Etidronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women.

BACKGROUND: Osteoporosis is an abnormal reduction in bone mass and bone deterioration, leading to increased fracture risk. Etidronate belongs to the bisphosphonate class of drugs which act to inhibit bone resorption by interfering with the activity of osteoclasts - bone cells that break down bone tissue. This is an update of a Cochrane review first published in 2008. For clinical relevance, we investigated etidronate's effects on postmenopausal women stratified by fracture risk (low versus high). OBJECTIVES: To assess the benefits and harms of intermittent/cyclic etidronate in the primary and secondary prevention of osteoporotic fractures in postmenopausal women at lower and higher risk of fracture, respectively. SEARCH METHODS: We searched the Cochrane Central Register of Control Trials (CENTRAL), MEDLINE, Embase, two clinical trial registers, the websites of drug approval agencies, and the bibliographies of relevant systematic reviews. We identified eligible trials published between 1966 and February 2023. SELECTION CRITERIA: We included randomized controlled trials that assessed the benefits and harms of etidronate in the prevention of fractures for postmenopausal women. Women in the experimental arms must have received at least one year of etidronate, with or without other anti-osteoporotic drugs and concurrent calcium/vitamin D. Eligible comparators were placebo (i.e. no treatment; or calcium, vitamin D, or both) or another anti-osteoporotic drug. Major outcomes were clinical vertebral, non-vertebral, hip, and wrist fractures, withdrawals due to adverse events, and serious adverse events. We classified a study as secondary prevention if its population fulfilled one or more of the following hierarchical criteria: a diagnosis of osteoporosis, a history of vertebral fractures, a low bone mineral density T-score (≤ -2.5), or aged 75 years or older. If none of these criteria were met, we considered the study to be primary prevention. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. The review has three main comparisons: (1) etidronate 400 mg/day versus placebo; (2) etidronate 200 mg/day versus placebo; (3) etidronate at any dosage versus another anti-osteoporotic agent. We stratified the analyses for each comparison into primary and secondary prevention studies. For major outcomes in the placebo-controlled studies of etidronate 400 mg/day, we followed our original review by defining a greater than 15% relative change as clinically important. For all outcomes of interest, we extracted outcome measurements at the longest time point in the study. MAIN RESULTS: Thirty studies met the review's eligibility criteria. Of these, 26 studies, with a total of 2770 women, reported data that we could extract and quantitatively synthesize. There were nine primary and 17 secondary prevention studies. We had concerns about at least one risk of bias domain in each study. None of the studies described appropriate methods for allocation concealment, although 27% described adequate methods of random sequence generation. We judged that only 8% of the studies avoided performance bias, and provided adequate descriptions of appropriate blinding methods. One-quarter of studies that reported efficacy outcomes were at high risk of attrition bias, whilst 23% of studies reporting safety outcomes were at high risk in this domain. The 30 included studies compared (1) etidronate 400 mg/day to placebo (13 studies: nine primary and four secondary prevention); (2) etidronate 200 mg/day to placebo (three studies, all secondary prevention); or (3) etidronate (both dosing regimens) to another anti-osteoporotic agent (14 studies: one primary and 13 secondary prevention). We discuss only the etidronate 400 mg/day versus placebo comparison here. For primary prevention, we collected moderate- to very low-certainty evidence from nine studies (one to four years in length) including 740 postmenopausal women at lower risk of fractures. Compared to placebo, etidronate 400 mg/day probably results in little to no difference in non-vertebral fractures (risk ratio (RR) 0.56, 95% confidence interval (CI) 0.20 to 1.61); absolute risk reduction (ARR) 4.8% fewer, 95% CI 8.9% fewer to 6.1% more) and serious adverse events (RR 0.90, 95% CI 0.52 to 1.54; ARR 1.1% fewer, 95% CI 4.9% fewer to 5.3% more), based on moderate-certainty evidence. Etidronate 400 mg/day may result in little to no difference in clinical vertebral fractures (RR 3.03, 95% CI 0.32 to 28.44; ARR 0.02% more, 95% CI 0% fewer to 0% more) and withdrawals due to adverse events (RR 1.41, 95% CI 0.81 to 2.47; ARR 2.3% more, 95% CI 1.1% fewer to 8.4% more), based on low-certainty evidence. We do not know the effect of etidronate on hip fractures because the evidence is very uncertain (RR not estimable based on very low-certainty evidence). Wrist fractures were not reported in the included studies. For secondary prevention, four studies (two to four years in length) including 667 postmenopausal women at higher risk of fractures provided the evidence. Compared to placebo, etidronate 400 mg/day may make little or no difference to non-vertebral fractures (RR 1.07, 95% CI 0.72 to 1.58; ARR 0.9% more, 95% CI 3.8% fewer to 8.1% more), based on low-certainty evidence. The evidence is very uncertain about etidronate's effects on hip fractures (RR 0.93, 95% CI 0.17 to 5.19; ARR 0.0% fewer, 95% CI 1.2% fewer to 6.3% more), wrist fractures (RR 0.90, 95% CI 0.13 to 6.04; ARR 0.0% fewer, 95% CI 2.5% fewer to 15.9% more), withdrawals due to adverse events (RR 1.09, 95% CI 0.54 to 2.18; ARR 0.4% more, 95% CI 1.9% fewer to 4.9% more), and serious adverse events (RR not estimable), compared to placebo. Clinical vertebral fractures were not reported in the included studies. AUTHORS' CONCLUSIONS: This update echoes the key findings of our previous review that etidronate probably makes or may make little to no difference to vertebral and non-vertebral fractures for both primary and secondary prevention.

