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Co-occurring mental health and substance use (SU) disorders among adolescents are common, with two-thirds of adolescents who seek SU treatment also requiring support for mental health. Primary care physicians play a key role in the pharmacological treatment of mental health disorders among adolescents, however, little is known about the impact of these treatments on SU outcomes.This systematic review summarizes the evidence regarding commonly used pharmacotherapy interventions for mental health and their impact on adolescent SU.Literature searches were conducted across five databases as part of a larger systematic review of adolescent SU interventions. Studies were screened for eligibility by two researchers, and study data were extracted regarding study design, patient and treatment characteristics and results. Risk of bias analyses and qualitative syntheses were completed to evaluate the strength of the evidence and the impact of pharmacotherapy on SU outcomes.Ten randomized controlled trials exploring seven pharmacotherapies met criteria for inclusion. All studies had low to moderate risk of bias. Four studies evaluated pharmacotherapy for co-occurring depression and SU, three evaluated attention deficit hyperactivity disorder and SU, and three evaluated bipolar disorder and SU. Five of the 10 studies also included a behavioural intervention. We found no evidence that pharmacotherapy for co-occurring mental health diagnoses impacted SU.Family medicine clinicians prescribing pharmacotherapy for mental health should be aware that additional interventions will likely be needed to address co-occurring SU.Many adolescents have both mental health and substance use problems. Adolescents have difficulty getting effective treatment for both substance use and mental health concerns, in part because these treatments are often offered separately. Primary care physicians, who often care for adolescents with mental health concerns, may prescribe medications for diagnoses such as attention deficit hyperactivity disorder, depression or early symptoms of bipolar disorder. However, there is little research indicating whether these medications are helpful for co-occurring substance use disorder symptoms. This paper presents a review of existing research on medications used to treat common mental health disorders to evaluate their effect on substance use. Ten studies address this question and suggest that medications for mental health are insufficient for helping adolescents with substance use disorders or substance use problems.

Objectives Using recent systematic reviews (SRs), our objectives were to: (1) develop a framework to assess whether a given COS is relevant to the scope of a SR; (2) examine the proportion of SRs for which relevant COS exist; and (3) for SRs for which COS exist, examine the extent to which outcomes in the COS and outcomes in the SR match. Study Design and Setting We included a sample of SRs published by the Agency for Healthcare Research and Quality Evidence-based Practice Center Program between January 1, 2018 and October 12, 2020. We searched for potentially relevant COS from the Core Outcome Measures for Effectiveness Trials (COMET) database. We assessed the matching between outcomes recommended by COS and those included in corresponding SRs. When outcomes were matched, we considered matches to be specific (i.e., exact) or general (i.e., non-specific). Results Sixty-seven SRs met criteria. We found relevant COS for 36 of 67 SRs (54%). Our framework for comparing the scope of a SR and a COS describes 16 scenarios arising when the breadth of the populations and the interventions are considered. The framework guides systematic reviewers to determine whether a COS is very likely to be relevant, may be relevant, or unlikely to be relevant. Sixty-two percent of outcomes in COS (interquartile range, 40% – 80%) were either specific or general matches to outcomes in SRs. Conclusion We found a COS with relevant scope for more than half of the SRs in our sample, with almost two-thirds of the recommended core outcomes matched to outcomes chosen for the SRs. Consideration of COS appears relevant for SR planning and our framework for assessing relevance of a given COS may help with this process.

Purpose Among adult individuals with dry eye, assess the self-reported impact of the COVID-19 pandemic on (1) dry eye-related visual function, (2) reading efficiency, and (3) dry eye treatments used. Methods In June–July 2020, we conducted an online survey of adults with dry eye who spent at least somewhat more time at home during the pandemic than before. Consistent with TFOS DEWS II guidelines, we categorized respondents into mild, moderate, or severe dry eye based on treatment usage. Results We included 388 respondents: 97 respondents (25%) with mild, 80 (21%) with moderate, and 211 (54%) with severe dry eye. In all three groups, screen/reading time generally doubled during the pandemic. Reduced work-related efficiency was noted by a considerable proportion of respondents (moderate dry eye: 51%, mild: 39%, and severe: 38%). Compared with respondents with mild dry eye, respondents with moderate dry eye were considerably more likely to note worsening symptoms: eye pain (OR = 2.57, 95% CI 1.22–5.41), headache from eye symptoms (OR = 2.34, 95% CI 1.11–4.90), and difficulty concentrating because of eye symptoms (OR = 2.79, 95% CI 1.37–5.66). Respondents with moderate dry eye with Sjogren's syndrome were most likely to note these. Respondents with severe dry eye were more likely than respondents with mild dry eye to report losing access to dry eye-related treatments (OR = 2.62, 95% CI 1.36–5.03). Conclusions The COVID-19 pandemic-related eye strain may be impacting symptoms, performance, and ultimately employment, especially for those with moderate dry eye. This may be compounding the already-high dry eye-related societal burden.

Background Primary headaches (migraine, tension headache, cluster headache, and other trigeminal autonomic cephalgias) are common in pregnancy and postpartum. It is unclear how to best and most safely manage them. Objective We conducted a systematic review (SR) of interventions to prevent or treat primary headaches in women who are pregnant, attempting to become pregnant, postpartum, or breastfeeding. Methods We searched Medline, Embase, Cochrane CENTRAL, CINAHL, ClinicalTrials.gov, Cochrane Database of SRs, and Epistemonikos for primary studies of pregnant women with primary headache and existing SRs of harms in pregnant women regardless of indication. No date or language restrictions were applied. We assessed strength of evidence (SoE) using standard methods. Results We screened 8549 citations for studies and 2788 citations for SRs. Sixteen studies (mostly high risk of bias) comprising 14,185 patients (total) and 26 SRs met the criteria. For prevention, we found no evidence addressing effectiveness. Antiepileptics, venlafaxine, tricyclic antidepressants, benzodiazepines, β-blockers, prednisolone, and oral magnesium may be associated with fetal/child adverse effects, but calcium channel blockers and antihistamines may not be (1 single-group study and 11 SRs; low-to-moderate SoE). For treatment, combination metoclopramide and diphenhydramine may be more effective than codeine for migraine or tension headache (1 randomized controlled trial; low SoE). Triptans may not be associated with fetal/child adverse effects (8 nonrandomized comparative studies; low SoE). Acetaminophen, prednisolone, indomethacin, ondansetron, antipsychotics, and intravenous magnesium may be associated with fetal/child adverse effects, but low-dose aspirin may not be (indirect evidence; low-to-moderate SoE). We found insufficient evidence regarding non-pharmacologic treatments. Conclusions For prevention of primary headache, calcium channel blockers and antihistamines may not be associated with fetal/child adverse effects. For treatment, combination metoclopramide and diphenhydramine may be more effective than codeine. Triptans and low-dose aspirin may not be associated with fetal/child adverse effects. Future research should identify effective and safe interventions in pregnancy and postpartum.

Purpose To compare the burden related to dry eye with systemic symptoms of Sjogren syndrome; to estimate the burden related to ocular treatments; and to compare the impact of dry eye and extraocular manifestations of Sjogren syndrome on various aspects of patient life. Design Cross-sectional study. Methods We conducted a postal survey of adult patients with a history of physician-diagnosed Sjogren syndrome. Results The survey was completed by 2,961 patients (mean age 65.1 years, standard deviation 11.7 years), most of whom were women (96%) and white (94%). Forty-one patients younger than 18 years of age were excluded. More than half (53%) experienced severe dry eye (ie, dry eye daily/almost daily with major impact on their life). Corresponding proportions for dry mouth and fatigue were 48% and 45%, respectively. Almost all patients (97%) had used nonprescription eye drops/artificial tears/ointments. Compared with patients who did not experience dry eye, those who experienced significant dry eye (ie, daily/almost daily dry eye) more often agreed that living with Sjogren syndrome made every day a challenge (adjusted odds ratio [OR] 3.81, 95% confidence interval [CI] 2.49 to 5.86) and added a significant emotional burden (adjusted OR 2.22, 95% CI 1.49 to 3.31). Adjusted ORs for the impact of dry eye were generally lower than those for fatigue, but were similar to dry mouth and considerably higher than use of systemic treatments for serious manifestations of the disease and diagnosis of lymphoma. Conclusions Sjogren-related dry eye is more burdensome than systemic manifestations of the disease. While fatigue has the greatest impact on patient life, the impact of dry eye is comparable to that of other systemic manifestations.

