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Biomedical subjects

J A Berlin

Publications and source records attributed to J A Berlin.

At least 19 recordsLinked to original sources
PubMed1999

An efficient design for verifying disease outcome status in large cohorts with rare exposures and low disease rates.

Cohort studies require the use of large samples when the risk of the event is very low. Databases that are large and population-based, such as Medicaid files, are frequently used for cohort studies, since they provide access to the large samples required for adequate statistical power at a relatively affordable cost. Epidemiologic studies using these databases typically require verification of reported diagnoses, however, because of the potential for errors in disease reporting. When exposure prevalence is also low, as in many pharmacoepidemiologic investigations of drug toxicity, there are few exposed cases compared to the number of unexposed cases. Verification of all unexposed presumptive cases through medical records is costly. We investigate the statistical efficiency of a design in which all exposed cases but only a subsample of the unexposed cases are verified. We show that good efficiency can usually be achieved with a small subsample of unexposed cases. Published in 1999 by John Wiley & Sons, Ltd.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1999

Traumatic brain injury in young, amyloid-beta peptide overexpressing transgenic mice induces marked ipsilateral hippocampal atrophy and diminished Abeta deposition during aging.

Traumatic brain injury (TBI) is an epigenetic risk factor for Alzheimer's disease (AD). To test the hypothesis that TBI contributes to the onset and/or progression of AD-like beta-amyloid peptide (Abeta) deposits, we studied the long-term effects of TBI in transgenic mice that overexpress human Abeta from a mutant Abeta precursor protein (APP) minigene driven by a platelet derived (PD) growth factor promoter (PDAPP mice). TBI was induced in 4-month-old PDAPP and wild type (WT) mice by controlled cortical impact (CCI). Because Abeta begins to deposit progressively in the PDAPP brain by 6 months, we examined WT and PDAPP mice at 2, 5, and 8 months after TBI or sham treatment (i.e., at 6, 9, and 12 months of age). Hippocampal atrophy in the PDAPP mice was more severe ipsilateral versus contralateral to TBI, and immunohistochemical studies with antibodies to different Abeta peptides demonstrated a statistically significant reduction in hippocampus and cingulate cortex Abeta deposits ipsilateral versus contralateral to CCI in 9-12 month-old PDAPP mice. Hippocampal atrophy and reduced Abeta deposits were not seen in hippocampus or cingulate cortex of sham-injured PDAPP mice or in any WT mice. These data suggest that the vulnerability of brain cells to Abeta toxicity increases and that the accumulation of Abeta deposits decrease in the penumbra of CCI months after TBI. Thus, in addition to providing unique opportunities for elucidating genetic mechanisms of AD, transgenic mice that recapitulate AD pathology also may be relevant animal models for investigating the poorly understood role that TBI and other epigenetic risk factors play in the onset and/or progression of AD.

Alzheimer Disease↗
PubMed1999

Assessing the generalizability of prognostic information.

Physicians are often asked to make prognostic assessments but often worry that their assessments will prove inaccurate. Prognostic systems were developed to enhance the accuracy of such assessments. This paper describes an approach for evaluating prognostic systems based on the accuracy (calibration and discrimination) and generalizability (reproducibility and transportability) of the system's predictions. Reproducibility is the ability to produce accurate predictions among patients not included in the development of the system but from the same population. Transportability is the ability to produce accurate predictions among patients drawn from a different but plausibly related population. On the basis of the observation that the generalizability of a prognostic system is commonly limited to a single historical period, geographic location, methodologic approach, disease spectrum, or follow-up interval, we describe a working hierarchy of the cumulative generalizability of prognostic systems. This approach is illustrated in a structured review of the Dukes and Jass staging systems for colon and rectal cancer and applied to a young man with colon cancer. Because it treats the development of the system as a "black box" and evaluates only the performance of the predictions, the approach can be applied to any system that generates predicted probabilities. Although the Dukes and Jass staging systems are discrete, the approach can also be applied to systems that generate continuous predictions and, with some modification, to systems that predict over multiple time periods. Like any scientific hypothesis, the generalizability of a prognostic system is established by being tested and being found accurate across increasingly diverse settings. The more numerous and diverse the settings in which the system is tested and found accurate, the more likely it will generalize to an untested setting.

