Newer Pharmacologic Treatments in Adults With Type 2 Diabetes: A Clinical Guideline From the American College of Physicians.

DESCRIPTION: The American College of Physicians (ACP) developed this clinical guideline to update recommendations on newer pharmacologic treatments of type 2 diabetes. This clinical guideline is based on the best available evidence for effectiveness, comparative benefits and harms, consideration of patients' values and preferences, and costs. METHODS: This clinical guideline is based on a systematic review of the effectiveness and harms of newer pharmacologic treatments of type 2 diabetes, including glucagon-like peptide-1 (GLP-1) agonists, a GLP-1 agonist and glucose-dependent insulinotropic polypeptide agonist, sodium-glucose cotransporter-2 (SGLT-2) inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, and long-acting insulins, used either as monotherapy or in combination with other medications. The Clinical Guidelines Committee prioritized the following outcomes, which were evaluated using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach: all-cause mortality, major adverse cardiovascular events, myocardial infarction, stroke, hospitalization for congestive heart failure, progression of chronic kidney disease, serious adverse events, and severe hypoglycemia. Weight loss, as measured by percentage of participants who achieved at least 10% total body weight loss, was a prioritized outcome, but data were insufficient for network meta-analysis and were not rated with GRADE. AUDIENCE AND PATIENT POPULATION: The audience for this clinical guideline is physicians and other clinicians. The population is nonpregnant adults with type 2 diabetes. RECOMMENDATION 1: ACP recommends adding a sodium-glucose cotransporter-2 (SGLT-2) inhibitor or glucagon-like peptide-1 (GLP-1) agonist to metformin and lifestyle modifications in adults with type 2 diabetes and inadequate glycemic control (strong recommendation; high-certainty evidence). • Use an SGLT-2 inhibitor to reduce the risk for all-cause mortality, major adverse cardiovascular events, progression of chronic kidney disease, and hospitalization due to congestive heart failure. • Use a GLP-1 agonist to reduce the risk for all-cause mortality, major adverse cardiovascular events, and stroke. RECOMMENDATION 2: ACP recommends against adding a dipeptidyl peptidase-4 (DPP-4) inhibitor to metformin and lifestyle modifications in adults with type 2 diabetes and inadequate glycemic control to reduce morbidity and all-cause mortality (strong recommendation; high-certainty evidence).

Outpatient Treatment of Confirmed COVID-19: Living, Rapid Practice Points From the American College of Physicians (Version 2).

DESCRIPTION: Evidence for the use of outpatient treatments in adults with confirmed COVID-19 continues to evolve with new data. This is version 2 of the American College of Physicians (ACP) living, rapid practice points focusing on 22 outpatient treatments for COVID-19, specifically addressing the dominant SARS-CoV-2 Omicron variant. METHODS: The Population Health and Medical Science Committee (formerly the Scientific Medical Policy Committee) developed this version of the living, rapid practice points on the basis of a living, rapid review done by the ACP Center for Evidence Reviews at Cochrane Austria at the University for Continuing Education Krems (Danube University Krems). This topic will be maintained as living and rapid by continually monitoring and assessing the impact of new evidence. PRACTICE POINT 1: Consider molnupiravir to treat symptomatic patients with confirmed mild to moderate COVID-19 in the outpatient setting who are within 5 days of the onset of symptoms and at a high risk for progressing to severe disease. PRACTICE POINT 2: Consider nirmatrelvir-ritonavir combination therapy to treat symptomatic patients with confirmed mild to moderate COVID-19 in the outpatient setting who are within 5 days of the onset of symptoms and at a high risk for progressing to severe disease. PRACTICE POINT 3: Do not use ivermectin to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting. PRACTICE POINT 4: Do not use sotrovimab to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting.

GRADE guidance 23: considering cost-effectiveness evidence in moving from evidence to health-related recommendations.

BACKGROUND: This is the 23rd in a series of articles describing the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to grading the certainty of evidence and strength of recommendations for systematic reviews, health technology assessments, and clinical guideline development. OBJECTIVES: We outline how resource utilization and cost-effectiveness analyses are integrated into health-related recommendations, using the GRADE Evidence to Decision (EtD) frameworks. STUDY DESIGN AND SETTING: Through iterative discussions and refinement, in-person, and online meetings, and through e-mail communication, we developed draft guidance to incorporate economic evidence in the formulation of health-related recommendations. We developed scenarios to operationalize the guidance. We presented a summary of the results to members of the GRADE Economic Evaluation Project Group. RESULTS: We describe how to estimate the cost of preventing (or achieving) an event to inform assessments of cost-effectiveness of alternative treatments, when there are no published economic evaluations. Evidence profiles and Summary of Findings tables based on systematic reviews of cost-effectiveness analyses can be created to provide top-level summaries of results and quality of multiple published economic evaluations. We also describe how this information could be integrated in GRADE's EtD frameworks to inform health-related recommendations. Three scenarios representing various levels of available cost-effectiveness evidence were used to illustrate the integration process. CONCLUSION: This GRADE guidance provides practical information for presenting cost-effectiveness data and its integration in the development of health-related recommendations, using the EtD frameworks.

