERICAN JOURNAL OF MEDICINE Lane, N. E., Bloch, D. A., Wood, P. D., Fries, J. F. 1987; 82 (4): 772-780

    Abstract

    Four hundred ninety-eight long-distance runners aged 50 to 72 years were compared with 365 community control subjects to examine associations of repetitive, long-term physical impact (running) with musculoskeletal disability and medical service utilization in a cross-section study. Runners had less physical disability than age-matched control subjects (p less than 0.01) and maintained more functional capacity (p less than 0.001) as measured by a modified Health Assessment Questionnaire Disability Index. Runners sought medical services less often, but one third of the visits that they did make were for running-related injuries. No differences were found between groups in conditions thought to predispose to osteoarthritis and musculoskeletal disability. Ligamentous laxity and family history of arthritis were similar in both groups. Runners demonstrated better cardiovascular fitness and weighed less. Differences persisted after adjustment for age, occupation, and sex, and after inclusion or exclusion of subjects with major medical problems. Musculoskeletal disability appeared to develop with age at a lower rate in runners (0.003 units per year versus 0.028) than in community control subjects, and the decreased rate was observed with both lower extremity and upper extremity functions. These data suggest positive effects of systematic aerobic running activity upon functional aspects of musculoskeletal aging.

    View details for Web of Science ID A1987G855000014

    View details for PubMedID 3551605

  • COMPARATIVE TOXICITY OF TOTAL LYMPHOID IRRADIATION AND IMMUNOSUPPRESSIVE DRUG TREATED PATIENTS WITH INTRACTABLE RHEUMATOID-ARTHRITIS JOURNAL OF RHEUMATOLOGY Sherrer, Y., Bloch, D., Strober, S., Fries, J. 1987; 14 (1): 46-51

    Abstract

    Outcomes were compared between consecutive patients who had received either total lymphoid irradiation (TLI) or immunosuppressant treatment for intractable rheumatoid arthritis (RA). There were 33 TLI and 32 immunosuppressive recipients; all patients had failed standard therapy. Average followup from the start of therapy was 2.7 years for TLI and 5.9 years for immunosuppressive recipients. Final disability levels were the same in both groups; mortality was equal in both groups as well. There were more hospitalizations for infections in the TLI group and the infecting organisms tended to be staphylococcus or gram negative organisms. Apart from infections, there were more adverse effects reported in the immunosuppressive therapy group.

    View details for Web of Science ID A1987G460700013

    View details for PubMedID 3572934

  • SURVIVAL, PROGNOSIS, AND CAUSES OF DEATH IN RHEUMATOID-ARTHRITIS ARTHRITIS AND RHEUMATISM MITCHELL, D. M., SPITZ, P. W., Young, D. Y., Bloch, D. A., MCSHANE, D. J., Fries, J. F. 1986; 29 (6): 706-714

    Abstract

    The factors associated with mortality were examined in a prospective longitudinal study, over an average of 12 years, with 94% followup of patients diagnosed as having rheumatoid arthritis. Of 805 patients, 233 died during the period of the study. Survivorship of rheumatoid arthritis patients was approximately 50% less than that of population controls. Survivorship was decreased by the traditional demographic variables of greater age and male sex; however, a significant independent effect of variables reflecting disease severity (American Rheumatism Association functional class, rheumatoid factor titer, number of involved joints) was identified by multivariate analysis. Seventy-nine excess deaths (i.e., those that would not have been expected in a control population) were due in part to disease-related causes, to infections, and to gastrointestinal complications of therapy. Treatment with gold or prednisone did not seem to affect survivorship or cause of death, except for the clustering of deaths of patients with vasculitis within the prednisone group. Our findings indicate that rheumatoid arthritis, a chronic disabling disease, is also associated with a major decrease in survivorship.

    View details for Web of Science ID A1986C913700002

    View details for PubMedID 3718563

  • IMPACT OF SPECIFIC THERAPY UPON RHEUMATOID-ARTHRITIS ARTHRITIS AND RHEUMATISM Fries, J. F., SPITZ, P. W., MITCHELL, D. M., Roth, S. H., Wolfe, F., Bloch, D. A. 1986; 29 (5): 620-627

    Abstract

    We performed a prospective, parallel, descriptive study of 737 consecutive new uses for 11 drugs prescribed for patients with definite or classic rheumatoid arthritis. The patients were from 5 geographically dispersed sites. Researchers used validated outcome assessment instruments to measure endpoints of disability, pain, patient global assessment, medication costs, laboratory costs, and number of physician visits. Patients were studied by strict prospective protocol at 6-month intervals for 3 years. Controls included parallel results with other drugs, and before and after values for the individual patient. Beneficial effects were observed with the "disease-modifying" drugs: intramuscular gold, penicillamine, and methotrexate. Of these, gold had the most apparent effect. An average of 9 months of gold therapy resulted in highly significant reductions in disability (P less than 0.005), pain (P less than 0.001), and patient global assessment (P less than 0.005). However, patients receiving gold and methotrexate had nearly twice as many visits to physicians. In addition, drug costs increased strikingly with gold, and laboratory costs tripled. Relatively minor differences among nonsteroidal antiinflammatory agents were difficult to interpret. The outcome assessment techniques used in the study are sensitive measures, which confirm the results of experimental studies and extend observations to new outcomes, including cost and disability.

