Integrating large language models in systematic reviews: a framework and case study using ROBINS-I for risk of bias assessment.

Large language models (LLMs) may facilitate and expedite systematic reviews, although the approach to integrate LLMs in the review process is unclear. This study evaluates GPT-4 agreement with human reviewers in assessing the risk of bias using the Risk Of Bias In Non-randomised Studies of Interventions (ROBINS-I) tool and proposes a framework for integrating LLMs into systematic reviews. The case study demonstrated that raw per cent agreement was the highest for the ROBINS-I domain of 'Classification of Intervention'. Kendall agreement coefficient was highest for the domains of 'Participant Selection', 'Missing Data' and 'Measurement of Outcomes', suggesting moderate agreement in these domains. Raw agreement about the overall risk of bias across domains was 61% (Kendall coefficient=0.35). The proposed framework for integrating LLMs into systematic reviews consists of four domains: rationale for LLM use, protocol (task definition, model selection, prompt engineering, data entry methods, human role and success metrics), execution (iterative revisions to the protocol) and reporting. We identify five basic task types relevant to systematic reviews: selection, extraction, judgement, analysis and narration. Considering the agreement level with a human reviewer in the case study, pairing artificial intelligence with an independent human reviewer remains required.

Health-Related Factors Among Pilots in Aviation Accidents.

INTRODUCTION: Health-related factors can impact aviation safety. This study investigated the published, historical aviation accidents that have been investigated by the U.S. National Transportation Safety Board (NTSB) to understand medical conditions and medication use that have been determined to be causal to mishaps.METHODS: A two-part approach was adopted for this study: 1) a scoping review was conducted to provide an overview of the current medical literature addressing medical factors and flight safety; and 2) a comprehensive review of aviation accident reports from the NTSB database from January 2013 to October 2022.RESULTS: The literature review demonstrated that psychiatric, cardiovascular, and neurological medications were the major categories of medications reported in fatal aircraft accidents. Age was not found to be a risk factor. Review of the NTSB database demonstrated that, among 15,654 mishaps, medical factors were associated in 703 (4.5%) accidents. NTSB data showed that cardiovascular (1.3%), psychiatric (0.23%), and endocrine diseases (0.17%) were the most commonly reported diseases among pilots. In accident reports, cardiovascular medications (1.49%), sedating antihistamines (0.91%), and alcohol (0.70%) were the most commonly used medications at the time of the accidents.DISCUSSION: Health-related factors were a small yet likely underestimated proportion of the factors associated with accidents. Cardiovascular diseases and treatment were the most important factors. It is important to continue to investigate the association between health-related factors and the commission of mishaps.Zhu Y, Wolf ME, Alsibai RA, Abbas AS, Alsawaf Y, Saadi S, Farah MH, Wang Z, Murad MH. Health-related factors among pilots in aviation accidents. Aerosp Med Hum Perform. 2024; 95(2):79-83.

Partial breast irradiation compared with whole breast irradiation: a systematic review and meta-analysis.

BACKGROUND: Early-stage breast cancer is among the most common cancer diagnoses. Adjuvant radiotherapy is an essential component of breast-conserving therapy, and several options exist for tailoring its extent and duration. This study assesses the comparative effectiveness of partial-breast irradiation (PBI) compared with whole-breast irradiation (WBI). METHODS: A systematic review was completed to identify relevant randomized clinical trials and comparative observational studies. Independent reviewers working in pairs selected studies and extracted data. Randomized trial results were pooled using a random effects model. Prespecified main outcomes were ipsilateral breast recurrence (IBR), cosmesis, and adverse events (AEs). RESULTS: Fourteen randomized clinical trials and 6 comparative observational studies with 17 234 patients evaluated the comparative effectiveness of PBI. PBI was not statistically significantly different from WBI for IBR at 5 years (RR = 1.34, 95% CI = 0.83 to 2.18; high strength of evidence [SOE]) and 10 years (RR = 1.29, 95% CI = 0.87 to 1.91; high SOE). Evidence for cosmetic outcomes was insufficient. Statistically significantly fewer acute AEs were reported with PBI compared with WBI, with no statistically significant difference in late AEs. Data from subgroups according to patient, tumor, and treatment characteristics were insufficient. Intraoperative radiotherapy was associated with higher IBR at 5, 10, and over than 10 years (high SOE) compared with WBI. CONCLUSIONS: Ipsilateral breast recurrence was not statistically significantly different between PBI and WBI. Acute AEs were less frequent with PBI. This evidence supports the effectiveness of PBI among selected patients with early-stage, favorable-risk breast cancer who are similar to those represented in the included studies.