Screening for Colorectal Cancer in Asymptomatic Average-Risk Adults: A Guidance Statement From the American College of Physicians (Version 2).

DESCRIPTION: The purpose of this updated guidance statement is to guide clinicians on screening for colorectal cancer (CRC) in asymptomatic average-risk adults. The intended audience is all clinicians. The population is asymptomatic adults at average risk for CRC. METHODS: This updated guidance statement was developed using recently published and critically appraised clinical guidelines from national guideline developers since the publication of the American College of Physicians' 2019 guidance statement, "Screening for Colorectal Cancer in Asymptomatic Average-Risk Adults." The authors searched for national guidelines from the United States and other countries published in English using PubMed and the Guidelines International Network library from 1 January 2018 to 24 April 2023. The authors also searched for updates of guidelines included in the first version of our guidance statement. The Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument was used to assess the quality of eligible guidelines. Two guidelines were selected for adoption and adaptation by raters on the basis of the highest average overall AGREE II quality scores. The evidence reviews and modeling studies for these 2 guidelines were also used to synthesize the evidence of diagnostic test accuracy, effectiveness, and harms of CRC screening interventions and to develop our guidance statements. GUIDANCE STATEMENT 1: Clinicians should start screening for colorectal cancer in asymptomatic average-risk adults at age 50 years. GUIDANCE STATEMENT 2: Clinicians should consider not screening asymptomatic average-risk adults between the ages of 45 to 49 years. Clinicians should discuss the uncertainty around benefits and harms of screening in this population. GUIDANCE STATEMENT 3: Clinicians should stop screening for colorectal cancer in asymptomatic average-risk adults older than 75 years or in asymptomatic average-risk adults with a life expectancy of 10 years or less. GUIDANCE STATEMENT 4A: Clinicians should select a screening test for colorectal cancer in consultation with their patient based on a discussion of benefits, harms, costs, availability, frequency, and patient values and preferences. GUIDANCE STATEMENT 4B: Clinicians should select among a fecal immunochemical or high-sensitivity guaiac fecal occult blood test every 2 years, colonoscopy every 10 years, or flexible sigmoidoscopy every 10 years plus a fecal immunochemical test every 2 years as a screening test for colorectal cancer. GUIDANCE STATEMENT 4C: Clinicians should not use stool DNA, computed tomography colonography, capsule endoscopy, urine, or serum screening tests for colorectal cancer.

Pharmacologic Treatment of Primary Osteoporosis or Low Bone Mass to Prevent Fractures in Adults: A Living Clinical Guideline From the American College of Physicians.

DESCRIPTION: This guideline updates the 2017 American College of Physicians (ACP) recommendations on pharmacologic treatment of primary osteoporosis or low bone mass to prevent fractures in adults. METHODS: The ACP Clinical Guidelines Committee based these recommendations on an updated systematic review of evidence and graded them using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. AUDIENCE AND PATIENT POPULATION: The audience for this guideline includes all clinicians. The patient population includes adults with primary osteoporosis or low bone mass. RECOMMENDATION 1A: ACP recommends that clinicians use bisphosphonates for initial pharmacologic treatment to reduce the risk of fractures in postmenopausal females diagnosed with primary osteoporosis (strong recommendation; high-certainty evidence). RECOMMENDATION 1B: ACP suggests that clinicians use bisphosphonates for initial pharmacologic treatment to reduce the risk of fractures in males diagnosed with primary osteoporosis (conditional recommendation; low-certainty evidence). RECOMMENDATION 2A: ACP suggests that clinicians use the RANK ligand inhibitor (denosumab) as a second-line pharmacologic treatment to reduce the risk of fractures in postmenopausal females diagnosed with primary osteoporosis who have contraindications to or experience adverse effects of bisphosphonates (conditional recommendation; moderate-certainty evidence). RECOMMENDATION 2B: ACP suggests that clinicians use the RANK ligand inhibitor (denosumab) as a second-line pharmacologic treatment to reduce the risk of fractures in males diagnosed with primary osteoporosis who have contraindications to or experience adverse effects of bisphosphonates (conditional recommendation; low-certainty evidence). RECOMMENDATION 3: ACP suggests that clinicians use the sclerostin inhibitor (romosozumab, moderate-certainty evidence) or recombinant PTH (teriparatide, low-certainty evidence), followed by a bisphosphonate, to reduce the risk of fractures only in females with primary osteoporosis with very high risk of fracture (conditional recommendation). RECOMMENDATION 4: ACP suggests that clinicians take an individualized approach regarding whether to start pharmacologic treatment with a bisphosphonate in females over the age of 65 with low bone mass (osteopenia) to reduce the risk of fractures (conditional recommendation; low-certainty evidence).