Objective.To define the association between oral and systemic manifestations of Sjögren syndrome (SS) and quality of life (QOL).Methods.We analyzed a cross-sectional survey conducted by the Sjögren’s Foundation in 2016, with 2961 eligible responses. We defined oral symptom and sign exposures as parotid gland swelling, dry mouth, mouth ulcers/sores, oral candidiasis, trouble speaking, choking or dysphagia, sialolithiasis or gland infection, and dental caries. Systemic exposures included interstitial lung disease, purpura/petechiae/cryoglobulinemia, vasculitis, neuropathy, leukopenia, interstitial nephritis, renal tubular acidosis, autoimmune hepatitis, primary biliary cholangitis, or lymphoma. Outcomes included SS-specific QOL questions generated by SS experts and patients.Results.Using multivariable regression models adjusted for age, sex, race, and employment, we observed that mouth ulcers or sores, trouble speaking, and dysphagia were associated with poor quality of life. The following oral aspects had the greatest effect on the following QOL areas: (1) mouth ulcers/sores on the challenge and burden of living with SS (OR 4.26, 95% CI 2.89–6.28); (2) trouble speaking on memory and concentration (OR 4.24, 95% CI 3.28–5.48); and (3) dysphagia on functional interference (OR 4.25, 95% CI 3.13–5.79). In contrast, systemic manifestations were associated with QOL to a lesser extent or not at all.Conclusion.Oral manifestations of SS, particularly mouth ulcers or sores, trouble speaking, and dysphagia, were strongly associated with worse QOL. Further study and targeted treatment of these oral manifestations provides the opportunity to improve quality of life in patients with SS.

Background There is broad recognition of the importance of evidence in informing clinical decisions. When information from all studies included in a systematic review (“review”) does not contribute to a meta-analysis, decision-makers can be frustrated. Our objectives were to use the field of eyes and vision as a case study and examine the extent to which authors of Cochrane reviews conducted meta-analyses for their review’s pre-specified main outcome domain and the reasons that some otherwise eligible studies were not incorporated into meta-analyses. Methods We examined all completed systematic reviews published by Cochrane Eyes and Vision, as of August 11, 2017. We extracted information about each review’s outcomes and, using an algorithm, categorized one outcome as its “main” outcome. We calculated the percentage of included studies incorporated into meta-analyses for any outcome and for the main outcome. We examined reasons for non-inclusion of studies into the meta-analysis for the main outcome. Results We identified 175 completed reviews, of which 125 reviews included two or more studies. Across these 125 reviews, the median proportions of studies incorporated into at least one meta-analysis for any outcome and for the main outcome were 74% (interquartile range [IQR] 0–100%) and 28% (IQR 0–71%), respectively. Fifty-one reviews (41%) could not conduct a meta-analysis for the main outcome, mostly because fewer than two included studies measured the outcome (21/51 reviews) or the specific measurements for the outcome were inconsistent (16/51 reviews). Conclusions Outcome choice during systematic reviews can lead to few eligible studies included in meta-analyses. Core outcome sets and improved reporting of outcomes can help solve some of these problems.

Objective Summarize the psychometric properties of functional, ambulatory, and quality of life instruments among adult lower limb amputees, highlighting evidence deemed generalizable to the United States Medicare population. Data Sources Six databases and existing systematic reviews through October 30, 2017. Searches included terms for lower limb amputation or prostheses and outcome measures in humans, without language restriction. Study Selection We included peer-reviewed studies of at least 20 adults (≥18 years) with lower limb amputation. Eligible studies reported on psychometric properties of functional, ambulatory, or quality of life instruments. Fifty-three of 425 retrieved articles (12%) met criteria. Data Extraction Study characteristics and psychometric property data (validity, reliability, responsiveness, minimum detectable change, minimal important difference, or floor or ceiling effect) were extracted into a customized form based on standardized criteria. All extracted data were confirmed by 2 experts in systematic review and rehabilitation outcome measurement. Instruments were categorized regarding having been validated and found reliable. Other reported psychometric properties were recorded. Studies were also assessed for applicability to the Medicare population based on age and amputation etiology (dysvascular). Data Synthesis Fifty-six studies (in 53 articles) reported psychometric properties of 50 instruments. There is evidence for both validity and reliability for 30 instruments, 17 of which have evidence that was deemed generalizable to the Medicare population. Most of the remaining instruments have evidence of either validity or reliability, but not both. Twelve instruments have been assessed specifically among lower limb amputees prior to prosthesis prescription. Thirteen instruments have been assessed regarding their predictive properties for future outcomes. Conclusions Numerous instruments assessing ambulation, function, quality of life, and other patient-centered outcomes have evidence of validity and reliability for adults with lower limb amputations. Researchers and clinicians should use validated, reliable instruments when feasible. Many existing and new instruments require validation for use with lower limb amputees.

INTRODUCTION Venous serum and plasma are optimal specimens for serological testing but may be logistically infeasible. Dried blood spots (DBS) are a feasible alternative, provided results are adequately sensitive and specific. We aimed to assess the diagnostic accuracy of DBS to measure IgG and IgM antibodies for vaccine-preventable diseases and compare test validity of DBS with venous blood. AREAS COVERED In October 2020, we searched seven databases for peer-reviewed studies assessing the diagnostic accuracy of DBS specimens compared with serum in detecting antibodies to VPDs in humans. We extracted data and assessed risk of bias in all included studies. We calculated sensitivity and specificity with 95% confidence intervals for each index-reference test comparison. We narratively synthesized the identified evidence on diagnostic accuracy and blood collection and processing methods for DBS. Studies on measles and rubella IgG and IgM were the most frequently identified and reported generally high sensitivity and specificity. EXPERT OPINION Lack of standardization in collection, storage, and testing methods limited systematic comparison across studies. Our findings indicate a need for additional validation studies on the diagnostic accuracy of DBS to expand their use in serological surveillance. We recommend practical considerations to improve standardized reporting for DBS validation studies.

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To evaluate the effectiveness and safety of topical corticosteroids compared with placebo, artificial tears, other steroidal or non‐steroidal therapies, or a combination of therapies for dry eye disease.

Objectives. This systematic review evaluates breast reconstruction options for women after mastectomy for breast cancer (or breast cancer prophylaxis). We addressed six Key Questions (KQs): (1) implant-based reconstruction (IBR) versus autologous reconstruction (AR), (2) timing of IBR and AR in relation to chemotherapy and radiation therapy, (3) comparisons of implant materials, (4) comparisons of anatomic planes for IBR, (5) use versus nonuse of human acellular dermal matrices (ADMs) during IBR, and (6) comparisons of AR flap types. Data sources and review methods. We searched Medline®, Embase®, Cochrane CENTRAL, CINAHL®, and ClinicalTrials.gov from inception to March 23, 2021, to identify comparative and single group studies. We extracted study data into the Systematic Review Data Repository Plus (SRDR+). We assessed the risk of bias and evaluated the strength of evidence (SoE) using standard methods. The protocol was registered in PROSPERO (registration number CRD42020193183). Results. We found 8 randomized controlled trials, 83 nonrandomized comparative studies, and 69 single group studies. Risk of bias was moderate to high for most studies. KQ1: Compared with IBR, AR is probably associated with clinically better patient satisfaction with breasts and sexual well-being but comparable general quality of life and psychosocial well-being (moderate SoE, all outcomes). AR probably poses a greater risk of deep vein thrombosis or pulmonary embolism (moderate SoE), but IBR probably poses a greater risk of reconstructive failure in the long term (1.5 to 4 years) (moderate SoE) and may pose a greater risk of breast seroma (low SoE). KQ 2: Conducting IBR either before or after radiation therapy may result in comparable physical well-being, psychosocial well-being, sexual well-being, and patient satisfaction with breasts (all low SoE), and probably results in comparable risks of implant failure/loss or need for explant surgery (moderate SoE). We found no evidence addressing timing of IBR or AR in relation to chemotherapy or timing of AR in relation to radiation therapy. KQ 3: Silicone and saline implants may result in clinically comparable patient satisfaction with breasts (low SoE). There is insufficient evidence regarding double lumen implants. KQ 4: Whether the implant is placed in the prepectoral or total submuscular plane may not be associated with risk of infections that are not explicitly implant related (low SoE). There is insufficient evidence addressing the comparisons between prepectoral and partial submuscular and between partial and total submuscular planes. KQ 5: The evidence is inconsistent regarding whether human ADM use during IBR impacts physical well-being, psychosocial well-being, or satisfaction with breasts. However, ADM use probably increases the risk of implant failure/loss or need for explant surgery (moderate SoE) and may increase the risk of infections not explicitly implant related (low SoE). Whether or not ADM is used probably is associated with comparable risks of seroma and unplanned repeat surgeries for revision (moderate SoE for both), and possibly necrosis (low SoE). KQ 6: AR with either transverse rectus abdominis (TRAM) or deep inferior epigastric perforator (DIEP) flaps may result in comparable patient satisfaction with breasts (low SoE), but TRAM flaps probably increase the risk of harms to the area of flap harvest (moderate SoE). AR with either DIEP or latissimus dorsi flaps may result in comparable patient satisfaction with breasts (low SoE), but there is insufficient evidence regarding thromboembolic events and no evidence regarding other surgical complications. Conclusion. Evidence regarding surgical breast reconstruction options is largely insufficient or of only low or moderate SoE. New high-quality research is needed, especially for timing of IBR and AR in relation to chemotherapy and radiation therapy, for comparisons of implant materials, and for comparisons of anatomic planes of implant placement.

