A Systematic Review Supporting the Endocrine Society Clinical Practice Guidelines on Vitamin D.

CONTEXT: Low vitamin D status is common and is associated with various common medical conditions. OBJECTIVE: To support the development of the Endocrine Society's Clinical Practice Guideline on Vitamin D for the Prevention of Disease. METHODS: We searched multiple databases for studies that addressed 14 clinical questions prioritized by the guideline panel. Of the 14 questions, 10 clinical questions assessed the effect of vitamin D vs no vitamin D in the general population throughout the lifespan, during pregnancy, and in adults with prediabetes; 1 question assessed dosing; and 3 questions addressed screening with serum 25-hydroxyvitamin D (25[OH]D). The Grading of Recommendations Assessment, Development and Evaluation approach was used to assess certainty of evidence. RESULTS: Electronic searches yielded 37 007 citations, from which we included 151 studies. In children and adolescents, low-certainty evidence suggested reduction in respiratory tract infections with empiric vitamin D. There was no significant effect on select outcomes in healthy adults aged 19 to 74 years with variable certainty of evidence. There was a very small reduction in mortality among adults older than 75 years with high certainty of evidence. In pregnant women, low-certainty evidence suggested possible benefit on various maternal, fetal, and neonatal outcomes. In adults with prediabetes, moderate certainty of evidence suggested reduction in the rate of progression to diabetes. Administration of high-dose intermittent vitamin D may increase falls, compared to lower-dose daily dosing. We did not identify trials on the benefits and harms of screening with serum 25(OH)D. CONCLUSION: The evidence summarized in this systematic review addresses the benefits and harms of vitamin D for the prevention of disease. The guideline panel considered additional information about individuals' and providers' values and preferences and other important decisional and contextual factors to develop clinical recommendations.

Association of Shock Indices with Peri-Intubation Hypotension and Other Outcomes: A Sub-Study of the KEEP PACE Trial.

BACKGROUND: Based on current evidence, there appears to be an association between peri-intubation hypotension and patient morbidity and mortality. Studies have identified shock indices as possible pre-intubation risk factors for peri-intubation hypotension. Thus, we sought to evaluate the association between shock index (SI), modified shock index (MSI), and diastolic shock index (DSI) and peri-intubation hypotension along with other outcomes. METHODS: The present study is a sub-study of a randomized controlled trial involving critically ill patients undergoing intubation. We defined peri-intubation hypotension as a decrease in mean arterial pressure <65 mm Hg and/or a reduction of 40% from baseline; or the initiation of, or increase in infusion dosage of, any vasopressor medication (bolus or infusion) during the 30-min period following intubation. SI, MSI, and DSI were analyzed as continuous variables and categorically using pre-established cut-offs. We also explored the effect of age on shock indices. RESULTS: A total of 151 patients were included in the analysis. Mean pre-intubation SI was 1.0 ± 0.3, MSI 1.5 ± 0.5, and DSI 1.9 ± 0.7. Increasing SI, MSI, and DSI were significantly associated with peri-intubation hypotension (OR [95% CI] per 0.1 increase = 1.16 [1.04, 1.30], P = .009 for SI; 1.14 [1.05, 1.24], P = .003 for MSI; and 1.11 [1.04, 1.19], P = .003 for DSI). The area under the ROC curves did not differ across shock indices (0.66 vs 0.67 vs 0.69 for SI, MSI, and DSI respectively; P = .586). Increasing SI, MSI, and DSI were significantly associated with worse sequential organ failure assessment (SOFA) score (spearman rank correlation: r = 0.30, r = 0.40, and r = 0.45 for SI, MSI, and DSI, respectively, all P < .001) but not with other outcomes. There was no significant impact when incorporating age. CONCLUSIONS: Increasing SI, MSI, and DSI were all significantly associated with peri-intubation hypotension and worse SOFA scores but not with other outcomes. Shock indices remain a useful bedside tool to assess the potential likelihood of peri-intubation hypotension. TRIAL REGISTRATION: ClinicalTrials.gov identifier - NCT02105415.

