Development and Evaluation of a Framework for Identifying and Addressing Spin for Harms in Systematic Reviews of Interventions.

"Spin" refers to misleading reporting, interpretation, and extrapolation of findings in primary and secondary research (such as in systematic reviews). The study of spin primarily focuses on beneficial outcomes. The objectives of this research were threefold: first, to develop a framework for identifying spin associated with harms in systematic reviews of interventions; second, to apply the framework to a set of reviews, thereby pinpointing instances where spin may be present; and finally, to revise the spin examples, offering guidance on how spin can be rectified.The authors developed their framework through an iterative process that engaged an international group of researchers specializing in spin and reporting bias. The framework comprises 12 specific types of spin for harms, grouped by 7 categories across the 3 domains (reporting, interpretation, and extrapolation). The authors subsequently gathered instances of spin from a random sample of 100 systematic reviews of interventions. Of the 58 reviews that assessed harm and the 42 that did not, they found that 28 (48%) and 6 (14%), respectively, had at least 1 of the 12 types of spin for harms. Inappropriate extrapolation of the results and conclusions for harms to populations, interventions, outcomes, or settings not assessed in a review was the most common category of spin in 17 of 100 reviews.The authors revised the examples to remove spin, taking into consideration the context (for example, medical discipline, source population), findings for harms, and methodological limitations of the original reviews. They provide guidance for authors, peer reviewers, and editors in recognizing and rectifying or (preferably) avoiding spin, ultimately enhancing the clarity and accuracy of harms reporting in systematic review publications.

Epidemiology and reporting characteristics of preclinical systematic reviews.

In an effort to better utilize published evidence obtained from animal experiments, systematic reviews of preclinical studies are increasingly more common-along with the methods and tools to appraise them (e.g., SYstematic Review Center for Laboratory animal Experimentation [SYRCLE's] risk of bias tool). We performed a cross-sectional study of a sample of recent preclinical systematic reviews (2015-2018) and examined a range of epidemiological characteristics and used a 46-item checklist to assess reporting details. We identified 442 reviews published across 43 countries in 23 different disease domains that used 26 animal species. Reporting of key details to ensure transparency and reproducibility was inconsistent across reviews and within article sections. Items were most completely reported in the title, introduction, and results sections of the reviews, while least reported in the methods and discussion sections. Less than half of reviews reported that a risk of bias assessment for internal and external validity was undertaken, and none reported methods for evaluating construct validity. Our results demonstrate that a considerable number of preclinical systematic reviews investigating diverse topics have been conducted; however, their quality of reporting is inconsistent. Our study provides the justification and evidence to inform the development of guidelines for conducting and reporting preclinical systematic reviews.

Photochromic Ln-MOFs: A Platform for Metal-Photoswitch Cooperativity.

Optoelectronic devices based on lanthanide-containing materials are an emergent area of research due to imminent interest in a new generation of diode materials, optical and magnetic sensors, and ratiometric thermometers. Tailoring material properties through the employment of photo- or thermochromic moieties is a powerful approach that requires a deep fundamental understanding of possible cooperativity between lanthanide-based metal centers and integrated switchable units. In this work, we probe this concept through the synthesis, structural analysis, and spectroscopic characterization of novel photochromic lanthanide-based metal-organic materials containing noncoordinatively integrated photoresponsive 4,4'-azopyridine between lanthanide-based metal centers. As a result, a photophysical material response tailored on demand through the incorporation of photochromic compounds within a rigid matrix was investigated. The comprehensive analysis of photoresponsive metal-organic materials includes single-crystal X-ray diffraction and diffuse reflectance spectroscopic studies that provide guiding principles necessary for understanding photochromic unit-lanthanide-based metal-organic framework (MOF) cooperativity. Furthermore, steady-state and time-resolved diffuse reflectance spectroscopic studies revealed a rapid rate of photoresponsive moiety attenuation upon its integration within the rigid matrix of lanthanide-based MOFs in comparison with that in solution, highlighting a unique role and synergy that occurred between stimuli-responsive moieties and the lanthanide-based MOF platform, allowing for tunability and control of material photoisomerization kinetics.

Patterns in the Use of Emergency Telemedicine Support in the Management of Traumatic Road Crashes.

