Low intensity pulsed ultrasound (LIPUS) for bone healing: A clinical practice guideline

Does low intensity pulsed ultrasound (LIPUS) accelerate recovery in adults and children who have experienced bone fractures or osteotomy (cutting of a bone)? An expert panel rapidly produced these recommendations based on a linked systematic review triggered by a large multi-centre randomised trial in adults with tibial fracture

Prevalence, characteristics, and publication of discontinued randomized trials.

IMPORTANCE: The discontinuation of randomized clinical trials (RCTs) raises ethical concerns and often wastes scarce research resources. The epidemiology of discontinued RCTs, however, remains unclear. OBJECTIVES: To determine the prevalence, characteristics, and publication history of discontinued RCTs and to investigate factors associated with RCT discontinuation due to poor recruitment and with nonpublication. DESIGN AND SETTING: Retrospective cohort of RCTs based on archived protocols approved by 6 research ethics committees in Switzerland, Germany, and Canada between 2000 and 2003. We recorded trial characteristics and planned recruitment from included protocols. Last follow-up of RCTs was April 27, 2013. MAIN OUTCOMES AND MEASURES: Completion status, reported reasons for discontinuation, and publication status of RCTs as determined by correspondence with the research ethics committees, literature searches, and investigator surveys. RESULTS: After a median follow-up of 11.6 years (range, 8.8-12.6 years), 253 of 1017 included RCTs were discontinued (24.9% [95% CI, 22.3%-27.6%]). Only 96 of 253 discontinuations (37.9% [95% CI, 32.0%-44.3%]) were reported to ethics committees. The most frequent reason for discontinuation was poor recruitment (101/1017; 9.9% [95% CI, 8.2%-12.0%]). In multivariable analysis, industry sponsorship vs investigator sponsorship (8.4% vs 26.5%; odds ratio [OR], 0.25 [95% CI, 0.15-0.43]; P < .001) and a larger planned sample size in increments of 100 (-0.7%; OR, 0.96 [95% CI, 0.92-1.00]; P = .04) were associated with lower rates of discontinuation due to poor recruitment. Discontinued trials were more likely to remain unpublished than completed trials (55.1% vs 33.6%; OR, 3.19 [95% CI, 2.29-4.43]; P < .001). CONCLUSIONS AND RELEVANCE: In this sample of trials based on RCT protocols from 6 research ethics committees, discontinuation was common, with poor recruitment being the most frequently reported reason. Greater efforts are needed to ensure the reporting of trial discontinuation to research ethics committees and the publication of results of discontinued trials

Agreements between Industry and Academia on Publication Rights: A Retrospective Study of Protocols and Publications of Randomized Clinical Trials.

BACKGROUND: Little is known about publication agreements between industry and academic investigators in trial protocols and the consistency of these agreements with corresponding statements in publications. We aimed to investigate (i) the existence and types of publication agreements in trial protocols, (ii) the completeness and consistency of the reporting of these agreements in subsequent publications, and (iii) the frequency of co-authorship by industry employees. METHODS AND FINDINGS: We used a retrospective cohort of randomized clinical trials (RCTs) based on archived protocols approved by six research ethics committees between 13 January 2000 and 25 November 2003. Only RCTs with industry involvement were eligible. We investigated the documentation of publication agreements in RCT protocols and statements in corresponding journal publications. Of 647 eligible RCT protocols, 456 (70.5%) mentioned an agreement regarding publication of results. Of these 456, 393 (86.2%) documented an industry partner's right to disapprove or at least review proposed manuscripts; 39 (8.6%) agreements were without constraints of publication. The remaining 24 (5.3%) protocols referred to separate agreement documents not accessible to us. Of those 432 protocols with an accessible publication agreement, 268 (62.0%) trials were published. Most agreements documented in the protocol were not reported in the subsequent publication (197/268 [73.5%]). Of 71 agreements reported in publications, 52 (73.2%) were concordant with those documented in the protocol. In 14 of 37 (37.8%) publications in which statements suggested unrestricted publication rights, at least one co-author was an industry employee. In 25 protocol-publication pairs, author statements in publications suggested no constraints, but 18 corresponding protocols documented restricting agreements. CONCLUSIONS: Publication agreements constraining academic authors' independence are common. Journal articles seldom report on publication agreements, and, if they do, statements can be discrepant with the trial protocol