PURPOSE: Sjögren’s syndrome (SS) is a common autoimmune disease affecting about four million Americans. Although approximately 1 in 10 patients with clinically-significant aqueous deficient dry eye has underlying SS, widespread underappreciation of SS leads to significant underdiagnosis, delays in diagnosis, and consequent morbidity and mortality. The purpose of this article is to illustrate that in addition to dry eye, SS can cause serious, vision-threatening extraglandular ocular manifestations. METHODS: We conducted a narrative review of studies that have examined the dry eye and extraglandular ocular complications of SS. RESULTS: SS-related dry eye is a progressive condition with major negative impact on the quality-of-life of afflicted patients, not only due to symptoms of ocular discomfort but also visual dysfunction. In addition, SS can lead to corneal melt/perforation, uveitis, scleritis, retinal vasculitis, and optic neuritis. A major problem with currently-available SS disease activity measurement instruments is the lack of domains evaluating dry eye-related visual dysfunction. For example, one of the most commonly-used instruments for assessing patient symptoms in SS (the EULAR Sjögren’s Syndrome Patient Reported Index [ESSPRI]) only includes one item (out of three) that addresses the severity of overall dryness, without mention of dry eye symptoms or vision-related quality-of-life. Similarly, no extraglandular ocular complications are included in currently-available SS disease activity instruments (e.g., the EULAR Sjögren’s Syndrome Disease Activity Index [ESSDAI]). CONCLUSIONS: There needs to be a paradigm shift in which eye care providers and rheumatologists become more familiar with various SS-related extraglandular ocular manifestations. Existing disease activity measurement instruments must incorporate dry eye symptoms, particularly those related to visual dysfunction. An evidence-based screening algorithm for determining which patients with dry eye should be tested for underlying SS may be particularly helpful in preventing delays in diagnosis.

Background and purpose According to evidence-based clinical practice guidelines, patients presenting with disabling stroke symptoms should be treated with intravenous tissue plasminogen activator (IV tPA) within 4.5 h of time last known well. However, 25% of strokes are detected upon awakening (i.e., wake-up stroke [WUS]), which renders patients ineligible for IV tPA administered via time-based treatment algorithms, because it is impossible to establish a reliable time of symptom onset. We performed a systematic review and meta-analysis of the efficacy and safety of IV tPA compared with normal saline, placebo, or no treatment in patients with WUS using imaging-based treatment algorithms. Methods We searched MEDLINE, Web of Science, and Scopus between January 1, 2006 and April 30, 2020. We included controlled trials (randomized or nonrandomized), observational cohort studies (prospective or retrospective), and single-arm studies in which adults with WUS were administered IV tPA after magnetic resonance imaging (MRI)- or computed tomography (CT)-based imaging. Our primary outcome was recovery at 90 days (defined as a modified Rankin Scale [mRS] score of 0-2), and our secondary outcomes were symptomatic intracranial hemorrhage (sICH) within 36 h, mortality, and other adverse effects. Results We included 16 studies that enrolled a total of 14,017 patients. Most studies were conducted in Europe (37.5%) or North America (37.5%), and 1757 patients (12.5%) received IV tPA. All studies used MRI-based (five studies) or CT-based (10 studies) imaging selection, and one study used a combination of modalities. Sixty-one percent of patients receiving IV tPA achieved an mRS score of 0 to 2 at 90 days (95% confidence interval [CI]: 51%-70%, 12 studies), with a relative risk (RR) of 1.21 compared with patients not receiving IV tPA (95% CI: 1.01-1.46, four studies). Three percent of patients receiving IV tPA experienced sICH within 36 h (95% CI: 2.5%-4.1%; 16 studies), which is an RR of 4.00 compared with patients not receiving IV tPA (95% CI: 2.85-5.61, seven studies). Conclusions This systematic review and meta-analysis suggests that IV tPA is associated with a better functional outcome at 90 days despite the increased but acceptable risk of sICH. Based on these results, IV tPA should be offered as a treatment for WUS patients with favorable neuroimaging findings.

Introduction: Twenty-five percent of strokes are detected upon awakening (‘wake-up strokes’; WUS) and are not amenable to thrombolytic therapy via existing time-based treatment approaches. We performed a systematic review and meta-analysis of the efficacy and safety of thrombolysis in patients with WUS using imaging-based selection algorithms. Methods: This systematic review was registered through PROSPERO (CRD42020151552). We searched PubMed, Web of Science, and Scopus between January 1, 2006 and April 30, 2020 for controlled trials and observational cohort studies (prospective or retrospective), in which adults with WUS were administered thrombolysis after MR- or CT-based imaging. Our primary outcome was recovery (mRS 0-2) at 90 days and our secondary outcome was symptomatic intracranial hemorrhage (sICH). We assessed risk of bias using the Cochrane Risk of Bias 2.0 and ROBINS-I tools. Results: We included 16 studies that enrolled a total of 14,017 patients. Sixty-one percent of patients receiving tPA achieved a functional recovery at 90 days (95% CI: 51% to 70%; 12 studies), with a relative risk (RR) of recovery of 1.21 compared with patients not receiving tPA (95% CI 1.01 to 1.46; 4 comparative studies). As shown in Figure 1, 3% of patients receiving tPA in the treated WUS stroke group experienced sICH, an RR of 4.0 (95% CI 2.85-5.61) compared with patients not receiving tPA. On meta-regression, advancing age was negatively associated with the RR of recovery (p Conclusions: In patients with WUS, thrombolysis is associated with functional recovery and with a low risk of sICH. This risk is comparable to the sICH rate from tPA-treatment of stroke utilizing the standard protocol timeframe (2.4% in ECASS III). Thrombolysis should be considered in the treatment of WUS in patients with favorable neuroimaging.

Background: Outcome heterogeneity, selective reporting, and choosing outcomes that do not reflect needs and priorities of stakeholders, limit the examination of health intervention effects, particularly in late phase trials. Core outcome sets (COS) are a proposed solution to these issues. A COS is an agreed-upon, standardised set of outcomes that should be measured and reported as a minimum in all trials in a specific area of health or healthcare. COS are intended to increase standardisation of outcome measurement and reporting to better enable comparisons between, and synthesis of findings of trials in a particular health area. Methods: This study will examine late phase trials, published between October 2019 and March 2020 (inclusive), in the following five medical journals: New England Journal of Medicine, Journal of the American Medical Association, Lancet, BMJ, and Annals of Internal Medicine. Trials will be examined to determine if they refer to a COS, and whether they use a COS. Trialists for each identified trial will subsequently be contacted to complete an online survey examining trialists’ awareness of, and decisions to search for and use a COS. Discussion: This study will provide important information on uptake of COS by later phase trialists in major medical journals, and the views of these trialists on COS use in trials. These findings will inform approaches to increasing awareness and uptake of COS in future health trials.

Background Identifying factors that can predict severe disease in patients needing hospitalization for COVID-19 is crucial for early recognition of patients at greatest risk. Objective (1) Identify factors predicting intensive care unit (ICU) transfer and (2) develop a simple calculator for clinicians managing patients hospitalized with COVID-19. Methods A total of 2,685 patients with laboratory-confirmed COVID-19 admitted to a large metropolitan health system in Georgia, USA between March and July 2020 were included in the study. Seventy-five percent of patients were included in the training dataset (admitted March 1 to July 10). Through multivariable logistic regression, we developed a prediction model (probability score) for ICU transfer. Then, we validated the model by estimating its performance accuracy (area under the curve [AUC]) using data from the remaining 25% of patients (admitted July 11 to July 31). Results We included 2,014 and 671 patients in the training and validation datasets, respectively. Diabetes mellitus, coronary artery disease, chronic kidney disease, serum C-reactive protein, and serum lactate dehydrogenase were identified as significant risk factors for ICU transfer, and a prediction model was developed. The AUC was 0.752 for the training dataset and 0.769 for the validation dataset. We developed a free, web-based calculator to facilitate use of the prediction model (https://icucovid19.shinyapps.io/ICUCOVID19/). Conclusion Our validated, simple, and accessible prediction model and web-based calculator for ICU transfer may be useful in assisting healthcare providers in identifying hospitalized patients with COVID-19 who are at high risk for clinical deterioration. Triage of such patients for early aggressive treatment can impact clinical outcomes for this potentially deadly disease.