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.

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.

Perioperative Management of Vitamin K Antagonists and Direct Oral Anticoagulants: A Systematic Review and Meta-analysis.

BACKGROUND: The management of patients who are receiving chronic oral anticoagulation therapy and require an elective surgery or an invasive procedure is a common clinical scenario. RESEARCH QUESTION: What is the best available evidence to support the development of American College of Chest Physicians guidelines on the perioperative management of patients who are receiving long-term vitamin K agonist (VKA) or direct oral anticoagulant (DOAC) and require elective surgery or procedures? STUDY DESIGN AND METHODS: A literature search including multiple databases from database inception through July 16, 2020, was performed. Meta-analyses were conducted when appropriate. RESULTS: In patients receiving VKA (warfarin) undergoing elective noncardiac surgery, shorter (< 3 days) VKA interruption is associated with an increased risk of major bleeding. In patients who required VKA interruption, heparin bridging (mostly with low-molecular-weight heparin [LMWH]) was associated with a statistically significant increased risk of major bleed, representing a very low certainty of evidence (COE). Compared with DOAC interruption 1 to 4 days before surgery, continuing DOACs may be associated with higher risk of bleeding demonstrated in some, but not all studies. In patients who needed DOAC interruption, bridging with LMWH may be associated with a statistically significant increased risk of bleeding, representing a low COE. INTERPRETATION: The certainty in the evidence supporting the perioperative management of anticoagulants remains limited. No high-quality evidence exists to support the practice of heparin bridging during the interruption of VKA or DOAC therapy for an elective surgery or procedure, or for the practice of interrupting VKA therapy for minor procedures, including cardiac device implantation, or continuation of a DOAC vs short-term interruption of a DOAC in the perioperative period.

Perioperative Management of Antiplatelet Therapy: A Systematic Review and Meta-analysis.

Objective: To summarize the available evidence about the perioperative management of patients who are receiving long-term antiplatelet therapy and require elective surgery/procedures. Methods: This systematic review supports the development of the American College of Chest Physicians guideline on the perioperative management of antiplatelet therapy. A literature search of MEDLINE, EMBASE, Scopus and Cochrane databases was conducted from each database's inception to July 16, 2020. Meta-analyses were conducted when possible. Results: In patients receiving long-term antiplatelet therapy and undergoing elective noncardiac surgery, the available evidence did not show a significant difference in major bleeding between a shorter vs longer antiplatelet interruption, with low certainty of evidence (COE). Compared with patients who received placebo perioperatively, aspirin continuation was associated with increased risk of major bleeding (relative risk [RR], 1.31; 95% CI, 1.15-1.50; high COE) and lower risk of major thromboembolism (RR, 0.74; 95% CI, 0.58-0.94; moderate COE). During antiplatelet interruption, bridging with low-molecular-weight heparin was associated with increased risk of major bleeding compared with no bridging (RR, 1.86; 95% CI, 1.24-2.79; very low COE). Continuation of antiplatelets during minor dental and ophthalmologic procedures was not associated with a statistically significant difference in the risk of major bleeding (very low COE). Conclusion: This systematic review summarizes the current evidence about the perioperative management of antiplatelet therapy and highlights the urgent need for further research, particularly with the increasing prevalence of patients taking 1 or more antiplatelet agents.

A Systematic Review Supporting the Endocrine Society Clinical Practice Guideline for the Management of Hyperglycemia in Adults Hospitalized for Noncritical Illness or Undergoing Elective Surgical Procedures.