Calibration↗
PubMed1999

The role of meta-analysis in the regulatory process for foods, drugs, and devices.

Synthesis of research findings has a long-standing tradition in science. While synthesis is currently required in the US food and drug regulatory process, formal meta-analysis may substitute for a pivotal study or broaden the generalizability of drug efficacy through a preplanned meta-analysis. Preplanned meta-analysis of individual trials with deliberately introduced heterogeneity may maximize the generalizability of results from randomized trials. Combining observational data may help to support an alternative claim or to quantify adverse events. In this setting, methods to address potentially greater sources of bias are required. Overall, meta-analysis adds evidence through the synthesis study findings and permits examination of how treatment effects vary across of subgroups, such as age and sex, and across study settings.

Drug Approval↗
PubMed1999

The effect of race and sex on physicians' recommendations for cardiac catheterization.

BACKGROUND: Epidemiologic studies have reported differences in the use of cardiovascular procedures according to the race and sex of the patient. Whether the differences stem from differences in the recommendations of physicians remains uncertain. METHODS: We developed a computerized survey instrument to assess physicians' recommendations for managing chest pain. Actors portrayed patients with particular characteristics in scripted interviews about their symptoms. A total of 720 physicians at two national meetings of organizations of primary care physicians participated in the survey. Each physician viewed a recorded interview and was given other data about a hypothetical patient. He or she then made recommendations about that patient's care. We used multivariate logistic-regression analysis to assess the effects of the race and sex of the patients on treatment recommendations, while controlling for the physicians' assessment of the probability of coronary artery disease as well as for the age of the patient, the level of coronary risk, the type of chest pain, and the results of an exercise stress test. RESULTS: The physicians' mean (+/-SD) estimates of the probability of coronary artery disease were lower for women (probability, 64.1+/-19.3 percent, vs. 69.2+/-18.2 percent for men; P<0.001), younger patients (63.8+/-19.5 percent for patients who were 55 years old, vs. 69.5+/-17.9 percent for patients who were 70 years old; P<0.001), and patients with nonanginal pain (58.3+/-19.0 percent, vs. 64.4+/-18.3 percent for patients with possible angina and 77.1+/-14.0 percent for those with definite angina; P=0.001). Logistic-regression analysis indicated that women (odds ratio, 0.60; 95 percent confidence interval, 0.4 to 0.9; P=0.02) and blacks (odds ratio, 0.60; 95 percent confidence interval, 0.4 to 0.9; P=0.02) were less likely to be referred for cardiac catheterization than men and whites, respectively. Analysis of race-sex interactions showed that black women were significantly less likely to be referred for catheterization than white men (odds ratio, 0.4; 95 percent confidence interval, 0.2 to 0.7; P=0.004). CONCLUSIONS: Our findings suggest that the race and sex of a patient independently influence how physicians manage chest pain.

Age Factors↗
PubMed1999

Factors influencing the optimal control-to-case ratio in matched case-control studies.

Statistical power in matched case-control studies depends on both the correlation coefficient between cases and their matched controls (phi) and the prevalence of exposure among controls (P0). To examine the hypothesis that the value of increasing the control-to-case ratio beyond 5 varies with both phi and P0, the authors estimated statistical power for a hypothetical case-control study under different assumptions. The effect of increasing the control-to-case ratio depended on phi and, to a lesser extent, on P0. The results suggest that investigators consider including more than five controls per case when either phi is greater than about 0.2 or P, is less than about 0.15.

Bias↗
PubMed1999

Risk factors associated with the failure of a venous leg ulcer to heal.