ObjectivesA core outcome set (COS) is an agreed standardised minimum collection of outcomes that should be measured and reported in research in a specific area of health. Cochrane systematic reviews (‘reviews’) are rigorous reviews on health-related topics conducted under the auspices of Cochrane. This study examines the use of existing COS to inform the choice of outcomes in Cochrane systematic reviews (‘reviews’) and investigates the views of the coordinating editors of Cochrane Review Groups (CRGs) on this topic.MethodsA cohort of 100 recently published or updated Cochrane reviews were assessed for reference to a COS being used to inform the choice of outcomes for the review. Existing COS, published 2 or more years before the review publication, were then identified to assess how often a reviewer could have used a relevant COS if it was available. We asked 52 CRG coordinating editors about their involvement in COS development, how outcomes are selected for reviews in their CRG and their views of the advantages and challenges surrounding the standardisation of outcomes within their CRG.ResultsIn the cohort of reviews from 2019, 40% (40/100) of reviewers noted problems due to outcome inconsistency across the included studies. In 7% (7/100) of reviews, a COS was referenced in relation to the choice of outcomes for the review. Relevant existing COS could be considered for a review update in 35% of the others (33/93). Most editors who responded (31/36, 86%) thought that COS should definitely or possibly be used to inform the choice of outcomes in a review.ConclusionsSystematic reviewers are continuing to note outcome heterogeneity but are starting to use COS to inform their reviews. There is potential for greater uptake of COS in Cochrane reviews.

CONTEXT: Adolescents with problematic substance use (SU) are at risk for far-reaching adverse outcomes. OBJECTIVE: Synthesize the evidence regarding the effects of brief behavioral interventions for adolescents (12–20 years) with problematic SU. DATA SOURCES: We conducted literature searches in Medline, the Cochrane Central Register of Controlled Trials, Embase, Cumulative Index to Nursing and Allied Health Literature, and PsycInfo through October 31, 2019. STUDY SELECTION: We screened 33 272 records and citations for interventions in adolescents with at least problematic SU, retrieved 1831 articles, and selected 22 randomized controlled trials of brief interventions meeting eligibility criteria for meta-analysis. DATA EXTRACTION: We followed Agency for Healthcare Research and Quality guidelines. We categorized brief interventions into components, including motivational interviewing (MI), psychoeducation, and treatment as usual. Outcomes included SU (abstinence, days used per month) for alcohol and cannabis, and substance-related problem scales. Strength of evidence (SoE) was assessed. RESULTS: Both pairwise and network meta-analyses were conducted by using random effects models. Compared to treatment as usual, the use of MI reduces heavy alcohol use days by 0.7 days per month (95% credible interval [CrI]: −1.6 to 0.02; low SoE), alcohol use days by 1.1 days per month (95% CrI −2.2 to −0.3; moderate SoE), and overall substance-related problems by a standardized net mean difference of 0.5 (95% CrI –1.0 to 0; low SoE). The use of MI did not reduce cannabis use days, with a net mean difference of −0.05 days per month (95% CrI: −0.26 to 0.14; moderate SoE). LIMITATIONS: There was lack of consistently reported outcomes and limited available comparisons. CONCLUSIONS: The use of MI reduces heavy alcohol use, alcohol use days, and SU-related problems in adolescents but does not reduce cannabis use days.

Background Sequalae of opioid misuse constitute a public health emergency in the United States. A robust evidence base informs the use of medication for opioid use disorders (MOUD) in adults, with far less research in transition-age youth. This systematic review evaluates the effectiveness of MOUD for transition-age youth (age 16 to 25). Methods This synthesis was part of a larger systematic review focused on adolescent substance use interventions. The study team conducted literature searches in MEDLINE, the Cochrane CENTRAL Registry of Controlled Trials, EMBASE, PsycINFO, and CINAHL through October 31, 2019. We screened studies, extracted data, and assessed risk of bias using standard methods. The primary and secondary outcomes were the effect of MOUD on opioid abstinence and treatment retention, respectively. Results The study team screened a total of 33,272 records and examined 1831 full-text articles. Four randomized trials met criteria for inclusion in the current analysis. All four trials assessed a combination of buprenorphine plus cognitive behavioral therapy versus a comparison condition. Some trials included additional behavioral interventions, and the specific duration/dosage of buprenorphine varied. Risk of bias was moderate for all studies. Studies found that buprenorphine was more effective than clonidine, effectively augmented by memantine, and that longer medication taper durations were more effective than shorter tapers in promoting both abstinence and retention. Notably, we did not identify any studies of methadone or naltrexone, adjunctive behavioral interventions were sparingly described, and treatment durations were far shorter than recommended guidelines in adults. Discussion The literature guiding youth MOUD is limited, and more research should evaluate the effectiveness of options other than buprenorphine, optimal treatment duration, and the benefit of adjunctive behavioral interventions. Subgroup analyses of extant randomized clinical trials could help to extend knowledge of MOUD effectiveness in this age cohort.

IntroductionDry eye is a multifactorial chronic condition characterised by tear film insufficiency and instability, and ocular symptoms including foreign body sensation, itching, irritation, soreness and visual disturbance. The prevalence and incidence of dry eye are major determinants of the magnitude of economic and societal costs of the disease. This protocol proposes a systematic review and meta-analysis of the prevalence and incidence of dry eye in the USA.Methods and analysisWorking with an information specialist, we will develop search strategies for Ovid Medline and Embase for population-based cross-sectional and cohort studies involving US-based populations that report the prevalence and/or incidence of dry eye. We will include studies involving persons of all ages from 1 January 2010 to the current date with no language restrictions. We will also hand-search references of included studies, dry eye epidemiology-related systematic reviews, clinical practice guidelines and literature provided by agencies and organisations. Two investigators will independently screen the titles and abstracts, and then full-text reports to determine eligibility. One investigator will extract study data and perform risk of bias assessments using tools designed specifically for prevalence and incidence studies. A second investigator will verify all extracted study data and risk of bias assessments. We will assess heterogeneity, qualitatively and quantitatively. When appropriate, we will meta-analyse prevalence and incidence estimates.Ethics and disseminationThis review does not require approval by an ethics committee because it will use published studies. We will publish our results in a peer-reviewed journal and present at relevant conferences.PROSPERO registration numberCRD42021256934.

The choice of outcomes in systematic reviews of the effects of interventions is crucial, dictating which data are included and analysed. Full pre-specification of outcomes in systematic reviews can reduce the risk of outcome reporting bias but, this issue has not been widely investigated. This study is the first to analyse the nature and specification of outcomes used in Cochrane Wounds (CW) systematic reviews. Adequacy of outcome specification was assessed using a five-element framework of key outcome components: outcome domain, specific measurement, specific metric, method of aggregation, and time-points. We identified all CW review titles associated with a protocol published on or before 1 October 2014. We categorised all reported outcome domains and recorded whether they were primary or secondary outcomes. We explored outcome specification for outcome domains reported in 25% or more of the eligible protocols. We included 106 protocols and 126 outcome domains; 24.6% (31/126) domains were used as primary outcomes at least once. Eight domains were reported in ≥ 25% of protocols: wound healing, quality of life, costs, adverse events, resource use, pain, wound infection, and mortality. Wound healing was the most completely specified outcome domain (median 3; interquartile range [IQR] =1-5) along with resource use (median 3; IQR 2-4). Quality of life (median 1; IQR 1-3), pain (median 1; IQR 1-3), and costs (median 1; IQR 1-4) were the least completely specified outcome domains. Outcomes are frequently poorly pre-specified and the elements of metric, aggregation and time-point are rarely adequately specified. We strongly recommend that reviewers be more vigilant about pre-specifying outcomes, using the five-element framework. Better pre-specification is likely to improve review quality by reducing bias in data abstraction and analysis, and by reducing subjectivity in the decision of which outcomes to extract; it may also improve outcome specification in clinical trial design and reporting. This article is protected by copyright. All rights reserved.

Objective The objective of the study was to determine the reporting quality of systematic review (SR) abstracts presented at World Congresses on Pain (WCPs) and to quantify agreement in results presented in those abstracts with their corresponding full-length publications. Study Design and Setting We screened abstracts of five WCPs held from 2008 to 2016 to find abstracts describing SRs. Two authors searched for corresponding full publications using PubMed and Google Scholar in April 2018. Methods and outcomes extracted from abstracts were compared with their corresponding full publications. The reporting quality of abstracts was evaluated against the PRISMA for Abstracts (PRISMA-A) checklist. Results We identified 143 conference abstracts describing SRs. Of these, 90 (63%) were published as full-length articles in peer-reviewed journals by April 2018, with a median time from conference presentation to publication of 5 months (interquartile range: −0.25 to 14 months). Among 79 abstract–publication pairs evaluable for discordance, there was some form of discordance in 40% of pairs. Qualitative discordance (different direction of the effect) was found in 13 analyzed pairs (16%). The median adherence by abstracts to each PRISMA-A checklist item was 33% (interquartile range: 29% to 42%). Conclusion Conference abstracts of pain SRs are selectively published, not reliable, and poorly reported.