Diagnostic validity of somatosensory evoked potentials in subgroups of patients with sciatica

The diagnostic utility of scalp-recorded somatosensory evoked potentials (SEP) in patients with sciatica has generally been regarded as low. The purpose of the present study was to determine the validity of sensory nerve SEP in different subgroups of sciatic patients. A total of 65 consecutive patients with sciatica showing disc pathology and/or facet joint hypertrophy on lumbar computed tomography (CT) and/or myelography were studied. Symptomatic myelographically compressed nerve roots were defined as truly compromised roots. Asymptomatic myelographically normal nerve roots were defined as truly normal roots. Bilateral sensory nerve SEP representing nerve roots L4, L5, and S1 were performed in all patients. Evaluation of SEP included the use of P1 latency inter-root comparison. The false-positive rate of SEP was low. Pathological L4, L5, and S1 SEP therefore strongly indicate true compromise of the corresponding nerve roots. The true-positive rate was higher in patients with facet joint hypertrophy with or without additional disc disease than in patients with disc pathology only, and highest if the sciatic sensory symptoms were present during the SEP registration. Diagnostic validity was not influenced by previous episodes of sciatica, the duration of the present episode, or the number of spinal levels with ipsilateral myelographically compressed nerve roots. Pathological SEP strongly indicate sensory radiculopathy in patients with sciatica. Diagnostic efficacy is higher in patients with facet joint hypertrophy than in patients with disc pathology only and highest when the sciatic symptoms are present during registration.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42320/1/586-11-1-38_s005860100322.pd

Eaten out of house and home:impacts of grazing on ground-dwelling reptiles in Australian grasslands and grassy woodlands

Large mammalian grazers can alter the biotic and abiotic features of their environment through their impacts on vegetation. Grazing at moderate intensity has been recommended for biodiversity conservation. Few studies, however, have empirically tested the benefits of moderate grazing intensity in systems dominated by native grazers. Here we investigated the relationship between (1) density of native eastern grey kangaroos, Macropus giganteus, and grass structure, and (2) grass structure and reptiles (i.e. abundance, richness, diversity and occurrence) across 18 grassland and grassy Eucalyptus woodland properties in south-eastern Australia. There was a strong negative relationship between kangaroo density and grass structure after controlling for tree canopy cover. We therefore used grass structure as a surrogate for grazing intensity. Changes in grazing intensity (i.e. grass structure) significantly affected reptile abundance, reptile species richness, reptile species diversity, and the occurrence of several ground-dwelling reptiles. Reptile abundance, species richness and diversity were highest where grazing intensity was low. Importantly, no species of reptile was more likely to occur at high grazing intensities. Legless lizards (Delma impar, D. inornata) were more likely to be detected in areas subject to moderate grazing intensity, whereas one species (Hemiergis talbingoensis) was less likely to be detected in areas subject to intense grazing and three species (Menetia greyii, Morethia boulengeri, and Lampropholis delicata) did not appear to be affected by grazing intensity. Our data indicate that to maximize reptile abundance, species richness, species diversity, and occurrence of several individual species of reptile, managers will need to subject different areas of the landscape to moderate and low grazing intensities and limit the occurrence and extent of high grazing

Risk of dispersion or aerosol generation and infection transmission with nasopharyngeal and oropharyngeal swabs for detection of COVID-19: a systematic review

