Search PubMed⌕ Search

Biomedical subjects

M Egger

Publications and source records attributed to M Egger.

At least 55 records · Page 3Linked to original sources
PubMed2000

Promotion of condom use in a high-risk setting in Nicaragua: a randomised controlled trial.

BACKGROUND: In Latin America, motels rent rooms for commercial and non-commercial sex. We investigated the impact of providing health-education material and condoms on condom use in Managua, Nicaragua. METHODS: In a randomised controlled trial, in 19 motels, we gave condoms on request, made them available in rooms, or gave condoms directly to couples, with and without the presence of health-education material in the rooms. In a factorial design we assessed condom use directly by searching the rooms after couples had left. FINDINGS: 11 motels were used mainly by sex workers and their clients and eight mainly for non-commercial sex. 6463 couples attended the motels in 24 days. On 3106 (48.0%) occasions, at least one used condom was retrieved. Condom use was more frequent for commercial sex than for non-commercial sex (60.5 vs 20.2%). The presence of health-education material lowered the frequency of condom use for commercial sex (odds ratio 0.89 [95% CI 0.84-0.94]) and had no effect on use for non-commercial sex (1.03 [0.97-1.08]). Condom use increased for commercial (1.31 [1.09-1.75]) and non-commercial sex (1.81 (1.14-2.81) if condoms were available in rooms. Directly handing condoms to couples was similarly effective for commercial sex but less effective for non-commercial sex (1.32 [1.03-1.61] vs 1.52 [1.01-2.38]). INTERPRETATION: In Latin America, motels are key locations for promoting the use of condoms. Making condoms available in rooms is the most effective strategy to increase condom use, whereas use of health-education material was ineffective. These findings have important implications for HIV-prevention policies.

Condoms↗
PubMed2000

Effect of antiretroviral therapy on viral load, CD4 cell count, and progression to acquired immunodeficiency syndrome in a community human immunodeficiency virus-infected cohort. Swiss HIV Cohort Study.

OBJECTIVE: To examine the effect of different antiretroviral treatment regimens on viral load, CD4 lymphocyte counts, and rates of progression to clinical acquired immunodeficiency syndrome events among treatment-naive human immunodeficiency virus (HIV)-infected patients enrolled in a large community cohort study. METHODS: Based in 7 outpatient clinics, the Swiss HIV Cohort Study is a cohort with national coverage. Virological, immunologic, and clinical results of 755 treatment-naive patients (median age, 36 years; 28.2% female) who initiated antiretroviral therapy between July 1, 1995, and June 30, 1997, were analyzed. Patients started undergoing monotherapy with 1 reverse transcriptase inhibitor (RTI), combination therapy with at least 2 RTIs, or highly active antiretroviral therapy (HAART) with RTIs and protease inhibitors. RESULTS: Antiretroviral treatment led to a mean reduction of viremia of 1.8 log10 copies per milliliter with HAART, 1.2 log10 copies per milliliter with RTI combination therapy, and 0.4 log10 copies per milliliter with monotherapy. Virological failure, defined as less than 1 log10 reduction per milliliter in viremia, was present in 45 (20%) patients undergoing HAART, 180 (38%) undergoing RTI combination therapy, and 47 (82%) undergoing monotherapy. The proportion of patients reaching undetectable viremia was 12% (n = 7) for monotherapy, 41% (n = 197) for RTI combination therapy, and 63% (n = 137) for HAART. Similar gains of CD4 cells were achieved with RTI combination therapy and HAART. Kaplan-Meier estimates of progression rates to a new acquired immunodeficiency syndrome event at 18 months were 13.6% (monotherapy), 4.7% (RTI combination therapy), and 3.9% (HAART). CONCLUSIONS: The rate of virological failure of antiretroviral treatments was high in this population of treatment-naive patients, even among patients receiving combination regimens. Clinical progression rates were, however, low in patients treated with RTI combination therapy and HAART.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Paradoxical block of the Na+-Ca2+ exchanger by extracellular protons in guinea-pig ventricular myocytes.

