Is spinal neuromuscular function asymmetrical in adolescents with idiopathic scoliosis compared to those without scoliosis?: A narrative review of surface EMG studies

Adolescent idiopathic scoliosis (AIS) is a three-dimensional spinal deformity occurring between ages of 10–18 years. We aimed to present a reasoned synthesis of the published evidence for and against asymmetrical paraspinal muscle activation in AIS. PubMed and Embase databases were searched using terms: adolescent idiopathic scoliosis AND electromyogra* (EMG). Identified studies (n = 94) were screened for eligibility. We identified 16 studies, from which 136 EMG outcome measures contributed to the review.For EMG onset, one of two studies provided evidence of earlier muscle activation on the convex compared to concave side of the spine, particularly in those with progressive AIS. For EMG amplitude, 43 outcome measures provided evidence of convex > concave activation, 85 outcomes supported no difference between sides, and 8 outcomes supported concave > convex activation. Greater activity on the convex than concave side was more commonly demonstrated at the scoliosis curve apex level, in people with single right thoracic [progressive] curves, during postural tasks.Further research is needed to determine the relationships between muscle activity asymmetry and spinal curve parameters in a variety of motor tasks. Recommendations are provided to improve methodological quality for future studies of spinal neuromuscular function in AIS, as well as more comprehensive and transparent reporting of methods and results.     

The Use of Bayesian Networks to Assess the Quality of Evidence from Research Synthesis: 1.

Background

The grades of recommendation, assessment, development and evaluation (GRADE) approach is widely implemented in systematic reviews, health technology assessment and guideline development organisations throughout the world. A key advantage to this approach is that it aids transparency regarding judgments on the quality of evidence. However, the intricacies of making judgments about research methodology and evidence make the GRADE system complex and challenging to apply without training.

Methods

We have developed a semi-automated quality assessment tool (SAQAT) l based on GRADE. This is informed by responses by reviewers to checklist questions regarding characteristics that may lead to unreliability. These responses are then entered into the Bayesian network to ascertain the probabilities of risk of bias, inconsistency, indirectness, imprecision and publication bias conditional on review characteristics. The model then combines these probabilities to provide a probability for each of the GRADE overall quality categories. We tested the model using a range of plausible scenarios that guideline developers or review authors could encounter.

Results

Overall, the model reproduced GRADE judgements for a range of scenarios. Potential advantages over standard assessment are use of explicit and consistent weightings for different review characteristics, forcing consideration of important but sometimes neglected characteristics and principled downgrading where small but important probabilities of downgrading are accrued across domains.

Conclusions

Bayesian networks have considerable potential for use as tools to assess the validity of research evidence. The key strength of such networks lies in the provision of a statistically coherent method for combining probabilities across a complex framework based on both belief and evidence. In addition to providing tools for less experienced users to implement reliability assessment, the potential for sensitivity analyses and automation may be beneficial for application and the methodological development of reliability tools.     

Influence of CYP2C9 and VKORC1 on Patient Response to Warfarin: A Systematic Review and Meta-Analysis

Background

Warfarin is a highly effective anticoagulant however its effectiveness relies on maintaining INR in therapeutic range. Finding the correct dose is difficult due to large inter-individual variability. Two genes, CYP2C9 and VKORC1, have been associated with this variability, leading to genotype-guided dosing tables in warfarin labeling. Nonetheless, it remains unclear how genotypic information should be used in practice. Navigating the literature to determine how genotype will influence warfarin response in a particular patient is difficult, due to significant variation in patient ethnicity, outcomes investigated, study design, and methodological rigor. Our systematic review was conducted to enable fair and accurate interpretation of which variants affect which outcomes, in which patients, and to what extent.

Methodology/Principal Findings

A comprehensive search strategy was applied and 117 studies included. Primary outcomes were stable dose, time to stable dose and bleeding events. Methodological quality was assessed using criteria of Jorgensen and Williamson and data synthesized in meta-analyses using advanced methods. Pooled effect estimates were significant in most ethnic groups for CYP2C9*3 and stable dose (mutant types requiring between 1.1(0.7–1.5) and 2.3 (1.6–3.0)mg/day). Effect estimates were also significant for VKORC1 and stable dose for most ethnicities, although direction differed between asians and non-asians (mutant types requiring between 0.8(0.4–1.3) and 1.5(1.1–1.8)mg/day more in asians and between 1.5(0.7–2.2) and 3.1(2.7–3.6)mg/day less in non-asians). Several studies were excluded due to inadequate data reporting. Assessing study quality highlighted significant variability in methodological rigor. Notably, there was significant evidence of selective reporting, of outcomes and analysis approaches.