Risk of bias in cross-sectional studies: Protocol for a scoping review of concepts and tools.

Cross-sectional studies are commonly used to study human health and disease, but are especially susceptible to bias. This scoping review aims to identify and describe available tools to assess the risk of bias (RoB) in cross-sectional studies and to compile the key bias concepts relevant to cross-sectional studies into an item bank. Using the JBI scoping review methodology, the strategy to locate relevant RoB concepts and tools is a combination of database searches, prospective review of PROSPERO registry records; and consultation with knowledge users and content experts. English language records will be included if they describe tools, checklists, or instruments which describe or permit assessment of RoB for cross-sectional studies. Systematic reviews will be included if they consider eligible RoB tools or use RoB tools for RoB of cross-sectional studies. All records will be independently screened, selected, and extracted by one researcher and checked by a second. An analytic framework will be used to structure the extraction of data. Results for the scoping review are pending. Results from this scoping review will be used to inform future selection of RoB tools and to consider whether development of a new RoB tool for cross-sectional studies is needed.

Decision aids for people facing health treatment or screening decisions.

BACKGROUND: Patient decision aids are interventions designed to support people making health decisions. At a minimum, patient decision aids make the decision explicit, provide evidence-based information about the options and associated benefits/harms, and help clarify personal values for features of options. This is an update of a Cochrane review that was first published in 2003 and last updated in 2017. OBJECTIVES: To assess the effects of patient decision aids in adults considering treatment or screening decisions using an integrated knowledge translation approach. SEARCH METHODS: We conducted the updated search for the period of 2015 (last search date) to March 2022 in CENTRAL, MEDLINE, Embase, PsycINFO, EBSCO, and grey literature. The cumulative search covers database origins to March 2022. SELECTION CRITERIA: We included published randomized controlled trials comparing patient decision aids to usual care. Usual care was defined as general information, risk assessment, clinical practice guideline summaries for health consumers, placebo intervention (e.g. information on another topic), or no intervention. DATA COLLECTION AND ANALYSIS: Two authors independently screened citations for inclusion, extracted intervention and outcome data, and assessed risk of bias using the Cochrane risk of bias tool. Primary outcomes, based on the International Patient Decision Aid Standards (IPDAS), were attributes related to the choice made (informed values-based choice congruence) and the decision-making process, such as knowledge, accurate risk perceptions, feeling informed, clear values, participation in decision-making, and adverse events. Secondary outcomes were choice, confidence in decision-making, adherence to the chosen option, preference-linked health outcomes, and impact on the healthcare system (e.g. consultation length). We pooled results using mean differences (MDs) and risk ratios (RRs) with 95% confidence intervals (CIs), applying a random-effects model. We conducted a subgroup analysis of 105 studies that were included in the previous review version compared to those published since that update (n = 104 studies). We used Grading of Recommendations Assessment, Development, and Evaluation (GRADE) to assess the certainty of the evidence. MAIN RESULTS: This update added 104 new studies for a total of 209 studies involving 107,698 participants. The patient decision aids focused on 71 different decisions. The most common decisions were about cardiovascular treatments (n = 22 studies), cancer screening (n = 17 studies colorectal, 15 prostate, 12 breast), cancer treatments (e.g. 15 breast, 11 prostate), mental health treatments (n = 10 studies), and joint replacement surgery (n = 9 studies). When assessing risk of bias in the included studies, we rated two items as mostly unclear (selective reporting: 100 studies; blinding of participants/personnel: 161 studies), due to inadequate reporting. Of the 209 included studies, 34 had at least one item rated as high risk of bias. There was moderate-certainty evidence that patient decision aids probably increase the congruence between informed values and care choices compared to usual care (RR 1.75, 95% CI 1.44 to 2.13; 21 studies, 9377 participants). Regarding attributes related to the decision-making process and compared to usual care, there was high-certainty evidence that patient decision aids result in improved participants' knowledge (MD 11.90/100, 95% CI 10.60 to 13.19; 107 studies, 25,492 participants), accuracy of risk perceptions (RR 1.94, 95% CI 1.61 to 2.34; 25 studies, 7796 participants), and decreased decisional conflict related to feeling uninformed (MD -10.02, 95% CI -12.31 to -7.74; 58 studies, 12,104 participants), indecision about personal values (MD -7.86, 95% CI -9.69 to -6.02; 55 studies, 11,880 participants), and proportion of people who were passive in decision-making (clinician-controlled) (RR 0.72, 95% CI 0.59 to 0.88; 21 studies, 4348 participants). For adverse outcomes, there was high-certainty evidence that there was no difference in decision regret between the patient decision aid and usual care groups (MD -1.23, 95% CI -3.05 to 0.59; 22 studies, 3707 participants). Of note, there was no difference in the length of consultation when patient decision aids were used in preparation for the consultation (MD -2.97 minutes, 95% CI -7.84 to 1.90; 5 studies, 420 participants). When patient decision aids were used during the consultation with the clinician, the length of consultation was 1.5 minutes longer (MD 1.50 minutes, 95% CI 0.79 to 2.20; 8 studies, 2702 participants). We found the same direction of effect when we compared results for patient decision aid studies reported in the previous update compared to studies conducted since 2015. AUTHORS' CONCLUSIONS: Compared to usual care, across a wide variety of decisions, patient decision aids probably helped more adults reach informed values-congruent choices. They led to large increases in knowledge, accurate risk perceptions, and an active role in decision-making. Our updated review also found that patient decision aids increased patients' feeling informed and clear about their personal values. There was no difference in decision regret between people using decision aids versus those receiving usual care. Further studies are needed to assess the impact of patient decision aids on adherence and downstream effects on cost and resource use.