Objective: The introduction of emergency telemedicine care models is a common theme in health jurisdictions that include rural and remote populations. How the availability of these models influences the way clinicians manage traumatic road crashes is not yet fully understood. This study seeks to compare road crashes where telemedicine was and was not used and to identify any variables that may increase the likelihood of telemedicine usage by treating clinicians. Methods: Road crashes reported in the state Department of Transport and Main Roads (Queensland, Australia) crash database between January 1, 2019, and November 30, 2020 (n = 23,734) were compared to videoconferencing call logs to determine which crashes resulted in treatment that was supported by telemedicine (n = 204). Analysis was performed to examine differences in characteristics related to the crash depending on whether telemedicine support was requested. Results: Road crashes where telemedicine support was requested on average involved more casualties (1.6 vs. 1.41; t(11,287) = -3.26, p < 0.001, relative risk = 1.13). Crashes that occurred in rural settings accounted for most requests for telemedicine (65.68%; X2 = 159.2, p < 0.001) and a greater percentage of crashes in remote locations (3.36% vs. 2.35%; X2 = 256.97, p < 0.001, relative risk = 1.43). The use of telemedicine support for crashes was associated with a 13% increase in the mean number of casualties, compared to crashes where telemedicine support was not used. Conclusion: Telemedicine support is requested by clinicians providing emergency treatment in the management of road crashes that produce more severe injuries, involve multiple casualties, and take place in more rural settings or remote locations.

Splinting for carpal tunnel syndrome.