Importance Patient care should be informed by clinical practice guidelines, which in turn should be informed by evidence from reliable systematic reviews. The American Academy of Ophthalmology is updating its Preferred Practice Patterns (PPPs) for the management of the following 6 corneal diseases: bacterial keratitis, blepharitis, conjunctivitis, corneal ectasia, corneal edema and opacification, and dry eye syndrome. Objective To summarize the reliability of the existing systematic reviews addressing interventions for corneal diseases. Data Source The Cochrane Eyes and Vision US Satellite database. Study Selection In this study of published systematic reviews from 1997 to 2017 (median, 2014), the Cochrane Eyes and Vision US Satellite database was searched for systematic reviews evaluating interventions for the management of any corneal disease, combiningeyesandvisionkeywords and controlled vocabulary terms with a validated search filter. Data Extraction and Synthesis The study classified systematic reviews as reliable when each of the following 5 criteria were met: the systematic review specified eligibility criteria for inclusion of studies, conducted a comprehensive literature search for studies, assessed risk of bias of the individual included studies, used appropriate methods for quantitative syntheses (meta-analysis) (only assessed if meta-analysis was performed), and had conclusions that were supported by the results of the systematic review. They were classified as unreliable if at least 1 criterion was not met. Main Outcomes and Measures The proportion of systematic reviews that were reliable and the reasons for unreliability. Results This study identified 98 systematic reviews that addressed interventions for 15 corneal diseases. Thirty-three of 98 systematic reviews (34%) were classified as unreliable. The most frequent reasons for unreliability were that the systematic review did not conduct a comprehensive literature search for studies (22 of 33 [67%]), did not assess risk of bias of the individual included studies (13 of 33 [39%]), and did not use appropriate methods for quantitative syntheses (meta-analysis) (12 of 17 systematic reviews that conducted a quantitative synthesis [71%]). Sixty-five of 98 systematic reviews (66%) were classified as reliable. Forty-two of the 65 reliable systematic reviews (65%) addressed corneal diseases relevant to the 2018 American Academy of Ophthalmology PPPs; 33 of these 42 systematic reviews (79%) are cited in the 2018 PPPs. Conclusions and Relevance One in 3 systematic reviews addressing interventions for corneal diseases are unreliable and thus were not used to inform PPP recommendations. Careful adherence by systematic reviewers and journal editors to well-established best practices regarding systematic review conduct and reporting might help make future systematic reviews in eyes and vision more reliable.

Background Lower limb prosthesis (LLP) candidates are a heterogeneous group. Many LLP options exist. How to best match an amputee with an LLP is unclear. Optimal selection of devices should be guided by evidence on which amputees would do best with which LLP component or configuration, and which evaluation instruments are valid and reliable in this population. Methods We addressed questions pertaining to: assessing validity, reliability, and related psychometric properties for assessment techniques, predictor tools, and outcome measures in lower limb amputees; determining which patient and other characteristics may predict which LLP configuration or component would result in better clinical and patient-centered outcomes for different lower limb amputees (i.e., heterogeneity of treatment effect); determining whether patient expectations align with outcomes; evaluating whether patients are satisfied with the process of obtaining their LLPs; and describing long-term use of LLPs. The review does not evaluate overall comparative effectiveness among LLP components, nor does it include assessment of biomechanical outcomes. We searched six databases and other sources through October 2017 for eligible studies. Results We found eligible studies that assessed the psychometric properties of 50 instruments (classified as assessment techniques, prediction tools, and outcome measures). Of these, 30 have evidence for both validity and reliability, but only 17 of these have evidence that was deemed generalizable to the Medicare population. Most of the remaining instruments have evidence of either validity or reliability, but not both. Of 13 studies reporting data or analyses to allow assessment of heterogeneity of treatment effect, 7 used both predictor and outcome measures with evidence of validity. These studies mostly included younger men with unilateral transfemoral amputations due to trauma. Overall, studies did not identify participant characteristics that predict which lower limb amputees would benefit most or least from a given component (low strength of evidence); the studies were almost all underpowered to address this Key Question. Two studies provide low strength of evidence that people are satisfied with their encounters with their prosthetists. No eligible study addressed how study participants’ preprescription expectations of ambulation align with outcomes. Based on eight eligible studies, there is low strength of evidence that (1) about 11 to 22 percent of lower limb amputees who receive an LLP prescription stop using the prosthesis at about 1 year and (2) people with unilateral transfemoral amputations are about twice as likely to abandon their LLP than those with transtibial amputations. There is low strength of evidence that 24 to 29 percent of LLP recipients use their prostheses only indoors at 1 year. Conclusions Numerous instruments assessing ambulation, function, quality of life, and other patient-centered outcomes have evidence of validity and reliability for people with lower limb amputations. The literature does not provide adequate evidence regarding whether specific characteristics or preprescription instruments are predictive of which specific LLP component individuals should receive to maximize ambulation, function, and quality of life, or to minimize abandonment or limited use. Further high-quality research in representative samples of people with LLPs is needed to inform optimal matching of prosthetic components to patients and to assess patient expectations and satisfaction with care.

BACKGROUND: Conference abstracts are a potential source of new and relevant information about randomized controlled trials (RCTs). However, their dependability is questionable. The objectives of this study were to quantify the agreement between results of RCTs reported in abstracts presented at the four most recent World Congresses on Pain (WCP) and their corresponding full publications, and to analyse the completeness of reporting in those abstracts. METHODS: To identify RCTs, we screened all abstracts presented at four WCPs from 2008 to 2014. Two independent authors identified corresponding full-text reports published through August 2016. Data about the main outcomes in each abstract and full publication were extracted, including the outcome domains and numerical results reported. We reported discordance between abstracts and full texts. We evaluated abstracts against the CONSORT for Abstracts checklist. RESULTS: Approximately half of the 614 included abstracts had been fully published. Among the 306 abstract/publication pairs, eight pairs were not evaluable, and in the remaining 298 we found some form of discordance in 31% of the cases ; the majority of discordances were quantitative, i.e. numerical results were different in the two locations, but with the same direction of effect. In the abstract-publication pairs where the abstract presented only preliminary/interim results, 79% had some form of discordance, mostly quantitative. CONCLUSIONS: The reporting quality of the 614 abstracts was suboptimal ; the median adherence across all domains for all abstracts was 26%. In conclusion, conference abstracts of pain research are often not necessarily dependable information. Authors should be required to report abstracts according to reporting guidelines. SIGNIFICANCE: Abstracts of RCTs addressing pain are not often dependable information sources ; half of them are not published, their reporting quality is suboptimal. When published, 30% of abstracts- full text pairs have discordant results, with 78% discordance when abstracts present preliminary results.

Purpose Dry eye, a common yet underrecognized and evolving field, has few recommended treatment algorithms, mostly based on expert consensus rather than robust research evidence. There are high costs associated with managing dry eye and conducting research to identify effective and safe long-term treatments. To support evidence-based management of dry eye, our purpose was to identify and prioritize important clinical research questions for future clinical research. Methods We translated recommendations from the American Academy of Ophthalmology's 2013 Preferred Practice Patterns for dry eye into answerable clinical research questions about treatment effectiveness. Clinicians around the world who manage patients with dry eye rated each question's importance from 0 (not important) to 10 (very important) using a 2-round online Delphi survey. We considered questions as "important" if ≥75% of respondents assigned a rating of 6 or more in round 2. We mapped the identified important clinical research questions to reliable systematic reviews published up to March 2016. Results Seventy-five clinicians from at least 21 countries completed both Delphi rounds. Among the 58 questions, 24 met our definition of "important": 9/24 and 7/24 addressed topical and systemic treatments, respectively. All 4 questions with the highest 25th percentiles addressed topical treatments. Although 6/24 "important" questions were associated with 4 existing reliable systematic reviews, none of these reviews came to a definitive conclusion about treatment effectiveness. Conclusions We identified gaps pertaining to treatment options for dry eye. Future clinical research on the management of dry eye should strongly consider these prioritized questions.

