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Biomedical subjects

M Egger

Publications and source records attributed to M Egger.

At least 109 records · Page 6Linked to original sources
PubMed1997

Impact of new antiretroviral combination therapies in HIV infected patients in Switzerland: prospective multicentre study. Swiss HIV Cohort Study.

OBJECTIVES: To examine trends in disease progression and survival among patients enrolled in the Swiss HIV cohort study during 1988-96 and to assess the influence of new antiretroviral combination therapies. DESIGN: Prospective multicentre study, with follow up visits planned at six monthly intervals. SETTING: Seven HIV units at university centres and cantonal hospitals in Switzerland. PATIENTS: 3785 men (mean age 35.0 years) and 1391 women (30.3 years) infected with HIV. 2023 participants had a history of intravenous drug misuse; 1764 were men who had sex with men; 1261 were infected heterosexually; and 164 had other or unknown modes of transmission. 601 participants had had an AIDS defining illness. RESULTS: During more than 15,000 years of follow up, there were 1456 first AIDS defining diagnoses and 1903 deaths. Compared with those enrolled during 1988-90, the risk of progression to a first AIDS diagnosis was reduced by 18% (relative risk 0.82 (95% confidence interval 0.73 to 0.93)) among participants enrolled in 1991-2, by 23% (0.77 (0.65 to 0.91)) among those enrolled in 1993-4, and by 73% (0.27 (0.18 to 0.39)) among those enrolled in 1995-6. Mortality was reduced by 19% (0.81 (0.73 to 0.90)), 26% (0.74 (0.63 to 0.87)), and 62% (0.38 (0.25 to 0.97)) respectively. Compared with no antiretroviral treatment, the risk of an initial AIDS diagnosis after CD4 lymphocyte counts fell to < 200 cells x 10(6)/1 was reduced by 16% (0.84 (0.73 to 0.97)) with monotherapy, 24% (0.76 (0.63 to 0.91)) with dual therapy, and 42% (0.58 (0.37 to 0.92)) with triple therapy. Mortality was reduced by 23% (0.77 (0.68 to 0.88)), 31% (0.69 (0.60 to 0.80)), and 65% (0.35 (0.20 to 0.60)) respectively. CONCLUSIONS: The introduction of antiretroviral combination therapies outside the selected patient groups included in clinical trials has led to comparable reductions in disease progression and mortality.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Bias in meta-analysis detected by a simple, graphical test.

OBJECTIVE: Funnel plots (plots of effect estimates against sample size) may be useful to detect bias in meta-analyses that were later contradicted by large trials. We examined whether a simple test of asymmetry of funnel plots predicts discordance of results when meta-analyses are compared to large trials, and we assessed the prevalence of bias in published meta-analyses. DESIGN: Medline search to identify pairs consisting of a meta-analysis and a single large trial (concordance of results was assumed if effects were in the same direction and the meta-analytic estimate was within 30% of the trial); analysis of funnel plots from 37 meta-analyses identified from a hand search of four leading general medicine journals 1993-6 and 38 meta-analyses from the second 1996 issue of the Cochrane Database of Systematic Reviews. MAIN OUTCOME MEASURE: Degree of funnel plot asymmetry as measured by the intercept from regression of standard normal deviates against precision. RESULTS: In the eight pairs of meta-analysis and large trial that were identified (five from cardiovascular medicine, one from diabetic medicine, one from geriatric medicine, one from perinatal medicine) there were four concordant and four discordant pairs. In all cases discordance was due to meta-analyses showing larger effects. Funnel plot asymmetry was present in three out of four discordant pairs but in none of concordant pairs. In 14 (38%) journal meta-analyses and 5 (13%) Cochrane reviews, funnel plot asymmetry indicated that there was bias. CONCLUSIONS: A simple analysis of funnel plots provides a useful test for the likely presence of bias in meta-analyses, but as the capacity to detect bias will be limited when meta-analyses are based on a limited number of small trials the results from such analyses should be treated with considerable caution.

Bias↗
PubMed1997

Peripheral autonomic nerve dysfunction in asymptomatic leprosy contacts.

In endemic areas, subclinical autonomic nerve dysfunction may be a manifestation of infection with M. leprae and possibly allow detection before progression to clinical disease. Vasomotor reflex (VMR) testing was performed in 36 asymptomatic leprosy contacts (24 household contacts, 12 hospital contacts) and 47 age- and sex-matched controls in Pokhara, Nepal. Mean age was 30 years, two thirds were male. A Moor instruments DRT4 laser doppler monitor was used for velocimetry of microvascular blood flow. The flow reduction following an inspiratory gasp was recorded from finger and toe tips. Mean percent reduction was 57.8 (standard deviation 14.6) among household contacts, 61.9 (17.5) among hospital contacts and 66.8 (7.8) among controls (p=0.001 by analysis of variance). The prevalence of abnormal test results was 54% among household contacts, 42% among hospital contacts and 15% among controls (p=0.0005 by chi-square test for trend). Subclinical autonomic neuropathy is common among healthy contacts of leprosy patients. Prospective studies are now needed to clarify to what extent abnormal VMR tests predict the risk of progression to clinical disease.