Diagnostic accuracy of the physical examination in emergency department patients with acute vertigo or dizziness: A systematic review and meta-analysis for GRACE-3.

BACKGROUND: History and physical examination are key features to narrow the differential diagnosis of central versus peripheral causes in patients presenting with acute vertigo. We conducted a systematic review and meta-analysis of the diagnostic test accuracy of physical examination findings. METHODS: This study involved a patient-intervention-control-outcome (PICO) question: (P) adult ED patients with vertigo/dizziness; (I) presence/absence of specific physical examination findings; and (O) central (ischemic stroke, hemorrhage, others) versus peripheral etiology. Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) was assessed. RESULTS: From 6309 titles, 460 articles were retrieved, and 43 met the inclusion criteria: general neurologic examination-five studies, 869 patients, pooled sensitivity 46.8% (95% confidence interval [CI] 32.3%-61.9%, moderate certainty) and specificity 92.8% (95% CI 75.7%-98.1%, low certainty); limb weakness/hemiparesis-four studies, 893 patients, sensitivity 11.4% (95% CI 5.1%-23.6%, high) and specificity 98.5% (95% CI 97.1%-99.2%, high); truncal/gait ataxia-10 studies, 1810 patients (increasing severity of truncal ataxia had an increasing sensitivity for central etiology, sensitivity 69.7% [43.3%-87.9%, low] and specificity 83.7% [95% CI 52.1%-96.0%, low]); dysmetria signs-four studies, 1135 patients, sensitivity 24.6% (95% CI 15.6%-36.5%, high) and specificity 97.8% (94.4%-99.2%, high); head impulse test (HIT)-17 studies, 1366 patients, sensitivity 76.8% (64.4%-85.8%, low) and specificity 89.1% (95% CI 75.8%-95.6%, moderate); spontaneous nystagmus-six studies, 621 patients, sensitivity 52.3% (29.8%-74.0%, moderate) and specificity 42.0% (95% CI 15.5%-74.1%, moderate); nystagmus type-16 studies, 1366 patients (bidirectional, vertical, direction changing, or pure torsional nystagmus are consistent with a central cause of vertigo, sensitivity 50.7% [95% CI 41.1%-60.2%, moderate] and specificity 98.5% [95% CI 91.7%-99.7%, moderate]); test of skew-15 studies, 1150 patients (skew deviation is abnormal and consistent with central etiology, sensitivity was 23.7% [95% CI 15%-35.4%, moderate] and specificity 97.6% [95% CI 96%-98.6%, moderate]); HINTS (head impulse, nystagmus, test of skew)-14 studies, 1781 patients, sensitivity 92.9% (95% CI 79.1%-97.9%, high) and specificity 83.4% (95% CI 69.6%-91.7%, moderate); and HINTS+ (HINTS with hearing component)-five studies, 342 patients, sensitivity 99.0% (95% CI 73.6%-100%, high) and specificity 84.8% (95% CI 70.1%-93.0%, high). CONCLUSIONS: Most neurologic examination findings have low sensitivity and high specificity for a central cause in patients with acute vertigo or dizziness. In acute vestibular syndrome (monophasic, continuous, persistent dizziness), HINTS and HINTS+ have high sensitivity when performed by trained clinicians.

Diagnostic accuracy of neuroimaging in emergency department patients with acute vertigo or dizziness: A systematic review and meta-analysis for the guidelines for reasonable and appropriate care in the emergency department.