CONTEXT: Individuals with diabetes or newly recognized hyperglycemia account for over 30% of noncritically ill hospitalized patients. Management of hyperglycemia in these patients is challenging. OBJECTIVE: To support development of the Endocrine Society Clinical Practice Guideline for management of hyperglycemia in adults hospitalized for noncritical illness or undergoing elective surgical procedures. METHODS: We searched several databases for studies addressing 10 questions provided by a guideline panel from the Endocrine Society. Meta-analysis was conducted when feasible. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess certainty of evidence. RESULTS: We included 94 studies reporting on 135 553 patients. Compared with capillary blood glucose, continuous glucose monitoring increased the number of patients identified with hypoglycemia and decreased mean daily blood glucose (BG) (very low certainty). Data on continuation of insulin pump therapy in hospitalized adults were sparse. In hospitalized patients receiving glucocorticoids, combination neutral protamine hagedorn (NPH) and basal-bolus insulin was associated with lower mean BG compared to basal-bolus insulin alone (very low certainty). Data on NPH insulin vs basal-bolus insulin in hospitalized adults receiving enteral nutrition were inconclusive. Inpatient diabetes education was associated with lower HbA1c at 3 and 6 months after discharge (moderate certainty) and reduced hospital readmissions (very low certainty). Preoperative HbA1c level < 7% was associated with shorter length of stay, lower postoperative BG and a lower number of neurological complications and infections, but a higher number of reoperations (very low certainty). Treatment with glucagon-like peptide-1 agonists or dipeptidyl peptidase-4 inhibitors in hospitalized patients with type 2 diabetes and mild hyperglycemia was associated with lower frequency of hypoglycemic events than insulin therapy (low certainty). Caloric oral fluids before surgery in adults with diabetes undergoing surgical procedures did not affect outcomes (very low certainty). Counting carbohydrates for prandial insulin dosing did not affect outcomes (very low certainty). Compared with scheduled insulin (basal-bolus or basal insulin + correctional insulin), correctional insulin was associated with higher mean daily BG and fewer hypoglycemic events (low certainty). CONCLUSION: The certainty of evidence supporting many hyperglycemia management decisions is low, emphasizing importance of shared decision-making and consideration of other decisional factors.

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.

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.

A Systematic Review Supporting the American Society for Dermatologic Surgery Guidelines on the Prevention and Treatment of Adverse Events of Injectable Fillers.

BACKGROUND: As the use of injectable skin fillers increase in popularity, an increase in the reported adverse events is expected. OBJECTIVE: This systematic review supports the development of American Society for Dermatologic Surgery practice guideline on the management of adverse events of skin fillers. METHODS AND MATERIALS: Several databases for studies on risk factors or treatments of injection-related visual compromise (IRVC), skin necrosis, inflammatory events, and nodules were searched. Meta-analysis was conducted when feasible. RESULTS: The review included 182 studies. However, IRVC was very rare (1-2/1,000,000 patients) but had poor prognosis with improvement in 19% of cases. Skin necrosis was more common (approximately 5/1,000) with better prognosis (up to 77% of cases showing improvement). Treatments of IRVC and skin necrosis primarily depend on hyaluronidase injections. Risk of skin necrosis, inflammatory events, and nodules may be lower with certain fillers, brands, injection techniques, and volume. Treatment of inflammatory events and nodules with antibiotics, corticosteroids, 5-FU, and hyaluronidase was associated with high response rate (75%-80%). Most of the studies were small and noncomparative, making the evidence certainty very low. CONCLUSION: Practitioners must have adequate knowledge of anatomy, elicit history of skin filler use, and establish preemptive protocols that prepare the clinical practice to manage complications.

Risk factors for and prediction of post-intubation hypotension in critically ill adults: A multicenter prospective cohort study.

