Search

Abstract Background The ideal evidence to answer a question about the effectiveness of treatment is a systematic review. However, for many clinical questions a systematic review will not be available, or may not be up to date. One option could be to use the evidence from an individual trial to answer the question? Methods We assessed how often (a) the estimated effect and (b) the p-value in the most precise single trial in a meta-analysis agreed with the whole meta-analysis. For a random sample of 200 completed Cochrane Reviews (January, 2005) we identified a primary outcome and extracted: the number of trials, the statistical weight of the most precise trial, the estimate and confidence interval for both the highest weighted trial and the meta-analysis overall. We calculated the p-value for the most precise trial and meta-analysis. Results Of 200 reviews, only 132 provided a meta-analysis of 2 or more trials, with a further 35 effect estimates based on single trials. The average number of trials was 7.3, with the most precise trial contributing, on average, 51% of the statistical weight to the summary estimate from the whole meta-analysis. The estimates of effect from the most precise trial and the overall meta-analyses were highly correlated (rank correlation of 0.90). There was an 81% agreement in statistical conclusions. Results from the most precise trial were statistically significant in 60 of the 167 evaluable reviews, with 55 of the corresponding systematic reviews also being statistically significant. The five discrepant results were not strikingly different with respect to their estimates of effect, but showed considerable statistical heterogeneity between trials in these meta-analyses. However, among the 101 cases in which the most precise trial was not statistically significant, the corresponding meta-analyses yielded 31 statistically significant results. Conclusions Single most precise trials provided similar estimates of effects to those of the meta-analyses to which they contributed, and statistically significant results are generally in agreement. However, "negative" results were less reliable, as may be expected from single underpowered trials. For systematic reviewers we suggest that: (1) key trial(s) in a review deserve greater attention (2) systematic reviewers should check agreement of the most precise trial and the meta analysis. For clinicians using trials we suggest that when a meta-analysis is not available, a focus on the most precise trial is reasonable provided it is adequately powered.

Questions answered on headlice infestations and steroid injections for the management of hay fever. [ABSTRACT FROM AUTHOR]

Questions answered on headlice infestations and steroid injections for the management of hay fever. [ABSTRACT FROM AUTHOR]

Questions answered on double-dosing a feverish child and boule doses of immunizations; and Martin Davies returns with his view. [ABSTRACT FROM AUTHOR]

Questions answered on double-dosing a feverish child and boule doses of immunizations; and Martin Davies returns with his view. [ABSTRACT FROM AUTHOR]

Questions answered on antibiotics and suturing for treating dog bites. [ABSTRACT FROM AUTHOR]

This article focuses on a study in which possible sex differences in ultrastructural components of the dermo-epidermal junction in skin have been examined and it has been checked whether measurable adhesiveness of the dermo-epidermal junction could be correlated with structural characteristics, as anchoring fibril (AF) may traverse the basal lamina (BL) and cross the lamina lucida (LL). Skin samples from defined areas on the lower leg, thigh and upper arm from five healthy women were processed for transmission electron microscopy. The population densities of hemidesmosomes (HD), plasmalemmal vesicles and AF were calculated, and thickness of BL and LL, associated and between HD, were measured.

The extent to which the oro-faecal route contributes to the transmission of SARS-CoV-2 is not established.We systematically reviewed the evidence on the presence of infectious SARS-CoV-2 in faeces and other gastrointestinal sources by examining studies that used viral culture to investigate the presence of replication-competent virus in these samples. We conducted searches in the WHO COVID-19 Database, LitCovid, medRxiv, and Google Scholar for SARS-CoV-2 using keywords and associated synonyms, with a search date up to 28 November 2023.We included 13 studies involving 229 COVID-19 subjects - providing 308 faecal or rectal swab SARS-CoV2 reverse transcription-polymerase chain reaction (RT-PCR)-positive samples tested with viral culture. The methods used for viral culture across the studies were heterogeneous. Three studies (two cohorts and one case series) reported observing replication-competent SARS-CoV-2 confirmed by quantitative RT-PCR (qPCR) and whole-genome sequencing, and qPCR including appropriate cycle threshold changes. Overall, six (1.9%) of 308 faecal samples subjected to cell culture showed replication-competent virus. One study found replication-competent samples from one immunocompromised patient. No studies were identified demonstrating direct evidence of oro-faecal transmission to humans.Our review found a relatively low frequency of replication-competent SARS-CoV-2 in faecal and other gastrointestinal sources. Although it is biologically plausible, more research is needed using standardized cell culture methods, control groups, adequate follow-up, and robust epidemiologic methods, including whether secondary infections occurred, to determine the role of the oro-faecal route in the transmission of SARS-CoV-2.