BACKGROUND: Carpal tunnel syndrome (CTS) is a compression neuropathy of the median nerve causing pain and numbness and tingling typically in the thumb, index and middle finger. It sometimes results in muscle wasting, diminished sensitivity and loss of dexterity. Splinting the wrist (with or without the hand) using an orthosis is usually offered to people with mild-to-moderate findings, but its effectiveness remains unclear. OBJECTIVES: To assess the effects (benefits and harms) of splinting for people with CTS. SEARCH METHODS: On 12 December 2021, we searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase, AMED, CINAHL, ClinicalTrials.gov, and WHO ICTRP with no limitations. We checked the reference lists of included studies and relevant systematic reviews for studies. SELECTION CRITERIA: Randomised trials were included if the effect of splinting could be isolated from other treatment modalities. The comparisons included splinting versus no active treatment (or placebo), splinting versus another disease-modifying non-surgical treatment, and comparisons of different splint-wearing regimens. We excluded studies comparing splinting with surgery or one splint design with another. We excluded participants if they had previously undergone surgical release. DATA COLLECTION AND ANALYSIS: Review authors independently selected trials for inclusion, extracted data, assessed study risk of bias and the certainty in the body of evidence for primary outcomes using the GRADE approach, according to standard Cochrane methodology. MAIN RESULTS: We included 29 trials randomising 1937 adults with CTS. The trials ranged from 21 to 234 participants, with mean ages between 42 and 60 years. The mean duration of CTS symptoms was seven weeks to five years. Eight studies with 523 hands compared splinting with no active intervention (no treatment, sham-kinesiology tape or sham-laser); 20 studies compared splinting (or splinting delivered along with another non-surgical intervention) with another non-surgical intervention; and three studies compared different splinting regimens (e.g. night-time only versus full time). Trials were generally at high risk of bias for one or more domains, including lack of blinding (all included studies) and lack of information about randomisation or allocation concealment in 23 studies. For the primary comparison, splinting compared to no active treatment, splinting may provide little or no benefits in symptoms in the short term (< 3 months). The mean Boston Carpal Tunnel Questionnaire (BCTQ) Symptom Severity Scale (SSS) (scale 1 to 5, higher is worse; minimal clinically important difference (MCID) 1 point) was 0.37 points better with splint (95% confidence interval (CI) 0.82 better to 0.08 worse; 6 studies, 306 participants; low-certainty evidence) compared with no active treatment. Removing studies with high or unclear risk of bias due to lack of randomisation or allocation concealment supported our conclusion of no important effect (mean difference (MD) 0.01 points worse with splint; 95% CI 0.20 better to 0.22 worse; 3 studies, 124 participants). In the long term (> 3 months), we are uncertain about the effect of splinting on symptoms (mean BCTQ SSS 0.64 better with splinting; 95% CI 1.2 better to 0.08 better; 2 studies, 144 participants; very low-certainty evidence). Splinting probably does not improve hand function in the short term and may not improve hand function in the long term. In the short term, the mean BCTQ Functional Status Scale (FSS) (1 to 5, higher is worse; MCID 0.7 points) was 0.24 points better (95% CI 0.44 better to 0.03 better; 6 studies, 306 participants; moderate-certainty evidence) with splinting compared with no active treatment. In the long term, the mean BCTQ FSS was 0.25 points better (95% CI 0.68 better to 0.18 worse; 1 study, 34 participants; low-certainty evidence) with splinting compared with no active treatment. Night-time splinting may result in a higher rate of overall improvement in the short term (risk ratio (RR) 3.86, 95% CI 2.29 to 6.51; 1 study, 80 participants; number needed to treat for an additional beneficial outcome (NNTB) 2, 95% CI 2 to 2; low-certainty evidence).  We are uncertain if splinting decreases referral to surgery, RR 0.47 (95% CI 0.14 to 1.58; 3 studies, 243 participants; very low-certainty evidence).  None of the trials reported health-related quality of life. Low-certainty evidence from one study suggests that splinting may have a higher rate of adverse events, which were transient, but the 95% CIs included no effect. Seven of 40 participants (18%) reported adverse effects in the splinting group and 0 of 40 participants (0%) in the no active treatment group (RR 15.0, 95% CI 0.89 to 254.13; 1 study, 80 participants).  There was low- to moderate-certainty evidence for the other comparisons: splinting may not provide additional benefits in symptoms or hand function when given together with corticosteroid injection (moderate-certainty evidence) or with rehabilitation (low-certainty evidence); nor when compared with corticosteroid (injection or oral; low certainty), exercises (low certainty), kinesiology taping (low certainty), rigid taping (low certainty), platelet-rich plasma (moderate certainty), or extracorporeal shock wave treatment (moderate certainty). Splinting for 12 weeks may not be better than six weeks, but six months of splinting may be better than six weeks of splinting in improving symptoms and function (low-certainty evidence). AUTHORS' CONCLUSIONS: There is insufficient evidence to conclude whether splinting benefits people with CTS. Limited evidence does not exclude small improvements in CTS symptoms and hand function, but they may not be clinically important, and the clinical relevance of small differences with splinting is unclear. Low-certainty evidence suggests that people may have a greater chance of experiencing overall improvement with night-time splints than no treatment. As splinting is a relatively inexpensive intervention with no plausible long-term harms, small effects could justify its use, particularly when patients are not interested in having surgery or injections. It is unclear if a splint is optimally worn full time or at night-time only and whether long-term use is better than short-term use, but low-certainty evidence suggests that the benefits may manifest in the long term.

Do brushings taken during bronchoscopy for suspected primary lung cancer increase diagnostic yield? An audit of real-world clinical practice.

We reviewed clinical records to determine whether the use of bronchial brushings improved diagnostic yield in a setting where bronchoscopy for suspected primary lung cancer is routinely guided by prior chest computed tomography but endobronchial ultrasound-guided sampling is unavailable. For 29% of cases who had brushings and at least one other test taken (bronchial biopsies or washings), the histological diagnosis was made solely on the basis of samples obtained by brushings.

How often do cancer researchers make their data and code available and what factors are associated with sharing?