OBJECTIVE: Hypotension following endotracheal intubation in the ICU is associated with poor outcomes. There is no formal prediction tool to help estimate the onset of this hemodynamic compromise. Our objective was to derive and validate a prediction model for immediate hypotension following endotracheal intubation. METHODS: A multicenter, prospective, cohort study enrolling 934 adults who underwent endotracheal intubation across 16 medical/surgical ICUs in the United States from July 2015-January 2017 was conducted to derive and validate a prediction model for immediate hypotension following endotracheal intubation. We defined hypotension as: 1) mean arterial pressure <65 mmHg; 2) systolic blood pressure <80 mmHg and/or decrease in systolic blood pressure of 40% from baseline; 3) or the initiation or increase in any vasopressor in the 30 minutes following endotracheal intubation. RESULTS: Post-intubation hypotension developed in 344 (36.8%) patients. In the full cohort, 11 variables were independently associated with hypotension: increasing illness severity; increasing age; sepsis diagnosis; endotracheal intubation in the setting of cardiac arrest, mean arterial pressure <65 mmHg, and acute respiratory failure; diuretic use 24 hours preceding endotracheal intubation; decreasing systolic blood pressure from 130 mmHg; catecholamine and phenylephrine use immediately prior to endotracheal intubation; and use of etomidate during endotracheal intubation. A model excluding unstable patients' pre-intubation (those receiving catecholamine vasopressors and/or who were intubated in the setting of cardiac arrest) was also developed and included the above variables with the exception of sepsis and etomidate. In the full cohort, the 11 variable model had a C-statistic of 0.75 (95% CI 0.72, 0.78). In the stable cohort, the 7 variable model C-statistic was 0.71 (95% CI 0.67, 0.75). In both cohorts, a clinical risk score was developed stratifying patients' risk of hypotension. CONCLUSIONS: A novel multivariable risk score predicted post-intubation hypotension with accuracy in both unstable and stable critically ill patients. STUDY REGISTRATION: Clinicaltrials.gov identifier: NCT02508948 and Registered Report Identifier: RR2-10.2196/11101.

American Society of Hematology 2020 guidelines for sickle cell disease: management of acute and chronic pain.

BACKGROUND: The management of acute and chronic pain for individuals living with sickle cell disease (SCD) is a clinical challenge. This reflects the paucity of clinical SCD pain research and limited understanding of the complex biological differences between acute and chronic pain. These issues collectively create barriers to effective, targeted interventions. Optimal pain management requires interdisciplinary care. OBJECTIVE: These evidence-based guidelines developed by the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in pain management decisions for children and adults with SCD. METHODS: ASH formed a multidisciplinary panel, including 2 patient representatives, that was thoroughly vetted to minimize bias from conflicts of interest. The Mayo Evidence-Based Practice Research Program supported the guideline development process, including updating or performing systematic reviews. Clinical questions and outcomes were prioritized according to importance for clinicians and patients. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used, including GRADE evidence-to-decision frameworks, to assess evidence and make recommendations, which were subject to public comment. RESULTS: The panel reached consensus on 18 recommendations specific to acute and chronic pain. The recommendations reflect a broad pain management approach, encompassing pharmacological and nonpharmacological interventions and analgesic delivery. CONCLUSIONS: Because of low-certainty evidence and closely balanced benefits and harms, most recommendations are conditional. Patient preferences should drive clinical decisions. Policymaking, including that by payers, will require substantial debate and input from stakeholders. Randomized controlled trials and comparative-effectiveness studies are needed for chronic opioid therapy, nonopioid therapies, and nonpharmacological interventions.

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.

A systematic review and meta-analysis of the management of visceral artery aneurysms.

BACKGROUND: The evidence supporting management decisions of visceral artery aneurysms (VAAs) is sparse. Practice guidelines are needed to help patients and surgeons choose between endovascular and open surgery approaches. METHODS: We searched MEDLINE, EMBASE, Cochrane databases, and Scopus for studies of patients with VAAs. Studies were selected and appraised by pairs of independent reviewers. Meta-analysis was performed when appropriate. RESULTS: We included 80 observational studies that were mostly noncomparative. Data were available for 2845 aneurysms, comprising 1279 renal artery, 775 splenic artery, 359 hepatic artery, 226 pancreaticoduodenal and gastroduodenal arteries, 95 superior mesenteric artery, 87 celiac artery, 15 jejunal, ileal and colic arteries, and 9 gastric and gastroepiploic arteries. Differences in mortality between open and endovascular approaches were not statistically significant. The endovascular approach was used more often by surgeons. The endovascular approach was associated with shorter hospital stay and lower rates of cardiovascular complications but higher rates of reintervention. Postembolization syndrome rates ranged from 9% (renal) to 38% (splenic). Coil migration ranged from 8% (splenic) to 29% (renal). Otherwise, access site complication were low (<5%). Pseudoaneurysms tended to have higher mortality and reintervention rates. CONCLUSIONS: This systematic review provides event rates for outcomes important to patients with VAAs. Despite the low certainty warranted by the evidence, these rates along, with surgical expertise and anatomic feasibility, can help patients and surgeons in shared-decision making.

