Biomedical subjects
Publications and source records attributed to J Lau.
This is the first reported case of successful management of a mycotic aneurysm of the inferior mesenteric artery. The only helpful clinical manifestations were episodes of previous abdominal pain and a history of bacterial endocarditis. The surgical management involved simple excision without revascularization of the inferior mesenteric artery.
Few cases have been reported to date of cardiac surgery performed on patients with von Willebrand's disease. This report details the management of such a patient, who underwent aortic valve replacement for severe calcific aortic stenosis.
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CONTEXT: Randomized trials with adequate sample size offer an opportunity to assess the safety of new medications in a controlled setting; however, generalizable data on drug safety reporting are sparse. OBJECTIVE: To scrutinize the completeness of safety reporting in randomized trials. DESIGN, SETTING, AND PATIENTS: Survey of safety reporting in 192 randomized drug trials 7 diverse topics with sample sizes of at least 100 patients and at least 50 patients in a study arm (N = 130074 patients). Trial reports were identified from comprehensive meta-analyses in 7 medical areas. MAIN OUTCOME MEASURES: Adequate reporting of specific adverse effects and frequency and reasons for withdrawals due to toxic effects; article space allocated to safety reporting and predictors of such reporting. RESULTS: Severity of clinical adverse effects and laboratory-determined toxicity was adequately defined in only 39% and 29% of trial reports, respectively. Only 46% of trials stated the frequency of specific reasons for discontinuation of study treatment due to toxicity. For these 3 parameters, there was significant heterogeneity in rates of adequate reporting across topics (P =.003, P<.001, and P =.02, respectively). Overall, the median space allocated to safety results was 0.3 page. A similar amount of space was devoted to contributor names and affiliations (P =.16). On average, the percentage of space devoted to safety in the results section was 9.3% larger in trials involving dose comparisons than in those that did not (P<.001) and 3.8% smaller in trials reporting statistically significant results for efficacy outcomes (P =.047). CONCLUSIONS: The quality and quantity of safety reporting vary across medical areas, study designs, and settings but they are largely inadequate. Current standards for safety reporting in randomized trials should be revised to address this inadequacy.
The importance of blood flow in duodenal ulcer healing is unclear. Endoscopic reflectance spectrophotometry measures the index of oxygen saturation (ISO2), which is significantly correlated with blood flow. In 97 consecutive patients who presented with duodenal ulcer bleeding, the difference in the index of oxygen saturation (delta ISO2: ulcer margin ISO2 minus adjacent mucosa ISO2) was determined during the initial endoscopic examination. Endoscopic examinations were repeated until the ulcers had healed (n = 86). Relative to the adjacent mucosa, 78% of the ulcer margins had increased blood flow (positive delta ISO2) and 22% had decreased blood flow (negative delta ISO2). Stepwise multi-linear regression analysis selected delta ISO2, ulcer size, and stigmata of recent hemorrhage as predictors of delayed healing. A significant negative linear correlation between delta ISO2 and ulcer healing time (r = -0.35, p < 0.001, n = 86) was demonstrated. The scatter in the data precludes prediction of ulcer healing based on delta ISO2 measurement in an individual patient. Multi-variate logistic regression analysis selected concurrent medical illness, duodenal deformity, frequent use of non-steroidal anti-inflammatory drugs, and stigmata of recent hemorrhage as factors significantly associated with delayed (longer than 5 weeks) ulcer healing. The results support the hypothesis that prognostic factors are identifiable at the time of ulcer diagnosis, even in patients who present with bleeding. Blood flow remains an equivocal factor that deserves to be re-studied taking multiple measurements around the ulcer and including a larger number of slow healers.