Sensorimotor and inhibitory control in aging FMR1 premutation carriers.

Aging FMR1 premutation carriers are at risk of developing neurodegenerative disorders, including fragile X-associated tremor/ataxia syndrome (FXTAS), and there is a need to identify biomarkers that can aid in identification and treatment of these disorders. While FXTAS is more common in males than females, females can develop the disease, and some evidence suggests that patterns of impairment may differ across sexes. Few studies include females with symptoms of FXTAS, and as a result, little information is available on key phenotypes for tracking disease risk and progression in female premutation carriers. Our aim was to examine quantitative motor and cognitive traits in aging premutation carriers. We administered oculomotor tests of visually guided/reactive saccades (motor) and antisaccades (cognitive control) in 22 premutation carriers (73% female) and 32 age- and sex-matched healthy controls. Neither reactive saccade latency nor accuracy differed between groups. FMR1 premutation carriers showed increased antisaccade latencies relative to controls, both when considering males and females together and when analyzing females separately. Reduced saccade accuracy and increased antisaccade latency each were associated with more severe clinically rated neuromotor impairments. Findings indicate that together male and female premutation carriers show a reduced ability to rapidly exert volitional control over prepotent responses and that quantitative differences in oculomotor behavior, including control of visually guided and antisaccades, may track with FXTAS - related degeneration in male and female premutation carriers.

Crowd-sourcing and automation facilitated the identification and classification of randomized controlled trials in a living review.

OBJECTIVES: To evaluate an approach using automation and crowdsourcing to identify and classify randomized controlled trials (RCTs) for rheumatoid arthritis (RA) in a living systematic review (LSR). METHODS: Records from a database search for RCTs in RA were screened first by machine learning and Cochrane Crowd to exclude non-RCTs, then by trainee reviewers using a Population, Intervention, Comparison, and Outcome (PICO) annotator platform to assess eligibility and classify the trial to the appropriate review. Disagreements were resolved by experts using a custom online tool. We evaluated the efficiency gains, sensitivity, accuracy, and interrater agreement (kappa scores) between reviewers. RESULTS: From 42,452 records, machine learning and Cochrane Crowd excluded 28,777 (68%), trainee reviewers excluded 4,529 (11%), and experts excluded 7,200 (17%). The 1,946 records eligible for our LSR represented 220 RCTs and included 148/149 (99.3%) of known eligible trials from prior reviews. Although excluded from our LSRs, 6,420 records were classified as other RCTs in RA to inform future reviews. False negative rates among trainees were highest for the RCT domain (12%), although only 1.1% of these were for the primary record. Kappa scores for two reviewers ranged from moderate to substantial agreement (0.40-0.69). CONCLUSION: A screening approach combining machine learning, crowdsourcing, and trainee participation substantially reduced the screening burden for expert reviewers and was highly sensitive.

Health Security Perceptions: Initial Psychometric Analysis of the Construct of Health Security in Chronic Illness Among Patients With a Cardiac Device.

Scale measuring the construct of "health security in chronic illness" (HSCI) was piloted in Canadian cardiac device patients (N = 176) enrolled in a remote-monitoring study at 2 timepoints. Analysis revealed a 2-factor solution, labeled as "support" and "certainty". Patients reported receiving less support over time, but consistent health certainty. Patients with implantable cardioverter defibrillators felt less secure over time and reported lower levels of health security in chronic illness than pacemaker patients.