BACKGROUND: Venous leg ulcers afflict a significant portion of the population. The most popular form of therapy for venous leg ulcers is a compression bandage (eg, Unna boot), a therapy that is frequently unsuccessful. OBJECTIVE: To describe risk factors associated with the failure of a wound to heal when treated with a limb-compression bandage for 24 weeks. DESIGN: A retrospective cohort study. SETTING: Single-center outpatient specialty clinic at an academic medical center. PARTICIPANTS: Two hundred sixty consecutive patients with chronic venous leg ulcers. MAIN OUTCOME MEASURE: The magnitude of the effect of a given risk factor on the probability that a wound will heal within 24 weeks of care. RESULTS: Based on an assessment of leg wounds during initial office visits, we observed that the failure of a wound to heal within 24 weeks was significantly associated with larger wound area, measured in square centimeters (odds ratio [OR], 1.19; 95% confidence interval [CI], 1.11-1.27), duration of the wound in months (OR, 1.09; 95% CI, 1.04-1.16), history of venous ligation or venous stripping (OR, 4.58; 95% CI, 1.84-11.36), history of hip or knee replacement surgery (OR, 3.52; 95% CI, 1.12-11.08), ankle brachial index of less than 0.80 (OR, 3.52; 95% CI, 1.12-11.08), and the presence of fibrin on more than 50% of the wound surface (OR, 3.42; 95% CI, 1.38-8.45). CONCLUSIONS: Several risk factors are associated with the failure of a patient's venous leg ulcer to heal while using limb-compression therapy. It is prudent to consider these factors when referring a patient to a wound care subspecialists or for alternative therapies.

Aged↗
PubMed1999

Diffuse axonal pathology detected with magnetization transfer imaging following brain injury in the pig.

This study was designed to evaluate with magnetization transfer imaging (MTI) and conventional magnetic resonance (MR) imaging the manifestation of diffuse axonal injury (DAI) in an animal model of injury via nonimpact coronal plane rotational acceleration. A second objective was to investigate the diagnostic use of quantitative MTR imaging based on statistical parameters in a single subject, as opposed to grouped analysis. Seven mini-swine were subjected to brain trauma known to produce isolated DAI and to MR imaging at two time points. Following sacrifice, the brains were harvested for histopathologic examination. Magnetization transfer ratio (MTR) maps were generated for double-blinded comparison of regions with abnormal MTR values and regions with documented DAI. Positive and negative predictive values for MTR detection of DAI were 67 and 56%, respectively, and in acute studies alone, 89 and 61%. Gains in sensitivity over conventional imaging for detection of DAI were demonstrated.

Animals↗
PubMed1999

A comparison of sensitivity analyses of the effect of wound duration on wound healing.

The effect of an unmeasured exposure on the association between an exposure and outcome can never be fully known in an observational study. The purpose of the current study was to evaluate the sensitivity to unmeasured confounding of the previously published association between wound duration and wound healing in a chronic venous leg ulcer. This was estimated using two methods of sensitivity analysis, called Rosenbaum's method and Greenland's external adjustment. The association between wound duration and wound healing was insensitive to confounding unless the odds ratio for the association between the confounder and a younger wound was almost nine (Rosenbaum). In fact, the association between this hypothetical confounder and healing must have an odds ratio of 100 to remove the effect of duration fully (Greenland). Both of these techniques provide useful and complementary information when assessing the effects of a potential unmeasured confounder.

Bandages↗
PubMed1999

Racial differences in menopause information and the experience of hot flashes.

OBJECTIVE: To compare the prevalence of hot flashes and health education regarding menopause in African-American and white American women in the late reproductive years. DESIGN: Cross-sectional study. SETTING: Population-based sample recruited through random digit dialing. PARTICIPANTS: The sample was 436 women between the ages of 35 and 48 years with regular menses. Half the sample was African American and half was white American. MAIN RESULTS: African-American women (53%) were more likely than white American women (29%) to have experienced hot flashes (p < .001). The difference remained after adjustment for body-mass index, education, menstrual cycle characteristics, and gynecologic and medical history. Despite the high prevalence of symptoms, few women had discussed menopausal management with their physicians. For white women the media were the primary source of menopause-related information, whereas African-American women reported that their family was the primary source of information. CONCLUSIONS: These results indicate that hot flashes occur commonly among women in their thirties and forties who have regular menstrual cycles and that the prevalence of hot flashes appears to differ by race. Studies should be designed to evaluate the hormonal and physiologic implications of these symptoms among women in their late reproductive years. Few of these women had discussed menopause with their physicians. Given the differences in sources of information about menopause, development of culture-specific health education programs should be considered.