Background: Maritime and river travel may be associated with respiratory viral spread via infected passengers and/or crew and potentially through other transmission routes. The transmission models of SARS-CoV-2 associated with cruise ship travel are based on transmission dynamics of other respiratory viruses. We aimed to provide a summary and evaluation of relevant data on SARS-CoV-2 transmission aboard cruise ships, report policy implications, and highlight research gaps. Methods: We searched four electronic databases (up to 26 May 2022) and included studies on SARS-CoV-2 transmission aboard cruise ships. The quality of the studies was assessed based on five criteria, and relevant findings were reported. Results: We included 23 papers on onboard SARS-CoV-2 transmission (with 15 reports on different aspects of the outbreak on Diamond Princess and nine reports on other international cruises), 2 environmental studies, and 1 systematic review. Three articles presented data on both international cruises and the Diamond Princess. The quality of evidence from most studies was low to very low. Index case definitions were heterogeneous. The proportion of traced contacts ranged from 0.19 to 100%. Studies that followed up >80% of passengers and crew reported attack rates (AR) up to 59%. The presence of a distinct dose−response relationship was demonstrated by findings of increased ARs in multi-person cabins. Two studies performed viral cultures with eight positive results. Genomic sequencing and phylogenetic analyses were performed in individuals from three cruises. Two environmental studies reported PCR-positive samples (cycle threshold range 26.21−39.00). In one study, no infectious virus was isolated from any of the 76 environmental samples. Conclusion: Our review suggests that crowding and multiple persons per cabin were associated with an increased risk of transmission on cruise ships. Variations in design, methodology, and case ascertainment limit comparisons across studies and quantification of transmission risk. Standardized guidelines for conducting and reporting studies on cruise ships of acute respiratory infection transmission should be developed.

Systematic reviews of 591 primary studies of the modes of transmission for SARS-CoV-2 show significant methodological shortcomings and heterogeneity in the design, conduct, testing, and reporting of SARS-CoV-2 transmission. While this is partly understandable at the outset of a pandemic, evidence rules of proof for assessing the transmission of this virus are needed for present and future pandemics of viral respiratory pathogens. We review the history of causality assessment related to microbial etiologies with a focus on respiratory viruses and suggest a hierarchy of evidence to integrate clinical, epidemiologic, molecular, and laboratory perspectives on transmission. The hierarchy, if applied to future studies, should narrow the uncertainty over the twin concepts of causality and transmission of human respiratory viruses. We attempt to address the translational gap between the current research evidence and the assessment of causality in the transmission of respiratory viruses with a focus on SARS-CoV-2. Experimentation, consistency, and independent replication of research alongside our proposed framework provide a chain of evidence that can reduce the uncertainty over the transmission of respiratory viruses and increase the level of confidence in specific modes of transmission, informing the measures that should be undertaken to prevent transmission.