BACKGROUND: Patients presenting to the emergency department (ED) with acute vertigo or dizziness represent a diagnostic challenge. Neuroimaging has variable indications and yield. We aimed to conduct a systematic review and meta-analysis of the diagnostic test accuracy of neuroimaging for patients presenting with acute vertigo or dizziness. METHODS: An electronic search was designed following patient-intervention-control-outcome (PICO) question-(P) adult patients with acute vertigo or dizziness presenting to the ED; (I) neuroimaging including computed tomography (CT), CT angiography (CTA), magnetic resonance imaging (MRI), magnetic resonance angiography (MRA), and ultrasound (US); (C) MRI/clinical criterion standard; and (O) central causes (stroke, hemorrhage, tumor, others) versus peripheral causes of symptoms. Articles were assessed in duplicate. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) was used to assess certainty of evidence in pooled estimates. RESULTS: We included studies that reported diagnostic test accuracy. From 6309 titles, 460 articles were retrieved, and 12 were included: noncontrast CT scan-six studies, 771 patients, pooled sensitivity 28.5% (95% confidence interval [CI] 14.4%-48.5%, moderate certainty) and specificity 98.9% (95% CI 93.4%-99.8%, moderate certainty); MRI-five studies, 943 patients, sensitivity 79.8% (95% CI 71.4%-86.2%, high certainty) and specificity 98.8% (95% CI 96.2%-100%, high certainty); CTA-one study, 153 patients, sensitivity 14.3% (95% CI 1.8%-42.8%) and specificity 97.7% (95% CI 93.8%-99.6%), CT had higher sensitivity than CTA (21.4% and 14.3%) for central etiology; MRA-one study, 24 patients, sensitivity 60.0% (95% CI 26.2%-87.8%) and specificity 92.9% (95% CI 66.1%-99.8%); US-three studies, 258 patients, sensitivity ranged from 30% to 53.6%, specificity from 94.9% to 100%. CONCLUSIONS: Noncontrast CT has very low sensitivity and MRI will miss approximately one in five patients with stroke if imaging is obtained early after symptom onset. The evidence does not support neuroimaging as the only tool for ruling out stroke and other central causes in patients with acute dizziness or vertigo presenting to the ED.

A Systematic Review Supporting the Endocrine Society Clinical Practice Guideline on the Treatment of Hypercalcemia of Malignancy in Adults.

CONTEXT: Hypercalcemia is a common complication of malignancy that is associated with high morbidity and mortality. OBJECTIVE: To support development of the Endocrine Society Clinical Practice Guideline for the treatment of hypercalcemia of malignancy in adults. METHODS: We searched multiple databases for studies that addressed 8 clinical questions prioritized by a guideline panel from the Endocrine Society. Quantitative and qualitative synthesis was performed. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess certainty of evidence. RESULTS: We reviewed 1949 citations, from which we included 21 studies. The risk of bias for most of the included studies was moderate. A higher proportion of patients who received bisphosphonate achieved resolution of hypercalcemia when compared to placebo. The incidence rate of adverse events was significantly higher in the bisphosphonate group. Comparing denosumab to bisphosphonate, there was no significant difference in the rate of patients who achieved resolution of hypercalcemia. Two-thirds of patients with refractory/recurrent hypercalcemia of malignancy who received denosumab following bisphosphonate therapy achieved resolution of hypercalcemia. Addition of calcitonin to bisphosphonate therapy did not affect the resolution of hypercalcemia, time to normocalcemia, or hypocalcemia. Only indirect evidence was available to address questions on the management of hypercalcemia in tumors associated with high calcitriol levels, refractory/recurrent hypercalcemia of malignancy following the use of bisphosphonates, and the use of calcimimetics in the treatment of hypercalcemia associated with parathyroid carcinoma. The certainty of the evidence to address all 8 clinical questions was low to very low. CONCLUSION: The evidence summarized in this systematic review addresses the benefits and harms of treatments of hypercalcemia of malignancy. Additional information about patients' values and preferences, and other important decisional and contextual factors is needed to facilitate the development of clinical recommendations.

A systematic review supporting the Society for Vascular Surgery Guidelines on the management of carotid artery disease.

BACKGROUND: To support the development of guidelines on the management of carotid disease, a writing committee from the Society for Vascular Surgery has commissioned this systematic review. METHODS: We searched multiple data bases for studies addressing five questions: medical management vs carotid revascularization (CEA) in asymptomatic patients, CEA vs carotid artery stenting (CAS) in symptomatic low surgical risk patients, the optimal timing of revascularization after acute stroke, screening high-risk patients for carotid disease, and the optimal sequence of interventions in patients with combined coronary and carotid disease. Studies were selected and appraised by pairs of independent reviewers. Meta-analyses were performed when feasible. RESULTS: Medical management compared with carotid interventions in asymptomatic patients was associated with better early outcome during the first 30 days. However, CEA was associated with significantly lower long-term rate of stroke/death at 5 years. In symptomatic low-risk surgical patients, CEA was associated with a lower risk of stroke, but a significant increase in myocardial infarction compared with CAS during the first 30 days. When the long-term outcome of transfemoral CAS vs CEA in symptomatic patients were examined using preplanned pooled analysis of individual patient data from four randomized trials, the risk of death or stroke within 120 days of the index procedure was 5.5% for CEA and 8.7% for CAS, which lends support that, over the long term, CEA has a superior outcome compared with transfemoral CAS. When managing acute stroke, the comparison of CEA during the first 48 hours to that between day 2 and day 14 did not reveal a statistically significant difference on outcomes during the first 30 days. Registry data show good results with CEA performed in the first week, but not within the first 48 hours. A single risk factor, aside from peripheral artery disease, was associated with low carotid screening yield. Multiple risk factors greatly increase the yield of screening. Evidence on the timing of interventions in patients with combined carotid and coronary disease was sparse and imprecise. Patients without carotid symptoms, who had the carotid intervention first, compared with a combined carotid intervention and coronary artery bypass grafting, had better outcomes. CONCLUSIONS: This updated evidence summary supports the Society for Vascular Surgery clinical practice guidelines for commonly raised clinical scenarios. CEA was superior to medical therapy in the long-term prevention of stroke/death over medical therapy. CEA was also superior to transfemoral CAS in minimizing long-term stroke/death for symptomatic low risk surgical patients. CEA should optimally be performed between 2 and 14 days from the onset of acute stroke. Having multiple risk factors increases the value of carotid screening.