Objective To assess whether conference abstracts that report higher estimates of diagnostic accuracy are more likely to reach full-text publication in a peer-reviewed journal. Study Design and Setting We identified abstracts describing diagnostic accuracy studies, presented between 2007 and 2010 at the Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting. We extracted reported estimates of sensitivity, specificity, area under the receiver operating characteristic curve (AUC), and diagnostic odds ratio (DOR). Between May and July 2015, we searched MEDLINE and EMBASE to identify corresponding full-text publications; if needed, we contacted abstract authors. Cox regression was performed to estimate associations with full-text publication, where sensitivity, specificity, and AUC were logit transformed, and DOR was log transformed. Results A full-text publication was found for 226/399 (57%) included abstracts. There was no association between reported estimates of sensitivity and full-text publication (hazard ratio [HR] 1.09 [95% confidence interval {CI} 0.98, 1.22]). The same applied to specificity (HR 1.00 [95% CI 0.88, 1.14]), AUC (HR 0.91 [95% CI 0.75, 1.09]), and DOR (HR 1.01 [95% CI 0.94, 1.09]). Conclusion Almost half of the ARVO conference abstracts describing diagnostic accuracy studies did not reach full-text publication. Studies in abstracts that mentioned higher accuracy estimates were not more likely to be reported in a full-text publication.

Background The usefulness of clinical trials and systematic reviews is compromised when they report different outcomes. We compared outcomes in reviews of HIV/AIDS and the trials included in the reviews. Study Design and Setting We examined all Cochrane reviews of HIV/AIDS (as of June 2013) that included ≥1 trial and the trials that the reviews included. We compared outcomes within subgroups defined by type of intervention: clinical management, biomedical prevention, behavioral prevention, and health services. Results We included 84 reviews that encompassed 524 trials. Although the median number of outcomes per trial (8) and per review (7.5) was similar, the trials reported a considerably greater number of unique outcomes than the reviews (779 vs. 218), ranging from 2.3 times greater (clinical management) to 5.4 times greater (behavioral prevention). High proportions of trial outcomes were not in any review: 68% (clinical management) to 83% (behavioral prevention). Lower proportions of review outcomes were not in any trial: 11% (clinical management) to 39% (health services). Conclusion Outcomes in trials and reviews are not well aligned for appropriate inclusion of trial results in reviews and meta-analyses. Differences in perspectives, goals, and constraints between trialists and reviewers may explain differences in outcomes they consider important.

Background People with cystic fibrosis experience chronic airway infections as a result of mucus build up within the lungs. Repeated infections often cause lung damage and disease. Airway clearance therapies aim to improve mucus clearance, increase sputum production, and improve airway function. The active cycle of breathing technique (also known as ACBT) is an airway clearance method that uses a cycle of techniques to loosen airway secretions including breathing control, thoracic expansion exercises, and the forced expiration technique. This is an update of a previously published review. Objectives To compare the clinical effectiveness of the active cycle of breathing technique with other airway clearance therapies in cystic fibrosis. Search methods We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews. Date of last search: 25 April 2016. Selection criteria Randomised or quasi-randomised controlled clinical studies, including cross-over studies, comparing the active cycle of breathing technique with other airway clearance therapies in cystic fibrosis. Data collection and analysis Two review authors independently screened each article, abstracted data and assessed the risk of bias of each study. Main results Our search identified 62 studies, of which 19 (440 participants) met the inclusion criteria. Five randomised controlled studies (192 participants) were included in the meta-analysis; three were of cross-over design. The 14 remaining studies were cross-over studies with inadequate reports for complete assessment. The study size ranged from seven to 65 participants. The age of the participants ranged from six to 63 years (mean age 22.33 years). In 13 studies, follow up lasted a single day. However, there were two long-term randomised controlled studies with follow up of one to three years. Most of the studies did not report on key quality items, and therefore, have an unclear risk of bias in terms of random sequence generation, allocation concealment, and outcome assessor blinding. Due to the nature of the intervention, none of the studies blinded participants or the personnel applying the interventions. However, most of the studies reported on all planned outcomes, had adequate follow up, assessed compliance, and used an intention-to-treat analysis. Included studies compared the active cycle of breathing technique with autogenic drainage, airway oscillating devices, high frequency chest compression devices, conventional chest physiotherapy, and positive expiratory pressure. Preference of technique varied: more participants preferred autogenic drainage over the active cycle of breathing technique; more preferred the active cycle of breathing technique over airway oscillating devices; and more were comfortable with the active cycle of breathing technique versus high frequency chest compression. No significant difference was seen in quality of life, sputum weight, exercise tolerance, lung function, or oxygen saturation between the active cycle of breathing technique and autogenic drainage or between the active cycle of breathing technique and airway oscillating devices. There was no significant difference in lung function and the number of pulmonary exacerbations between the active cycle of breathing technique alone or in conjunction with conventional chest physiotherapy. All other outcomes were either not measured or had insufficient data for analysis. Authors' conclusions There is insufficient evidence to support or reject the use of the active cycle of breathing technique over any other airway clearance therapy. Five studies, with data from eight different comparators, found that the active cycle of breathing technique was comparable with other therapies in outcomes such as participant preference, quality of life, exercise tolerance, lung function, sputum weight, oxygen saturation, and number of pulmonary exacerbations. Longer-term studies are needed to more adequately assess the effects of the active cycle of breathing technique on outcomes important for people with cystic fibrosis such as quality of life and preference.

Background Discrepancies between information in conference abstracts and full publications describing the same randomized controlled trial have been reported. The association between author conflicts of interest and the publication of randomized controlled trials is unclear. The objective of this study was to use randomized controlled trials in ophthalmology to evaluate (1) the agreement in the reported main outcome results by comparing abstracts and corresponding publications and (2) the association between the author conflicts of interest and publication of the results presented in the abstracts. Methods We considered abstracts describing results of randomized controlled trials presented at the 2001–2004 Association for Research in Vision and Ophthalmology conferences as eligible for our study. Through electronic searching and by emailing abstract authors, we identified the earliest publication (journal article) containing results of each abstract’s main outcome through November 2013. We categorized the discordance between the main outcome results in the abstract and its paired publication as qualitative (a difference in the direction of the estimated effect) or as quantitative. We used the Association for Research in Vision and Ophthalmology categories for conflicts of interest: financial interest, employee of business with interest, consultant to business with interest, inventor/developer with patent, and receiving ≥ 1 gift from industry in the past year. We calculated the relative risks (RRs) of publication associated with the categories of conflicts of interest for abstracts with results that were statistically significant, not statistically significant, or not reported. Results We included 513 abstracts, 230 (44.8 %) of which reached publication. Among the 86 pairs with the same main outcome domain at the same time point, 47 pairs (54.7 %) had discordant results: qualitative discordance in 7 pairs and quantitative discordance in 40 pairs. Quantitative discordance was indicated as 20 %, and unclear in 14, 5, 14, and 7 pairs, respectively. First authors reporting of one or more conflicts of interest was associated with a greater likelihood of publication (RR = 1.31; 95 % CI = 1.04 to 1.64) and a shorter time-to-publication (log-rank p = 0.026). First author conflicts of interests that were associated with publication were financial support (RR = 1.50; 95 % CI = 1.19 to 1.90) and one or more gifts (RR = 1.42; 95 % CI = 1.05 to 1.92). The association between conflicts of interest and publication remained, irrespective of the statistical significance of the results. Conclusions More than half the abstract/publication pairs exhibited some amount of discordance in the main outcome results, calling into question the dependability of conference abstracts. Regardless of the main outcome results, the conflicts of interests of the abstract’s first author were associated with publication. Electronic supplementary material The online version of this article (doi:10.1186/s13063-016-1343-z) contains supplementary material, which is available to authorized users.

Identification of unanswered research questions about the management of gestational diabetes mellitus (GDM) is necessary to focus future research endeavors. We developed a process for elucidating the highest priority research questions on GDM.Using a systematic review on GDM as a starting point, we developed an eight-step process: (1) identification of research gaps, (2) feedback from the review's authors, (3) translation of gaps into researchable questions using population, intervention, comparators, outcomes, setting (PICOS) framework, (4) local institutions' stakeholders' refinement of research questions, (5) national stakeholders' use of Delphi method to develop consensus on the importance of research questions, (6) prioritization of outcomes, (7) conceptual framework, and (8) evaluation.We identified 15 high priority research questions for GDM. The research questions focused on medication management of GDM (e.g., various oral agents vs. insulin), delivery management for women with GDM (e.g., induction vs. expectant management), and identification of risk factors for, prevention of, and screening for type 2 diabetes in women with prior GDM. Stakeholders rated the development of chronic diseases in offspring, cesarean delivery, and birth trauma as high priority outcomes to measure in future studies.We developed an eight-step process using a multidisciplinary group of stakeholders to identify 15 research questions of high clinical importance. Researchers, policymakers, and funders can use this list to direct research efforts and resources to the highest priority areas to improve care for women with GDM.