BACKGROUND: Various stakeholders are calling for increased availability of data and code from cancer research. However, it is unclear how commonly these products are shared, and what factors are associated with sharing. Our objective was to evaluate how frequently oncology researchers make data and code available and explore factors associated with sharing. METHODS: A cross-sectional analysis of a random sample of 306 cancer-related articles indexed in PubMed in 2019 which studied research subjects with a cancer diagnosis was performed. All articles were independently screened for eligibility by two authors. Outcomes of interest included the prevalence of affirmative sharing declarations and the rate with which declarations connected to data complying with key FAIR principles (e.g. posted to a recognised repository, assigned an identifier, data license outlined, non-proprietary formatting). We also investigated associations between sharing rates and several journal characteristics (e.g. sharing policies, publication models), study characteristics (e.g. cancer rarity, study design), open science practices (e.g. pre-registration, pre-printing) and subsequent citation rates between 2020 and 2021. RESULTS: One in five studies declared data were publicly available (59/306, 19%, 95% CI: 15-24%). However, when data availability was investigated this percentage dropped to 16% (49/306, 95% CI: 12-20%), and then to less than 1% (1/306, 95% CI: 0-2%) when data were checked for compliance with key FAIR principles. While only 4% of articles that used inferential statistics reported code to be available (10/274, 95% CI: 2-6%), the odds of reporting code to be available were 5.6 times higher for researchers who shared data. Compliance with mandatory data and code sharing policies was observed in 48% (14/29) and 0% (0/6) of articles, respectively. However, 88% of articles (45/51) included data availability statements when required. Policies that encouraged data sharing did not appear to be any more effective than not having a policy at all. The only factors associated with higher rates of data sharing were studying rare cancers and using publicly available data to complement original research. CONCLUSIONS: Data and code sharing in oncology occurs infrequently, and at a lower rate than would be expected given the prevalence of mandatory sharing policies. There is also a large gap between those declaring data to be available, and those archiving data in a way that facilitates its reuse. We encourage journals to actively check compliance with sharing policies, and researchers consult community-accepted guidelines when archiving the products of their research.

Towards realizing the vision of precision medicine: AI based prediction of clinical drug response.

Accurate and individualized prediction of response to therapies is central to precision medicine. However, because of the generally complex and multifaceted nature of clinical drug response, realizing this vision is highly challenging, requiring integrating different data types from the same individual into one prediction model. We used the anti-epileptic drug brivaracetam as a case study and combine a hybrid data/knowledge-driven feature extraction with machine learning to systematically integrate clinical and genetic data from a clinical discovery dataset (n = 235 patients). We constructed a model that successfully predicts clinical drug response [area under the curve (AUC) = 0.76] and show that even with limited sample size, integrating high-dimensional genetics data with clinical data can inform drug response prediction. After further validation on data collected from an independently conducted clinical study (AUC = 0.75), we extensively explore our model to gain insights into the determinants of drug response, and identify various clinical and genetic characteristics predisposing to poor response. Finally, we assess the potential impact of our model on clinical trial design and demonstrate that, by enriching for probable responders, significant reductions in clinical study sizes may be achieved. To our knowledge, our model represents the first retrospectively validated machine learning model linking drug mechanism of action and the genetic, clinical and demographic background in epilepsy patients to clinical drug response. Hence, it provides a blueprint for how machine learning-based multimodal data integration can act as a driver in achieving the goals of precision medicine in fields such as neurology.

Early childhood epilepsies: epidemiology, classification, aetiology, and socio-economic determinants.

Epilepsies of early childhood are frequently resistant to therapy and often associated with cognitive and behavioural comorbidity. Aetiology focused precision medicine, notably gene-based therapies, may prevent seizures and comorbidities. Epidemiological data utilizing modern diagnostic techniques including whole genome sequencing and neuroimaging can inform diagnostic strategies and therapeutic trials. We present a 3-year, multicentre prospective cohort study, involving all children under 3 years of age in Scotland presenting with epilepsies. We used two independent sources for case identification: clinical reporting and EEG record review. Capture-recapture methodology was then used to improve the accuracy of incidence estimates. Socio-demographic and clinical details were obtained at presentation, and 24 months later. Children were extensively investigated for aetiology. Whole genome sequencing was offered for all patients with drug-resistant epilepsy for whom no aetiology could yet be identified. Multivariate logistic regression modelling was used to determine associations between clinical features, aetiology, and outcome. Three hundred and ninety children were recruited over 3 years. The adjusted incidence of epilepsies presenting in the first 3 years of life was 239 per 100 000 live births [95% confidence interval (CI) 216-263]. There was a socio-economic gradient to incidence, with a significantly higher incidence in the most deprived quintile (301 per 100 000 live births, 95% CI 251-357) compared with the least deprived quintile (182 per 100 000 live births, 95% CI 139-233), χ2 odds ratio = 1.7 (95% CI 1.3-2.2). The relationship between deprivation and incidence was only observed in the group without identified aetiology, suggesting that populations living in higher deprivation areas have greater multifactorial risk for epilepsy. Aetiology was determined in 54% of children, and epilepsy syndrome was classified in 54%. Thirty-one per cent had an identified genetic cause for their epilepsy. We present novel data on the aetiological spectrum of the most commonly presenting epilepsies of early childhood. Twenty-four months after presentation, 36% of children had drug-resistant epilepsy (DRE), and 49% had global developmental delay (GDD). Identification of an aetiology was the strongest determinant of both DRE and GDD. Aetiology was determined in 82% of those with DRE, and 75% of those with GDD. In young children with epilepsy, genetic testing should be prioritized as it has the highest yield of any investigation and is most likely to inform precision therapy and prognosis. Epilepsies in early childhood are 30% more common than previously reported. Epilepsies of undetermined aetiology present more frequently in deprived communities. This likely reflects increased multifactorial risk within these populations.

