The rapid growth of human genetics creates countless opportunities for studies of disease association. Given the number of potentially identifiable genetic markers and the multitude of clinical ...outcomes to which these may be linked, the testing and validation of statistical hypotheses in genetic epidemiology is a task of unprecedented scale. Meta-analysis provides a quantitative approach for combining the results of various studies on the same topic, and for estimating and explaining their diversity. Here, we have evaluated by meta-analysis 370 studies addressing 36 genetic associations for various outcomes of disease. We show that significant between-study heterogeneity (diversity) is frequent, and that the results of the first study correlate only modestly with subsequent research on the same association. The first study often suggests a stronger genetic effect than is found by subsequent studies. Both bias and genuine population diversity might explain why early association studies tend to overestimate the disease protection or predisposition conferred by a genetic polymorphism. We conclude that a systematic meta-analytic approach may assist in estimating population-wide effects of genetic risk factors in human disease.
There is substantial debate about whether the results of nonrandomized studies are consistent with the results of randomized controlled trials on the same topic.
To compare results of randomized and ...nonrandomized studies that evaluated medical interventions and to examine characteristics that may explain discrepancies between randomized and nonrandomized studies.
MEDLINE (1966-March 2000), the Cochrane Library (Issue 3, 2000), and major journals were searched.
Forty-five diverse topics were identified for which both randomized trials (n = 240) and nonrandomized studies (n = 168) had been performed and had been considered in meta-analyses of binary outcomes.
Data on events per patient in each study arm and design and characteristics of each study considered in each meta-analysis were extracted and synthesized separately for randomized and nonrandomized studies.
Very good correlation was observed between the summary odds ratios of randomized and nonrandomized studies (r = 0.75; P<.001); however, nonrandomized studies tended to show larger treatment effects (28 vs 11; P =.009). Between-study heterogeneity was frequent among randomized trials alone (23%) and very frequent among nonrandomized studies alone (41%). The summary results of the 2 types of designs differed beyond chance in 7 cases (16%). Discrepancies beyond chance were less common when only prospective studies were considered (8%). Occasional differences in sample size and timing of publication were also noted between discrepant randomized and nonrandomized studies. In 28 cases (62%), the natural logarithm of the odds ratio differed by at least 50%, and in 15 cases (33%), the odds ratio varied at least 2-fold between nonrandomized studies and randomized trials.
Despite good correlation between randomized trials and nonrandomized studies-in particular, prospective studies-discrepancies beyond chance do occur and differences in estimated magnitude of treatment effect are very common.
BACKGROUND Increased prevalence of abnormal aminotransferase levels and/or ultrasonographic evidence of hepatic steatosis (HS) have been found in women with polycystic ovary syndrome (PCOS). However, ...factors associated with non-alcoholic fatty liver disease (NAFLD) in PCOS are still under investigation. The aim of this case–control study was to investigate the presence of NAFLD and to assess factors associated with this condition in PCOS patients. METHODS A prospective study of 57 premenopausal PCOS patients and 60 age- and weight-matched control women, with a history of no or minimal alcohol consumption was conducted. Anthropometric variables, biochemical and hormonal parameters were determined and NAFLD was evaluated by abdominal ultrasonography and biochemical testing, after excluding causes of secondary liver disease. Insulin resistance was assessed by homeostasis model assessment of insulin resistance (HOMA-IR) and free androgen index (FAI) was calculated. RESULTS PCOS patients had an increased prevalence of HS 21/57 patients (36.8%) versus 12/60 controls (20.0%), P < 0.05 and abnormal (≥40 IU/l) serum aminotransferase levels 13/57 patients (22.8%) versus 2/60 controls (3.3%), P < 0.01 than controls. All patients and controls with metabolic syndrome had HS. Factors associated with HS were PCOS diagnosis, older age, increased BMI, waist circumference (WC), HOMA-IR and FAI values and decreased high-density lipid cholesterol and sex hormone binding globulin levels. PCOS patients had an OR of 3.55 (95% CI: 1.02–5.35) for HS versus controls, after adjustment for age, BMI and WC. CONCLUSIONS NAFLD is common in PCOS patients and increased androgen bioavailability may be implicated, in combination with metabolic abnormalities. Liver evaluation is proposed in PCOS patients, especially in those with metabolic syndrome.
Anticonvulsants for alcohol withdrawal Polycarpou, A; Papanikolaou, P; Ioannidis, J P A ...
Cochrane database of systematic reviews,
2005-Jul-20
3
Journal Article
Recenzirano
Alcohol withdrawal syndrome is a cluster of symptoms that occurs in alcohol-dependent people after cessation or reduction in alcohol use. This systematic review focuses on the evidence of ...anticonvulsants' use in the treatment of alcohol withdrawal symptoms.
To evaluate the effectiveness and safety of anticonvulsants in the treatment of alcohol withdrawal.
We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 3, 2004); MEDLINE (1966 to October 2004); EMBASE (1988 to October 2004) and EU-PSI PSI-Tri database with no language and publication restrictions and references of articles.
All randomized controlled trials examining the effectiveness, safety and overall risk-benefit of an anticonvulsant in comparison with a placebo or other pharmacological treatment or another anticonvulsant were considered.
The authors independently assessed trial quality extracted data.