ObjectivesSARS-CoV-2-related disease, referred to as COVID-19, has emerged as a global pandemic since December 2019. While there is growing recognition regarding possible airborne transmission, particularly in the setting of aerosol-generating procedures and treatments, whether nasopharyngeal and oropharyngeal swabs for SARS-CoV-2 generate aerosols remains unclear.DesignSystematic review.Data sourcesWe searched Ovid MEDLINE and EMBASE up to 3 November 2020. We also searched the China National Knowledge Infrastructure, Chinese Medical Journal Network, medRxiv and ClinicalTrials.gov up to 29 March 2020.Eligibility criteriaAll comparative and non-comparative studies that evaluated dispersion or aerosolisation of viable airborne organisms, or transmission of infection associated with nasopharyngeal or oropharyngeal swab testing.ResultsOf 7702 citations, only one study was deemed eligible. Using a dedicated sampling room with negative pressure isolation room, personal protective equipment including N95 or higher masks, strict sterilisation protocols, structured training with standardised collection methods and a structured collection and delivery system, a tertiary care hospital proved a 0% healthcare worker infection rate among eight nurses conducting over 11 000 nasopharyngeal swabs. No studies examining transmissibility with other safety protocols, nor any studies quantifying the risk of aerosol generation with nasopharyngeal or oropharyngeal swabs for detection of SARS-CoV-2, were identified.ConclusionsThere is limited to no published data regarding aerosol generation and risk of transmission with nasopharyngeal and oropharyngeal swabs for the detection of SARS-CoV-2. Field experiments to quantify this risk are warranted. Vigilance in adhering to current standards for infection control is suggested.</jats:sec

Credibility of claims of subgroup effects in randomised controlled trials : Systematic review

Objective: To investigate the credibility of authors' claims of subgroup effects using a representative sample of recently published randomised controlled trials. Design: Systematic review. Data source: Core clinical journals, as defined by the National Library of Medicine, in Medline. Study selection: Randomised controlled trials published in 2007. Using prespecified criteria, teams of trained reviewers independently judged whether authors claimed subgroup effects and the strength of their claims. Reviewers assessed each of these claims against 10 predefined criteria, developed through a search of existing criteria and a consensus process. Results: Of 207 randomised controlled trials reporting subgroup analyses, 64 (31%) made claims for the primary outcome. Of those, 20 were strong claims and 28 claims of a likely effect. Authors included subgroup variables measured at baseline in 60 (94%) trials, used subgroup variable as a stratification factor at randomisation in 13 (20%), clearly prespecified their hypotheses in 26 (41%), correctly prespecified direction in 4 (6%), tested a small number of hypotheses in 28 (44%), carried out a test of interaction that proved statistically significant in 6 (9%), documented replication of a subgroup effect with previous related studies in 21 (33%), identified consistency of a subgroup effect across related outcomes in 19 (30%), and provided a compelling indirect evidence for the effect in 14 (22%). In the 19 trials making more than one claim, only one (5%) checked the independence of the interaction. Of the 64 claims, 54 (84%) met four or fewer of the 10 criteria. For strong claims, more than 50%failed each of the individual criteria, and only three (15%) met more than five criteria. Conclusion: Authors often claim subgroup effects in their trial report. However, the credibility of subgroup effects, even when claims are strong, is usually low. Users of the information should treat claims that fail to meet most criteria with scepticism. Trial researchers should report the conduct of subgroup analyses and provide sufficient evidence when claiming a subgroup effect or suggesting a possible effect

Buffering effects of soil seed banks on plant community composition in response to land use and climate