Efficacy of corticosteroids for hand osteoarthritis - a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: There is some evidence that corticosteroids may have a beneficial effect in hand osteoarthritis. We examined the efficacy of corticosteroids on symptoms and structural outcomes in hand osteoarthritis. METHODS: Ovid MEDLINE, Embase and Cochrane Central Register of Controlled Trials were searched from inception to October 2021 for randomized controlled trials investigating the efficacy of corticosteroids in hand osteoarthritis. Two authors independently screened records, extracted data, and assessed risk of bias using the RoB 2 tool. Standardized mean difference (SMD) or mean difference (MD) was calculated, and random-effects meta-analyses were performed. RESULTS: Of 13 included trials, 3 examined oral corticosteroids and clinical outcomes in any hand joints, 9 examined intra-articular injection of corticosteroids and clinical outcomes at the first carpometacarpal joint and one in the interphalangeal joints. In meta-analysis, oral corticosteroids reduced pain (SMD -0.53, 95% CI -0.79 to -0.28) and improved stiffness (MD -5.03, 95% CI -9.91 to -0.15; Australian Canadian Osteoarthritis Hand Index stiffness subscale) and function (SMD -0.37, 95% CI -0.63 to -0.12) at 4-6 weeks. However, there was no significant persistent effect on pain and function at 3 months which was 6-8 weeks after study medication was stopped. There was no significant effect of intra-articular corticosteroids on pain or function at 4-6 weeks or over 3-12 months in first carpometacarpal osteoarthritis. Two trials evaluated joint structure at 4-6 weeks: one study showed oral corticosteroids reduced synovial thickening, neither showed an effect on synovitis. CONCLUSIONS: There was low-certainty evidence for a medium effect of oral corticosteroids on pain relief and stiffness improvement and small-to-medium effect on functional improvement at 4-6 weeks, with no significant effect for intra-articular corticosteroids. Corticosteroids had no significant effect on any outcomes over longer term (3-12 months) off treatment. No trials examined the effect of corticosteroids on disease progression. The role of corticosteroids in hand osteoarthritis is limited.

Implementing the 27 PRISMA 2020 Statement items for systematic reviews in the sport and exercise medicine, musculoskeletal rehabilitation and sports science fields: the PERSiST (implementing Prisma in Exercise, Rehabilitation, Sport medicine and SporTs science) guidance.

Poor reporting of medical and healthcare systematic reviews is a problem from which the sports and exercise medicine, musculoskeletal rehabilitation, and sports science fields are not immune. Transparent, accurate and comprehensive systematic review reporting helps researchers replicate methods, readers understand what was done and why, and clinicians and policy-makers implement results in practice. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement and its accompanying Explanation and Elaboration document provide general reporting examples for systematic reviews of healthcare interventions. However, implementation guidance for sport and exercise medicine, musculoskeletal rehabilitation, and sports science does not exist. The Prisma in Exercise, Rehabilitation, Sport medicine and SporTs science (PERSiST) guidance attempts to address this problem. Nineteen content experts collaborated with three methods experts to identify examples of exemplary reporting in systematic reviews in sport and exercise medicine (including physical activity), musculoskeletal rehabilitation (including physiotherapy), and sports science, for each of the PRISMA 2020 Statement items. PERSiST aims to help: (1) systematic reviewers improve the transparency and reporting of systematic reviews and (2) journal editors and peer reviewers make informed decisions about systematic review reporting quality.