Outpatient Treatment of Confirmed COVID-19: Living, Rapid Practice Points From the American College of Physicians (Version 1).

DESCRIPTION: Strategies to manage COVID-19 in the outpatient setting continue to evolve as new data emerge on SARS-CoV-2 variants and the availability of newer treatments. The Scientific Medical Policy Committee (SMPC) of the American College of Physicians (ACP) developed these living, rapid practice points to summarize the best available evidence on the treatment of adults with confirmed COVID-19 in an outpatient setting. These practice points do not evaluate COVID-19 treatments in the inpatient setting or adjunctive COVID-19 treatments in the outpatient setting. METHODS: The SMPC developed these living, rapid practice points on the basis of a living, rapid review done by the ACP Center for Evidence Reviews at Cochrane Austria at the University for Continuing Education Krems (Danube University Krems). The SMPC will maintain these practice points as living by monitoring and assessing the impact of new evidence. PRACTICE POINT 1: Consider molnupiravir to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting who are within 5 to 7 days of the onset of symptoms and at high risk for progressing to severe disease. PRACTICE POINT 2: Consider nirmatrelvir-ritonavir combination therapy to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting who are within 5 days of the onset of symptoms and at high risk for progressing to severe disease. PRACTICE POINT 3: Consider remdesivir to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting who are within 7 days of the onset of symptoms and at high risk for progressing to severe disease. PRACTICE POINT 4: Do not use azithromycin to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting. PRACTICE POINT 5: Do not use chloroquine or hydroxychloroquine to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting. PRACTICE POINT 6: Do not use ivermectin to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting. PRACTICE POINT 7: Do not use nitazoxanide to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting. PRACTICE POINT 8: Do not use lopinavir-ritonavir combination therapy to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting. PRACTICE POINT 9: Do not use casirivimab-imdevimab combination therapy to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting unless it is considered effective against a SARS-CoV-2 variant or subvariant locally in circulation. PRACTICE POINT 10: Do not use regdanvimab to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting unless it is considered effective against a SARS-CoV-2 variant or subvariant locally in circulation. PRACTICE POINT 11: Do not use sotrovimab to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting unless it is considered effective against a SARS-CoV-2 variant or subvariant locally in circulation. PRACTICE POINT 12: Do not use convalescent plasma to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting. PRACTICE POINT 13: Do not use ciclesonide to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting. PRACTICE POINT 14: Do not use fluvoxamine to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting.

Colonoscopy for Diagnostic Evaluation and Interventions to Prevent Recurrence After Acute Left-Sided Colonic Diverticulitis: A Clinical Guideline From the American College of Physicians.

DESCRIPTION: The American College of Physicians (ACP) developed this guideline to provide clinical recommendations on the role of colonoscopy for diagnostic evaluation of colorectal cancer (CRC) after a presumed diagnosis of acute left-sided colonic diverticulitis and on the role of pharmacologic, nonpharmacologic, and elective surgical interventions to prevent recurrence after initial treatment of acute complicated and uncomplicated left-sided colonic diverticulitis. This guideline is based on the current best available evidence about benefits and harms, taken in the context of costs and patient values and preferences. METHODS: The ACP Clinical Guidelines Committee (CGC) based these recommendations on a systematic review on the role of colonoscopy after acute left-sided colonic diverticulitis and pharmacologic, nonpharmacologic, and elective surgical interventions after initial treatment. The systematic review evaluated outcomes rated by the CGC as critical or important. This guideline was developed using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) method. TARGET AUDIENCE AND PATIENT POPULATION: The target audience is all clinicians, and the target patient population is adults with recent episodes of acute left-sided colonic diverticulitis. RECOMMENDATION 1: ACP suggests that clinicians refer patients for a colonoscopy after an initial episode of complicated left-sided colonic diverticulitis in patients who have not had recent colonoscopy (conditional recommendation; low-certainty evidence). RECOMMENDATION 2: ACP recommends against clinicians using mesalamine to prevent recurrent diverticulitis (strong recommendation; high-certainty evidence). RECOMMENDATION 3: ACP suggests that clinicians discuss elective surgery to prevent recurrent diverticulitis after initial treatment in patients who have either uncomplicated diverticulitis that is persistent or recurs frequently or complicated diverticulitis (conditional recommendation; low-certainty evidence). The informed decision whether or not to undergo surgery should be personalized based on a discussion of potential benefits, harms, costs, and patient's preferences.