Derivation and validation of a computable phenotype for acute decompensated heart failure in hospitalized patients.

BACKGROUND: With higher adoption of electronic health records at health-care centers, electronic search algorithms (computable phenotype) for identifying acute decompensated heart failure (ADHF) among hospitalized patients can be an invaluable tool to enhance data abstraction accuracy and efficacy in order to improve clinical research accrual and patient centered outcomes. We aimed to derive and validate a computable phenotype for ADHF in hospitalized patients. METHODS: We screened 256, 443 eligible (age > 18 years and with prior research authorization) individuals who were admitted to Mayo Clinic Hospital in Rochester, MN, from January 1, 2006, through December 31, 2014. Using a randomly selected derivation cohort of 938 patients, several iterations of a free-text electronic search were developed and refined. The computable phenotype was subsequently validated in an independent cohort 100 patients. The sensitivity and specificity of the computable phenotype were compared to the gold standard (expert review of charts) and International Classification of Diseases-9 (ICD-9) codes for Acute Heart Failure. RESULTS: In the derivation cohort, the computable phenotype achieved a sensitivity of 97.5%, and specificity of 100%, whereas ICD-9 codes for Acute Heart Failure achieved a sensitivity of 47.5% and specificity of 96.7%. When all Heart Failure codes (ICD-9) were used, sensitivity and specificity were 97.5 and 86.6%, respectively. In the validation cohort, the sensitivity and specificity of the computable phenotype were 100 and 98.5%. The sensitivity and specificity for the ICD-9 codes (Acute Heart Failure) were 42 and 98.5%. Upon use of all Heart Failure codes (ICD-9), sensitivity and specificity were 96.8 and 91.3%. CONCLUSIONS: Our results suggest that using computable phenotype to ascertain ADHF from the clinical notes contained within the electronic medical record are feasible and reliable. Our computable phenotype outperformed ICD-9 codes for the detection of ADHF.

Effect of Ketamine/Propofol Admixture on Peri-Induction Hemodynamics: A Systematic Review and Meta-Analysis.

To evaluate the effectiveness of an admixture of ketamine and propofol on peri-induction hemodynamics during airway manipulation, we searched electronic databases of randomized controlled trials from January 1, 2000, to October 17, 2018. Trial screening, selection, and data extraction were done independently by two reviewers with outcomes pooled across included trials using the random-effects model. We included 10 randomized trials (722 patients, mean age of 53.99 years, 39.96% female). American Society of Anesthesiologists physical status was reported in 9 trials with classes I and II representing the majority. Ketamine/propofol admixture was associated with a nonsignificant increase in heart rate (weighted mean difference, 3.36 beats per minute (95% CI, -0.88, 7.60), I 2 = 88.6%), a statistically significant increase in systolic blood pressure (weighted mean difference, 9.67 mmHg (95% CI, 1.48, 17.86), I 2 = 87.2%), a nonsignificant increase in diastolic blood pressure (weighted mean difference, 2.18 mmHg (95% CI, -2.82, 7.19), I 2 = 73.1%), and a nonsignificant increase in mean arterial pressure (weighted mean difference, 3.28 mmHg (95% CI, -0.94, 7.49), I 2 = 69.9%) compared to other agents. The risk of bias was high and the certainty of evidence was low. In conclusion, among patients undergoing airway manipulation and needing sedation, the use of a ketamine/propofol admixture may be associated with better hemodynamics compared to nonketamine/propofol sedation. This trial is registered with CRD42019125725.