1. The Na+-Ca2+ exchange is a major pathway for removal of cytosolic Ca2+ in cardiac myocytes. It is known to be inhibited by changes of intracellular pH that may occur, for example, during ischaemia. In the present study, we examined whether extracellular protons (pHo) can also affect the cardiac exchange. 2. Na+-Ca2+ exchange currents (INa-Ca) were recorded from single adult guinea-pig ventricular myocytes in the whole-cell voltage-clamp configuration while [Ca2+]i was simultaneously imaged with fluo-3 and a laser-scanning confocal microscope. To activate INa-Ca, intracellular Ca2+ concentration jumps were generated by laser flash photolysis of caged Ca2+ (DM-nitrophen). 3. Exposure of the cell to moderately and extremely acidic conditions (pHo 6 and 4) was accompanied by a decrease of the peak INa-Ca to 70 % and less than 10 %, respectively. The peak INa-Ca was also inhibited to about 45 % of its initial value by increasing pHo to 10. The largest INa-Ca was found at pHo approximately 7.6. 4. Simultaneous measurements of [Ca2+]i and INa-Ca during partial proton block of the Na+-Ca2+ exchanger revealed that the exchange current was more inhibited by acidic pHo than the rate of Ca2+ transport. This observation is consistent with a change in the electrogenicity of the Na+-Ca2+ exchange cycle after protonation of the transporter. 5. We conclude that both extracellular alkalinization and acidification affect the Na+-Ca2+ exchanger during changes of pHo that may be present under pathophysiological conditions. During both extreme acidification or alkalinization the Na+-Ca2+ exchanger is strongly inhibited, suggesting that extracellular protons may interact with the Na+-Ca2+ exchanger at multiple sites. In addition, the electrogenicity and stoichiometry of the Na+-Ca2+ exchange may be modified by extracellular protons.

Acids↗
PubMed2000

Publication and related bias in meta-analysis: power of statistical tests and prevalence in the literature.

Publication and selection biases in meta-analysis are more likely to affect small studies, which also tend to be of lower methodological quality. This may lead to "small-study effects," where the smaller studies in a meta-analysis show larger treatment effects. Small-study effects may also arise because of between-trial heterogeneity. Statistical tests for small-study effects have been proposed, but their validity has been questioned. A set of typical meta-analyses containing 5, 10, 20, and 30 trials was defined based on the characteristics of 78 published meta-analyses identified in a hand search of eight journals from 1993 to 1997. Simulations were performed to assess the power of a weighted regression method and a rank correlation test in the presence of no bias, moderate bias or severe bias. We based evidence of small-study effects on P < 0.1. The power to detect bias increased with increasing numbers of trials. The rank correlation test was less powerful than the regression method. For example, assuming a control group event rate of 20% and no treatment effect, moderate bias was detected with the regression test in 13.7%, 23.5%, 40.1% and 51.6% of meta-analyses with 5, 10, 20 and 30 trials. The corresponding figures for the correlation test were 8.5%, 14.7%, 20.4% and 26.0%, respectively. Severe bias was detected with the regression method in 23.5%, 56.1%, 88.3% and 95.9% of meta-analyses with 5, 10, 20 and 30 trials, as compared to 11.9%, 31.1%, 45.3% and 65.4% with the correlation test. Similar results were obtained in simulations incorporating moderate treatment effects. However the regression method gave false-positive rates which were too high in some situations (large treatment effects, or few events per trial, or all trials of similar sizes). Using the regression method, evidence of small-study effects was present in 21 (26.9%) of the 78 published meta-analyses. Tests for small-study effects should routinely be performed in meta-analysis. Their power is however limited, particularly for moderate amounts of bias or meta-analyses based on a small number of small studies. When evidence of small-study effects is found, careful consideration should be given to possible explanations for these in the reporting of the meta-analysis.

Bias↗
PubMed2000

Topical lidocaine exaggerates laryngomalacia during flexible bronchoscopy.