Context: Determining which patients with thyroid nodules require surgery is limited by cytologically indeterminate findings. A new approach for preoperative molecular classification of cytologically indeterminate thyroid nodules has a reported sensitivity of 91% and specificity of 75%; however, its cost-effectiveness has yet to be assessed. Objective: Our objective was to evaluate the 5-yr cost-effectiveness of routine use of a molecular test in adult patients with indeterminate fine-needle aspiration biopsy results from a societal perspective. Design: A 16-state Markov decision model was developed. Probabilities, costs, and quality-adjusted life years (QALY) were estimated from literature review, U.S. Department of Health and Human Services data, Medicare reimbursement schedules, and expert opinion. Setting and Subjects: Decision analysis of a hypothetical group of adult patients with cytologically indeterminate thyroid nodules was conducted. Main Outcome Measures: Incremental cost-effectiveness ratio wa...

Objectives: Evidence-based guideline committees are multidisciplinary and explicitly consider the existing evidence. They are thus in an ideal position to identify research gaps. However, gaps have not been systematically identified through guidelines. We pilot tested a method to systematically identify and classify gaps from evidence-based guidelines.Methods: We reviewed all evidence-based guidelines published by the Cystic Fibrosis Foundation. We identified research gaps as topics for which there was insufficient evidence (recommendations were not made or consensus recommendations were made) and topics specified as needing further research. We characterized gaps using a standard framework and classified them by type of management issue, specificity of target population, and age of target population.Results: We identified sixty-two research gaps in five guidelines (mean = 12.4/guidelines document). While thirteen gaps were topics specified as needing further research, most (n = 49) were topics with insufficient evidence. Of these forty-nine, recommendations were not made for twenty-two topics while consensus recommendations were made for twenty-seven topics. Most gaps were issues of comparative effectiveness (44/62), addressed the general cystic fibrosis population (40/62), and were specific to infants (33/62). Relevant comparisons and outcomes were explicitly stated for only 7 percent and 16 percent of gaps respectively.Conclusions: Almost 80 percent of the gaps were not topics identified as future research needs in the guidelines documents but rather were topics with insufficient evidence for making recommendations. Although we used cystic fibrosis in the United States as an example, the method we developed could be applied in other settings, including other countries and for different diseases.

Importance Dry eye is a common ocular surface condition with significant influence on patient quality of life and societal economic burden. There is an urgent need to prioritize new research for dry eye. Objective To identify and rank research questions and outcomes important to patients with dry eye. Design, Setting, and Participants This study was conducted using the following 6 steps: (1) identifying research questions from a previous survey of clinicians who treat patients with dry eye; (2) identifying outcomes from existing research (systematic reviews and their cited clinical trials in the Cochrane Eyes and Vision US Satellite database of eyes and vision reviews, and National Eye Institute–funded clinical trials registered on ClinicalTrials.gov) as of June 13, 2017; (3) identifying a sample of patients with dry eye from the email subscribers to the online newsletter KeratoScoop ; (4) and (5) conducting a 2-round Delphi survey of those patients online in November and December 2017, respectively; and (6) designating and ranking questions and outcomes as important. Main Outcomes and Measures Importance assigned to research questions and outcomes for dry eye. A research question or outcome ranked by at least 75% of patients as 6 or higher on a scale of 0 to 10 was considered important. Results Among the 420 patients from 15 countries who completed both rounds of the Delphi survey, most were 60 years of age or older (233 [56%]), female (348 [83%]), white (393 [94%]), and of non-Hispanic ethnicity (398 [95%]). Among the 12 questions that clinicians had previously prioritized, patients rated 8 as important. The top 3 questions pertained to effectiveness of patient education, environmental modifications, and topical anti-inflammatory eye drops for dry eye. Among the 109 outcomes identified in existing research on dry eye, patients rated 26 as important. Ten of these 26 were unpopular in existing research, with fewer than 10% of 158 studies reporting these outcomes. Of the 10 most important outcomes, 9 were associated with symptoms or quality of life. The 3 outcomes rated most important by patients were ocular burning or stinging, ocular discomfort, and ocular pain. Conclusions and Relevance This study identified research questions and outcomes important to patients with dry eye. A considerable gap was noted between outcomes in existing research on dry eye and outcomes patients consider important. Future research on dry eye should consider addressing the important research questions and outcomes identified herein, taking into account the patient perspective.

Context: There has not been a comprehensive compilation of data regarding the epidemiology of all endocrine and metabolic disorders in the United States. Evidence Acquisition: We included 54 disorders with clinical and public health significance. We identified population-based studies that provided U.S. prevalence and/or incidence data by searching PubMed in December 2007 for English-language reports, hand-searching reference lists of six textbooks of endocrinology, obtaining additional resources from identified experts in each subspecialty, and searching epidemiological databases and web sites of relevant organizations. When available, we selected articles with data from 1998 or later. Otherwise, we selected the article with the most recent data, broadest geographical coverage, and most stratifications by sex, ethnicity, and/or age. Ultimately, we abstracted data from 70 articles and 40 cohorts. Evidence Synthesis: Endocrine disorders with U.S. prevalence estimates of at least 5% in adults included diabetes mellitus, impaired fasting glucose, impaired glucose tolerance, obesity, metabolic syndrome, osteoporosis, osteopenia, mild-moderate hypovitaminosis D, erectile dysfunction, dyslipidemia, and thyroiditis. Erectile dysfunction and osteopenia/osteoporosis had the highest incidence in males and females, respectively. The least prevalent conditions, affecting less than 1% of the U.S. population, were diabetes mellitus in children and pituitary adenoma. Conditions with the lowest incidence were adrenocortical carcinoma, pheochromocytoma, and pituitary adenomas. Certain disorders, such as hyperparathyroidism and thyroid disorders, were more common in females. As expected, the prevalence of diabetes mellitus was highest among ethnic minorities. Sparse data were available on pituitary, adrenal, and gonadal disorders. Conclusions: The current review shows high prevalence and incidence of common endocrine and metabolic disorders. Defining the epidemiology of these conditions will provide clues to risk factors and identify areas to allocate public health and research resources.

Objectives Methods to develop core outcome sets, the minimum outcomes that should be measured in research in a topic area, vary. We applied social network analysis methods to understand outcome co-occurrence patterns in human immunodeficiency virus (HIV)/AIDS systematic reviews and identify outcomes central to the network of outcomes in HIV/AIDS. Study Design and Setting We examined all Cochrane reviews of HIV/AIDS as of June 2013. We defined a tie as two outcomes (nodes) co-occurring in ≥2 reviews. To identify central outcomes, we used normalized node betweenness centrality (nNBC) (the extent to which connections between other outcomes in a network rely on that outcome as an intermediary). We conducted a subgroup analysis by HIV/AIDS intervention type (i.e., clinical management, biomedical prevention, behavioral prevention, and health services). Results The 140 included reviews examined 1,140 outcomes, 294 of which were unique. The most central outcome overall was all-cause mortality (nNBC = 23.9). The most central and most frequent outcomes differed overall and within subgroups. For example, “adverse events (specified)” was among the most central but not among the most frequent outcomes, overall. Conclusion Social network analysis methods are a novel application to identify central outcomes, which provides additional information potentially useful for developing core outcome sets.

Importance Suboptimal overlap in outcomes reported in clinical trials and systematic reviews compromises efforts to compare and summarize results across these studies. Objectives To examine the most frequent outcomes used in trials and reviews of the 4 most prevalent eye diseases (age-related macular degeneration [AMD], cataract, diabetic retinopathy [DR], and glaucoma) and the overlap between outcomes in the reviews and the trials included in the reviews. Design, Setting, and Participants This cross-sectional study examined all Cochrane reviews that addressed AMD, cataract, DR, and glaucoma; were published as of July 20, 2016; and included at least 1 trial and the trials included in the reviews. For each disease, a pair of clinical experts independently classified all outcomes and resolved discrepancies. Outcomes (outcome domains) were then compared separately for each disease. Main Outcomes and Measures Proportion of review outcomes also reported in trials and vice versa. Results This study included 56 reviews that comprised 414 trials. Although the median number of outcomes per trial and per review was the same (n = 5) for each disease, the trials included a greater number of outcomes overall than did the reviews, ranging from 2.9 times greater (89 vs 30 outcomes for glaucoma) to 4.9 times greater (107 vs 22 outcomes for AMD). Most review outcomes, ranging from 14 of 19 outcomes (73.7%) (for DR) to 27 of 29 outcomes (93.1%) (for cataract), were also reported in the trials. For trial outcomes, however, the proportion also named in reviews was low, ranging from 19 of 107 outcomes (17.8%) (for AMD) to 24 of 89 outcomes (27.0%) (for glaucoma). Only 1 outcome (visual acuity) was consistently reported in greater than half the trials and greater than half the reviews. Conclusions and Relevance Although most review outcomes were reported in the trials, most trial outcomes were not reported in the reviews. The current analysis focused on outcome domains, which might underestimate the problem of inconsistent outcomes. Other important elements of an outcome (ie, specific measurement, specific metric, method of aggregation, and time points) might have differed even though the domains overlapped. Inconsistency in trial outcomes may impede research synthesis and indicates the need for disease-specific core outcome sets in ophthalmology.

