Search

Background: The heterogeneity statistic I(2), interpreted as the percentage of variability due to heterogeneity between studies rather than sampling error, depends on precision, that is, the size of the studies included.Methods: Based on a real meta-analysis, we simulate artificially 'inflating' the sample size under the random effects model. For a given inflation factor M = 1, 2, 3,... and for each trial i, we create a M-inflated trial by drawing a treatment effect estimate from the random effects model, using s(i)(2)/M as within-trial sampling variance.Results: As precision increases, while estimates of the heterogeneity variance tau(2) remain unchanged on average, estimates of I(2) increase rapidly to nearly 100%. A similar phenomenon is apparent in a sample of 157 meta-analyses.Conclusion: When deciding whether or not to pool treatment estimates in a meta-analysis, the yard-stick should be the clinical relevance of any heterogeneity present. tau(2), rather than I(2), is the appropriate measure for this purpose. [ABSTRACT FROM AUTHOR]

Background: Simpson's paradox is sometimes referred to in the areas of epidemiology and clinical research. It can also be found in meta-analysis of randomized clinical trials. However, though readers are able to recalculate examples from hypothetical as well as real data, they may have problems to easily figure where it emerges from.Method: First, two kinds of plots are proposed to illustrate the phenomenon graphically, a scatter plot and a line graph. Subsequently, these can be overlaid, resulting in a overlay plot. The plots are applied to the recent large meta-analysis of adverse effects of rosiglitazone on myocardial infarction and to an example from the literature. A large set of meta-analyses is screened for further examples.Results: As noted earlier by others, occurrence of Simpson's paradox in the meta-analytic setting, if present, is associated with imbalance of treatment arm size. This is well illustrated by the proposed plots. The rosiglitazone meta-analysis shows an effect reversion if all trials are pooled. In a sample of 157 meta-analyses, nine showed an effect reversion after pooling, though non-significant in all cases.Conclusion: The plots give insight on how the imbalance of trial arm size works as a confounder, thus producing Simpson's paradox. Readers can see why meta-analytic methods must be used and what is wrong with simple pooling. [ABSTRACT FROM AUTHOR]

Background: Healthcare workers (HCW) are at increased risk of infection with SARS-CoV-2. Vulnerable patient populations in particular must be protected, and clinics should not become transmission hotspots to avoid delaying medical treatments independent of COVID. Because asymptomatic transmission has been described, routine screening of asymptomatic HCW would potentially be able to interrupt chains of infection through early detection.Methods: A systematic search was conducted in the Cochrane COVID-19 Study Register, Web of Science and WHO COVID-19 Global literature on coronavirus with regard to non-incident related testing of healthcare workers using polymerase chain reaction on May 4th 2021. Studies since January 2020 were included. An assessment of risk of bias and representativeness was performed.Results: The search identified 39 studies with heterogeneous designs. Data collection of the included studies took place from January to August 2020. The studies were conducted worldwide and the sample size of the included HCW ranged from 70 to 9449 participants. In total, 1000 of 51,700 (1.9%) asymptomatic HCW were tested positive for SARS-CoV-2 using PCR testing. The proportion of positive test results ranged between 0 and 14.3%. No study reported on HCW-screening related reductions in infected person-days.Discussion and Conclusions: The heterogeneous proportions might be explained by different regional incidences, lock-downs, and pre-analytical pitfalls that reduce the sensitivity of the nasopharyngeal swab. The very high prevalence in some studies indicates that screening HCW for SARS-CoV-2 may be important particularly in geographical regions and pandemic periods with a high-incidence. With low numbers and an increasing rate of vaccinated HCW, a strict cost-benefit consideration must be made, especially in times of low incidences. Since we found no studies that reported on HCW-screening related reductions in infected person-days, re-evaluation should be done when these are available. [ABSTRACT FROM AUTHOR]

