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Biomedical subjects

H S Sacks

Publications and source records attributed to H S Sacks.

85 records · Page 5Linked to original sources

Similar responsiveness of diabetic ketoacidosis to low-dose insulin by intramuscular injection and albumin-free infusion.

We compared low-dose insulin regimens in a prospective randomized trial in 30 patients with diabetic ketoacidosis. One group received a loading dose of 0.44 U/kg body weight of regular insulin half intramuscularly and half intravenously followed by 7 U/h intramuscularly, whereas the other group received a loading dose of 0.44 U/kg intravenously followed immediately by a constant infusion of 7 U/h in albumin-free saline. The time for metabolic control of the ketoacidosis was not significantly different in the two groups. Five patients in each group developed mild hypokalemia (serum potassium, 3.0 to 3.4 meq/litre). No patient became hypoglycemic, and there were no deaths within the follow-up period (24 h). In the treatment of diabetic ketoacidosis, low doses of insulin administered by the priming dose-intermittent intramuscular route are as effective as the constant infusion method.

Adult↗

Clostridium botulinum type E toxin: effect of pH and method of purification on molecular weight.

The toxin of Clostridium botulinum type E was isolated from intact cells and from toxic culture filtrates by column chromatography at three pH values, 4.5, 5.3, and 6.0. At pH 6.0 and 5.3, the isolated toxin was in a form with a molecular weight (MW) of 86,000. This toxin was homogeneous on polyacrylamide gel electrophoresis and gel filtration and had an optical density ratio, 280 nm/260 nm, greater than 2.0. It did not dissociate at higher pH levels, but was dissociated into nontoxic components of approximately 12,000 MW when reduced and alkylated in the presence of 6 M guanidine hydrochloride. At pH 4.5, smaller amounts of an impure toxic moiety with a MW of 12,000 were found. After storage for 6 months, the 86,000-MW moiety had lost 60% of its lethality. Gel filtration revealed that the bulk of the toxicity was associated with a component having a MW of 150,000. Toxic components with MW of 12,000 and over 200,000 were also found. The toxin appears to polymerize or aggregate when in a pure form, so that most, if not all, of the MW previously reported for the toxin may belong to different polymers of a monomer with a MW of 12,000 or less. Treatment of the 86,000-MW toxin with trypsin resulted in an 18- to 128-fold increase in lethality, but no detectable change in MW.

Ammonium Sulfate↗

Meta-analysis of clinical trials as a scientific discipline. I: Control of bias and comparison with large co-operative trials.

Meta-analysis is an important method of bridging the gap between undersized randomized control trials and the treatment of patients. However, as in any retrospective study, the opportunities for bias to distort the results are widespread. Attempts must be made to introduce the controls found in prospective studies by blinding the selection of papers and extraction of data and making blinded duplicate determinations. Informal and personalized methods of obtaining data are probably more liable to error and bias than employing only published data. Publication bias is a serious problem requiring further research. There also need to be more comparisons of meta-analysed small studies with large co-operative trials.

Adrenergic beta-Antagonists↗

Meta-analysis of clinical trials as a scientific discipline. II: Replicate variability and comparison of studies that agree and disagree.

The replicate variability of meta-analyses of controlled clinical trials has been assessed as a measure of scientific precision. 46 of 91 known meta-analysis papers were divided into 20 cohorts of studies of the same therapies. Ten cohorts contained meta-analyses with different statistical conclusions; 14 contained differing clinical conclusions with a wider spread than the statistically differing studies. Possible causes of variability, such as different trials included, different policies regarding the inclusion of non-randomized and unpublished trials, and different statistical methodologies, were not obvious causes of differing conclusions. Further work in this area should include multivariate analyses in order to explore possible interactions in the factors accounting for the variability found in replicate meta-analyses.

Clinical Trials as Topic↗

BCG vaccination to prevent tuberculosis in health care workers: a decision analysis.

OBJECTIVE: To perform a decision analysis to determine the optimal strategy to prevent tuberculosis (TB) in health care workers with negative tuberculin skin tests. METHODS: We used a Markov model to study the occurrence of events each year and compared BCG vaccination to annual tuberculin testing plus isoniazid (INH) preventive therapy for those who become skin test positive. The outcome measures studied were the number of cases and deaths from TB and BCG and/or INH adverse reactions over 10 years. RESULTS: Annual tuberculin testing decreases the number of TB cases by 9% and BCG vaccination decreases the number by 49%, relative to no prevention intervention. BCG vaccination results in fewer deaths than annual tuberculin testing if the workplace incidence of Mycobacterium tuberculosis infection is greater than 0.06%, BCG vaccination effectiveness exceeds 3%, or the rate of fatal BCG adverse reactions is less than 15 times the rate reported in the literature. CONCLUSIONS: BCG vaccination results in less morbidity and mortality than annual tuberculin skin testing for health care workers in workplaces with documented TB transmission despite comprehensive infection control policies and procedures. Current policy on the prevention of TB among health care workers should be reconsidered.