Ensuring Prevention Science Research is Synthesis-Ready for Immediate and Lasting Scientific Impact.

When seeking to inform and improve prevention efforts and policy, it is important to be able to robustly synthesize all available evidence. But evidence sources are often large and heterogeneous, so understanding what works, for whom, and in what contexts can only be achieved through a systematic and comprehensive synthesis of evidence. Many barriers impede comprehensive evidence synthesis, which leads to uncertainty about the generalizability of intervention effectiveness, including inaccurate titles/abstracts/keywords terminology (hampering literature search efforts), ambiguous reporting of study methods (resulting in inaccurate assessments of study rigor), and poorly reported participant characteristics, outcomes, and key variables (obstructing the calculation of an overall effect or the examination of effect modifiers). To address these issues and improve the reach of primary studies through their inclusion in evidence syntheses, we provide a set of practical guidelines to help prevention scientists prepare synthesis-ready research. We use a recent mindfulness trial as an empirical example to ground the discussion and demonstrate ways to ensure the following: (1) primary studies are discoverable; (2) the types of data needed for synthesis are present; and (3) these data are readily synthesizable. We highlight several tools and practices that can aid authors in these efforts, such as using a data-driven approach for crafting titles, abstracts, and keywords or by creating a repository for each project to host all study-related data files. We also provide step-by-step guidance and software suggestions for standardizing data design and public archiving to facilitate synthesis-ready research.

[The PRISMA 2020 statement: an updated guideline for reporting systematic reviewsDeclaración PRISMA 2020: una guía actualizada para la publicación de revisiones sistemáticas]. / A declaração PRISMA 2020: diretriz atualizada para relatar revisões sistemáticas.

The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement, published in 2009, was designed to help systematic reviewers transparently report why the review was done, what the authors did, and what they found. Over the past decade, advances in systematic review methodology and terminology have necessitated an update to the guideline. The PRISMA 2020 statement replaces the 2009 statement and includes new reporting guidance that reflects advances in methods to identify, select, appraise, and synthesise studies. The structure and presentation of the items have been modified to facilitate implementation. In this article, we present the PRISMA 2020 27-item checklist, an expanded checklist that details reporting recommendations for each item, the PRISMA 2020 abstract checklist, and the revised flow diagrams for original and updated reviews.

La declaración PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses), publicada en 2009, se diseñó para ayudar a los autores de revisiones sistemáticas a documentar de manera transparente el porqué de la revisión, qué hicieron los autores y qué encontraron. Durante la última década, ha habido muchos avances en la metodología y terminología de las revisiones sistemáticas, lo que ha requerido una actualización de esta guía. La declaración PRISMA 2020 sustituye a la declaración de 2009 e incluye una nueva guía de presentación de las publicaciones que refleja los avances en los métodos para identificar, seleccionar, evaluar y sintetizar estudios. La estructura y la presentación de los ítems ha sido modificada para facilitar su implementación. En este artículo, presentamos la lista de verificación PRISMA 2020 con 27 ítems, y una lista de verificación ampliada que detalla las recomendaciones en la publicación de cada ítem, la lista de verificación del resumen estructurado PRISMA 2020 y el diagrama de flujo revisado para revisiones sistemáticas.

PRISMA 2020 and PRISMA-S: common questions on tracking records and the flow diagram.

The PRISMA 2020 and PRISMA-S guidelines help systematic review teams report their reviews clearly, transparently, and with sufficient detail to enable reproducibility. PRISMA 2020, an updated version of the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) statement, is complemented by PRISMA-S, an extension to PRISMA focusing on reporting the search components of systematic reviews. Several significant changes were implemented in PRISMA 2020 and PRISMA-S when compared with the original version of PRISMA in 2009, including the recommendation to report search strategies for all databases, registries, and websites that were searched. PRISMA-S also recommends reporting the number of records identified from each information source. One of the most challenging aspects of the new guidance from both documents has been changes to the flow diagram. In this article, we review some of the common questions about using the PRISMA 2020 flow diagram and tracking records through the systematic review process.

The PRISMA 2020 statement: An updated guideline for reporting systematic reviews.

Matthew Page and co-authors describe PRISMA 2020, an updated reporting guideline for systematic reviews and meta-analyses.