Summary: Postoperative nausea and vomiting is a common adverse effect of anaesthesia. Although dozens of different anti‐emetics are available for clinical practice, there is currently no comparative ranking of efficacy and safety of these drugs to inform clinical practice. We performed a systematic review with network meta‐analyses to compare, and rank in terms of efficacy and safety, single anti‐emetic drugs and their combinations, including 5‐hydroxytryptamine3, dopamine‐2 and neurokinin‐1 receptor antagonists; corticosteroids; antihistamines; and anticholinergics used to prevent postoperative nausea and vomiting in adults after general anaesthesia. We systematically searched for placebo‐controlled and head‐to‐head randomised controlled trials up to November 2017 (updated in April 2020). We assessed how trustworthy the evidence was using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) and Confidence In Network Meta‐Analysis (CINeMA) approaches for vomiting within 24 h postoperatively, serious adverse events, any adverse event and drug class‐specific side‐effects. We included 585 trials (97,516 participants, 83% women) testing 44 single drugs and 51 drug combinations. The studies' overall risk of bias was assessed as low in only 27% of the studies. In 282 trials, 29 out of 36 drug combinations and 10 out of 28 single drugs lowered the risk of vomiting at least 20% compared with placebo. In the ranking of treatments, combinations of drugs were generally more effective than single drugs. Single neurokinin‐1 receptor antagonists were as effective as other drug combinations. Out of the 10 effective single drugs, certainty of evidence was high for aprepitant, with risk ratio (95%CI) 0.26 (0.18–0.38); ramosetron, 0.44 (0.32–0.59); granisetron, 0.45 (0.38–0.54); dexamethasone, 0.51 (0.44–0.57); and ondansetron, 0.55 (0.51–0.60). It was moderate for fosaprepitant, 0.06 (0.02–0.21) and droperidol, 0.61 (0.54–0.69). Granisetron and amisulpride are likely to have little or no increase in any adverse event compared with placebo, while dimenhydrinate and scopolamine may increase the number of patients with any adverse event compared with placebo. So far, there is no convincing evidence that other single drugs effect the incidence of serious, or any, adverse events when compared with placebo. Among drug class specific side‐effects, evidence for single drugs is mostly not convincing. There is convincing evidence regarding the prophylactic effect of at least seven single drugs for postoperative vomiting such that future studies investigating these drugs will probably not change the estimated beneficial effect. However, there is still considerable lack of evidence regarding safety aspects that does warrant investigation. [ABSTRACT FROM AUTHOR]

Background: The German Research Foundation (DFG) and the Federal Ministry of Education and Research (BMBF) initiated large research programs to foster high quality clinical research in the academic area. These investigator initiated trials (IITs) cover important areas of medical research and often go beyond the scope of industry sponsored trials (ISTs). The purpose of this project was to understand to what extent results of randomized controlled IITs and ISTs have an impact on medical practice, measured by their availability for decisions in healthcare and their implementation in clinical practice. We aimed to determine study characteristics influencing a trial's impact such as type of sponsor and place of conduct. In this article, we describe the rationale and design of this project and present the characteristics of the trials included in our study cohort.Methods: The research impact of the following sub-cohorts was compared: German IITs (funded by DFG and BMBF or by other German non-commercial organizations), international IITs (without German contribution), German ISTs, and international ISTs. Trials included were drawn from the DFG-/BMBF-Websites, the German Clinical Trials Register, and from ClinicalTrials.gov . Research impact was measured as follows: 1) proportion of published trials, 2) time to publication, 3) proportion of publications appropriately indexed in biomedical databases, 4) proportion of openly accessible publications, 5) broadness of publication's target group, 6) citation of publications by systematic reviews or meta-analyses, and 7) appearance of publications or citing systematic reviews or meta-analyses in clinical practice guidelines. We also aimed to identify study characteristics associated with the impact of trials.Results: We included 691 trials: 120 German IITs, 200 International IITs, 171 German ISTs and 200 International ISTs. The median number of participants was 150, 30% were international trials and 70% national trials, 48% drug-trials and 52% non-drug trials. Overall, 72% of the trials had one pre-defined primary endpoint, 28% two or more (max. 36).Conclusions: The results of this project deepen our understanding of the impact of biomedical research on clinical practice and healthcare policy, add important insights for the efficient allocation of scarce research resources and may facilitate providing accountability to the different stakeholders involved. [ABSTRACT FROM AUTHOR]