In 156 infants and children referred for flexible fiberoptic bronchoscopy (FFB) we examined the larynx before and after application of 2% lidocaine solution to see what effect topical anesthesia might have on laryngeal function. All patients received midazolam and nalbuphine intravenously. Using blinded, randomly re-recorded key segments of the original video recordings of bronchoscopy, we used an empirical scoring system (Table 2) to grade signs of laryngomalacia on a scale of 0 to 8 points before and after application of the lidocaine solution. This score was based on the magnitude of collapse of the arytenoids and folding of the epiglottis during inspiration. Topical lidocaine was more likely to result in an increase in signs of laryngomalacia than in a decrease in such signs (p < 0.0001). Younger patients were more likely to have signs of laryngomalacia before topical anesthesia (odds ratio, 1.83). In a group of 10 additional patients, selected for history and physical findings consistent with laryngomalacia, application of a normal saline solution had no effect on the laryngomalacia score, but application of 2% lidocaine solution to the larynx resulted in a significant increase in this score (p < 0.001). Thus, this study has clearly demonstrated that topical anesthesia in infants and children undergoing FFB exaggerates the findings commonly associated with laryngomalacia. Because overestimation of these findings might lead to unnecessary treatment, it is important to examine the larynx and contiguous structures before applying topical anesthesia.

Administration, Topical↗
PubMed2000

Circumcision in men and the prevention of HIV infection: a 'meta-analysis' revisited.

There is debate on the role of male circumcision in HIV transmission. Most case-control and cohort studies from Africa have shown an association between a lack of circumcision and an increased risk of HIV infection in men. The evidence is conflicting, however, with cross-sectional surveys from Tanzania and Rwanda either showing no relationship or an association in the opposite direction. A recent review and meta-analysis of the literature concluded that the risk of HIV infection was lower in uncircumcised men (combined odds ratio 0.94, 95% confidence interval 0.89 to 0.99). However, the analysis was performed by simply pooling the data from 33 diverse studies, which is an inappropriate method for combining studies. We re-analysed the data, stratifying by study, and found that an intact foreskin was associated with an increased risk of HIV infection: combined odds ratio 1.43 (1.32 to 1.54) with a fixed effect model and 1.67 (1.25 to 2.24) with a random effect model. There was significant between-study heterogeneity (P<0.0001) which was partly explained by stronger associations in studies in high-risk groups. The results from this re-analysis thus support the contention that male circumcision may offer protection against HIV infection, particularly in high-risk groups where genital ulcers and other STDs 'drive' the HIV epidemic. A systematic review is required to clarify this issue. Such a review should be based on an extensive search for relevant studies, published and unpublished, and should include a careful assessment of the design and methodological quality of studies. Much emphasis should be given to the exploration of possible sources of heterogeneity. In view of the continued high prevalence and incidence of HIV in many countries in sub-Saharan Africa, the question of whether circumcision could contribute to prevent infections is of great importance, and a sound systematic review of the available evidence should be performed without delay.

Africa↗
PubMed2000

Nebulised steroid in the treatment of croup: a systematic review of randomised controlled trials.

BACKGROUND: Croup is one of the commonest respiratory complaints among children. There is growing evidence that steroids may be an effective treatment. AIM: To assess the effectiveness of treatment with nebulised steroid for children with croup. METHOD: Systematic review of randomised controlled trials comparing administration of nebulised steroid with placebo. Trials were identified from searches of three bibliographic databases, the Cochrane Controlled Trials Register, correspondence with the manufacturers of nebulised steroid, and one round of manual citation searching. RESULTS: Eight randomised controlled trials were identified including 574 children with mild to severe croup. Overall, the mean age was 25.2 months and 72% of children were male. All trials were hospital-based and of good methodological quality, with adequate concealment of treatment allocation and blind outcome assessment. Children treated with nebulised steroid were significantly more likely to show an improvement in croup score by five hours (combined relative risk = 1.48, 95% confidence interval [CI] = 1.27 to 1.74) and significantly less likely to need hospital admission after attending the emergency department (combined relative risk = 0.56, 95% CI = 0.42 to 0.75) than the placebo group. The funnel plot indicated the presence of publication bias, with smaller studies showing the larger effects, but this could also be owing to less pronounced effects in studies of older children with milder croup. CONCLUSIONS: Nebulised steroids are effective in the treatment of children attending hospital departments with croup. A meta-analysis based on individual patient data could clarify to what extent the effect depends on age and severity of disease. New trials are needed to define the indications for, and effectiveness of, steroid treatment of croup in the community.

Anti-Inflammatory Agents↗
PubMed1999

Uniform risk of clinical progression despite differences in utilization of highly active antiretroviral therapy: Swiss HIV Cohort Study.