Adult↗
PubMed1999

Effect of testosterone treatment on bone mineral density in men over 65 years of age.

As men age, their serum testosterone concentrations decrease, as do their bone densities. Because bone density is also low in hypogonadal men, we hypothesized that increasing the serum testosterone concentrations of men over 65 yr to those found in young men would increase their bone densities. We randomized 108 men over 65 yr of age to wear either a testosterone patch or a placebo patch double blindly for 36 months. We measured bone mineral density by dual energy x-ray absorptiometry before and during treatment. Ninety-six men completed the entire 36-month protocol. The mean serum testosterone concentration in the men treated with testosterone increased from 367 +/- 79 ng/dL (+/-SD; 12.7 +/- 2.7 nmol/L) before treatment to 625 +/- 249 ng/dL (21.7 +/- 8.6 nmol/L; P < 0.001) at 6 months of treatment and remained at that level for the duration of the study. The mean bone mineral density of the lumbar spine increased (P < 0.001) in both the placebo-treated (2.5 +/- 0.6%) and testosterone-treated (4.2 +/- 0.8%) groups, but the mean changes did not differ between the groups. Linear regression analysis, however, demonstrated that the lower the pretreatment serum testosterone concentration, the greater the effect of testosterone treatment on lumbar spine bone density from 0-36 months (P = 0.02). This analysis showed a minimal effect (0.9 +/- 1.0%) of testosterone treatment on bone mineral density for a pretreatment serum testosterone concentration of 400 ng/dL (13.9 nmol/L), but an increase of 5.9 +/- 2.2% for a pretreatment testosterone concentration of 200 ng/dL (6.9 nmol/L). Increasing the serum testosterone concentrations of normal men over 65 yr of age to the midnormal range for young men did not increase lumbar spine bone density overall, but did increase it in those men with low pretreatment serum testosterone concentrations.

Administration, Cutaneous↗
PubMed1999

Effect of testosterone treatment on body composition and muscle strength in men over 65 years of age.

As men age, serum testosterone concentrations decrease, the percentage of body mass that is fat increases, the percentage of lean body mass decreases, and muscle strength decreases. Because these changes are similar to those that occur in hypogonadal men, we hypothesized that increasing the serum testosterone concentration of men over 65 yr of age to that in young men would decrease their fat mass, increase their lean mass, and increase their muscle strength. We randomized 108 men over 65 yr of age to wear either a testosterone patch or a placebo patch in a double blind study for 36 months. We measured body composition by dual energy x-ray absorptiometry and muscle strength by dynamometer before and during treatment. Ninety-six men completed the entire 36-month protocol. Fat mass decreased (-3.0+/-0.5 kg) in the testosterone-treated men during the 36 months of treatment, which was significantly different (P = 0.001) from the decrease (-0.7+/-0.5 kg) in the placebo-treated men. Lean mass increased (1.9+/-0.3 kg) in the testosterone-treated men, which was significantly different (P < 0.001) from that (0.2+/-0.2 kg) in the placebo-treated men. The decrease in fat mass in the testosterone-treated men was principally in the arms (-0.7+/-0.1 kg; P < 0.001 compared to the placebo group) and legs (-1.1+/-0.2 kg; P < 0.001), and the increase in lean mass was principally in the trunk (1.9+/-0.3 kg; P < 0.001). The change in strength of knee extension and flexion at 60 degrees and 180 degrees angular velocity during treatment, however, was not significantly different between the two groups. We conclude that increasing the serum testosterone concentrations of normal men over 65 yr of age to the midnormal range for young men decreased fat mass, principally in the arms and legs, and increased lean mass, principally in the trunk, but did not increase the strength of knee extension and flexion, as measured by dynamometer.

Aged↗
PubMed1999

Predictors of injury among adult recreational in-line skaters: a multicity study.

OBJECTIVES: This study examined risk factors for injury, injury prevalence, safety gear use, and skating habits of adult recreational in-line skaters. METHODS: Randomly selected in-line skaters in 6 major US cities were interviewed. RESULTS: Only 6% of skaters consistently wore all 4 recommended types of safety gear. Skaters with greater skating experience were more likely to perform tricks, wear less safety gear, and sustain an injury. CONCLUSION: More experienced adult recreational in-line skaters are at increased risk for injury. Safety gear use in alarmingly low in adult recreational in-line skaters, especially experienced skaters. Safe skating education programs should consider targeting this newly recognized at-risk skating population.