Une échelle mesurant le concept de la « sécurité en matière de santé en présence d'une maladie chronique ¼ a fait l'objet d'un projet pilote auprès de patients canadiens porteurs de dispositifs cardiaques (N = 176) inscrits dans une étude de télésurveillance comportant deux évaluations. L'analyse a révélé une solution à deux facteurs, soit le soutien et la certitude. Les patients ont déclaré qu'ils recevaient moins de soutien au fil du temps, mais que la certitude quant à leur santé était constante. Les porteurs d'un défibrillateur cardioverteur implantable se sentaient moins en sécurité au fil du temps et signalaient de plus bas niveaux de sécurité en matière de santé, relativement à leur maladie chronique, que les porteurs d'un stimulateur cardiaque.

Sensorimotor Behavior in Individuals with Autism Spectrum Disorder and Their Unaffected Biological Parents.

Background: Sensorimotor impairments are common in autism spectrum disorder (ASD) and evident in unaffected first-degree relatives, suggesting that they may serve as important endophenotypes associated with inherited risk. We tested the familiality of sensorimotor impairments in ASD across multiple motor behaviors and effector systems and in relation to parental broader autism phenotypic (BAP) characteristics. Methods: Fifty-eight autistic individuals (probands), 109 parents, and 89 control participants completed tests of manual motor and oculomotor control. Sensorimotor tests varied in their involvement of rapid, feedforward control and sustained, sensory feedback control processes. Subgroup analyses compared families with at least one parent showing BAP traits (BAP+) and those in which neither parent showed BAP traits (BAP-). Results: Probands with BAP- parents (BAP- probands) showed rapid manual motor and oculomotor deficits, while BAP+ probands showed sustained motor impairments compared to controls. BAP- parents showed impaired rapid oculomotor and sustained manual motor abilities relative to BAP+ parents and controls. Atypical rapid oculomotor impairments also were familial. Limitations: Larger samples of ASD families including greater samples of probands with BAP+ parents are needed. Genetic studies also are needed to link sensorimotor endophenotype findings directly to genes. Conclusions: Results indicate rapid sensorimotor behaviors are selectively impacted in BAP- probands and their parents and may reflect familial liabilities for ASD that are independent of familial autistic traits. Sustained sensorimotor behaviors were affected in BAP+ probands and BAP- parents re ecting familial traits that may only confer risk when combined with parental autistic trait liabilities. These findings provide new evidence that rapid and sustained sensorimotor alterations represent strong but separate familial pathways of ASD risk that demonstrate unique interactions with mechanisms related to parental autistic traits.

Extended dual antiplatelet therapy following percutaneous coronary intervention in clinically important patient subgroups: a systematic review and meta-analysis.

BACKGROUND: Dual antiplatelet therapy (DAPT) is routinely given to patients after percutaneous coronary intervention (PCI) with stenting; however, optimal duration remains uncertain in some situations. We assessed the benefits and harms of extending DAPT beyond 1 year after PCI in clinically important patient subgroups. METHODS: We conducted a systematic review and meta-analysis. We searched electronic databases (Embase, MEDLINE, PubMed, Cochrane Library) and grey literature (from inception to Nov. 5, 2021) and included randomized controlled trials (RCTs) of extended DAPT (> 12 mo) compared with DAPT for 6-12 months following PCI with stenting. The primary outcome was death (all cause, cardiovascular, noncardiovascular); secondary outcomes included major adverse cardiovascular and cerebrovascular events, myocardial infarction (MI), stroke, stent thrombosis and bleeding. Subgroups were based on prespecified patient characteristics (prior MI, acute coronary syndrome [ACS], diabetes mellitus, age, smoking status). Data were analyzed by random-effects pairwise meta-analysis. RESULTS: We identified 9 RCTs that provided subgroup data. We found that extended DAPT reduced the risk of MI and stent thrombosis but increased the risk of bleeding, compared with standard DAPT, with no difference in the risk of all-cause death (relative risk [RR] 1.07, 95% confidence interval [CI] 0.80-1.42) or cardiovascular death (RR 0.98, 95% CI 0.74-1.30). We found that patients with a prior MI, with ACS at presentation, without diabetes or aged younger than 75 years may derive the most benefit from extended DAPT. Among patients who received extended DAPT, the risk of all-cause death was significantly increased among those with no prior MI (RR 1.64, 95% CI 1.08-2.24), whereas there was no significant difference in the risk of all-cause death between standard and extended DAPT for patients with ACS (RR 1.20, 95% CI 0.51-2.83), with diabetes (RR 1.27, 95% CI 0.86-1.89), aged older than 75 years (RR 1.32, 95% CI 0.39-4.54) or who smoked (RR 0.90, 95% CI 0.42-1.92). Similar results were found for cardiovascular death, where data were available. INTERPRETATION: Patients with a previous MI with ACS at presentation, without diabetes, or aged younger than 75 years may derive the most benefit from extended DAPT. These findings support the need for careful selection of patients who may benefit most from extended DAPT. STUDY REGISTRATION: PROSPERO no. CRD42018082587.