Forty-eight studies, involving 3610 people were included. Despite the considerable number of randomized controlled trials, there was a variety of outcomes and of different rating scales that led to a limited quantitative synthesis of data. For the anticonvulsant versus placebo comparison, therapeutic success tended to be more common among the anticonvulsant-treated patients (relative risk (RR) 1.32; 95% confidence interval (CI) 0.92 to 1.91), and anticonvulsant tended to show a protective benefit against seizures (RR 0.57; 95% CI 0.27 to 1.19), but no effect reached formal statistical significance. For the anticonvulsant versus other drug comparison, CIWA-Ar score showed non-significant differences for the anticonvulsants compared to the other drugs at the end of treatment (weighted mean difference (WMD) -0.73; 95% CI -1.76 to 0.31). For the subgroup analysis of carbamazepine versus benzodiazepine, a statistically significant protective effect was found for the anticonvulsant (WMD -1.04; 95% CI -1.89 to -0.20), p = 0.02), but this was based on only 260 randomized participants. There was a non-significant decreased incidence of seizures (RR 0.50; 95% CI 0.18 to 1.34) favouring the patients that were treated with anticonvulsants than other drugs, and side-effects tended to be less common in the anticonvulsant-group (RR 0.56; 95% CI 0.31 to 1.02).
It is not possible to draw definite conclusions about the effectiveness and safety of anticonvulsants in alcohol withdrawal, because of the heterogeneity of the trials both in interventions and the assessment of outcomes. The extremely small mortality rate in all these studies is reassuring, but data on other safety outcomes are sparse and fragmented.
We describe the seasonal variation of acute toxoplasmosis in the United States. Acute toxoplasmic lymphadenopathy (ATL) can be a surrogate of acute toxoplasmosis in patients in whom the date of onset ...of lymphadenopathy matches the window of acute infection predicted by serological tests performed at a reference laboratory. We used the electronic database of the Palo Alto Medical Foundation Toxoplasma Serology Laboratory (PAMF-TSL) (1997–2011) to identify cases of ATL. We tested the uniformity of distribution of ATL cases per month, across the 12 calendar months, using circular statistics uniformity tests. We identified 112 consecutive cases of ATL. The distribution of cases was not uniform across the 12 calendar months. We observed the highest peak of cases in December and a second highest peak in September. Similar months were identified in patients with acute toxoplasmosis in rural areas in France. The results were similar when we performed weighted analyses, weighting for the total number of Toxoplasma gondii IgG tests performed per month in the PAMF-TSL laboratory. This is the largest study to date of the seasonal variation of ATL in the United States. Physicians should advise high-risk individuals to avoid risk factors associated with T. gondii infections especially around those months.
Summary
The early detection of potential malfunctions at process systems can significantly reduce downtime and improve their overall operability. In that context, this paper demonstrates the behavior ...and response, through a comparative analysis, of novel data‐driven diagnosis methods for interdependent time series. The proposed real‐time slope statistic profile method utilizes a self‐adaptive sliding window based on a real‐time classification technique of linear trend profiles of both interdependent time series and internal condition so as to avoid misdetections. The calculation of the linear trend profile is based on a standard parametric linear trend test, and the selection of possible incidents is based on its two‐level cross‐checking. All possible combinations for the calculation of the trend test and cross‐checking are created to explore their efficiency. The proposed methods are tested against real data sets from a chemical process system of the Centre for Research and Technology Hellas/Chemical Process Energy and Resources Institute derived from specific scenarios during nominal operating conditions.
This paper proposes an innovative gait identification and authentication method based on the use of novel 2-D and 3-D features. Depth-related data are assigned to the binary image silhouette ...sequences using two new transforms: the 3-D radial silhouette distribution transform and the 3-D geodesic silhouette distribution transform. Furthermore, the use of a genetic algorithm is presented for fusing information from different feature extractors. Specifically, three new feature extraction techniques are proposed: the two of them are based on the generalized radon transform, namely the radial integration transform and the circular integration transform, and the third is based on the weighted Krawtchouk moments. Extensive experiments carried out on USF ldquoGait Challengerdquo and proprietary HUMABIO gait database demonstrate the validity of the proposed scheme.
Plants of Ocimum basilicum L. grown under glass were exposed to short treatments with supplementary UV‐B. The effect of UV‐B on volatile essential oil content was analysed and compared with ...morphological effects on the peltate and capitate glandular trichomes. In the absence of UV‐B, both peltate and capitate glands were incompletely developed in both mature and developing leaves, the oil sacs being wrinkled and only partially filled. UV‐B was found to have two main effects on the glandular trichomes. During the first 4 d of treatment, both peltate and capitate glands filled and their morphology reflected their ‘normal’ mature development as reported in the literature. During the following days there was a large increase in the number of broken oil sacs among the peltate glands as the mature glands broke open, releasing volatiles. Neither the number of glands nor the qualitative or quantitative composition of the volatiles was affected by UV‐B. There seems to be a requirement for UV‐B for the filling of the glandular trichomes of basil.
A meta-analysis of 8 randomized trials (1792 patients, 2947 patient-years of follow-up) showed that acyclovir (⩾3200 mg/day) offered a significant survival benefit (P = .006 by log-rank test) in ...human immunodeficiency virus (HIV) infection. The treatment effect did not vary significantly in patient subgroups of different CD4 cell counts, hemoglobin levels, age, race, and sex, and with or without AIDS diagnosis. Acyclovir treatment (hazard ratio, 0.78; 95% confidence interval CI, 0.65–0.93), higher CD4 cell count (P < .001), higher hemoglobin level (P < .001), and younger age (P < .001) reduced the hazard of mortality. Acyclovir decreased herpes simplex virus infections (odds ratio OR, 0.28; 95% CI, 0.21–0.37) and varicella-zoster virus infections (OR, 0.29; 95% CI, 0.13–0.63) but not cytomegalovirus disease or mortality from lymphoma or Kaposi's sarcoma. A survival advantage was seen specifically in studies with high incidence of clinical herpesvirus infections (⩾25% per year). Given the wide confidence intervals, the small effect in low-risk patients, and recent changes in HIV therapeutics, the results should be interpreted cautiously, but the meta-analysis supports the importance of pathogenetic interactions between herpesviruses and HIV.
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