Conclusions/Significance

Genetic associations with warfarin response vary between ethnicities. In order to achieve unbiased estimates in different populations, a high level of methodological rigor must be maintained and studies should report sufficient data to enable inclusion in meta-analyses. We propose minimum reporting requirements, suggest methodological guidelines and provide recommendations for reducing the risk of selective reporting.     

The implementation research institute: training mental health implementation researchers in the United States

Background

Healthcare decision makers face challenges when using guidelines, including understanding the quality of the evidence or the values and preferences upon which recommendations are made, which are often not clear.

Methods

GRADE is a systematic approach towards assessing the quality of evidence and the strength of recommendations in healthcare. GRADE also gives advice on how to go from evidence to decisions. It has been developed to address the weaknesses of other grading systems and is now widely used internationally. The Developing and Evaluating Communication Strategies to Support Informed Decisions and Practice Based on Evidence (DECIDE) consortium (http://www.decide-collaboration.eu/), which includes members of the GRADE Working Group and other partners, will explore methods to ensure effective communication of evidence-based recommendations targeted at key stakeholders: healthcare professionals, policymakers, and managers, as well as patients and the general public. Surveys and interviews with guideline producers and other stakeholders will explore how presentation of the evidence could be improved to better meet their information needs. We will collect further stakeholder input from advisory groups, via consultations and user testing; this will be done across a wide range of healthcare systems in Europe, North America, and other countries. Targeted communication strategies will be developed, evaluated in randomized trials, refined, and assessed during the development of real guidelines.

Discussion

Results of the DECIDE project will improve the communication of evidence-based healthcare recommendations. Building on the work of the GRADE Working Group, DECIDE will develop and evaluate methods that address communication needs of guideline users. The project will produce strategies for communicating recommendations that have been rigorously evaluated in diverse settings, and it will support the transfer of research into practice in healthcare systems globally.     

Startle-evoked changes in diaphragmatic activity during wakefulness and sleep

Tonic inhibition of some respiratory muscles occurs as part of the generalized muscle atonia of rapid-eye-movement sleep (REMS). A second type of inhibition of the diaphragm during REMS, fractionations, consists of brief pauses in the diaphragmatic electromyogram (DIA EMG) in association with phasic events. Because motor inhibition can occur as part of the startle response, and the brain is highly activated during REMS, we hypothesized that the neural basis of the fractionations might be activation of a startle network. To test this hypothesis, tone bursts (100 dB, 20-ms duration at 15-s intervals) were applied to cats at a fixed inspiratory level in the DIA moving average during REMS, non-rapid-eye-movement sleep (NREMS), and wakefulness. Parallel sham studies (no tone applied) were obtained for each state. The response of the DIA EMG was averaged over 100 ms by using the tone pulse as a trigger, and the following parameters of the DIA EMG were measured: latency to peak and/or nadir, increment or decrement in activity, and duration of peak and/or nadir. After a tone, all five animals studied displayed a profound suppression of DIA activity during REMS (latency to nadir 42.4 +/- 10.0 ms, duration of suppression 35.9 +/- 17.6 ms). Similarly, DIA activity was suppressed in all cats during NREMS (latency to nadir 40.9 +/- 13.3 ms, duration 23.9 +/- 13.4 ms). An excitatory response was observed in only two cats during NREMS and wakefulness. The similarity of startle-induced DIA EMG pauses to spontaneous fractionations of DIA activity during REMS suggests that the latter result from activation of a central startle system.     

Polymorphisms of microRNA Sequences or Binding Sites and Lung Cancer: A Meta-Analysis and Systematic Review

Objective

Functional single nucleotide polymorphisms (SNPs) of microRNA (miRNA) sequences or binding sites (miRNA-SNPs) are associated with lung cancer risk and survival. The objective of this study was to systematically review genetic association studies about miRNA-SNPs in lung cancer.

Methods

Eligible genetic association studies were retrieved from databases of PubMed, EMBASE, China National Knowledge Infrastructure and SinoMed. Two investigators selected related studies and assessed methodological quality independently. Quantitative data synthesis was conducted for common SNPs of miRNA (miRNA-196a2 rs11614913, miRNA146a rs2910164, miRNA149 rs2292832, miRNA-605 rs2043556 and miRNA499 rs3746444). GRADE profiler was used to grade the quality of evidence for each miRNA-SNP.