A systematic review supporting the Society for Vascular Surgery, the American Venous Forum, and the American Vein and Lymphatic Society guidelines on the management of varicose veins.

BACKGROUND: Several diagnostic tests and treatment options for patients with lower extremity varicose veins have existed for decades. The purpose of this systematic review was to summarize the latest evidence to support the forthcoming updates of the clinical practice guidelines on the management of varicose veins for the Society for Vascular Surgery (SVS), the American Venous Forum (AVF) and the American Vein and Lymphatic Society. METHODS: We searched multiple databases for studies that addressed four clinical questions identified by the AVF and the SVS guideline committee about evaluating and treating patients with varicose veins. Studies were selected and appraised by pairs of independent reviewers. A meta-analysis was conducted when feasible. RESULTS: We included 73 original studies (45 were randomized controlled trials) and 1 systematic review from 12,915 candidate references. Moderate certainty of evidence supported the usefulness of duplex ultrasound (DUS) examination as the gold standard test for diagnosing saphenous vein incompetence in patients with varicose veins and chronic venous insufficiency (clinical, etiological, anatomic, pathophysiological classification [CEAP] class C2-C6). High ligation and stripping (HL/S) was associated with higher anatomic closure rates at 30 days and 5 years when compared with radiofrequency ablation and ultrasound-guided foam sclerotherapy (UGFS) (moderate certainty), while no significant difference was seen when compared with endovenous laser ablation (EVLA) at 5 years. UGFS was associated with an increased risk of recurrence compared with HL/S. EVLA was associated with lower anatomic closure rates at 30 days than cyanoacrylate closure (CAC) and higher rates at one and 5 years when compared with UGFS. Thermal interventions were associated with lower generic quality of life scores and an increased risk of adverse events when compared with CAC or n-butyl cyanoacrylate (low certainty). Thermal interventions were associated with a lower risk of recurrent incompetence when compared with UGFS and an increased risk of recurrent incompetence than CAC. The evidence for great saphenous vein ablation alone to manage perforator disease was inconclusive. CONCLUSIONS: The current systematic review summarizes the evidence to develop and support forthcoming updated SVS/AVF/American Vein and Lymphatic Society clinical practice guideline recommendations. The evidence supports duplex scanning for evaluating patients with varicose veins and confirms that HL/S resulted in similar long-term saphenous vein closure rates as EVLA and in better rates than radiofrequency ablation and UGFS. Thermal interventions were associated with inferior generic quality of life scores than nonthermal interventions, but had a lower risk of recurrent incompetence than UGFS. The recommendations in the guidelines should consider this information as well as other factors such as patients' values and preferences, anatomic considerations of individual patients, and surgical expertise.

Association of study design features and treatment effects in trials of chronic medical conditions: a meta-epidemiological study.

OBJECTIVES: To evaluate the association of study design features and treatment effects in randomised controlled trials (RCTs) evaluating therapies for individuals with chronic medical conditions. DESIGN: Meta-epidemiological study. SETTING: RCTs from meta-analyses published in the 10 general medical journals with the highest impact factor published between 1 January 2007 and 10 June 2019 and evaluated a drug, procedure or device treatment of chronic medical conditions. MAIN OUTCOME MEASURES: The association between trial design features and the effect size, reporting a ratio of ORs (ROR) and 95% confidence interval (CI). RESULTS: We included 1098 trials from 86 meta-analyses. The most common outcome in the trials was mortality (52%), followed by disease progression (16%) and adverse events (12%). Lack of blinding of patients and study personnel was associated with a larger treatment effect (ROR 1.12; 95% CI 1.00 to 1.25). There was no statistically significant association with random sequence generation, allocation concealment, blinding of outcome assessors, incomplete outcome data, whether trials were stopped early, study funding, type of interventions or with type of outcomes (objective vs subjective). CONCLUSION: The meta-epidemiological study did not demonstrate a clear pattern of association between risk of bias indicators and treatment effects in RCTs in chronic medical conditions. The unpredictability of the direction of bias emphasises the need to make every attempt to adhere to blinding, allocation concealment and reduce attrition bias. TRIAL REGISTRATION NUMBER: Not applicable.