Symptoms of acute febrile respiratory tract infection are often unspecific, but the rapid identification of pathogens allows optimised patient management. The objective of this study was to evaluate a novel multiplex polymerase chain reaction (PCR) suspension microarray which detects 19 viral and four atypical bacterial targets. A comprehensive set of sensitive monoplex real-time PCR assays was used for each pathogen as the gold standard. A panel of archived as well as 300 prospectively collected clinical samples was analysed by both methods. At least one target was detected in 165/300 (55 %) samples by monoplex PCR and in 140/300 (46 %) samples by multiplex PCR, respectively. The positivity rate was significantly higher in paediatric patients compared to adults [126/154 (82 %) vs. 39/146 (27 %) by monoplex and 114/154 (74 %) vs. 26/146 (18 %) by multiplex PCR, respectively]. Among all samples, 17/300 (5.6 %) were positive for atypical bacteria by monoplex and 8/300 (2.6 %) by multiplex PCR, respectively. Multiple detections were recorded in 35/300 (11.6 %) samples by monoplex and 26/300 (8.7 %) by multiplex PCR. For the most common pathogens, the sensitivity ranged from 57 to 93 % and the specificity ranged from 95 to 100 %. The overall concordance between both methods was 77 % [95 % confidence interval (CI) 72-81 %]. False-negative results by multiplex PCR were mainly due to the low target concentration. Compared to monoplex PCR, the novel microarray assay proved its principle but displayed overall lower sensitivities, potentially restricting its use to paediatric patients. For some targets, only small numbers of positive samples were available, requiring larger studies to firmly assess the sensitivity and specificity. [ABSTRACT FROM AUTHOR]

Background: In Borderline Personality Disorder (BPD), pharmacotherapy is used for the treatment of specific BPD pathology facets, such as cognitive-perceptual, affective, or impulsivity symptoms. Due to the polymorphic phenomenology of the disorder, different classes of drugs are used, e.g., antipsychotics, antidepressants, or mood stabilizers. Aims: To evaluate the up-to-date evidence of drug treatment efficacy for BPD. Method: A systematic review and metaanalysis of randomised controlled trials was done. All randomised comparisons of drug vs. placebo, drug vs. drug, or drug vs. a combination of drugs in adult BPD patients were eligible for inclusion. Outcomes comprised BPD core pathology as depicted by DSM criteria, associated pathology, i.e., depression and anxiety, general measures of overall psychopathology severity and mental health status, tolerability, and adverse effects. With support of the Cochrane Collaboration, a thorough search was conducted to identify both published and unpublished trials. The findings were scrutinized by two reviewers independently. Results: Twenty-six trials were included, investigating first- and second-generation antipsychotics, mood stabilizers, antidepressants, and omega-3 fatty acids. Conclusion: Findings indicate beneficial effects for all classes of drugs investigated, and suggest mood stabilizers and second-generation antipsychotic agents as first-line treatments for BPD due to their efficacy in the treatment of different domains of BPD and associated pathology. However, psychotherapeutic treatment should clearly be targeted at predefined specific symptoms. [Copyright &y& Elsevier]

Background: In Borderline Personality Disorder (BPD), pharmacotherapy is used for the treatment of specific BPD pathology facets, such as cognitive-perceptual, affective, or impulsivity symptoms. Due to the polymorphic phenomenology of the disorder, different classes of drugs are used, e.g., antipsychotics, antidepressants, or mood stabilizers. Aims: To evaluate the up-to-date evidence of drug treatment efficacy for BPD. Method: A systematic review and metaanalysis of randomised controlled trials was done. All randomised comparisons of drug vs. placebo, drug vs. drug, or drug vs. a combination of drugs in adult BPD patients were eligible for inclusion. Outcomes comprised BPD core pathology as depicted by DSM criteria, associated pathology, i.e., depression and anxiety, general measures of overall psychopathology severity and mental health status, tolerability, and adverse effects. With support of the Cochrane Collaboration, a thorough search was conducted to identify both published and unpublished trials. The findings were scrutinized by two reviewers independently. Results: Twenty-six trials were included, investigating first- and second-generation antipsychotics, mood stabilizers, antidepressants, and omega-3 fatty acids. Conclusion: Findings indicate beneficial effects for all classes of drugs investigated, and suggest mood stabilizers and second-generation antipsychotic agents as first-line treatments for BPD due to their efficacy in the treatment of different domains of BPD and associated pathology. However, psychotherapeutic treatment should clearly be targeted at predefined specific symptoms. [Copyright &y& Elsevier]