Results

15 eligible studies and 27 miRNA-SNPs were retrieved and 10 miRNA-SNPs were reported with a significant association with susceptibility to or survival of lung cancer. Methodological quality of eligible studies was adequate with an average score of 8.5. miRNA-196a2 rs11614913 polymorphism was associated with increased lung cancer risk (homozygote comparison, OR = 1.299, 95% CI: 1.096–1.540; dominant model, OR = 1.217, 95% CI: 1.041–1.421) and decreased survival. And according to GRADE profiler, quality of evidence was moderate for MYCL1 rs3134615, while quality of the other significant associations was low.

Conclusions

Based on this first systematic review about miRNA-SNPs in lung cancer, quality of evidence was low for most genetic association studies. Polymorphisms of miRNA-196a2 rs11614913 and MYCL1 rs3134615 could be potential biomarkers of lung cancer.     

Non-Surgical Interventions for Adolescents with Idiopathic Scoliosis: An Overview of Systematic Reviews

Background

Non-surgical interventions for adolescents with idiopathic scoliosis remain highly controversial. Despite the publication of numerous reviews no explicit methodological evaluation of papers labeled as, or having a layout of, a systematic review, addressing this subject matter, is available.

Objectives

Analysis and comparison of the content, methodology, and evidence-base from systematic reviews regarding non-surgical interventions for adolescents with idiopathic scoliosis.

Design

Systematic overview of systematic reviews.

Methods

Articles meeting the minimal criteria for a systematic review, regarding any non-surgical intervention for adolescent idiopathic scoliosis, with any outcomes measured, were included. Multiple general and systematic review specific databases, guideline registries, reference lists and websites of institutions were searched. The AMSTAR tool was used to critically appraise the methodology, and the Oxford Centre for Evidence Based Medicine and the Joanna Briggs Institute’s hierarchies were applied to analyze the levels of evidence from included reviews.

Results

From 469 citations, twenty one papers were included for analysis. Five reviews assessed the effectiveness of scoliosis-specific exercise treatments, four assessed manual therapies, five evaluated bracing, four assessed different combinations of interventions, and one evaluated usual physical activity. Two reviews addressed the adverse effects of bracing. Two papers were high quality Cochrane reviews, Three were of moderate, and the remaining sixteen were of low or very low methodological quality. The level of evidence of these reviews ranged from 1 or 1+ to 4, and in some reviews, due to their low methodological quality and/or poor reporting, this could not be established.

Conclusions

Higher quality reviews indicate that generally there is insufficient evidence to make a judgment on whether non-surgical interventions in adolescent idiopathic scoliosis are effective. Papers labeled as systematic reviews need to be considered in terms of their methodological rigor; otherwise they may be mistakenly regarded as high quality sources of evidence.

Protocol registry number

CRD42013003538, PROSPERO     

Standard guidelines for the publication of telomere qPCR results in evolutionary ecology

Telomere length has been used as a proxy of fitness, aging and lifespan in vertebrates. In the last decade, dozens of articles reporting on telomere dynamics in the fields of ecology and evolution have been published for a wide range of taxa. With this growing interest, it is necessary to ensure the accuracy and reproducibility of telomere length measurement techniques. Real‐time quantitative PCR (qPCR) is routinely applied to measure relative telomere length. However, this technique is highly sensitive to several methodological variables and the optimization of qPCR telomere assays remains highly variable between studies. Therefore, standardized guidelines are required to enable the optimization of robust protocols, and to help in judging the validity of the presented results. This review provides an overview of preanalytical and analytical factors that can lead to qPCR inconsistencies and biases, including: (a) sample type, collection and storage; (b) DNA extraction, storage and quality; (c) qPCR primers, laboratory reagents, and assay conditions; and (d) data analysis. We propose a minimum level of information for publication of qPCR telomere assays in evolutionary ecology considering the methodological pitfalls and sources of error. This review highlights the complexity of the optimization and validation of qPCR for telomere measurement per se, demonstrating the importance of transparency and clarity of reporting methodological details required for reliable, reproducible and comparable qPCR telomere assays. We encourage efforts to implement standardized protocols that ensure the rigour and quality of telomere dynamics studies.     