Acute Treatments for Episodic Migraine in Adults: A Systematic Review and Meta-analysis.

Importance: Migraine is common and can be associated with significant morbidity, and several treatment options exist for acute therapy. Objective: To evaluate the benefits and harms associated with acute treatments for episodic migraine in adults. Data Sources: Multiple databases from database inception to February 24, 2021. Study Selection: Randomized clinical trials and systematic reviews that assessed effectiveness or harms of acute therapy for migraine attacks. Data Extraction and Synthesis: Independent reviewers selected studies and extracted data. Meta-analysis was performed with the DerSimonian-Laird random-effects model with Hartung-Knapp-Sidik-Jonkman variance correction or by using a fixed-effect model based on the Mantel-Haenszel method if the number of studies was small. Main Outcomes and Measures: The main outcomes included pain freedom, pain relief, sustained pain freedom, sustained pain relief, and adverse events. The strength of evidence (SOE) was graded with the Agency for Healthcare Research and Quality Methods Guide for Effectiveness and Comparative Effectiveness Reviews. Findings: Evidence on triptans and nonsteroidal anti-inflammatory drugs was summarized from 15 systematic reviews. For other interventions, 115 randomized clinical trials with 28 803 patients were included. Compared with placebo, triptans and nonsteroidal anti-inflammatory drugs used individually were significantly associated with reduced pain at 2 hours and 1 day (moderate to high SOE) and increased risk of mild and transient adverse events. Compared with placebo, calcitonin gene-related peptide receptor antagonists (low to high SOE), lasmiditan (5-HT1F receptor agonist; high SOE), dihydroergotamine (moderate to high SOE), ergotamine plus caffeine (moderate SOE), acetaminophen (moderate SOE), antiemetics (low SOE), butorphanol (low SOE), and tramadol in combination with acetaminophen (low SOE) were significantly associated with pain reduction and increase in mild adverse events. The findings for opioids were based on low or insufficient SOE. Several nonpharmacologic treatments were significantly associated with improved pain, including remote electrical neuromodulation (moderate SOE), transcranial magnetic stimulation (low SOE), external trigeminal nerve stimulation (low SOE), and noninvasive vagus nerve stimulation (moderate SOE). No significant difference in adverse events was found between nonpharmacologic treatments and sham. Conclusions and Relevance: There are several acute treatments for migraine, with varying strength of supporting evidence. Use of triptans, nonsteroidal anti-inflammatory drugs, acetaminophen, dihydroergotamine, calcitonin gene-related peptide antagonists, lasmiditan, and some nonpharmacologic treatments was associated with improved pain and function. The evidence for many other interventions, including opioids, was limited.

Prospective Surveillance and Risk Reduction of Cancer Treatment-Related Lymphedema: Systematic Review and Meta-Analysis.

PROBLEM IDENTIFICATION: Secondary lymphedema is a chronic condition that may result from cancer-related treatments. Evidence is emerging on prospective surveillance and risk reduction. LITERATURE SEARCH: Databases were systematically searched through April 1, 2019, for comparative studies evaluating interventions aiming to prevent lymphedema in patients with cancer. DATA EVALUATION: A random-effects model was used to perform meta-analysis, when appropriate. SYNTHESIS: A total of 26 studies (4,095 patients) were included, with 23 providing data sufficient for meta-analysis. Surveillance programs increased the likelihood of detecting lymphedema. Physiotherapy, exercise programs, and delayed exercise reduced the incidence of lymphedema. IMPLICATIONS FOR RESEARCH: Future research should standardize (a) evidence-based interventions to reduce the development of lymphedema and increase the likelihood of early detection and (b) outcome measures to build a body of evidence that leads to practice change. SUPPLEMENTAL MATERIAL CAN BE FOUND AT HTTPS: //onf.ons.org/supplementary-material-systematic-review-cancer-treatment-related-lymphedema.

Targeted Therapy- and Chemotherapy-Associated Skin Toxicities: Systematic Review and Meta-Analysis.