Corrigendum: Cerebellar volumes and sensorimotor behavior in autism spectrum disorder.

[This corrects the article DOI: 10.3389/fnint.2022.821109.].

Paper 4: a review of reporting and disseminating approaches for rapid reviews in health policy and systems research.

BACKGROUND: Transparent reporting of rapid reviews enables appropriate use of research findings and dissemination strategies can strengthen uptake and impact for the targeted knowledge users, including policy-makers and health system managers. The aim of this literature review was to understand reporting and dissemination approaches for rapid reviews and provide an overview in the context of health policy and systems research. METHODS: A literature review and descriptive summary of the reporting and disseminating approaches for rapid reviews was conducted, focusing on available guidance and methods, considerations for engagement with knowledge users, and optimizing dissemination. MEDLINE, PubMed, Google scholar, as well as relevant websites and reference lists were searched from January 2017 to March 2021 to identify the relevant literature with no language restrictions. Content was abstracted and charted. RESULTS: The literature review found limited guidance specific to rapid reviews. Building on the barriers and facilitators to systematic review use, we provide practical recommendations on different approaches and methods for reporting and disseminating expedited knowledge synthesis considering the needs of health policy and systems knowledge users. Reporting should balance comprehensive accounting of the research process and findings with what is "good enough" or sufficient to meet the requirements of the knowledge users, while considering the time and resources available to conduct a review. Typical approaches may be used when planning the dissemination of rapid review findings; such as peer-reviewed publications or symposia and clear and ongoing engagement with knowledge users in crafting the messages is essential so they are appropriately tailored to the target audience. Consideration should be given to providing different products for different audiences. Dissemination measures and bibliometrics are also useful to gauge impact and reach. CONCLUSIONS: Limited guidance specific to the reporting and dissemination of rapid reviews is available. Although approaches to expedited synthesis for health policy and systems research vary, considerations for the reporting and dissemination of findings are pertinent to all.

Cerebellar Volumes and Sensorimotor Behavior in Autism Spectrum Disorder.

Background: Sensorimotor issues are common in autism spectrum disorder (ASD), though their neural bases are not well understood. The cerebellum is vital to sensorimotor control and reduced cerebellar volumes in ASD have been documented. Our study examined the extent to which cerebellar volumes are associated with multiple sensorimotor behaviors in ASD. Materials and Methods: Fifty-eight participants with ASD and 34 typically developing (TD) controls (8-30 years) completed a structural MRI scan and precision grip testing, oculomotor testing, or both. Force variability during precision gripping as well as absolute error and trial-to-trial error variability of visually guided saccades were examined. Volumes of cerebellar lobules, vermis, and white matter were quantified. The relationships between each cerebellar region of interest (ROI) and force variability, saccade error, and saccade error variability were examined. Results: Relative to TD controls, individuals with ASD showed increased force variability. Individuals with ASD showed a reduced volume of cerebellar vermis VI-VII relative to TD controls. Relative to TD females, females with ASD showed a reduced volume of bilateral cerebellar Crus II/lobule VIIB. Increased volume of Crus I was associated with increased force variability. Increased volume of vermal lobules VI-VII was associated with reduced saccade error for TD controls but not individuals with ASD. Increased right lobule VIII and cerebellar white matter volumes as well as reduced right lobule VI and right lobule X volumes were associated with greater ASD symptom severity. Reduced volumes of right Crus II/lobule VIIB were associated with greater ASD symptom severity in only males, while reduced volumes of right Crus I were associated with more severe restricted and repetitive behaviors only in females. Conclusion: Our finding that increased force variability in ASD is associated with greater cerebellar Crus I volumes indicates that disruption of sensory feedback processing supported by Crus I may contribute to skeletomotor differences in ASD. Results showing that volumes of vermal lobules VI-VII are associated with saccade precision in TD but not ASD implicates atypical organization of the brain systems supporting oculomotor control in ASD. Associations between volumes of cerebellar subregions and ASD symptom severity suggest cerebellar pathological processes may contribute to multiple developmental challenges in ASD.

Comparative efficacy and safety of antihyperglycemic drug classes for patients with type 2 diabetes following failure with metformin monotherapy: A systematic review and network meta-analysis of randomized controlled trials.