Background: The role of SARS-Cov-2-infected persons who develop symptoms after testing (presymptomatics) or not at all (asymptomatics) in the pandemic spread is unknown., Objectives: To determine infectiousness and probable contribution of asymptomatic persons (at the time of testing) to pandemic SARS-CoV-2 spread., Data Sources: LitCovid, medRxiv, Google Scholar, and WHO Covid-19 databases (to 31 March 2021) and references in included studies., Study Eligibility Criteria: Studies with a proven or hypothesized transmission chain based either on serial PCR cycle threshold readings and/or viral culture and/or gene sequencing, with adequate follow-up., Participants: People exposed to SARS-CoV-2 within 2-14 days to index asymptomatic (at time of observation) infected individuals., Interventions: Reliability of symptom and signs was assessed within contemporary knowledge; transmission likelihood was assessed using adapted causality criteria., Methods: Systematic review. We contacted all included studies' corresponding authors requesting further details., Results: We included 18 studies from a diverse setting with substantial methodological variation (this field lacks standardized methodology). At initial testing, prevalence of asymptomatic cases was 12.5-100%. Of these, 6-100% were later determined to be presymptomatic, this proportion varying according to setting, methods of case ascertainment and population. Nursing/care home facilities reported high rates of presymptomatic: 50-100% (n = 3 studies). Fourteen studies were classified as high risk of, and four studies as at moderate risk of symptom ascertainment bias. High-risk studies may be less likely to distinguish between presymptomatic and asymptomatic cases. Six asymptomatic studies and four presymptomatic studies reported culturing infectious virus; data were too sparse to determine infectiousness duration. Three studies provided evidence of possible and three of probable/likely asymptomatic transmission; five studies provided possible and two probable/likely presymptomatic SARS-CoV-2 transmission., Conclusion: High-quality studies provide probable evidence of SARS-CoV-2 transmission from presymptomatic and asymptomatic individuals, with highly variable estimated transmission rates., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: We aimed to review the evidence from studies relating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) culture with the results of reverse-transcription polymerase chain reaction (RT-PCR) and other variables that may influence the interpretation of the test, such as time from symptom onset., Methods: We searched LitCovid, medRxiv, Google Scholar, and the World Health Organization coronavirus disease 2019 (COVID-19) database for COVID-19 up to 10 September 2020. We included studies attempting to culture or observe SARS-CoV-2 in specimens with RT-PCR positivity. Studies were dual-extracted and the data summarized narratively by specimen type. Where necessary, we contacted corresponding authors of included papers for additional information. We assessed quality using a modified Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS 2) risk-of-bias tool., Results: We included 29 studies reporting attempts at culturing, or observing tissue infection by, SARS-CoV-2 in sputum, nasopharyngeal or oropharyngeal, urine, stool, blood, and environmental specimens. The quality of the studies was moderate with lack of standardized reporting. The data suggest a relationship between the time from onset of symptom to the timing of the specimen test, cycle threshold (Ct), and symptom severity. Twelve studies reported that Ct values were significantly lower and log copies higher in specimens producing live virus culture. Two studies reported that the odds of live virus culture were reduced by approximately 33% for every 1-unit increase in Ct. Six of 8 studies reported detectable RNA for >14 days, but infectious potential declined after day 8 even among cases with ongoing high viral loads. Four studies reported viral culture from stool specimens., Conclusions: Complete live viruses are necessary for transmission, not the fragments identified by PCR. Prospective routine testing of reference and culture specimens and their relationship to symptoms, signs, and patient co-factors should be used to define the reliability of PCR for assessing infectious potential. Those with high Ct are unlikely to have infectious potential., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Rationale for the Review: Air travel may be associated with viruses spread via infected passengers and potentially through in-flight transmission. Given the novelty of the Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, transmission associated with air travel is based on transmission dynamics of other respiratory viruses. Our objective was to provide a rapid summary and evaluation of relevant data on SARS-CoV-2 transmission aboard aircraft, report policy implications and to highlight research gaps requiring urgent attention., Methods: We searched four electronic databases (1 February 2020-27 January 2021) and included studies on SARS-CoV-2 transmission aboard aircraft. We assessed study quality based on five criteria and reported important findings., Key Findings: We included 18 studies on in-flight SARS-CoV-2 transmission (130 unique flights) and 2 studies on wastewater from aircraft. The quality of evidence from most published studies was low. Two wastewater studies reported PCR-positive samples with high cycle threshold values (33-39). Index case definition was heterogeneous across studies. The proportion of contacts traced ranged from 0.68 to 100%. Authors traced 2800/19 729 passengers, 140/180 crew members and 8/8 medical staff. Altogether, 273 index cases were reported, with 64 secondary cases. Three studies, each investigating one flight, reported no secondary cases. Secondary attack rate among studies following up >80% of passengers and crew (including data on 10 flights) varied between 0 and 8.2%. The studies reported on the possibility of SARS-CoV-2 transmission from asymptomatic, pre-symptomatic and symptomatic individuals. Two studies performed viral cultures with 10 positive results. Genomic sequencing and phylogenetic analysis were performed in individuals from four flights., Conclusion: Current evidence suggests SARS-CoV-2 can be transmitted during aircraft travel, but published data do not permit any conclusive assessment of likelihood and extent. The variation in design and methodology restricts the comparison of findings across studies. Standardized guidelines for conducting and reporting future studies of transmission on aircraft should be developed., (© International Society of Travel Medicine 2021. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Evidence synthesis is a key element of evidence-based medicine. However, it is currently hampered by being labour intensive meaning that many trials are not incorporated into robust evidence syntheses and that many are out of date. To overcome this, a variety of techniques are being explored, including using automation technology. Here, we describe a fully automated evidence synthesis system for intervention studies, one that identifies all the relevant evidence, assesses the evidence for reliability and collates it to estimate the relative effectiveness of an intervention. Techniques used include machine learning, natural language processing and rule-based systems. Results are visualised using modern visualisation techniques. We believe this to be the first, publicly available, automated evidence synthesis system: an evidence mapping tool that synthesises evidence on the fly., Competing Interests: Competing interests: Both JB and CP are shareholders in Trip Database. JB is also a member of the editorial board of BMJ EBM. No other declared competing interests from the other authors., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Emotional flexibility advancement has been found to be highly effective in clinical settings to treat, for example, depression, anxiety, and chronic pain. Developing these skills in the working context has also shown very encouraging results in public sector settings. Also, a few studies have revealed effectiveness in a private sector setting, but no studies have yet looked at the effectiveness of developing these skills amongst high-paced, high-demanding, and highly-educated knowledge workers. In this pilot training intervention study, we report evidence that emotional flexibility can be developed in this context. We conducted an experiment with treatment and control groups, with only the treatment group receiving an emotional flexibility training. Emotional flexibility improved significantly for the treatment group, whereas the improvements were minimal or negative for the control group. Furthermore, we reveal that General self-efficacy improved amongst treatment group participants (and not for control group participants), and that this is associated with emotional flexibility. Finally, we show that the improvements were higher for participants starting from a lower baseline., Competing Interests: The 1st author is a part-time employee of the organization where the research was performed and a part-time affiliated researcher at three Universities. The 4th author is an employee of the same organization and invited the research as part of an employee well-being program. None of the other authors are part of this organization and served as academic researchers. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Objective: To simulate possible changes in systematic review results if rapid review methods were used., Study Design and Setting: We recalculated meta-analyses for binary primary outcomes in Cochrane systematic reviews, simulating rapid review methods. We simulated searching only PubMed, excluding older articles (5, 7, 10, 15, and 20 years before the search date), excluding smaller trials (<50, <100, and <200 participants), and using the largest trial only. We examined percentage changes in pooled odds ratios (ORs) (classed as no important change [<5%], small [<20%], moderate [<30%], or large [≥30%]), statistical significance, and biases observed using rapid methods., Results: Two thousand five hundred and twelve systematic reviews (16,088 studies) were included. Rapid methods resulted in the loss of all data in 3.7-44.7% of meta-analyses. Searching only PubMed had the smallest risk of changed ORs (19% [477/2,512] were small changes or greater; 10% [260/2,512] were moderate or greater). Changes in ORs varied substantially with each rapid review method; 8.4-21.3% were small, 1.9-8.8% were moderate, and 4.7-34.1% were large. Changes in statistical significance occurred in 6.5-38.6% of meta-analyses. Changes from significant to nonsignificant were most common (2.1-13.7% meta-analyses). We found no evidence of bias with any rapid review method., Conclusion: Searching PubMed only might be considered where a ∼10% risk of the primary outcome OR changing by >20% could be tolerated. This could be the case in scoping reviews, resource limitation, or where syntheses are needed urgently. Other situations, such as clinical guidelines and regulatory decisions, favor more comprehensive systematic review methods., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: Cochrane systematic reviews require more methodological support from Cochrane Review Groups (CRGs) than is customarily received by authors from journals; CRGs must therefore prioritize reviews to conserve resources. The TRIP database provided a data set of questions to guide prioritization for the acute respiratory infections (ARIs) CRG., Study Design and Setting: We extracted the ARI searches from the TRIP database (2010 to 2017) that contained at least one disease and one clinical management term, (defined as a "search"), and tabulated these by frequency., Results: There were 314,346 ARI searches from which we inferred 45,497 clinical questions, covering 365 topics. Two-thirds (30,541) of these addressed 20 clinical questions, of which treatment were the most frequent, followed by diagnosis, mortality, and prognosis. The five most frequent clinical questions were "Influenza + Vaccination" 4,989 (12.1%), "acute otitis media + antibiotics" 3,578 (8.7%), "common cold + vitamin C" 3,528 (8.6%), "meningitis + corticosteroids" 1,910 (4.6%), and "pneumonia + general treatment" 1,765 (4.3%). The 20 most frequent clinical questions were addressed by Cochrane reviews or protocols., Conclusion: ARI questions are common and repeated often. Most may have been addressed by Cochrane reviews. The remainder form the basis of a priority list to assign resources for future Cochrane topics., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Many Management (sub-)disciplines, from Organizational Behavior and Marketing to Accounting and Strategy, are interested in antecedents and consequences of individual attitudes and traits. A key aspect of personality profiles are explicit and implicit motives. Yet, Management scholars mainly focus on explicit motives, with limited attention to implicit motives. We argue that this state of affairs probably came into being because current Management researchers mainly rely on implicit motive measures that are either difficult to apply or to develop, hampering researchers from applying implicit motive measures. To overcome the downsides of available instruments, we develop a Brief Implicit Association Test (BIAT) as an efficient, reliable and valid measure of implicit motives, particularly the needs for achievement, affiliation and power. To explore our BIAT's predictive validity, we apply this measure to a specific research domain within Management: Entrepreneurship. We examine implicit motives' association with entrepreneurial self-efficacy, business founding, and financial profitability. Our results show that the introduction of implicit motives can unlock stranded discussions in this research domain. Overall, we argue that implicit motives can help to push the boundaries of the study of deep-level attributes in a wide range of organizational and managerial settings., Competing Interests: The authors have declared that no competing interests exist.