Recommended reporting items for epidemic forecasting and prediction research: The EPIFORGE 2020 guidelines

BackgroundThe importance of infectious disease epidemic forecasting and prediction research is underscored by decades of communicable disease outbreaks, including COVID-19. Unlike other fields of medical research, such as clinical trials and systematic reviews, no reporting guidelines exist for reporting epidemic forecasting and prediction research despite their utility. We therefore developed the EPIFORGE checklist, a guideline for standardized reporting of epidemic forecasting research.Methods and findingsWe developed this checklist using a best-practice process for development of reporting guidelines, involving a Delphi process and broad consultation with an international panel of infectious disease modelers and model end users. The objectives of these guidelines are to improve the consistency, reproducibility, comparability, and quality of epidemic forecasting reporting. The guidelines are not designed to advise scientists on how to perform epidemic forecasting and prediction research, but rather to serve as a standard for reporting critical methodological details of such studies.ConclusionsThese guidelines have been submitted to the EQUATOR network, in addition to hosting by other dedicated webpages to facilitate feedback and journal endorsement.

Simon Pollett and co-workers describe EPIFORGE, a guideline for reporting research on epidemic forecasting.     

Facts and figures from road testing the guidance on organizational life cycle assessment

Purpose

Organizational life cycle assessment (O-LCA) is an emerging method to analyze the inputs, outputs, and environmental impacts of an organization throughout its value chain. To facilitate the method’s application, the Guidance on Organizational Life Cycle Assessment was published within the UNEP/SETAC Life Cycle Initiative and applied by 12 “road-testing” organizations. In this paper, different aspects of the road testers’ studies are displayed and analyzed according to the feedback of the road testers.

Methods

An anonymous survey about the method application was conducted among the road testers. The analysis assessed, among others: (i) which goals the organizations initially pursued and their achievement; (ii) how previous experience with environmental tools contributed to the study design; (iii) which methodological options were chosen (like the scope of the study, data collection approaches, impact assessment methods and tools, and data sources); and (iv) which methodological challenges were faced.

Results and discussion

The survey showed that analytical goals were of priority for most road testers and obtained a higher achievement level than managerial and societal goals for which either long-term measures or the inclusion of stakeholders are needed. Previous experience with product- or organization-related tools considering the whole life cycle proves useful due to available data and/or organizational models. The categorization of organizational activities, data collection, data quality assessment, and interpretation proved being the most challenging methodological elements. In addition, three cross-cutting issues of method application were identified: aligning the O-LCA study to previous environmental activities, designing the study, and availability of personnel and software resources.

Conclusions

The road-testing organizations verified the applicability and usefulness of the O-LCA Guidance and significantly widened the pool of case studies available. On the other hand, additional guidance for methodological challenges particular of the organizational level, the availability of software tools able to support O-LCA application, region-specific LCI databases, and a broadly recognized data quality assessment scheme would facilitate conducting O-LCA case studies.

     

The Contribution of Systematic Review and Meta-Analysis Methods to Human Health Risk Assessment: Neurobehavioral Effects of Manganese

Current methods of human health risk assessment may lack transparency in respect of identification, review, and synthesis of potentially relevant human and animal evidence. The nature, degree, and source of uncertainties are often unclear. This article aims to demonstrate the contribution that systematic review and meta-analysis methods can make to providing more structured, transparent, and systematic risk assessments. We focus on disparities between five risk assessments for neurobehavioral effects of manganese, and then illustrate advantages of a systematic approach. Fifty-five human epidemiological studies and 37 animal experiments were identified. Where appropriate, meta-analysis methods demonstrated consistent adverse effects associated with manganese exposure across species. In particular, there was reduced activity in subjects exposed to manganese, although exposed rats tended to be more active than controls. Limitations of exposure measurement and reporting restricted use of more quantitative methods of evidence synthesis. From a methodological viewpoint, we conclude that systematic review and meta-analysis methods can contribute to a more systematic and transparent human health risk assessment making more efficient use of available evidence, compared to current methods of risk assessment. More complex methods could encompass further differences between relevant studies and so further improve the risk assessment process.     

Application of singular spectrum-based change-point analysis to EMG-onset detection

While many approaches have been proposed to identify the signal onset in EMG recordings, there is no standardized method for performing this task. Here, we propose to use a change-point detection procedure based on singular spectrum analysis to determine the onset of EMG signals. This method is suitable for automated real-time implementation, can be applied directly to the raw signal, and does not require any prior knowledge of the EMG signal’s properties. The algorithm proposed by Moskvina and Zhigljavsky (2003) was applied to EMG segments recorded from wrist and trunk muscles. Wrist EMG data was collected from 9 Parkinson’s disease patients with and without tremor, while trunk EMG data was collected from 13 healthy able-bodied individuals. Along with the change-point detection analysis, two threshold-based onset detection methods were applied, as well as visual estimates of the EMG onset by trained practitioners. In the case of wrist EMG data without tremor, the change-point analysis showed comparable or superior frequency and quality of detection results, as compared to other automatic detection methods. In the case of wrist EMG data with tremor and trunk EMG data, performance suffered because other changes occurring in these signals caused larger changes in the detection statistic than the changes caused by the initial muscle activation, suggesting that additional criteria are needed to identify the onset from the detection statistic other than its magnitude alone. Once this issue is resolved, change-point detection should provide an effective EMG-onset detection method suitable for automated real-time implementation.     