AIMS: To compare the efficacy and safety of antihyperglycemic agents, taken in combination with metformin, for the treatment of type 2 diabetes mellitus (T2DM). METHODS: A previous 2016 comprehensive search of Ovid MEDLINE, PubMed, and Cochrane CENTRAL was updated to October 2018, and a systematic review and network meta-analysis (NMA) was conducted. Randomized controlled trials (RCTs) of patients with T2DM taking an antihyperglycemic agent in combination with metformin were included. Bayesian NMA was performed to assess the relative efficacy and safety of the antihyperglycemic classes. RESULTS: In total, 204 RCTs were included, which assessed the efficacy and safety of eight antihyperglycemic drug classes (i.e., sulfonylureas, meglitinides, alpha-glucosidase inhibitors, thiazolidinediones, basal and biphasic insulin, dipeptidyl peptidase 4 inhibitors, glucagon-like-peptide-1 receptor agonists and sodium-glucose cotransport-2 inhibitors). All drug classes significantly reduced haemoglobin A1c (HbA1c) compared to metformin monotherapy (mean reduction from 0.50 to 0.92). The drug classes varied in their relative effects on hypoglycemia, body weight, body mass index, systolic and diastolic blood pressure, total cholesterol, high and low density lipoprotein cholesterol, and the classes had differing safety profiles on total adverse events, urogenital adverse events, heart failure, serious adverse events, and withdraw due to adverse events. CONCLUSIONS: All eight antihyperglycemic drug classes, taken in combination with metformin, reduced HbA1c levels; however, the effects of the agents on other outcomes varied among the classes.

NUQUEST-NUtrition QUality Evaluation Strengthening Tools: development of tools for the evaluation of risk of bias in nutrition studies.

BACKGROUND: Dietary exposure assessments are a critical issue in evaluating human nutrition studies; however, nutrition-specific criteria are not consistently included in existing bias assessment tools. OBJECTIVES: Our objective was to develop a set of risk of bias (RoB) tools that integrated nutrition-specific criteria into validated generic assessment tools to address RoB issues, including those specific to dietary exposure assessment. METHODS: The Nutrition QUality Evaluation Strengthening Tools (NUQUEST) development and validation process included 8 steps. The first steps identified 1) a development strategy; 2) generic assessment tools with demonstrated validity; and 3) nutrition-specific appraisal issues. This was followed by 4) generation of nutrition-specific items and 5) development of guidance to aid users of NUQUEST. The final steps used established ratings of selected studies and feedback from independent raters to 6) assess reliability and validity; 7) assess formatting and usability; and 8) finalize NUQUEST. RESULTS: NUQUEST is based on the Scottish Intercollegiate Guidelines Network checklists for randomized controlled trials, cohort studies, and case-control studies. Using a purposive sample of 45 studies representing the 3 study designs, interrater reliability was high (Cohen's κ: 0.73; 95% CI: 0.52, 0.93) across all tools and at least moderate for individual tools (range: 0.57-1.00). The use of a worksheet improved usability and consistency of overall interrater agreement across all study designs (40% without worksheet, 80%-100% with worksheet). When compared to published ratings, NUQUEST ratings for evaluated studies demonstrated high concurrent validity (93% perfect or near-perfect agreement). Where there was disagreement, the nutrition-specific component was a contributing factor in discerning exposure methodological issues. CONCLUSIONS: NUQUEST integrates nutrition-specific criteria with generic criteria from assessment tools with demonstrated reliability and validity. NUQUEST represents a consistent and transparent approach for evaluating RoB issues related to dietary exposure assessment commonly encountered in human nutrition studies.

Guidance for using artificial intelligence for title and abstract screening while conducting knowledge syntheses.

BACKGROUND: Systematic reviews are the cornerstone of evidence-based medicine. However, systematic reviews are time consuming and there is growing demand to produce evidence more quickly, while maintaining robust methods. In recent years, artificial intelligence and active-machine learning (AML) have been implemented into several SR software applications. As some of the barriers to adoption of new technologies are the challenges in set-up and how best to use these technologies, we have provided different situations and considerations for knowledge synthesis teams to consider when using artificial intelligence and AML for title and abstract screening. METHODS: We retrospectively evaluated the implementation and performance of AML across a set of ten historically completed systematic reviews. Based upon the findings from this work and in consideration of the barriers we have encountered and navigated during the past 24 months in using these tools prospectively in our research, we discussed and developed a series of practical recommendations for research teams to consider in seeking to implement AML tools for citation screening into their workflow. RESULTS: We developed a seven-step framework and provide guidance for when and how to integrate artificial intelligence and AML into the title and abstract screening process. Steps include: (1) Consulting with Knowledge user/Expert Panel; (2) Developing the search strategy; (3) Preparing your review team; (4) Preparing your database; (5) Building the initial training set; (6) Ongoing screening; and (7) Truncating screening. During Step 6 and/or 7, you may also choose to optimize your team, by shifting some members to other review stages (e.g., full-text screening, data extraction). CONCLUSION: Artificial intelligence and, more specifically, AML are well-developed tools for title and abstract screening and can be integrated into the screening process in several ways. Regardless of the method chosen, transparent reporting of these methods is critical for future studies evaluating artificial intelligence and AML.

Remote Monitoring of Cardiovascular Implantable Electronic Devices in Canada: Survey of Patients and Device Health Care Professionals.