Adult↗
PubMed1999

Healing of diabetic neuropathic foot ulcers receiving standard treatment. A meta-analysis.

OBJECTIVE: The aim of the study was to determine the percentage of individuals with neuropathic diabetic foot ulcers receiving good wound care who heal within a defined period of time. RESEARCH DESIGN AND METHODS: We conducted a systematic review of the control groups of clinical trials that evaluated a treatment for diabetic neuropathic foot ulcers. The meta-analytic techniques used include an estimation of the weighted mean percentage healed by end point, an evaluation of the homogeneity of trials, and an estimate of the 95% CI of the grouped data. Grouped-data univariate and multivariate logistic regression was conducted to assess the impact of mean age, ulcer size, and duration on the percentage of ulcers healed at end point. RESULTS: We found a total of 10 control groups meeting our criteria. Six control groups used 20 weeks as the end point for healing or nonhealing. For the six control arms with a 20-week end point, we found a weighted mean healing rate of 30.9% (95% CI 26.6-35.1). A similar analysis for the four 12-week arms found a mean healing rate of 24.2% (19.5-28.8). We failed to detect any statistically significant heterogeneity for either the 20-week or the 12-week trials. CONCLUSIONS: After 20 weeks of good wound care, approximately 31% of diabetic neuropathic ulcers heal. Similarly, after 12 weeks of good care, approximately 24% of neuropathic ulcers attain complete healing. Further patient-level analyses are necessary to definitively determine the associations of age, wound size, and wound duration with likelihood of healing.

Diabetic Foot↗
PubMed1998

Dental and cardiac risk factors for infective endocarditis. A population-based, case-control study.

BACKGROUND: Although antibiotic prophylaxis against infective endocarditis is recommended, the true risk factors for infective endocarditis are unclear. OBJECTIVE: To quantitate the risk for endocarditis from dental treatment and cardiac abnormalities. DESIGN: Population-based, case-control study. SETTING: 54 hospitals in the Philadelphia area. PATIENTS: Persons with community-acquired infective endocarditis not associated with intravenous drug use were compared with community residents, matched by age, sex, and neighborhood of residence. MEASUREMENTS: Information on demographic characteristics, host risk factors, and dental treatment was obtained from structured telephone interviews, dental records, and medical records. RESULTS: During the preceding 3 months, dental treatment was no more frequent among case-patients than controls (adjusted odds ratio, 0.8 [95% CI, 0.4 to 1.5]). Of 273 case-patients, 104 (38%) knew of previous cardiac lesions compared with 17 controls (6%) (adjusted odds ratio, 16.7 [CI, 7.4 to 37.4]). Case-patients more often had a history of mitral valve prolapse (adjusted odds ratio, 19.4 [CI, 6.4 to 58.4]), congenital heart disease (adjusted odds ratio, 6.7 [CI, 2.3 to 19.4]), cardiac valvular surgery (adjusted odds ratio, 74.6 [CI, 12.5 to 447]), rheumatic fever (adjusted odds ratio, 13.4 [CI, 4.5 to 39.5]), and heart murmur without other known cardiac abnormalities (adjusted odds ratio, 4.2 [CI, 2.0 to 8.9]). Among case-patients with known cardiac lesions--the target of prophylaxis--dental therapy was significantly (P = 0.03) less common than among controls (adjusted odds ratio, 0.2 [CI, 0.04 to 0.7] over 3 months). Few participants received prophylactic antibiotics. CONCLUSIONS: Dental treatment does not seem to be a risk factor for infective endocarditis, even in patients with valvular abnormalities, but cardiac valvular abnormalities are strong risk factors. Few cases of infective endocarditis would be preventable with antibiotic prophylaxis, even with 100% effectiveness assumed. Current policies for prophylaxis should be reconsidered.

Adolescent↗
PubMed1998

Does masking author identity improve peer review quality? A randomized controlled trial. PEER Investigators.