ROB-MEN: a tool to assess risk of bias due to missing evidence in network meta-analysis.

BACKGROUND: Selective outcome reporting and publication bias threaten the validity of systematic reviews and meta-analyses and can affect clinical decision-making. A rigorous method to evaluate the impact of this bias on the results of network meta-analyses of interventions is lacking. We present a tool to assess the Risk Of Bias due to Missing Evidence in Network meta-analysis (ROB-MEN). METHODS: ROB-MEN first evaluates the risk of bias due to missing evidence for each of the possible pairwise comparison that can be made between the interventions in the network. This step considers possible bias due to the presence of studies with unavailable results (within-study assessment of bias) and the potential for unpublished studies (across-study assessment of bias). The second step combines the judgements about the risk of bias due to missing evidence in pairwise comparisons with (i) the contribution of direct comparisons to the network meta-analysis estimates, (ii) possible small-study effects evaluated by network meta-regression, and (iii) any bias from unobserved comparisons. Then, a level of "low risk", "some concerns", or "high risk" for the bias due to missing evidence is assigned to each estimate, which is our tool's final output. RESULTS: We describe the methodology of ROB-MEN step-by-step using an illustrative example from a published NMA of non-diagnostic modalities for the detection of coronary artery disease in patients with low risk acute coronary syndrome. We also report a full application of the tool on a larger and more complex published network of 18 drugs from head-to-head studies for the acute treatment of adults with major depressive disorder. CONCLUSIONS: ROB-MEN is the first tool for evaluating the risk of bias due to missing evidence in network meta-analysis and applies to networks of all sizes and geometry. The use of ROB-MEN is facilitated by an R Shiny web application that produces the Pairwise Comparisons and ROB-MEN Table and is incorporated in the reporting bias domain of the CINeMA framework and software.

Are all blood-based postal sampling kits the same? A comparative service evaluation of the performance of dried blood spot and mini tube sample collection systems for postal HIV and syphilis testing.

OBJECTIVES: We comparatively evaluated two HIV and syphilis blood sampling kits (dried blood spot (DBS) and mini tube (MT)) as part of an online STI postal sampling service that included tests for chlamydia and gonorrhoea. We aimed to see how the blood collection systems compared regarding sample return rates and result rates. Additionally, we aimed to observe differences in false-positive results and describe a request-to-result ratio (RRR)-the required number of kit requests needed to obtain one successful result. METHODS: We reviewed data from an online postal STI kit requesting service for a client transitioning from MT to DBS blood collection systems. We described service user baseline characteristics and compared kit requests, kit and blood sample return rates, and the successful resulting rates for HIV and syphilis for MT and DBS. Pearson's χ2 and Fisher's exact test were used to determine statistical differences, and statistical formulae were applied to produce CIs for differences in proportions. RESULTS: 5670 STI postal kit requests from a Midlands region were reviewed from 6 September 2016-2 January 2019 (1515 MT and 4155 DBS). Baseline characteristics between the two groups were comparable (68.0% female, 74.0% white British and 87.5% heterosexual, median age 26 years). Successful processing rates for DBS were 94.6% and 54.4% for MT (p<0.001) with a percentage difference of 40.2% (95% CI 36.9% to 43.4%). The RRR for MT was 2.9 cf. 1.6 for DBS. False-positive results for MT samples were 5.2% (HIV) and 0.4% (syphilis), and those for DBS were 0.4% (HIV) and 0.0% (syphilis). CONCLUSIONS: This comparative analysis demonstrated the superior successful processing rates for postal DBS collection systems compared with MT. Reasons for this included insufficient volumes, high false-positive rates and degradation of blood quality in MT samples. A postal sampling service using DBS to screen for HIV, syphilis and other blood-borne viruses could be a viable alternative.

Evaluating the relationship between citation set size, team size and screening methods used in systematic reviews: a cross-sectional study.