BACKGROUND: Remote monitoring is used to supplement in-clinic follow-up for patients with cardiac implantable electronic devices (CIEDs) every 6-12 months. There is a need to optimize remote management for CIEDs because of the consistent increases in CIED implants over the past decade. The objective of this study was to investigate real and perceived barriers to the use of remote patient management strategies in Canada and to better understand how remote models of care can be optimized. METHODS: We surveyed 512 CIED patients and practitioners in 22 device clinics in Canada. RESULTS: Device clinic surveys highlighted significant variation and inconsistency in follow-up care for in-clinic and remote visits across and within clinics. This survey showed that funding policies and management of additional workflow are barriers to optimal use and uptake. Despite this, device clinics perceive remote follow-up as a valuable resource and an efficient way to manage patient follow-up. Patients were broadly satisfied with their CIED follow-up care but identified barriers related to coordination of care, visit logistics, and information needs. Views varied as a function of clinical or sociodemographic characteristics. Most patients (n = 228; 91%) expressed a desire to receive a phone call from their device clinic after a remote transmission has been received. CONCLUSIONS: Lack of a unified, guideline-supported approach to follow-up after CIED implant, and discrepant funding policies across jurisdictions, are significant barriers to the use of remote patient management strategies in Canada. Efforts to increase or expand use of remote follow-up must recognize these barriers and the needs of specific subgroups of patients.

INTRODUCTION: La télésurveillance sert de complément à la consultation en clinique des patients porteurs d'un dispositif cardiaque électronique implantable (DCEI) tous les 6 à 12 mois. Il est nécessaire d'optimiser la prise en charge à distance des patients porteurs de DCEI en raison de la constante augmentation des implantations de DCEI au cours de la dernière décennie. L'objectif de la présente étude était d'examiner les obstacles réels et perçus à l'utilisation des stratégies de prise en charge à distance des patients du Canada et de mieux comprendre la façon d'optimiser les modèles de soins à distance. MÉTHODES: Nous avons interrogé 512 patients porteurs de DCEI et praticiens de 22 cliniques spécialisées en DCEI du Canada. RÉSULTATS: Les enquêtes des cliniques spécialisées en DCEI ont fait ressortir la variation importante et le manque d'uniformité dans les soins de suivi lors des consultations en clinique et à distance au sein de toutes les cliniques et entre elles. Cette enquête a montré que les politiques de financement et la gestion du flux de travail supplémentaire sont les obstacles qui empêchent l'utilisation optimale et l'adoption. Malgré cela, les cliniques spécialisées en DCEI perçoivent le suivi à distance comme une ressource très utile et un moyen efficace de prendre en charge le suivi du patient. Les patients étaient dans l'ensemble satisfaits de leurs soins de suivi relatifs à leur DCEI, mais relevaient des obstacles liés à la coordination des soins, à la logistique des consultations et à leurs besoins d'information. Les points de vue variaient en fonction des caractéristiques cliniques et sociodémographiques. La plupart des patients (n = 228 ; 91 %) ont fait part de leur souhait de recevoir un appel téléphonique de leur clinique spécialisée en DCEI après la réception de la transmission à distance. CONCLUSIONS: L'absence d'une approche unifiée et fondée sur les lignes directrices qui porte sur le suivi après l'implantation de DCEI, et la divergence des politiques de financement des provinces et territoires sont des obstacles importants à l'utilisation de stratégies de prise en charge à distance des patients au Canada. Les efforts visant à accroître ou à étendre l'utilisation du suivi à distance doivent tenir compte de ces obstacles et des besoins des sous-groupes particuliers de patients.

Reduced Proactive Control Processes Associated With Behavioral Response Inhibition Deficits in Autism Spectrum Disorder.

Impairments in inhibitory control are common in individuals with autism spectrum disorder (ASD) and associated with multiple clinical issues. Proactive (i.e., delaying response onset) and reactive control mechanisms (i.e., stopping quickly) contribute to successful inhibitory control in typically developing individuals and may be compromised in ASD. We assessed inhibitory control in 58 individuals with ASD and 63 typically developing controls aged 5-29 years using an oculomotor stop-signal task during which participants made rapid eye movements (i.e., saccades) toward peripheral targets (i.e., GO trials) or inhibited saccades (i.e., STOP trials). Individuals with ASD exhibited reduced ability to inhibit saccades, reduced reaction time slowing (GO RT slowing), and faster stop-signal reaction times (SSRT) compared to controls. Across participants, stopping accuracy was positively related to GO RT slowing, and increased age was associated with higher stopping accuracy and GO RT slowing. Our results indicate that failures to proactively delay prepotent responses in ASD underpin deficits of inhibitory control and may contribute to difficulties modifying their behavior according to changes in contextual demands. These findings implicate frontostriatal brain networks in inhibitory control and core symptoms of ASD. LAY SUMMARY: Difficulties stopping actions are common in individuals with autism spectrum disorder (ASD) and are related to repetitive behaviors. This study compared the ability to stop eye movements in individuals with ASD and healthy peers. We found that individuals with ASD were less able to stop eye movements and that this difficulty was related to a reduced ability to delay their eye movements before seeing the cue to stop, not their ability to react quickly to this cue.