OBJECTIVE: To compare the initiation of highly active antiretroviral therapy (HAART) in HIV-infected patients according to sex, route of HIV acquisition and education, and to assess the impact of differences in utilization on the probability of progression to AIDS. DESIGN AND SETTING: Swiss HIV Cohort Study, a national prospective multi-centre study. PARTICIPANTS: A total of 3342 patients, including 1007 (30%) women. HIV was acquired through injection drug use in 1155 (35%) cases and through sex between men in 1172 (35%). Twenty-eight per cent (957) of participants had attained only the minimum level of schooling. At baseline, the median CD4 cell count was 269x10(6)/l cells, median HIV-1 RNA was 4.3 log10 copies/ml and 2917 (87%) were free of AIDS. METHODS: Kaplan-Meier life tables and Cox proportional hazards regression. RESULTS: During 7007 person-years of follow-up 2285 (69%) patients started HAART and 318 (10%) developed a new AIDS event. In multivariable analysis controlling for CD4 cell count, viral load and disease stage at baseline, the probability of starting HAART was lower in injection drug users compared with men who have sex with men, hazard ratio 0.63 (95% confidence intervals 0.56-0.70) and in patients with minimum schooling compared with those with vocational training, hazard ratio 0.82 (0.75-0.91). The risk of progression to AIDS was similar among men and women, patients with a history of injecting drug use, and patients with lower educational attainment in both univariable and multivariable analysis. CONCLUSION: HIV-infected injecting drug users and those with lower levels of educational attainment start HAART later than other patient groups. The deferred initiation of therapy in these patients does not, however, appear to translate into an increased risk of clinical disease progression. This observation has important implications for treatment policy and the design of future clinical trials.

Acquired Immunodeficiency Syndrome↗
PubMed1999

AIDS-related opportunistic illnesses occurring after initiation of potent antiretroviral therapy: the Swiss HIV Cohort Study.

CONTEXT: Acquired immunodeficiency syndrome-related opportunistic illnesses (Ols) continue to occur after initiation of potent antiretroviral therapy in patients with human immunodeficiency virus (HIV) infection. Risk factors for clinical progression to Ols during potent therapy are not well defined. OBJECTIVE: To examine the incidence of and risk factors for Ols among patients treated with potent antiretroviral therapy in a population-based study. DESIGN: The Swiss HIV Cohort Study, a prospective cohort study of adult HIV-infected persons. SETTING: Seven study centers throughout Switzerland. PATIENTS: A total of 2410 cohort study participants with a potential follow-up of at least 15 months after starting potent therapy between September 1995 and December 1997. MAIN OUTCOME MEASURES: Disease-specific incidence of Ols during the 6 months preceding potent antiretroviral therapy and at 3 intervals after initiating therapy; risk factors for development of Ols during therapy. RESULTS: Of the 2410 participants, 143 developed 186 Ols after initiation of potent antiretroviral therapy. Incidence of any OI decreased from 15.1 per 100 person-years in the 6 months before therapy to 7.7 in the first 3 months after starting treatment, 2.6 in the following 6 months, and 2.2 per 100 person-years between 9 and 15 months. Reductions in incidence ranged from 38% per month for Kaposi sarcoma (P<.001) to 5% per month for non-Hodgkin lymphoma (P = .31). Baseline CD4 cell count continued to predict the risk of disease progression after initiating potent therapy. Compared with CD4 cell counts above 200 x 10(6)/L, the hazard ratio for developing Ols was 2.5 (95% confidence interval [CI], 1.4-4.5) for counts between 51 and 200 x 10(6)/L and 5.8 (95% CI, 3.2-10.5) for counts below 51 x 10(6)/L at baseline. Independent of baseline CD4 cell count, a rise in CD4 cell count by 50 x 10(6)/L or more and undetectable HIV-1 RNA in plasma (<400 copies/mL) by 6 months reduced risk of subsequent events, with hazard ratios of 0.32 (95% CI, 0.20-0.52) and 0.39 (0.24-0.65), respectively. CONCLUSIONS: Our data indicate that the risk of developing an OI for a person receiving potent antiretroviral therapy is highest during the initial months of therapy. Baseline CD4 cell count and immunologic and virologic response to treatment were strong predictors of disease progression in patients receiving potent therapy. Individuals with CD4 cell counts of 50 x 10(6)/L or below may need close clinical surveillance after initiation of potent therapy.