Methods for the guideline-based development of quality indicators--a systematic review

Background

Quality indicators (QIs) are used in many healthcare settings to measure, compare, and improve quality of care. For the efficient development of high-quality QIs, rigorous, approved, and evidence-based development methods are needed. Clinical practice guidelines are a suitable source to derive QIs from, but no gold standard for guideline-based QI development exists. This review aims to identify, describe, and compare methodological approaches to guideline-based QI development.

Methods

We systematically searched medical literature databases (Medline, EMBASE, and CINAHL) and grey literature. Two researchers selected publications reporting methodological approaches to guideline-based QI development. In order to describe and compare methodological approaches used in these publications, we extracted detailed information on common steps of guideline-based QI development (topic selection, guideline selection, extraction of recommendations, QI selection, practice test, and implementation) to predesigned extraction tables.

Results

From 8,697 hits in the database search and several grey literature documents, we selected 48 relevant references. The studies were of heterogeneous type and quality. We found no randomized controlled trial or other studies comparing the ability of different methodological approaches to guideline-based development to generate high-quality QIs. The relevant publications featured a wide variety of methodological approaches to guideline-based QI development, especially regarding guideline selection and extraction of recommendations. Only a few studies reported patient involvement.

Conclusions

Further research is needed to determine which elements of the methodological approaches identified, described, and compared in this review are best suited to constitute a gold standard for guideline-based QI development. For this research, we provide a comprehensive groundwork.     

Sensitivity of trapezius electromyography to differences between work tasks - influence of gap definition and normalisation methods.

Surface electromyography (EMG) has been used extensively to estimate muscular load in studies of work related musculoskeletal disorders, especially for the trapezius muscle. The occurrences of periods of EMG silence (gaps), the time below a predetermined threshold level (muscular rest) and various percentiles of the amplitude distribution (APDF) are commonly used summary measures. However, the effects of the criteria used to calculate these measures (e.g., gap duration, threshold level, normalisation method) on the sensitivity of these measures to accurately differentiate work loads is not well known.Bilateral trapezius EMG was recorded, for a full workday, for 58 subjects following both maximal (MVE) and submaximal (RVE) reference contractions. Gap frequency, muscular rest, and percentiles were derived for eight fundamental work tasks. The calculations were performed using different gap duration criteria, threshold levels and normalisation methods.A gap duration of less than 1/2 s, and threshold level approximately 0.3% MVE for gap frequency, and approximately 0.5% MVE for muscular rest, were the criteria that optimised sensitivity to task differences. Minimal sensitivity to tasks and a high sensitivity to individuals was obtained using gap frequency with a threshold level of approximately 1% MVE. Normalisation to RVE, rather than MVE, improved sensitivity to differences between tasks, and reduced undesirable variability. Muscular rest was more sensitive to task differences than APDF percentiles.     

Strengthening the Reporting of Observational Studies in Epidemiology (STROBE): explanation and elaboration

Much medical research is observational. The reporting of observational studies is often of insufficient quality. Poor reporting hampers the assessment of the strengths and weaknesses of a study and the generalisability of its results. Taking into account empirical evidence and theoretical considerations, a group of methodologists, researchers, and editors developed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) recommendations to improve the quality of reporting of observational studies. The STROBE Statement consists of a checklist of 22 items, which relate to the title, abstract, introduction, methods, results and discussion sections of articles. Eighteen items are common to cohort studies, case-control studies and cross-sectional studies and four are specific to each of the three study designs. The STROBE Statement provides guidance to authors about how to improve the reporting of observational studies and facilitates critical appraisal and interpretation of studies by reviewers, journal editors and readers. This explanatory and elaboration document is intended to enhance the use, understanding, and dissemination of the STROBE Statement. The meaning and rationale for each checklist item are presented. For each item, one or several published examples and, where possible, references to relevant empirical studies and methodological literature are provided. Examples of useful flow diagrams are also included. The STROBE Statement, this document, and the associated Web site (http://www.strobe-statement.org/) should be helpful resources to improve reporting of observational research.