PROBLEM IDENTIFICATION: Preventing and managing skin toxicities can minimize treatment disruptions and improve well-being. This systematic review aimed to evaluate the effectiveness of interventions for the prevention and management of cancer treatment-related skin toxicities. LITERATURE SEARCH: The authors systematically searched for comparative studies published before April 1, 2019. Study selection and appraisal were conducted by pairs of independent reviewers. DATA EVALUATION: The random-effects model was used to conduct meta-analysis when appropriate. SYNTHESIS: 39 studies (6,006 patients) were included; 16 of those provided data for meta-analysis. Prophylactic minocycline reduced the development of all-grade and grade 1 acneform rash in patients who received erlotinib. Prophylaxis with pyridoxine 400 mg in capecitabine-treated patients lowered the risk of grade 2 or 3 hand-foot syndrome. Several treatments for hand-foot skin reaction suggested benefit in heterogeneous studies. Scalp cooling significantly reduced the risk for severe hair loss or total alopecia associated with chemotherapy. IMPLICATIONS FOR RESEARCH: Certainty in the available evidence was limited for several interventions, suggesting the need for future research. SUPPLEMENTAL MATERIAL CAN BE FOUND AT HTTPS: //onf.ons.org/supplementary-material-targeted-therapy-and-chemotherapy-associated-skin-toxicity-systematic-review.

A Framework for Evidence Synthesis Programs to Respond to a Pandemic.

The coronavirus disease 2019 (COVID-19) pandemic requires making rapid decisions based on sparse and rapidly changing evidence. Evidence synthesis programs conduct systematic reviews for guideline developers, health systems clinicians, and decision-makers that usually take an average 6 to 8 months to complete. We present a framework for evidence synthesis programs to respond to pandemics that has proven feasible and practical during the COVID-19 response in a large multistate health system employing more than 78,000 people. The framework includes four components: an approach for conducting rapid reviews, a repository of rapid reviews, a registry for all original studies about COVID-19, and twice-weekly prioritized update of new evidence sent to key stakeholders. As COVID-19 will not be our last pandemic, we share the details of this framework to allow replication in other institutions and re-implementation in future pandemics.

Nonpharmacologic Therapies in Patients With Exacerbation of Chronic Obstructive Pulmonary Disease: A Systematic Review With Meta-Analysis.

OBJECTIVE: To evaluate the effectiveness and adverse events of nonpharmacologic interventions in patients with exacerbation of chronic obstructive pulmonary disease (COPD). PATIENTS AND METHODS: We searched Embase, MEDLINE, Cochrane databases, Scopus, and clinicaltrials.gov from database inception to January 2, 2019, for randomized controlled trials that enrolled adults with exacerbation of COPD and evaluated the effect of nonpharmacologic interventions on clinical outcomes and/or lung function. RESULTS: We included 30 randomized controlled trials with 2643 participants. Improvement in 6-minute walking test distance was associated with resistance training (weighted mean difference [WMD], 74.42; 95% CI, 46.85 to 101.99), pulmonary rehabilitation (WMD, 20.02; 95% CI, 12.06 to 28.67), whole body vibration (WMD, 89.42; 95% CI, 45.18 to 133.66), and transcutaneous electrical nerve stimulation (WMD, 64.54; 95% CI, 53.76 to 75.32). Improvement in quality of life was associated with resistance training (WMD, 18.7; 95% CI, 5.06 to 32.34), combined breathing technique and range of motion exercises (WMD, 14.89; 95% CI, 5.30 to 24.50), whole body vibration (WMD, -12.02; 95% CI, -21.41 to -2.63), and intramuscular vitamin D (WMD, -4.67; 95% CI, -6.00 to -3.35 at the longest follow-up). Oxygen titration with a target oxygen saturation range of 88% to 92% was associated with reduced mortality compared with high flow oxygen (odds ratio, 0.36; 95% CI, 0.14 to 0.88). All findings were based on low strength of evidence. CONCLUSION: In patients hospitalized for exacerbation of COPD, exercise interventions and pulmonary rehabilitation programs may ameliorate functional decline. Oxygen should be titrated with a target oxygen saturation of 88% to 92% in these patients. TRIAL REGISTRATION: PROSPERO Identifier: CRD42018111609.

Pharmacologic Therapies in Patients With Exacerbation of Chronic Obstructive Pulmonary Disease: A Systematic Review With Meta-analysis.