Adult↗
PubMed1997

Language bias in randomised controlled trials published in English and German.

BACKGROUND: Some randomised controlled trials (RCTs) done in German-speaking Europe are published in international English-language journals and others in national German-language journals. We assessed whether authors are more likely to report trials with statistically significant results in English than in German. METHODS: We studied pairs of RCT reports, matched for first author and time of publication, with one report published in German and the other in English. Pairs were identified from reports round in a manual search of five leading German-language journals and from reports published by the same authors in English found on Medline. Quality of methods and reporting were assessed with two different scales by two investigators who were unaware of authors' identities, affiliations, and other characteristics of trial reports. Main study endpoints were selected by two investigators who were unaware of trial results. Our main outcome was the number of pairs of studies in which the levels of significance (shown by p values) were discordant. FINDINGS: 62 eligible pairs of reports were identified but 19 (31%) were excluded because they were duplicate publications. A further three pairs (5%) were excluded because no p values were given. The remaining 40 pairs were analysed. Design characteristics and quality features were similar for reports in both languages. Only 35% of German-language articles, compared with 62% of English-language articles, reported significant (p < 0.05) differences in the main endpoint between study and control groups (p = 0.002 by McNemar's test). Logistic regression showed that the only characteristic that predicted publication in an English-language journal was a significant result. The odds ratio for publication of trials with significant results in English was 3.75 (95% CI 1.25-11.3). INTERPRETATION: Authors were more likely to publish RCTs in an English-language journal if the results were statistically significant. English language bias may, therefore, be introduced in reviews and meta-analyses if they include only trials reported in English. The effort of the Cochrane Collaboration to identify as many controlled trials as possible, through the manual search of many medical journals published in different languages will help to reduce such bias.

Bias↗
PubMed1997

Disseminated Mycobacterium avium complex disease in the Swiss HIV Cohort Study: increasing incidence, unchanged prognosis.

OBJECTIVES: Disseminated disease due to Mycobacterium avium complex (MAC) bacteria is thought to occur less frequently in Europe than in the USA. This study investigated time trends in the occurrence of, and survival with, disseminated MAC disease in the Swiss HIV Cohort Study (SHCS). DESIGN, SETTING AND PARTICIPANTS: The SHCS participants who were free of disseminated MAC disease at registration were stratified by calendar period (1987-1989, 1990-1992, 1993-1995) in which the first recorded CD4 count was 0-49, 50-99, or 100-199 x 10(6)/l. Kaplan-Meier estimates of the probability of developing and surviving disseminated MAC disease were calculated for these nine independent groups. Multivariate analyses were performed using Cox proportional hazards regression. RESULTS: The analysis was based on 6052 participants enrolled between January 1987 and December 1995 and 202 incident episodes of disseminated MAC disease recorded during a mean follow-up time of 3.5 years. The cumulative probability of MAC disease at 2 years in individuals with CD4 counts of 0-49 x 10(6)/l in 1987-1989 was 9.8% [95% confidence interval (CI) 4.4-15.2%], increasing to 29.8% (95% CI, 20.8-38.8%) in 1993-1995. Amongst those with CD4 counts from 50-99 x 10(6)/l these probabilities were 11.9% (95% CI, 5.9-17.8%), and 21.6% (95% CI, 13.9-29.2%), respectively. After adjusting for CD4 count the relative hazard of developing disseminated MAC disease in 1993-1995, compared with 1987-1989, was 1.37 (95% CI, 0.92-2.04). Median survival following diagnosis was 7.9 months with no improvement over time. CONCLUSIONS: The incidence of disseminated MAC disease among SHCS participants has increased over time. More profound levels of immunosuppression amongst recent study entrants were found to explain this. When compared with US cohorts studied over the same calendar period the incidence of disseminated MAC disease in the SHCS appears to be lower. These findings are consistent with a secular effect of a more mature HIV epidemic in the US but direct comparison between the SHCS and a similar prospective cohort in the US should be undertaken to clarify this issue.

AIDS-Related Opportunistic Infections↗
PubMed1997

[A young man with sore throat and infection].

Postanginal septicemia (Lemierre's syndrome) is an infection with anaerobes that ensues from certain oropharyngeal infections: septic thrombophlebitis of the internal jugular vein leads to abscess formation in the lungs and possibly in other organs. Based upon a recently observed typical case the syndrome is presented and its possible importance for empirical therapy of tonsillopharyngitis and septicemias involving unknown organisms is briefly discussed.