CONTEXT: All authors may not be equal in the eyes of reviewers. Specifically, well-known authors may receive less objective (poorer quality) reviews. One study at a single journal found a small improvement in review quality when reviewers were masked to author identity. OBJECTIVES: To determine whether masking reviewers to author identity is generally associated with higher quality of review at biomedical journals, and to determine the success of routine masking techniques. DESIGN AND SETTING: A randomized controlled trial performed on external reviews of manuscripts submitted to Annals of Emergency Medicine, Annals of Internal Medicine, JAMA, Obstetrics & Gynecology, and Ophthalmology. INTERVENTIONS: Two peers reviewed each manuscript. In one study arm, both peer reviewers received the manuscript according to usual masking practice. In the other arm, one reviewer was randomized to receive a manuscript with author identity masked, and the other reviewer received an unmasked manuscript. MAIN OUTCOME MEASURE: Review quality on a 5-point Likert scale as judged by manuscript author and editor. A difference of 0.5 or greater was considered important. RESULTS: A total of 118 manuscripts were randomized, 26 to usual practice and 92 to intervention. In the intervention arm, editor quality assessment was complete for 77 (84%) of 92 manuscripts. Author quality assessment was complete on 40 (54%) of 74 manuscripts. Authors and editors perceived no significant difference in quality between masked (mean difference, 0.1; 95% confidence interval [CI], -0.2 to 0.4) and unmasked (mean difference, -0.1; 95% CI, -0.5 to 0.4) reviews. We also found no difference in the degree to which the review influenced the editorial decision (mean difference, -0.1; 95% CI,-0.3 to 0.3). Masking was often unsuccessful (overall, 68% successfully masked; 95% CI, 58%-77%), although 1 journal had significantly better masking success than others (90% successfully masked; 95% CI, 73%-98%). Manuscripts by generally known authors were less likely to be successfully masked (odds ratio, 0.3; 95% CI, 0.1-0.8). When analysis was restricted to manuscripts that were successfully masked, review quality as assessed by editors and authors still did not differ. CONCLUSIONS: Masking reviewers to author identity as commonly practiced does not improve quality of reviews. Since manuscripts of well-known authors are more difficult to mask, and those manuscripts may be more likely to benefit from masking, the inability to mask reviewers to the identity of well-known authors may have contributed to the lack of effect.

Authorship↗
PubMed1998

Masking author identity in peer review: what factors influence masking success? PEER Investigators.

CONTEXT: In a previous study, we found that masking success was higher at a journal that masked reviewers to author identity. We hypothesized that masking policy or other factors could be associated with masking success. OBJECTIVES: To evaluate differences in success of masking reviewers to author identity at 7 biomedical journals and to identify factors associated with these differences. DESIGN: Written questionnaire. PARTICIPANTS: Reviewers at 3 journals with a long-standing policy of masking author identity (Annals of Emergency Medicine, Epidemiology, and Journal of the American Geriatrics Society) and 4 journals without a policy of masking author identity (Annals of Internal Medicine, JAMA, Obstetrics & Gynecology, and Ophthalmology). MAIN OUTCOME MEASURES: Masking success (percentage of reviewers successfully masked) and reviewer characteristics associated with masking. RESULTS: There was no significant difference in masking success between journals with a policy of masking (60%) and those without (58%) (P= .92). We found no association between masking success and a policy of masking when adjusted for the reviewer characteristics of age, sex, years of reviewing experience, number of articles published, number of articles reviewed, percentage of time spent in research, editorial experience, or academic rank (odds ratio [OR], 1.3; 95% confidence interval [CI], 0.64-2.8; P=.43). In multivariable analysis of reviewer characteristics, reviewers spending a greater percentage of time in research, the only significant predictor of masking success, were less likely to be successfully masked (OR, 1.01; 95% CI, 1.00-1.02) (P=.04). CONCLUSIONS: Masking success appears unrelated to a journal policy of masking, but is associated with reviewers' research experience and could be affected by other characteristics. Using reviewers with less research and reviewing experience might increase masking success, but the effect on review quality is unknown.

Authorship↗