This article is part of a series featured from the Catalogue of Bias introduced in this volume of BMJ Evidence-Based Medicine that describes biases and outlines their potential impact in research studies. Observer bias is systematic discrepancy from the truth during the process of observing and recording information for a study. Many healthcare observations are at risk of this bias. Evidence shows that treatment effect estimates can be exaggerated by a third to two-thirds in the presence of observer bias in outcome assessment. Preventing observer bias involves proper masking in intervention studies including the use of matched placebo interventions where appropriate and training of observers to make assessment consistent and reduce biases resulting from conscious or unconscious prejudices. Where observers are involved in a research study, it is probably not possible for the study to be entirely free of observer biases., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

In this paper, an identification approach for the Population (e.g. patients with headache), the Intervention (e.g. aspirin) and the Comparison (e.g. vitamin C) in Randomized Controlled Trials (RCTs) is proposed. Contrary to previous approaches, the identification is done on a word level, rather than on a sentence level. Additionally, we classify the sentiment of RCTs to determine whether an Intervention is more effective than its Comparison. Two new corpora were created to evaluate both approaches. In the experiments, an average F1 score of 0.85 for the PIC identification and 0.72 for the sentiment classification was achieved.

Background: The ideal evidence to answer a question about the effectiveness of treatment is a systematic review. However, for many clinical questions a systematic review will not be available, or may not be up to date. One option could be to use the evidence from an individual trial to answer the question?, Methods: We assessed how often (a) the estimated effect and (b) the p-value in the most precise single trial in a meta-analysis agreed with the whole meta-analysis. For a random sample of 200 completed Cochrane Reviews (January, 2005) we identified a primary outcome and extracted: the number of trials, the statistical weight of the most precise trial, the estimate and confidence interval for both the highest weighted trial and the meta-analysis overall. We calculated the p-value for the most precise trial and meta-analysis., Results: Of 200 reviews, only 132 provided a meta-analysis of 2 or more trials, with a further 35 effect estimates based on single trials. The average number of trials was 7.3, with the most precise trial contributing, on average, 51% of the statistical weight to the summary estimate from the whole meta-analysis. The estimates of effect from the most precise trial and the overall meta-analyses were highly correlated (rank correlation of 0.90).There was an 81% agreement in statistical conclusions. Results from the most precise trial were statistically significant in 60 of the 167 evaluable reviews, with 55 of the corresponding systematic reviews also being statistically significant. The five discrepant results were not strikingly different with respect to their estimates of effect, but showed considerable statistical heterogeneity between trials in these meta-analyses. However, among the 101 cases in which the most precise trial was not statistically significant, the corresponding meta-analyses yielded 31 statistically significant results., Conclusions: Single most precise trials provided similar estimates of effects to those of the meta-analyses to which they contributed, and statistically significant results are generally in agreement. However, "negative" results were less reliable, as may be expected from single underpowered trials. For systematic reviewers we suggest that: (1) key trial(s) in a review deserve greater attention (2) systematic reviewers should check agreement of the most precise trial and the meta analysis. For clinicians using trials we suggest that when a meta-analysis is not available, a focus on the most precise trial is reasonable provided it is adequately powered.

Objectives: Clinicians and patients are increasingly accessing information through Internet searches. This study aimed to examine clinicians' current search behavior when using the Turning Research Into Practice (TRIP) database to examine search engine use and the ways it might be improved., Methods: A Web log analysis was undertaken of the TRIP database-a meta-search engine covering 150 health resources including MEDLINE, The Cochrane Library, and a variety of guidelines. The connectors for terms used in searches were studied, and observations were made of 9 users' search behavior when working with the TRIP database., Results: Of 620,735 searches, most used a single term, and 12% (n = 75,947) used a Boolean operator: 11% (n = 69,006) used "AND" and 0.8% (n = 4,941) used "OR." Of the elements of a well-structured clinical question (population, intervention, comparator, and outcome), the population was most commonly used, while fewer searches included the intervention. Comparator and outcome were rarely used. Participants in the observational study were interested in learning how to formulate better searches., Conclusions: Web log analysis showed most searches used a single term and no Boolean operators. Observational study revealed users were interested in conducting efficient searches but did not always know how. Therefore, either better training or better search interfaces are required to assist users and enable more effective searching.