Antitubercular Agents↗

Preventive medicine for HIV-infected patients: an analysis of isoniazid prophylaxis for tuberculin reactors and for anergic patients.

OBJECTIVE: To analyze the policies of isoniazid prophylaxis for human immunodeficiency virus (HIV)-infected tuberculin reactors and for HIV-infected anergic patients with unknown tuberculin status. METHODS: Transition-state model of clinical immune deterioration of HIV-infection over ten years, review of published data, and a survey of AIDS experts. Outcome measures are the numbers of tuberculosis cases and deaths prevented and isoniazid toxicity cases and deaths occurring with prophylaxis. PATIENTS: Hypothetical cohorts of HIV-infected 40-year-olds. RESULTS: Because the tuberculosis activation rate is so high in HIV-infected patients, the benefits of prophylaxis far outweigh the risks of isoniazid toxicity for tuberculin reactors with HIV infection at any stage of immune function: 1,469-2,868 tuberculosis cases and 170-274 deaths are prevented per 10,000 cohort over ten years, depending upon the cohort's initial immune state. The benefits of prophylaxis outweigh the risks of isoniazid toxicity for anergic HIV-infected patients if they come from a community with a 2% to 3% or greater prevalence of Mycobacterium tuberculosis infection. CONCLUSIONS: Isoniazid prophylaxis is a reasonable prevention measure for HIV-infected tuberculin reactors and for many HIV-infected anergic patients.

AIDS-Related Opportunistic Infections↗

Zidovudine prophylaxis for needlestick exposure to human immunodeficiency virus: a decision analysis.

OBJECTIVE: To perform a decision analysis to determine the thresholds of safety and effectiveness that would justify short-term zidovudine (AZT) administration for persons with accidental percutaneous exposure to HIV-positive blood. DESIGN: Published data were used to estimate the seroconversion rate (0.42%), rate of developing AIDS if HIV-infected (5%/year), and survival with AIDS (50%/year). No information is available on zidovudine effectiveness and little is known about fatal toxicity of zidovudine. Death from AIDS or from zidovudine toxicity was used as the endpoint. RESULTS: For those with exposure to blood known to be HIV-seropositive, the benefits of zidovudine outweight the risks if efficacy is above approximately 3% to 8%. Wide variations in the assumptions have little effect on the thresholds. CONCLUSIONS: Since clinical trials to determine zidovudine effectiveness in this setting will probably never be done, decision analysis offers the only quantitative method for addressing this question. Unless future studies show zidovudine to be both ineffective and toxic, the benefits of short-term administration of zidovudine outweigh the risks immediately after exposure to HIV-positive blood. Zidovudine benefits do not clearly outweigh the risks after exposure to blood of unknown serologic status, or if there is a delay in starting therapy.

Acquired Immunodeficiency Syndrome↗

Meta-analysis: an update.

A fairly new type of research, termed meta-analysis, attempts to analyze and combine the results of previous reports. In 1992 we updated our 1987 survey of 86 meta-analyses of randomized control trial reports in the english language literature with an additional 78. We evaluated the quality of these meta-analyses using a scoring method that lists 23 items in six major areas: study design, combinability, control of bias, statistical analysis, sensitivity analysis, and application of results. Of the 23 individual items, the mean number satisfactorily addressed was 7.63 +/- 2.84 (mean +/- S.D.) for 40 papers published from 1955 through 1982, 6.80 +/- 3.86 for 66 papers published from 1983 through 1986, and 11.91 +/- 4.79 for 58 papers published from 1987 through 1990 (F = 31.3, p < .001). We noted that methodology has definitely improved since our first survey of meta-analyses, but an urgent need still exists for a better search of the literature, quality evaluation of trials, and a synthesis of the results. Recently, meta-analysis has expanded to cover non-randomized studies, including evaluation of diagnostic tests and pooling of epidemiologic studies. There is growing concern for standards, and several methodologic issues remain unresolved.

Bias↗