Background Respiratory syncytial virus infection causes acute lung infection in infants and young children worldwide, resulting in considerable morbidity and mortality. Children with cystic fibrosis are prone to recurrent lung inflammation, bacterial colonisation and subsequent chronic airway disease, putting them at risk for severe respiratory syncytial virus infections requiring intensive care and respiratory support. No treatment currently exists, hence prevention is important. Palivizumab is effective in reducing respiratory syncytial virus hospitalisation rates and is recommended for prophylaxis in high-risk children with other conditions. It is unclear if palivizumab can prevent respiratory syncytial virus hospitalisations and intensive care unit admissions in children with cystic fibrosis. This is an update of a previously published review. Objectives To determine the efficacy and safety of palivizumab (Synagis®) compared with placebo, no prophylaxis or other prophylaxis, in preventing hospitalisation and mortality from respiratory syncytial virus infection in children with cystic fibrosis. Search methods We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register and scanned references of the eligible study and related reviews. Date of last search: 05 May 2016. Selection criteria Randomised and quasi-randomised studies. Data collection and analysis The authors independently extracted data and assessed risk of bias. Main results One study (186 infants up to two years old) comparing five monthly doses of palivizumab (N = 92) to placebo (N = 94) over one respiratory syncytial virus season was identified and met our inclusion criteria. We judged there to be a low risk of bias with respect to the concealment of the randomization schedule (although it was not clear how this was generated) and to blinding of participants and study personnel. There is also a low risk of bias with regards to incomplete outcome data. However, we judged there to be a high risk of bias from selective reporting (summary statements presented but no data) and the fact that this industry-supported study has not been published as a full report in a peer-reviewed journal. At six months follow-up, one participant in each group was hospitalised due to respiratory syncytial virus; there were no deaths in either group. In the palivizumab and placebo groups, 86 and 90 children experienced any adverse event, while five and four children had related adverse events respectively. Nineteeen children receiving palivizumab and 16 receiving placebo suffered serious adverse events; one participant receiving palivizumab discontinued due to this. At 12 months follow-up, there were no significant differences between groups in number of Pseudomonas bacterial colonisations or change in weight-to-height ratio. Authors' conclusions We identified one randomised controlled trial comparing five monthly doses of palivizumab to placebo in infants up to two years old with cystic fibrosis. While the overall incidence of adverse events was similar in both groups, it is not possible to draw firm conclusions on the safety and tolerability of respiratory syncytial virus prophylaxis with palivizumab in infants with cystic fibrosis. Six months after treatment, the authors reported no clinically meaningful differences in outcomes. Additional randomised studies are needed to establish the safety and efficacy of palivizumab in children with cystic fibrosis.

Background For people with cystic fibrosis and advanced pulmonary damage, lung transplantation is an available and viable option. However, graft rejection is an important potential consequence after lung transplantation. Immunosuppressive therapy is needed to prevent episodes of graft rejection and thus subsequently reduce morbidity and mortality in this population. There are a number of classes of immunosuppressive drugs which act on different components of the immune system. There is considerable variability in the use of immunosuppressive agents after lung transplantation in cystic fibrosis. While much of the research in immunosuppressive drug therapy has focused on the general population of lung transplant recipients, little is known about the comparative effectiveness and safety of these agents in people with cystic fibrosis. This is an update of a previously published review. Objectives To assess the effects of individual drugs or combinations of drugs compared to placebo or other individual drugs or combinations of drugs in preventing rejection following lung transplantation in people with cystic fibrosis. Search methods We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register and scanned references of the potentially eligible study. We also searched the www.clinicaltrials.gov registry and the World Health Organisation (WHO) International Clinical Trials Registry Platform (ICTRP) to obtain information on unpublished and ongoing studies.Date of latest search: 29 May 2018. Selection criteria Randomised and quasi-randomised studies. Data collection and analysis We independently assessed the studies identified from our searches for inclusion in the review. Should eligible studies be identified and included in future updates of the review, we will independently extract data and assess the risk of bias. We will use GRADE to summarize our results through a summary of findings table for each comparison we present in the review. Main results While five studies addressed the interventions of interest, we did not include them in the review because the investigators of the studies did not report any information specific to people with cystic fibrosis. Our attempts to obtain this information have not yet been successful. We will include any provided data in future updates of the review. Authors' conclusions The lack of currently available evidence makes it impossible to draw conclusions about the comparative efficacy and safety of the various immunosuppressive drugs among people with cystic fibrosis after lung transplantation. A 2013 Cochrane Review comparing tacrolimus with cyclosporine in all lung transplant recipients (not restricted to those with cystic fibrosis) reported no significant difference in mortality and risk of acute rejection. However, tacrolimus use was associated with lower risk of broncholitis obliterans syndrome and arterial hypertension and higher risk of diabetes mellitus. It should be noted that this wider review contained only a small number of included studies (n = 3) with a high risk of bias. Additional randomised studies are required to provide evidence for the benefit and safety of the use of immunosuppressive therapy among people with cystic fibrosis after lung transplantation.

Objective To inform the development of Cystic Fibrosis (CF) Foundation guidelines on the care of infants with CF, we systematically reviewed the evidence for diagnosis and assessment of pancreatic and pulmonary disorders; management of pancreatic and pulmonary function; management of nutrition and nutritional disorders; and prevention and control of infections. Study design In May-June 2008, we searched The Cochrane Library for existing reviews; and MEDLINE, the National Guideline Clearinghouse, the CF Foundation Clinical Practice Guidelines and Consensus Statements, and the UK CF Trust for existing guidelines. MEDLINE, Cumulative Index to Nursing and Allied Health Literature (CINAHL) and the Excerpta Medica Database (EMBASE) were searched for primary studies in January 2008. Bibliographies of eligible articles were searched and expert input was sought. We selected English-language articles of any study design that provided original data on any of our questions on infants up to 2 years of age. Results We identified 14 relevant guidelines and 3 Cochrane reviews. Fifty-nine articles (55 primary studies) were included. Only four of these were randomized controlled trials. Sample sizes of infants ranged from 2 to 768 study participants; the median sample size was 24. Of our 21 review topics, 5 topics had only one study while for 5 we identified no relevant studies. We identified one or no primary studies for 20 of 32 review questions. Conclusions There is a paucity of evidence on the care of infants diagnosed with CF. For several of the review questions no guidelines or primary studies were identified, but for other questions, studies limited by weak design and small sample sizes were the only studies identified. With increasing numbers of infants with CF being diagnosed by newborn screening there is an opportunity to study the management of infants diagnosed with CF.

Introduction Choice of outcomes is critical for clinical trialists and systematic reviewers. It is currently unclear how systematic reviewers choose and pre-specify outcomes for systematic reviews. Our objective was to assess the completeness of pre-specification and comparability of outcomes in all Cochrane reviews addressing four common eye conditions. Methods We examined protocols for all Cochrane reviews as of June 2013 that addressed glaucoma, cataract, age-related macular degeneration (AMD), and diabetic retinopathy (DR). We assessed completeness and comparability for each outcome that was named in ≥25% of protocols on those topics. We defined a completely-specified outcome as including information about five elements: domain, specific measurement, specific metric, method of aggregation, and time-points. For each domain, we assessed comparability in how individual elements were specified across protocols. Results We identified 57 protocols addressing glaucoma (22), cataract (16), AMD (15), and DR (4). We assessed completeness and comparability for five outcome domains: quality-of-life, visual acuity, intraocular pressure, disease progression, and contrast sensitivity. Overall, these five outcome domains appeared 145 times (instances). Only 15/145 instances (10.3%) were completely specified (all five elements) (median = three elements per outcome). Primary outcomes were more completely specified than non-primary (median = four versus two elements). Quality-of-life was least completely specified (median = one element). Due to largely incomplete outcome pre-specification, conclusive assessment of comparability in outcome usage across the various protocols per condition was not possible. Discussion Outcome pre-specification was largely incomplete; we encourage systematic reviewers to consider all five elements. This will indicate the importance of complete specification to clinical trialists, on whose work systematic reviewers depend, and will indirectly encourage comparable outcome choice to reviewers undertaking related research questions. Complete pre-specification could improve efficiency and reduce bias in data abstraction and analysis during a systematic review. Ultimately, more completely specified and comparable outcomes could make systematic reviews more useful to decision-makers.