    View details for Web of Science ID A1986C604700006

    View details for PubMedID 3718554

  • THE DEVELOPMENT OF DISABILITY IN RHEUMATOID-ARTHRITIS ARTHRITIS AND RHEUMATISM Sherrer, Y. S., Bloch, D. A., MITCHELL, D. M., Young, D. Y., Fries, J. F. 1986; 29 (4): 494-500

    Abstract

    Six hundred eighty-one consecutive patients with rheumatoid arthritis were followed for an average of 11.9 years to identify initial factors that predicted subsequent disability. Of 39 potentially predictive variables obtained at study onset and studied by stepwise regression methods, age was found to be the most powerful single predictor of disability, followed by radiologic grade, sex, and initial functional class. The worst prognosis for disability was found in patients who were older women and who showed radiologic worsening and developed functional impairment early in the disease course. Both disability and radiologic progression of disease were found to develop most rapidly during the first years after disease onset and to assume a slow, nearly linear rate of increase after 10 years. Approximately 10% of patients did not develop significant disability. This study suggests that it is possible to identify, early in the disease course, those patients who are likely to develop severe disability, and that "disease-modifying" therapy might well be initiated earlier in such patients and used consistently throughout the subsequent treatment.

    View details for Web of Science ID A1986C150000006

    View details for PubMedID 3707627

  • LONG-DISTANCE RUNNING, BONE-DENSITY, AND OSTEOARTHRITIS JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Lane, N. E., Bloch, D. A., Jones, H. H., Marshall, W. H., Wood, P. D., Fries, J. F. 1986; 255 (9): 1147-1151

    Abstract

    Forty-one long-distance runners aged 50 to 72 years were compared with 41 matched community controls to examine associations of repetitive, long-term physical impact (running) with osteoarthritis and osteoporosis. Roentgenograms of hands, lateral lumbar spine, and knees were assessed without knowledge of running status. A computed tomographic scan of the first lumbar vertebra was performed to quantitate bone mineral content. Runners, both male and female, have approximately 40% more bone mineral than matched controls. Female runners, but not male runners, appear to have somewhat more sclerosis and spur formation in spine and weight-bearing knee x-ray films, but not in hand x-ray films. There were no differences between groups in joint space narrowing, crepitation, joint stability, or symptomatic osteoarthritis. Running is associated with increased bone mineral but not, in this cross-sectional study, with clinical osteoarthritis.

    View details for Web of Science ID A1986A209300019

    View details for PubMedID 3945033

  • ASSESSMENT OF RADIOLOGIC PROGRESSION IN RHEUMATOID-ARTHRITIS - A RANDOMIZED, CONTROLLED TRIAL ARTHRITIS AND RHEUMATISM Fries, J. F., Bloch, D. A., Sharp, J. T., MCSHANE, D. J., Spitz, P., BLUHM, G. B., Forrester, D., Genant, H., GOFTON, P., Richman, S., Weissman, B., Wolfe, F. 1986; 29 (1): 1-9

    Abstract

    Radiologic assessment of progressive joint destruction in rheumatoid arthritis is generally considered to be the ultimate standard for evaluation of treatment. We compared alternative radiologic techniques by performing a randomized, controlled trial in which hand films of rheumatoid arthritis patients were read by several skilled observes. The number of joints evaluated (34 versus 18) was found to make relatively little difference, but the number of readers and their experience level was critical. Films should be read in pairs. Joint space narrowing and erosion scores were shown to contribute independent information. Use of recommended techniques can reduce the number of patients required and, thus, can reduce the cost of a clinical trial by more than half and can substantially increase the sensitivity and efficiency of a trial. Therefore, critical selection of the method of assessing study endpoint is of great importance.

    View details for Web of Science ID A1986C133500001

    View details for PubMedID 3947405

  • CANCER IN RHEUMATOID-ARTHRITIS - A PROSPECTIVE LONG-TERM STUDY OF MORTALITY AMERICAN JOURNAL OF MEDICINE Fries, J. F., Bloch, D., Spitz, P., MITCHELL, D. M. 1985; 78 (1A): 56-59

    Abstract

    Eight hundred and five consecutive patients with definite or classic rheumatoid arthritis, representative of a general population, were followed prospectively over an average of 12 years with 94 percent follow-up, during which time 233 patients died. Mortality rates were increased in rheumatoid arthritis by approximately 50 percent compared with population controls. "Excess deaths" (78) were due, in part, to disease-related causes, infections, and gastrointestinal problems secondary to therapy. Thirty-one deaths (14.1 percent) were due to malignancy, compared with 22.8 percent in non-age-adjusted population controls. Frequency of malignancy type (colon seven, lung four, breast three, prostate three, leukemia three, ovary three, stomach two, and lymphoma zero) did not differ significantly from the general population. Age-adjusted figures showed lower malignancy rates for patients with rheumatoid arthritis except after age 80. Two treatments were suitable for analysis. Gold-treated patients trended toward lower malignancy rates (11 versus 17 percent) than did those not treated with gold, and prednisone-treated patients had less malignancy (11 versus 20 percent) than did those not treated with prednisone. These data indicate that there is not an important increase in deaths due to malignancy in rheumatoid arthritis, and that at least two treatments, gold and prednisone, are not associated with higher risk of malignancy.

    View details for Web of Science ID A1985ABJ9500012

    View details for PubMedID 3970042

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