Background: Chronic obstructive pulmonary disease (COPD) is characterized by frequent exacerbations. Purpose: To evaluate the comparative effectiveness and adverse events (AEs) of pharmacologic interventions for adults with exacerbation of COPD. Data Sources: English-language searches of several bibliographic sources from database inception to 2 January 2019. Study Selection: 68 randomized controlled trials that enrolled adults with exacerbation of COPD treated in out- or inpatient settings other than intensive care and compared pharmacologic therapies with placebo, "usual care," or other pharmacologic interventions. Data Extraction: Two reviewers independently extracted data and rated study quality and strength of evidence (SOE). Data Synthesis: Compared with placebo or management without antibiotics, antibiotics given for 3 to 14 days were associated with increased exacerbation resolution at the end of the intervention (odds ratio [OR], 2.03 [95% CI, 1.47 to 2.80]; moderate SOE) and less treatment failure at the end of the intervention (OR, 0.54 [CI, 0.34 to 0.86]; moderate SOE), independent of severity of exacerbations in out- and inpatients. Compared with placebo in out- and inpatients, systemic corticosteroids given for 9 to 56 days were associated with less treatment failure at the end of the intervention (OR, 0.01 [CI, 0.00 to 0.13]; low SOE) but also with a higher number of total and endocrine-related AEs. Compared with placebo or usual care in inpatients, other pharmacologic interventions (aminophyllines, magnesium sulfate, anti-inflammatory agents, inhaled corticosteroids, and short-acting bronchodilators) had insufficient evidence, showing either no or inconclusive effects (with the exception of the mucolytic erdosteine) or improvement only in lung function. Limitation: Scant evidence for many interventions; several studies had unclear or high risk of bias and inadequate reporting of AEs. Conclusion: Antibiotics and systemic corticosteroids reduce treatment failure in adults with mild to severe exacerbation of COPD. Primary Funding Source: Agency for Healthcare Research and Quality. (PROSPERO: CRD42018111609).

Can Patients Trust Online Health Information? A Meta-narrative Systematic Review Addressing the Quality of Health Information on the Internet.

BACKGROUND: The Internet has become a leading source of health information accessed by patients and the general public. It is crucial that this information is reliable and accurate. OBJECTIVES: The purpose of this systematic review was to evaluate the overall quality of online health information targeting patients and the general public. METHODS: The systematic review is based on a pre-established protocol and is reported according to the PRISMA statement. Eleven databases and Internet searches were performed for relevant studies. Descriptive statistics were used to synthesize data. The NIH Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies was used to assess the methodological quality of the included studies. RESULTS: Out of 3393 references, we included 153 cross-sectional studies evaluating 11,785 websites using 14 quality assessment tools. The quality level varied across scales. Using DISCERN, none of the websites received a category of excellent in quality, 37-79% were rated as good, and the rest were rated as poor quality. Only 18% of websites were HON Code certified. Quality varied by affiliation (governmental was higher than academic, which was higher than other media sources) and by health specialty (likely higher in internal medicine and anesthesiology). CONCLUSION: This comprehensive systematic review demonstrated suboptimal quality of online health information. Therefore, the Internet at the present time does not provide reliable health information for laypersons. The quality of online health information requires significant improvement which should be a mandate for policymakers and private and public organizations.

Treatment of stable chronic obstructive pulmonary disease: protocol for a systematic review and evidence map.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a progressive lung disease, usually caused by tobacco smoking, but other important risk factors include exposures to combustion products of biomass fuels and environmental pollution. The introduction of several new (combination) inhaler therapies, increasing uncertainty about the role of inhaled corticosteroids and a rapid proliferation of the literature on management of stable COPD in general, call for novel ways of evidence synthesis in this area. A systematic review and evidence map can provide the basis for shared decision-making tools and help to establish a future research agenda. METHODS AND ANALYSIS: This systematic review will follow an umbrella systematic review design (also called overview of reviews). We plan to conduct a comprehensive literature search of Ovid MEDLINE (including epub ahead of print, in process and other non-indexed citations), Ovid Embase, Ovid Cochrane Database of Systematic Reviews and Scopus from database inception to the present. We will include systematic reviews that assessed the effectiveness of any pharmacological or non-pharmacological intervention on one or more patient-important outcomes and/or lung function in patients with stable COPD. For every intervention/outcome pair, one systematic review will be included. An a priori protocol will guide, which systematic reviews will be chosen, how their credibility will be evaluated, and how the quality of the body of evidence will be rated. Data will be synthesised into an evidence map that will present a matrix that depicts each available treatment for stable COPD with a quantitative estimate on symptoms/outcomes from the patient perspective, along with an indication of the size and certainty in the evidence. ETHICS AND DISSEMINATION: Approval by a research ethics committee is not required since the review will only include published data. The systematic review will be published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42018095079.