Aim Climate and land use are key determinants of biodiversity, with past and ongoing changes posing serious threats to global ecosystems. Unlike most other organism groups, plant species can possess dormant life‐history stages such as soil seed banks, which may help plant communities to resist or at least postpone the detrimental impact of global changes. This study investigates the potential for soil seed banks to achieve this. Location Europe. Time period 1978–2014. Major taxa studied Flowering plants. Methods Using a space‐for‐time/warming approach, we study plant species richness and composition in the herb layer and the soil seed bank in 2,796 community plots from 54 datasets in managed grasslands, forests and intermediate, successional habitats across a climate gradient. Results Soil seed banks held more species than the herb layer, being compositionally similar across habitats. Species richness was lower in forests and successional habitats compared to grasslands, with annual temperature range more important than mean annual temperature for determining richness. Climate and land‐use effects were generally less pronounced when plant community richness included seed bank species richness, while there was no clear effect of land use and climate on compositional similarity between the seed bank and the herb layer. Main conclusions High seed bank diversity and compositional similarity between the herb layer and seed bank plant communities may provide a potentially important functional buffer against the impact of ongoing environmental changes on plant communities. This capacity could, however, be threatened by climate warming. Dormant life‐history stages can therefore be important sources of diversity in changing environments, potentially underpinning already observed time‐lags in plant community responses to global change. However, as soil seed banks themselves appear, albeit less, vulnerable to the same changes, their potential to buffer change can only be temporary, and major community shifts may still be expected

Prophylaxis against covid-19: living systematic review and network meta-analysis

Abstract Objective To determine and compare the effects of drug prophylaxis on SARS-CoV-2 infection and covid-19. Design Living systematic review and network meta-analysis. Data sources World Health Organization covid-19 database, a comprehensive multilingual source of global covid-19 literature to 25 March 2021, and six additional Chinese databases to 20 February 2021. Study selection Randomised trials of people at risk of covid-19 who were assigned to receive prophylaxis or no prophylaxis (standard care or placebo). Pairs of reviewers independently screened potentially eligible articles. Methods Random effects bayesian network meta-analysis was performed after duplicate data abstraction. Included studies were assessed for risk of bias using a modification of the Cochrane risk of bias 2.0 tool, and certainty of evidence was assessed using the grading of recommendations assessment, development, and evaluation (GRADE) approach. Results The first iteration of this living network meta-analysis includes nine randomised trials—six of hydroxychloroquine (n=6059 participants), one of ivermectin combined with iota-carrageenan (n=234), and two of ivermectin alone (n=540), all compared with standard care or placebo. Two trials (one of ramipril and one of bromhexine hydrochloride) did not meet the sample size requirements for network meta-analysis. Hydroxychloroquine has trivial to no effect on admission to hospital (risk difference 1 fewer per 1000 participants, 95% credible interval 3 fewer to 4 more; high certainty evidence) or mortality (1 fewer per 1000, 2 fewer to 3 more; high certainty). Hydroxychloroquine probably does not reduce the risk of laboratory confirmed SARS-CoV-2 infection (2 more per 1000, 18 fewer to 28 more; moderate certainty), probably increases adverse effects leading to drug discontinuation (19 more per 1000, 1 fewer to 70 more; moderate certainty), and may have trivial to no effect on suspected, probable, or laboratory confirmed SARS-CoV-2 infection (15 fewer per 1000, 64 fewer to 41 more; low certainty). Owing to serious risk of bias and very serious imprecision, and thus very low certainty of evidence, the effects of ivermectin combined with iota-carrageenan on laboratory confirmed covid-19 (52 fewer per 1000, 58 fewer to 37 fewer), ivermectin alone on laboratory confirmed infection (50 fewer per 1000, 59 fewer to 16 fewer) and suspected, probable, or laboratory confirmed infection (159 fewer per 1000, 165 fewer to 144 fewer) remain very uncertain. Conclusions Hydroxychloroquine prophylaxis has trivial to no effect on hospital admission and mortality, probably increases adverse effects, and probably does not reduce the risk of SARS-CoV-2 infection. Because of serious risk of bias and very serious imprecision, it is highly uncertain whether ivermectin combined with iota-carrageenan and ivermectin alone reduce the risk of SARS-CoV-2 infection. Systematic review registration This review was not registered. The protocol established a priori is included as a supplement. Readers’ note This article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication. </jats:sec