BACKGROUND: Standard practice for conducting systematic reviews (SRs) is time consuming and involves the study team screening hundreds or thousands of citations. As the volume of medical literature grows, the citation set sizes and corresponding screening efforts increase. While larger team size and alternate screening methods have the potential to reduce workload and decrease SR completion times, it is unknown whether investigators adapt team size or methods in response to citation set sizes. Using a cross-sectional design, we sought to understand how citation set size impacts (1) the total number of authors or individuals contributing to screening and (2) screening methods. METHODS: MEDLINE was searched in April 2019 for SRs on any health topic. A total of 1880 unique publications were identified and sorted into five citation set size categories (after deduplication): < 1,000, 1,001-2,500, 2,501-5,000, 5,001-10,000, and > 10,000. A random sample of 259 SRs were selected (~ 50 per category) for data extraction and analysis. RESULTS: With the exception of the pairwise t test comparing the under 1000 and over 10,000 categories (median 5 vs. 6, p = 0.049) no statistically significant relationship was evident between author number and citation set size. While visual inspection was suggestive, statistical testing did not consistently identify a relationship between citation set size and number of screeners (title-abstract, full text) or data extractors. However, logistic regression identified investigators were significantly more likely to deviate from gold-standard screening methods (i.e. independent duplicate screening) with larger citation sets. For every doubling of citation size, the odds of using gold-standard screening decreased by 15 and 20% at title-abstract and full text review, respectively. Finally, few SRs reported using crowdsourcing (n = 2) or computer-assisted screening (n = 1). CONCLUSIONS: Large citation set sizes present a challenge to SR teams, especially when faced with time-sensitive health policy questions. Our study suggests that with increasing citation set size, authors are less likely to adhere to gold-standard screening methods. It is possible that adjunct screening methods, such as crowdsourcing (large team) and computer-assisted technologies, may provide a viable solution for authors to complete their SRs in a timely manner.

PRISMA-S: an extension to the PRISMA statement for reporting literature searches in systematic reviews.

BACKGROUND: Literature searches underlie the foundations of systematic reviews and related review types. Yet, the literature searching component of systematic reviews and related review types is often poorly reported. Guidance for literature search reporting has been diverse and, in many cases, does not offer enough detail to authors who need more specific information about reporting search methods and information sources in a clear, reproducible way. This document presents the PRISMA-S (Preferred Reporting Items for Systematic reviews and Meta-Analyses literature search extension) checklist, and explanation and elaboration. METHODS: The checklist was developed using a three-stage Delphi survey process, followed by a consensus conference and public review process. RESULTS: The final checklist includes sixteen reporting items, each of which is detailed with exemplar reporting and rationale. CONCLUSIONS: The intent of PRISMA-S is to complement the PRISMA Statement and its extensions by providing a checklist that could be used by interdisciplinary authors, editors, and peer reviewers to verify that each component of a search is completely reported and, therefore, reproducible.

Assessing risk of bias: a proposal for a unified framework for observational studies and randomized trials.

BACKGROUND: Evidence based medicine aims to integrate scientific evidence, clinical experience, and patient values and preferences. Individual health care professionals need to appraise the evidence from randomized trials and observational studies when guidelines are not yet available. To date, tools for assessment of bias and terminologies for bias are specific for each study design. Moreover, most tools appeal only to methodological knowledge to detect bias, not to subject matter knowledge, i.e. in-depth medical knowledge about a topic. We propose a unified framework that enables the coherent assessment of bias across designs. METHODS: Epidemiologists traditionally distinguish between three types of bias in observational studies: confounding, information bias, and selection bias. These biases result from a common cause, systematic error in the measurement or common effect of the intervention and outcome respectively. We applied this conceptual framework to randomized trials and show how it can be used to identify bias. The three sources of bias were illustrated with graphs that visually represent researchers' assumptions about the relationships between the investigated variables (causal diagrams). RESULTS: Critical appraisal of evidence started with the definition of the research question in terms of the population of interest, the compared interventions and the main outcome. Next, we used causal diagrams to illustrate how each source of bias can lead to over- or underestimated treatment effects. Then, we discussed how randomization, blinded outcome measurement and intention-to-treat analysis minimize bias in trials. Finally, we identified study aspects that can only be appraised with subject matter knowledge, irrespective of study design. CONCLUSIONS: The unified framework encompassed the three main sources of bias for the effect of an assigned intervention on an outcome. It facilitated the integration of methodological and subject matter knowledge in the assessment of bias. We hope that graphical diagrams will help clarify debate among professionals by reducing misunderstandings based on different terminology for bias.