Non-pharmacological treatment of depression: a systematic review and evidence map.

BACKGROUND: The comparative effectiveness of non-pharmacological treatments of depression remains unclear. METHODS: We conducted an overview of systematic reviews to identify randomised controlled trials (RCTs) that compared the efficacy and adverse effects of non-pharmacological treatments of depression. We searched multiple electronic databases through February 2016 without language restrictions. Pairs of reviewers determined eligibility, extracted data and assessed risk of bias. Meta-analyses were conducted when appropriate. RESULT: We included 367 RCTs enrolling ∼20 000 patients treated with 11 treatments leading to 17 unique head-to-head comparisons. Cognitive behavioural therapy, naturopathic therapy, biological interventions and physical activity interventions reduced depression severity as measured using standardised scales. However, the relative efficacy among these non-pharmacological interventions was lacking. The effect of these interventions on clinical response and remission was unclear. Adverse events were lower than antidepressants. LIMITATION: The quality of evidence was low to moderate due to inconsistency and unclear or high risk of bias, limiting our confidence in findings. CONCLUSIONS: Non-pharmacological therapies of depression reduce depression symptoms and should be considered along with antidepressant therapy for the treatment of mild-to-severe depression. A shared decision-making approach is needed to choose between non-pharmacological therapies based on values, preferences, clinical and social context.

RADIOTHERAPY VERSUS RADIOSURGERY IN TREATING PATIENTS WITH ACROMEGALY: A SYSTEMATIC REVIEW AND META-ANALYSIS.

OBJECTIVE: When patients with acromegaly have residual disease following surgery, adjuvant radiation therapy is considered. Both stereotactic radiosurgery (SRS) and conventional fractionated radiotherapy (RT) are utilized. We conducted a systematic review and meta-analysis to synthesize the existing evidence and compare outcomes for SRS and RT in patients with acromegaly. METHODS: We searched Medline In-Process & Other Non-Indexed Citations, MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus through April 2014 for studies in which SRS or RT were used in patients with acromegaly. Outcomes evaluated were serum insulin-like growth factor-I (IGF-I) and growth hormone (GH) levels, biochemical remission, all-cause mortality, hypopituitarism, headaches, and secondary malignancies. We pooled outcomes using a random-effects model. RESULTS: The final search yielded 30 eligible studies assessing 2,464 patients. Compared to RT, SRS was associated with a nonsignificant increase in remission rate at the latest follow-up period (52% vs. 36%; P = .14) and a significantly lower follow-up IGF-I level (-409.72 µg/L vs. -102 µg/L, P = .002). SRS had a lower incidence of hypopituitarism than RT; however, the difference was not statistically significant (32% vs. 51%, respectively; P = .05). CONCLUSION: SRS may be associated with better biochemical remission, and it had a lower risk of hypopituitarism with at least 1 deficient axis when compared with RT; however, the confidence in such evidence is very low due to the noncomparative nature of the studies, high heterogeneity, and imprecision.

Radiotherapy vs. Radiosurgery in Treating Patients with Acromegaly: Systematic Review and Meta-Analysis.

OBJECTIVE: When patients with acromegaly have residual disease following surgery, adjuvant radiation therapy is considered. Both stereotactic radiosurgery (SRS) and conventional fractionated radiotherapy (RT) are utilized. We conducted a systematic review and meta-analysis to synthesize the existing evidence to compare outcomes with SRS and RT in patients with acromegaly. METHODS: We searched Medline In-Process & Other Non-Indexed Citations, MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus through April 2014 for studies in which SRS or RT were used in patients with acromegaly. Outcomes evaluated were serum IGF-1 and GH levels, biochemical remission, all-cause mortality, hypopituitarism, headaches and secondary malignancies. We pooled outcomes using the random-effects model. RESULTS: The final search yielded 30 eligible studies enrolling 2464 patients. When compared to RT, SRS was associated with a non-significant increase in remission rate at the latest follow-up period (52% vs. 36%; p = 0.14), and a significantly lower follow-up IGF-1 level (decline of - 409.72 µg/1 vs. -102 µg/1; p = 0.002). SRS was associated with lower incidence of hypopituitarism than RT; however the difference was not statistically significant [(32% vs.51%, respectively; p = 0.05). CONCLUSIONS: SRS may be associated with better biochemical remission and lower risk of hypopituitarism with at least one deficient axis when compared with RT; however, the confidence in such evidence is very low due to the non-comparative nature of the studies, high heterogeneity, and imprecision.