The aim of this study was to compare the metabolic effects of a single equimolar subcutaneous injection of hepatic directed vesicle-insulin (HDV-insulin) and regular insulin on glucose levels and intermediary metabolism during a 75-g oral glucose tolerance test (OGTT). Nine Type 1 diabetic patients underwent two experiments separated by 4 weeks. Each experimental protocol consisted of an identical evening meal followed by overnight euglycemic control achieved by a continuous low-dose insulin infusion. The next morning a subcutaneous injection (0.1 U/kg) of HDV-insulin or regular insulin was administered 30 min before a 75-g OGTT. The overnight basal insulin infusion was maintained unaltered throughout the 150-min OGTT. Plasma glucose, glucoregulatory hormones (insulin, glucagon, cortisol), and intermediary metabolites (lactate, alanine, glycerol, NEFA, beta-hydroxybutyrate) were measured to assess the metabolic effects of the two insulin preparations. Compared to regular insulin, an equivalent subcutaneous dose of HDV-insulin significantly lowered glucose levels during OGTT (mean reduction 2.2+/-0.4 mmol/l; P<.005). Plasma levels of insulin and glucagon were equivalent during both series of experiments. Blood lactate, glycerol and plasma NEFA levels were not different during OGTT indicating similar peripheral action of the insulins. beta-Hydroxybutyrate levels were significantly reduced (P<.05) following HDV-insulin supporting a preferential hepatic action of the preparation. We conclude that HDV-insulin can significantly lower plasma glucose excursions compared to an equivalent dose of regular insulin during an OGTT in Type 1 diabetic patients. The metabolic profile of equivalent peripheral insulin, glucagon and glycerol levels but reduced beta-hydroxybutyrate values support a hepatospecific effect of HDV-insulin.
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CONTEXT: A meta-analysis found that primary percutaneous transluminal coronary angioplasty (PTCA) was more effective than thrombolytic therapy in reducing mortality from acute myocardial infarction. However, fewer than 20% of U.S. hospitals have facilities to perform PTCA and many clinicians must choose between immediate thrombolytic therapy and delayed PTCA. COUNT: The number of minutes of PTCA-related delay that would nullify its benefits. CALCULATION: For 10 published randomized trials, we calculated the following: PTCA-related delay = median "door-to-balloon" time--median "door-to-needle" time Survival benefit = 30-day mortality after thrombolytic therapy--30-day mortality after PTCA The relationship between delay and benefit was assessed with linear regression. RESULTS: The reported PTCA-related delay ranged from 7 to 59 minutes, while the absolute survival benefit ranged from -2.2% (favoring thrombolytic therapy) to 7.4% (favoring PTCA). Across trials, the survival benefit decreased as the PTCA-related delay increased: For each additional 10-minute delay, the benefit was predicted to decrease 1.7% (P < 0.001). Linear regression showed that at a PTCA-related delay of 50 minutes, PTCA and thrombolytic therapy yielded equivalent reductions in mortality. CONCLUSIONS: In clinical trials with short PTCA-related delays, PTCA produced better outcomes, while trials with longer delays favored thrombolytic therapy. A more precise estimate of the time interval to equipoise between the two therapies needs to be modeled with patient-level data. At experienced cardiac centers, PTCA is probably still preferable, even with delays longer than 50 minutes.
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OBJECTIVE: To evaluate the results of large clinical trials vs the pooled results of smaller trials. DATA IDENTIFICATION: Meta-analyses with at least 1 "large" study were identified from the Cochrane Pregnancy and Childbirth Database and from MEDLINE (1966-1995). STUDY SELECTION: We used a sample size approach to select 79 meta-analyses with at least 1 large study of 1000 or more patients. We used a statistical power approach to select 61 meta-analyses with at least 1 large study based on statistical power considerations. DATA EXTRACTION: The outcome of interest for each meta-analysis was the primary one stated in the original publication or, when not clearly specified, was decided on clinically. DATA SYNTHESIS: By random effects calculations, we found agreement between large and smaller trials in 90% of the meta-analyses selected by the sample size approach and in 82% of the meta-analyses selected by the statistical power approach. Twice as many disagreements appeared when the variability among large studies and among smaller studies was not considered (ie, fixed effects calculations). Of the 15 disagreements between results of large and smaller trials using the random effects model, plausible explanations were identified in 10 meta-analyses: 5 with differences in the control rate of events between large and smaller trials, 4 with specific protocol or study differences, and 1 with potential publication bias. Two other disagreements were not clinically important, and tentative reasons could be identified for 2 of the remaining 3 disagreements. CONCLUSIONS: Results of smaller studies are usually compatible with the results of large studies, but discrepancies do occur even when the diversity among both large studies and smaller studies is considered. Clinically important differences without a potential explanation are extremely uncommon. Future research should further examine sources of heterogeneity between the results of large and smaller trials.