Nitrogen saturation is currently one of the most important environmental issues in forests of Central Europe. In this study, a nested model design at different spatial scales is presented to predict the risk of elevated nitrate concentrations. The model was developed from a state-wide inventory at about 400 stands and a complementary regional survey of 64 stands in the forests around Munich. High deposition of ammonium and low precipitation were significantly associated with high nitrate concentrations. Especially site properties and forest type influenced the risk of nitrate leaching significantly. At the regional scale the forest coverage and the stand age contribute considerably to explain the variance of the nitrate concentrations. The results suggest that forestry policy and practice could contribute to mitigate nitrogen saturation and nitrate leaching by conversion of spruce stands into mixed stands with a high percentage of deciduous trees. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Low-dose aspirin given for secondary prevention of cardiovascular disease is frequently withdrawn prior to surgical or diagnostic procedures to reduce bleeding complications. This may expose patients to increased cardiovascular morbidity and mortality. Aim of the study was to review and quantify cardiovascular risks because of periprocedural aspirin withdrawal and bleeding risks with the continuation of aspirin. METHODS: We screened MEDLINE (January 1970-October 2004) with additional manual cross-referencing for clinical studies, surveys on the opinions of doctors and guidelines. RESULTS: Studies reporting the relative risk of acute cardiovascular events after aspirin withdrawal when compared with its continuation were not found. However, retrospective investigations revealed that aspirin withdrawal precedes up to 10.2% of acute cardiovascular syndromes. The time interval between discontinuation and acute cerebral events was 14.3 +/- 11.3 days, 8.5 +/- 3.6 days for acute coronary syndromes, and 25.8 +/- 18.1 days for acute peripheral arterial syndromes (P < 0.02 versus acute coronary syndromes). On aspirin-related bleeding risks, we obtained 41 (12 observational retrospective, 19 observational prospective, 10 randomized) studies, reporting on 49 590 patients (14 981 on aspirin). Baseline frequency of bleeding complications varied between 0 (skin lesion excision, cataract surgery) and 75% (transrectal prostate biopsy). Whilst aspirin increased the rate of bleeding complications by factor 1.5 (median, interquartile range: 1.0-2.5), it did not lead to a higher level of the severity of bleeding complications (exception: intracranial surgery, and possibly transurethral prostatectomy). Surveys amongst doctors on the management of this problem demonstrate wide variations. Available guidelines are scarce and in part contradictory. CONCLUSIONS: Only if low-dose aspirin may cause bleeding risks with increased mortality or sequels comparable with the observed cardiovascular risks after aspirin withdrawal, it should be discontinued prior to an intended operation or procedure. Controlled clinical studies are urgently needed. [ABSTRACT FROM AUTHOR]

Yarrow, Achillea millefohum L, is one of the commonest weeds of the Compositae family. Cases of allergic contact dermatitis have, been described since 1899. Although 10 sesquiterpene lactones (SL) and 3 polyines have previously been identified, the sensilizers of yarrow have eseaped detection. A reinvetigation of short either extracts of yarrow revealed the presence of 5 unsalurated hitherto unknown guaianolides of peroxide character. Tile main SL. identified as a strong, sensitizer in guinea pig sensitization experiments, was named α-peroxyachifolid. The minor SL also contribute marginally to the sensitizing capacity, while other known yarrow constituents like dehydromatricaria ester and pontica epoxide appear to play no role A 5-year follow-up (1985 1990) of Compositine-sensitive patients showed that more than 50% reacted when tested with a short either extract of ?arrows. Exacerbation of the patch test silos by irradiation with UV light was never observed. [ABSTRACT FROM AUTHOR]