Management of patellar tendinopathy: a systematic review and network meta-analysis of randomised studies.

OBJECTIVES: We performed a systematic review and network meta-analysis (NMA) of randomised controlled trials (RCTs) to provide insights into the effectiveness of available treatment modalities in patellar tendinopathy(PT). METHODS: Several databases were searched in May 2021 for RCTs assessing the effectiveness of any intervention compared with any other intervention, placebo or no treatment for pain and/or function in PT. The risk of bias and strength of evidence were assessed with the Cochrane Collaboration and GRADE (Grading of Recommendations, Assessment, Development and Evaluations)/GRADE-NMA tools. RESULTS: A total of 37 RCTs were eligible that assessed 33 different interventions and their combinations, most represented by single studies. Based on pairwise meta-analyses of two RCTs, extracorporeal shockwave therapy (ESWT) does not appear to be superior to sham ESWT (eccentric exercise in both groups) for short-term pain (mean differences (MD) +0.1, 95% CI (-0.8 to 1), p=0.84) or function (MD -1.8, 95% CI (-8 to 4.4), p=0.57). Based on a pairwise meta-analysis of three RCTs, isometric exercise appears as effective as isotonic exercise for immediate postintervention pain relief (MD -1.03, 95% CI (-2.6 to 0.5), p=0.19). Our NMA showed that topical glyceryl trinitrate (GTN) and hyaluronic acid injection, both combined with eccentric exercise and moderate, slow resistance exercise had the highest probability of being the most effective interventions (low/very low strength of evidence). CONCLUSIONS: Promising interventions with inadequate evidence, such as topical GTN, hyaluronic acid injections and isometric and slow resistance exercise, should be further investigated through high-quality RCTs. Meanwhile, eccentric loading with or without adjuncts should remain the first-line treatment for all individuals with patellar tendinopathy.

Male size and reproductive performance in three species of livebearing fishes (Gambusia spp.): A systematic review and meta-analysis.

The genus Gambusia represents approximately 45 species of polyandrous livebearing fishes with reversed sexual size dimorphism (i.e. males smaller than females) and with copulation predominantly via male coercion. Male body size has been suggested as an important sexually selected trait, but despite abundant research, evidence for sexual selection on male body size in this genus is mixed. Studies have found that large males have an advantage in both male-male competition and female choice, but that small males perform sneaky copulations better and at higher frequency and thus may sire more offspring in this coercive mating system. Here, we synthesized this inconsistent body of evidence using pre-registered methods and hypotheses. We performed a systematic review and meta-analysis of summary and primary (raw) data combining both published (n = 19 studies, k = 106 effect sizes) and unpublished effect sizes (n = 17, k = 242) to test whether there is overall selection on male body size across studies in Gambusia. We also tested several specific hypotheses to understand the sources of heterogeneity across effects. Meta-analysis revealed an overall positive correlation between male size and reproductive performance (r = 0.23, 95% confidence interval: 0.10-0.35, n = 36, k = 348, 4,514 males, three Gambusia species). Despite high heterogeneity, the large-male advantage appeared robust across all measures studied (i.e. female choice, mating success, paternity, sperm quantity and quality), and was considerably larger for female choice (r = 0.43, 95% confidence interval: 0.28-0.59, n = 14, k = 43). Meta-regressions found several important factors explaining heterogeneity across effects, including type of sperm characteristic, male-to-female ratio, female reproductive status and environmental conditions. We found evidence of publication bias; however, its influence on our estimates was attenuated by including a substantial amount of unpublished effects, highlighting the importance of open primary data for more accurate meta-analytic estimates. In addition to positive selection on male size, our study suggests that we need to rethink the role and form of sexual selection in Gambusia and, more broadly, to consider the ecological factors that affect reproductive behaviour in livebearing fishes.

COVID-US: A simplified approach to cardiopulmonary ultrasound in suspected and confirmed COVID-19 patients in surge crisis.

The severe acute respiratory syndrome coronavirus 2 (COVID-19) pandemic has placed an unprecedented challenge on healthcare systems across the globe. Rapid assessment of the cardiorespiratory function to monitor disease progression and guide treatment is essential. Therefore, we have designed the COVID-US: a simplified cardiopulmonary ultrasound approach to use in suspected and confirmed COVID-19 patients, to aid front-line health workers in their decision-making in a surge crisis.

Plantar Verrucae in Human Immunodeficiency Virus Infection: 25 Years of Research of a Viral Coinfection.

A higher incidence of plantar verrucae, commonly known as plantar warts, has been shown in patients infected with the human immunodeficiency virus. Several strains of human papillomavirus are associated with clinical manifestations of plantar verrucae. In this literature review, we examine the incidence and clinical manifestations of plantar verrucae in dual coinfection with human immunodeficiency virus and human papillomavirus. We discuss changes in the clinical scenario brought about by the introduction of human immunodeficiency virus antiretroviral therapy. As a clinical condition with notable presence in podiatric medicine, we also confer these findings to increase clinical awareness with treatment modalities.

Case-control matching: effects, misconceptions, and recommendations.

Misconceptions about the impact of case-control matching remain common. We discuss several subtle problems associated with matched case-control studies that do not arise or are minor in matched cohort studies: (1) matching, even for non-confounders, can create selection bias; (2) matching distorts dose-response relations between matching variables and the outcome; (3) unbiased estimation requires accounting for the actual matching protocol as well as for any residual confounding effects; (4) for efficiency, identically matched groups should be collapsed; (5) matching may harm precision and power; (6) matched analyses may suffer from sparse-data bias, even when using basic sparse-data methods. These problems support advice to limit case-control matching to a few strong well-measured confounders, which would devolve to no matching if no such confounders are measured. On the positive side, odds ratio modification by matched variables can be assessed in matched case-control studies without further data, and when one knows either the distribution of the matching factors or their relation to the outcome in the source population, one can estimate and study patterns in absolute rates. Throughout, we emphasize distinctions from the more intuitive impacts of cohort matching.

The E3 Ubiquitin Ligase TRIM9 Is a Filopodia Off Switch Required for Netrin-Dependent Axon Guidance.

Neuronal growth cone filopodia contain guidance receptors and contribute to axon guidance; however, the mechanism by which the guidance cue netrin increases filopodia density is unknown. Here, we demonstrate that TRIM9, an E3 ubiquitin ligase that localizes to filopodia tips and binds the netrin receptor DCC, interacts with and ubiquitinates the barbed-end polymerase VASP to modulate filopodial stability during netrin-dependent axon guidance. Studies with murine Trim9(+/+) and Trim9(-/-) cortical neurons, along with a non-ubiquitinatable VASP mutant, demonstrate that TRIM9-mediated ubiquitination of VASP reduces VASP filopodial tip localization, VASP dynamics at tips, and filopodial stability. Upon netrin treatment, VASP is deubiquitinated, which promotes VASP tip localization and filopodial stability. Trim9 deletion induces axon guidance defects in vitro and in vivo, whereas a gradient of deubiquitinase inhibition promotes axon turning in vitro. We conclude that a gradient of TRIM9-mediated ubiquitination of VASP creates a filopodial stability gradient during axon turning.