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).

Association of Home Noninvasive Positive Pressure Ventilation With Clinical Outcomes in Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-analysis.

Importance: The association of home noninvasive positive pressure ventilation (NIPPV) with outcomes in chronic obstructive pulmonary disease (COPD) and hypercapnia is uncertain. Objective: To evaluate the association of home NIPPV via bilevel positive airway pressure (BPAP) devices and noninvasive home mechanical ventilator (HMV) devices with clinical outcomes and adverse events in patients with COPD and hypercapnia. Data Sources: Search of MEDLINE, EMBASE, SCOPUS, Cochrane Central Registrar of Controlled Trials, Cochrane Database of Systematic Reviews, National Guideline Clearinghouse, and Scopus for English-language articles published from January 1, 1995, to November 6, 2019. Study Selection: Randomized clinical trials (RCTs) and comparative observational studies that enrolled adults with COPD with hypercapnia who used home NIPPV for more than 1 month were included. Data Extraction and Synthesis: Data extraction was completed by independent pairs of reviewers. Risk of bias was evaluated using the Cochrane Collaboration risk of bias tool for RCTs and select items from the Newcastle-Ottawa Scale for nonrandomized studies. Main Outcomes and Measures: Primary outcomes were mortality, all-cause hospital admissions, need for intubation, and quality of life at the longest follow-up. Results: A total of 21 RCTs and 12 observational studies evaluating 51 085 patients (mean [SD] age, 65.7 [2.1] years; 43% women) were included, among whom there were 434 deaths and 27 patients who underwent intubation. BPAP compared with no device was significantly associated with lower risk of mortality (22.31% vs 28.57%; risk difference [RD], -5.53% [95% CI, -10.29% to -0.76%]; odds ratio [OR], 0.66 [95% CI, 0.51-0.87]; P = .003; 13 studies; 1423 patients; strength of evidence [SOE], moderate), fewer patients with all-cause hospital admissions (39.74% vs 75.00%; RD, -35.26% [95% CI, -49.39% to -21.12%]; OR, 0.22 [95% CI, 0.11-0.43]; P < .001; 1 study; 166 patients; SOE, low), and lower need for intubation (5.34% vs 14.71%; RD, -8.02% [95% CI, -14.77% to -1.28%]; OR, 0.34 [95% CI, 0.14-0.83]; P = .02; 3 studies; 267 patients; SOE, moderate). There was no significant difference in the total number of all-cause hospital admissions (rate ratio, 0.91 [95% CI, 0.71-1.17]; P = .47; 5 studies; 326 patients; SOE, low) or quality of life (standardized mean difference, 0.16 [95% CI, -0.06 to 0.39]; P = .15; 9 studies; 833 patients; SOE, insufficient). Noninvasive HMV use compared with no device was significantly associated with fewer all-cause hospital admissions (rate ratio, 0.50 [95% CI, 0.35-0.71]; P < .001; 1 study; 93 patients; SOE, low), but not mortality (21.84% vs 34.09%; RD, -11.99% [95% CI, -24.77% to 0.79%]; OR, 0.56 [95% CI, 0.29-1.08]; P = .49; 2 studies; 175 patients; SOE, insufficient). There was no statistically significant difference in the total number of adverse events in patients using NIPPV compared with no device (0.18 vs 0.17 per patient; P = .84; 6 studies; 414 patients). Conclusions and Relevance: In this meta-analysis of patients with COPD and hypercapnia, home BPAP, compared with no device, was associated with lower risk of mortality, all-cause hospital admission, and intubation, but no significant difference in quality of life. Noninvasive HMV, compared with no device, was significantly associated with lower risk of hospital admission, but there was no significant difference in mortality risk. However, the evidence was low to moderate in quality, the evidence on quality of life was insufficient, and the analyses for some outcomes were based on small numbers of studies.