Pharmacologic treatment of attention deficit hyperactivity disorder in adults: A systematic review and network meta-analysis.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) affects approximately 3% of adults globally. Many pharmacologic treatments options exist, yet the comparative benefits and harms of individual treatments are largely unknown. We performed a systematic review and network meta-analysis to assess the relative effects of individual pharmacologic treatments for adults with ADHD. METHODS: We searched English-language published and grey literature sources for randomized clinical trials (RCTs) involving pharmacologic treatment of ADHD in adults (December 2018). The primary outcome was clinical response; secondary outcomes were quality of life, executive function, driving behaviour, withdrawals due to adverse events, treatment discontinuation, serious adverse events, hospitalization, cardiovascular adverse events, and emergency department visits. Data were pooled via pair-wise meta-analyses and Bayesian network meta-analyses. Risk of bias was assessed by use of Cochrane's Risk of Bias tool, and the certainty of the evidence was assessed by use of the GRADE framework. RESULTS: Eighty-one unique trials that reported at least one outcome of interest were included, most of which were at high or unclear risk of at least one important source of bias. Notably, only 5 RCTs were deemed at overall low risk of bias. Included pharmacotherapies were methylphenidate, atomoxetine, dexamfetamine, lisdexamfetamine, guanfacine, bupropion, mixed amphetamine salts, and modafinil. As a class, ADHD pharmacotherapy improved patient- and clinician-reported clinical response compared with placebo (range: 4 to 15 RCTs per outcome); however, these findings were not conserved when the analyses were restricted to studies at low risk of bias, and the certainty of the finding is very low. There were few differences among individual medications, although atomoxetine was associated with improved patient-reported clinical response and quality of life compared with placebo. There was no significant difference in the risk of serious adverse events or treatment discontinuation between ADHD pharmacotherapies and placebo; however, the proportion of participants who withdrew due to adverse events was significantly higher among participants who received any ADHD pharmacotherapy. Few RCTs reported on the occurrence of adverse events over a long treatment duration. CONCLUSIONS: Overall, despite a class effect of improving clinical response relative to placebo, there were few differences among the individual ADHD pharmacotherapies, and most studies were at risk of at least one important source of bias. Furthermore, the certainty of the evidence was very low to low for all outcomes, and there was limited reporting of long-term adverse events. As such, the choice between ADHD pharmacotherapies may depend on individual patient considerations, and future studies should assess the long-term effects of individual pharmacotherapies on patient-important outcomes, including quality of life, in robust blinded RCTs. REGISTRATION: PROSPERO no. CRD 42015026049.

Patient and healthcare provider reported barriers and enablers to virtual or remote-only follow-up models for cardiovascular implantable electronic devices: protocol for a qualitative framework synthesis.

BACKGROUND: Virtual care models are used to follow-up patients with cardiovascular implantable electronic devices (CIED), including pacemakers, implantable cardioverter defibrillators, and cardiac resynchronization therapy. There is increasing interest in the expansion of virtual, or even remote-only, CIED care models to alleviate resource and economic burden to both patients and specialty device clinics and to maintain or improve equity and access to high-quality cardiovascular care. This qualitative framework synthesis aims to identify barriers and enablers to virtual care models from both the perspective of the patient and device clinics. How setting, context, equity factors or other aspects influence these factors, or satisfaction with care, will also be investigated. METHODS: We will perform a systematic literature search in MEDLINE, Embase, PsycINFO, CINAHL, Proquest Dissertations & Theses, other EBM Reviews, and trial registry databases. Screening will be completed by two independent review authors. Original research articles having a qualitative component (i.e., qualitative, mixed-, or multi-method) are eligible. Study populations of interest are (a) individuals with a CIED or (b) healthcare providers involved in any aspect of virtual or remote follow-up of patients with CIEDs. Eligibility will be restricted to studies published after January 1, 2000 in English or French. Data will be captured using standardized templates based on the domains and constructs of the Theoretical Domains Framework and the Warwick Patient Experiences Framework. The Joanna Briggs Institute Critical Appraisal Checklist for Qualitative Research will be applied to all included studies. The GRADE-CERQual approach will be applied to assess and summarize confidence in key findings. Reporting will follow the enhancing transparency in reporting the synthesis of qualitative research (ENTREQ) statement. Detailed descriptive results will be presented, and summary of qualitative findings tables will be produced. DISCUSSION: While a number of trials have captured the clinical effectiveness and safety of virtual follow-up for CIEDs, there has been less attention given to factors affecting use and implementation of remote care by patients and healthcare providers or satisfaction with care. Results from this qualitative framework synthesis will provide important lived experience data from both patients and healthcare providers which will be essential to incorporate in clinical guidelines. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020160533.