AIDS-Related Opportunistic Infections↗
PubMed1999

Use of observational databases to evaluate the effectiveness of antiretroviral therapy for HIV infection: comparison of cohort studies with randomized trials. EuroSIDA, the French Hospital Database on HIV and the Swiss HIV Cohort Study Groups.

OBJECTIVES: It is important to assess the extent of bias when comparing the clinical efficacy of antiretroviral regimens in observational databases because, with the current lack of planned large trials, such analyses may represent the only means of assessing the risk of serious clinical events associated with new regimens. We aimed to compare the results from observational databases with those from randomized trials. METHODS: Three treatment comparisons from randomized trials [Delta, AIDS Clinical Trials Group (ACTG) 175, Community Programs for Clinical Research on AIDS (CPCRA) 007 and ACTC 320] were mimicked in cohorts: (i) zidovudine monotherapy versus combination regimens of two nucleoside analogues; (ii) zidovudine combined with either didanosine or zalcitabine; and (iii) a dual combination versus a triple regimen including a protease inhibitor. Data for over 10 000 patients from the French Hospital Database on HIV, the EuroSIDA study and the Swiss HIV cohort study were analysed for each of the comparisons. Progression to AIDS disease or death was analysed in Cox models, adjusting for baseline differences, and results compared with randomized trials. RESULTS: For comparison (i) the adjusted relative risk estimates from cohorts were between 0.61 and 0.84, favouring combinations over monotherapy, compared with 0.57 to 0.63 for trials. For comparison (ii) relative risk estimates from cohorts ranged from 0.81 to 1.01 compared with 0.77 to 0.92 for trials. For comparison (iii), two of the cohorts showed similar results to the ACTG 320 trial but one indicated a higher risk of progression on triple therapy [relative risk 1.20, 95% confidence interval (CI) 1.01-1.441, in direct contrast to the trial result (relative risk 0.50, 95% CI 0.33-0.76). CONCLUSION: Serious biases can be present when comparing outcomes from the use of antiretroviral regimens in observational studies. However, such bias is not inevitable and careful interpretation of the results from several observational studies considered together is likely to be informative, guiding the design of new trials.

Anti-HIV Agents↗
PubMed1999

The hazards of scoring the quality of clinical trials for meta-analysis.

CONTEXT: Although it is widely recommended that clinical trials undergo some type of quality review, the number and variety of quality assessment scales that exist make it unclear how to achieve the best assessment. OBJECTIVE: To determine whether the type of quality assessment scale used affects the conclusions of meta-analytic studies. DESIGN AND SETTING: Meta-analysis of 17 trials comparing low-molecular-weight heparin (LMWH) with standard heparin for prevention of postoperative thrombosis using 25 different scales to identify high-quality trials. The association between treatment effect and summary scores and the association with 3 key domains (concealment of treatment allocation, blinding of outcome assessment, and handling of withdrawals) were examined in regression models. MAIN OUTCOME MEASURE: Pooled relative risks of deep vein thrombosis with LMWH vs standard heparin in high-quality vs low-quality trials as determined by 25 quality scales. RESULTS: Pooled relative risks from high-quality trials ranged from 0.63 (95% confidence interval [CI], 0.44-0.90) to 0.90 (95% CI, 0.67-1.21) vs 0.52 (95% CI, 0.24-1.09) to 1.13 (95% CI, 0.70-1.82) for low-quality trials. For 6 scales, relative risks of high-quality trials were close to unity, indicating that LMWH was not significantly superior to standard heparin, whereas low-quality trials showed better protection with LMWH (P<.05). Seven scales showed the opposite: high quality trials showed an effect whereas low quality trials did not. For the remaining 12 scales, effect estimates were similar in the 2 quality strata. In regression analysis, summary quality scores were not significantly associated with treatment effects. There was no significant association of treatment effects with allocation concealment and handling of withdrawals. Open outcome assessment, however, influenced effect size with the effect of LMWH, on average, being exaggerated by 35% (95% CI, 1%-57%; P= .046). CONCLUSIONS: Our data indicate that the use of summary scores to identify trials of high quality is problematic. Relevant methodological aspects should be assessed individually and their influence on effect sizes explored.

Anticoagulants↗