Adolescent↗
PubMed1997

Risk of adverse effects of intensified treatment in insulin-dependent diabetes mellitus: a meta-analysis.

While the benefits of intensified insulin treatment in insulin-dependent (Type 1) diabetes mellitus (IDDM) are well recognized, the risks have not been comprehensively characterized. We examined the risk of severe hypoglycaemia, ketoacidosis, and death in a meta-analysis of randomized controlled trials. The MEDLINE database, reference lists, and specialist journals were searched electronically or by hand to identify relevant studies with at least 6 months of follow-up and the monitoring of glycaemia by glycosylated haemoglobin measurements. Logistic regression was used for calculation of combined odds ratios and 95% confidence intervals (95% CI). The influence of covariates was examined by including covariate-by-treatment interaction terms. Methodological study quality was assessed and sensitivity analyses were performed. Fourteen trials were identified. These contributed 16 comparisons with 1028 patients allocated to intensified and 1039 allocated to conventional treatment. A total of 846 patients suffered at least one episode of severe hypoglycaemia, 175 patients experienced ketoacidosis and 26 patients died. The combined odds ratio (95% CI) for hypoglycaemia was 2.99 (2.45-3.64), for ketoacidosis 1.74 (1.27-2.38) and for death from all causes 1.40 (0.65-3.01). The risk of severe hypoglycaemia was determined by the degree of normalization of glycaemia achieved (p=0.005 for interaction term), with the results from the Diabetes Control and Complications Trial (DCCT) in line with the other trials. Ketoacidosis risk depended on the type of intensified treatment used. Odds ratios (95% CI) were 7.20 (2.95-17.58) for exclusive use of pumps, 1.13 (0.15-8.35) for multiple daily injections and 1.28 (0.90-1.83) for trials offering a choice between the two (p = 0.004 for interaction). Mortality was significantly (p = 0.007) increased for causes potentially associated with acute complications (7 vs 0 deaths, 5 deaths attributed to ketoacidosis, and 2 sudden deaths), and non-significantly (p = 0.16) decreased for macrovascular causes (3 vs 8 deaths). We conclude that there is a substantial risk of severe adverse effects associated with intensified insulin treatment. Mortality from acute metabolic causes is increased; however, this is largely counterbalanced by a reduction in cardiovascular mortality. The excess of severe hypoglycemia in the DCCT is not exceptional. Multiple daily injection schemes may be safer than treatment with insulin pumps.

Blood Glucose↗
PubMed1996

[Sex differences in disease course: analysis of the Swiss HIV cohort study].

The Swiss HIV Cohort Study (SHCS) is a prospective multicentre study of HIV-infected adults. Participants have been followed up at six-monthly intervals since 1988. The purpose of the present study was to examine sex differences in developing AIDS-defining events and in survival among participants of the SHCS (1042 women, 1507 men). A statistically significant higher risk of Pneumocystis carinii pneumonia (PCP) was evident among women. This difference was particularly pronounced in 1989 (hazard ratio 2.11, p = 0.01). Other opportunistic events and survival showed no statistically significant sex differences. The results are compatible with slower introduction of PCP prophylaxis among women. A reason for this may be that women were less likely to be enrolled in clinical trials than men. This hypothesis will be examined in a further study.

AIDS-Related Opportunistic Infections↗
PubMed1996

Immunogenicity and adverse effects of inactivated virosome versus alum-adsorbed hepatitis A vaccine: a randomized controlled trial.

Immunogenicity and adverse effects of a novel inactivated hepatitis A vaccine based on virosomes (IRIV-HAV) was compared with a standard vaccine adsorbed to aluminium (Al-HAV). Seronegative volunteers (n = 301) were randomly allocated to one injection of IRIV-HAV or to two injections of Al-HAV, followed by a booster injection at 12 months. Two hundred and ninety-eight (99%) completed the first month and 215 (71%) could be evaluated at 1 year. Geometric mean antibody concentrations at days 0, 14 and at 12 months were similar in the two vaccine groups. Lower antibody concentrations were recorded with IRIV-HAV at day 28 (P < 0.0001) and at 13 months (P = 0.02). Seroconversion to protective antibody levels, however, was similar (98% at day 28, 94% at 12 months, 100% at 13 months). Local adverse effects were reported in 17% with IRIV-HAV but in 66% with Al-HAV (P < 0.0001) after the initial vaccination and in 32% and 42% following the booster vaccination (P = 0.05). In conclusion, IRIV-HAV may provide similar protection but cause less local adverse effects.

Alum Compounds↗