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Objectives. To evaluate the comparative effectiveness and harms of partial breast irradiation (PBI) compared with whole breast irradiation (WBI) for early-stage breast cancer, and how differences in effectiveness and harms may be influenced by patient, tumor, and treatment factors, including treatment modality, target volume, dose, and fractionation. We also evaluated the relative financial toxicity of PBI versus WBI. Data sources. MEDLINE®, Embase®, Cochrane Central Registrar of Controlled Trials, Cochrane Database of Systematic Reviews, Scopus, and various grey literature sources from database inception to June 30, 2022. Review methods. We included randomized clinical trials (RCTs) and observational studies that enrolled adult women with early-stage breast cancer who received one of six PBI modalities: multi-catheter interstitial brachytherapy, single-entry catheter brachytherapy (also known as intracavitary brachytherapy), 3-dimensional conformal external beam radiation therapy (3DCRT), intensity-modulated radiation therapy (IMRT), proton radiation therapy, intraoperative radiotherapy (IORT). Pairs of independent reviewers screened and appraised studies. Results. Twenty-three original studies with 17,510 patients evaluated the comparative effectiveness of PBI, including 14 RCTs, 6 comparative observational studies, and 3 single-arm observational studies. PBI was not significantly different from WBI in terms of ipsilateral breast recurrence (IBR), overall survival, or cancer-free survival at 5 and 10 years (high strength of evidence [SOE]). Evidence for cosmetic outcomes was insufficient. Results were generally consistent when PBI modalities were compared with WBI, whether compared individually or combined. These PBI approaches included 3DCRT, IMRT, and multi-catheter interstitial brachytherapy. Compared with WBI, 3DCRT showed no difference in IBR, overall survival, or cancer-free survival at 5 and 10 years (moderate to high SOE); IMRT showed no difference in IBR or overall survival at 5 and 10 years (low SOE); multi-catheter interstitial brachytherapy showed no difference in IBR, overall survival, or cancer-free survival at 5 years (low SOE). Compared with WBI, IORT was associated with a higher IBR rate at 5, 10, and over 10 years (high SOE), with no difference in overall survival, cancer-free survival, or mastectomy-free survival (low to high SOE). There were significantly fewer acute adverse events (AEs) with PBI compared with WBI, with no apparent difference in late AEs (moderate SOE). Data about quality of life were limited. Head-to-head comparisons between the different PBI modalities showed insufficient evidence to estimate an effect on main outcomes. There were no significant differences in IBR or other outcomes according to patient, tumor, and treatment characteristics; however, data for subgroups were insufficient to draw conclusions. Eight studies addressed concepts closely related to financial toxicity. Compared with conventionally fractionated WBI, accelerated PBI was associated with lower transportation costs and days away from work. PBI was also associated with less subjective financial difficulty at various time points after radiotherapy. Conclusions. Clinical trials that compared PBI with WBI demonstrate no significant difference in the risk of IBR. PBI is associated with fewer acute AEs and may be associated with less financial toxicity. The current evidence supports the use of PBI in appropriately selected patients with early-stage breast cancer. Further investigation is needed to evaluate the outcomes of PBI in patients with various clinical and tumor characteristics, and to define optimal radiation treatment dose and technique for PBI.

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.

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.

ObjectivesTo evaluate the association of study design features and treatment effects in randomised controlled trials (RCTs) evaluating therapies for individuals with chronic medical conditions.DesignMeta-epidemiological study.SettingRCTs 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 measuresThe association between trial design features and the effect size, reporting a ratio of ORs (ROR) and 95% confidence interval (CI).ResultsWe 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).ConclusionThe 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 numberNot applicable.

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.

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.

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.

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.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.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.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.

Chronic obstructive pulmonary disease (COPD) is characterized by frequent exacerbations.To evaluate the comparative effectiveness and adverse events (AEs) of pharmacologic interventions for adults with exacerbation of COPD.English-language searches of several bibliographic sources from database inception to 2 January 2019.68 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.Two reviewers independently extracted data and rated study quality and strength of evidence (SOE).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.Scant evidence for many interventions; several studies had unclear or high risk of bias and inadequate reporting of AEs.Antibiotics and systemic corticosteroids reduce treatment failure in adults with mild to severe exacerbation of COPD.Agency for Healthcare Research and Quality. (PROSPERO: CRD42018111609).

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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11606-019-05109-0) contains supplementary material, which is available to authorized users.

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.We searched Medline In-ProcessOther 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.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).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.

BACKGROUND Several pharmacologic and nonpharmacologic therapeutic options have been used to treat cough that is not associated with a pulmonary or extrapulmonary etiology. METHODS We conducted a systematic review to summarize the evidence supporting different cough management options in adults and children with psychogenic, tic, and habit cough. Medline, EMBASE, the Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus were searched from the earliest inception of each database to September 2013. Content experts were contacted, and we searched bibliographies of included studies to identify additional references. RESULTS A total of 18 uncontrolled studies were identified, enrolling 223 patients (46% male subjects, 96% children and adolescents). Psychogenic cough was the most common descriptive term used (90% of the studies). Most of the patients (95%) had no cough during sleep; barking or honking quality of cough was described in only eight studies. Hypnosis (three studies), suggestion therapy (four studies), and counseling and reassurance (seven studies) were the most commonly used interventions. Hypnosis was effective in resolving cough in 78% of the patients and improving it in another 5%. Suggestion therapy resolved cough successfully in 96% of the patients. The greatest majority of improvements noted with these forms of therapy occurred in the pediatric age group. The quality of evidence is low due to the lack of control groups, the retrospective nature of all the studies, heterogeneity of definitions and diagnostic criteria, and the high likelihood of reporting bias. CONCLUSIONS Only low-quality evidence exists to support a particular strategy to define and treat psychogenic, habit, and tic cough. Patient values, preferences, and availability of potential therapies should guide treatment choice.

IntroductionChronic 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 analysisThis 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 disseminationApproval 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 numberCRD42018095079

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.