Diagnosis and Management of Acute Left-Sided Colonic Diverticulitis: A Clinical Guideline From the American College of Physicians.

DESCRIPTION: The American College of Physicians (ACP) developed this guideline to provide clinical recommendations on the diagnosis and management of acute left-sided colonic diverticulitis in adults. This guideline is based on current best available evidence about benefits and harms, taken in the context of costs and patient values and preferences. METHODS: The ACP Clinical Guidelines Committee (CGC) developed this guideline based on a systematic review on the use of computed tomography (CT) for the diagnosis of acute left-sided colonic diverticulitis and on management via hospitalization, antibiotic use, and interventional percutaneous abscess drainage. The systematic review evaluated outcomes that the CGC rated as critical or important. This guideline was developed using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology. TARGET AUDIENCE AND PATIENT POPULATION: The target audience is all clinicians, and the target patient population is adults with suspected or known acute left-sided colonic diverticulitis. RECOMMENDATION 1: ACP suggests that clinicians use abdominal CT imaging when there is diagnostic uncertainty in a patient with suspected acute left-sided colonic diverticulitis (conditional recommendation; low-certainty evidence). RECOMMENDATION 2: ACP suggests that clinicians manage most patients with acute uncomplicated left-sided colonic diverticulitis in an outpatient setting (conditional recommendation; low-certainty evidence). RECOMMENDATION 3: ACP suggests that clinicians initially manage select patients with acute uncomplicated left-sided colonic diverticulitis without antibiotics (conditional recommendation; low-certainty evidence).

Comparing Load-Sharing Miniplate and Load-Bearing Plate Fixation in Atrophic Edentulous Mandibular Fractures: A Systematic Review and Meta-Analysis.

PURPOSE: To critically examine reported data to compare patient outcomes between load-sharing and load-bearing plate fixation for edentulous mandibular fractures. MATERIALS AND METHODS: A systematic review and meta-analysis were designed to test the null hypothesis of no difference in postoperative outcomes between load-sharing and load-bearing plate fixation in atrophic, edentulous mandibular fractures. The PubMed, EMBASE, Cochrane Library, Elsevier text mining tool database, and clinicaltrials.gov trial registries were queried up until July 2016. The quality of evidence was determined using the Grading of Recommendations Assessment, Development, and Evaluation method. RESULTS: A total of 1212 studies were screened for inclusion of which we included 1 high-quality Cochrane review, 6 narrative reviews, and 21 publications of case reports and case series. Overall, the quality of evidence was low. No difference was found between load-bearing and load-sharing fixation in functional recovery, nonunion, or infection. An uncontrolled case series portrayed complete functional and morphological restoration in 96.9% of patients (83.2-99.5; 95% confidence interval) in load-bearing osteosynthesis while another demonstrated the same outcome in only 40.0% of patients (17.5-65.0; 95% confidence interval). CONCLUSIONS: The authors did not find a statistically significant difference between load-bearing and load-sharing plate fixation in edentulous atrophic mandibular fracture patients; although this finding may be influenced by type 2 statistical error. Surgeons should continue to use their best clinical judgment in deciding on treatment approach for these challenging fractures. Future studies with higher level evidence are necessary to guide optimal fracture management.

Effects of antidepressants on QT interval in people with mental disorders.

INTRODUCTION: Drug-induced QT prolongation is associated with higher cardiovascular mortality. MATERIAL AND METHODS: We conducted a protocol-based comprehensive review of antidepressant-induced QT prolongation in people with mental disorders. RESULTS: Based on findings from 47 published randomized controlled trials (RCTs), 3 unpublished RCTs, 14 observational studies, 662 case reports of torsades de pointes, and 168 cases of QT prolongation, we conclude that all antidepressants should be used only with licensed doses, and that all patients receiving antidepressants require monitoring of QT prolongation and clinical symptoms of cardiac arrhythmias. Large observational studies suggest increased mortality associated with all antidepressants (RR = 1.62, 95% CI: 1.60-1.63, number of adults: 1,716,552), high doses of tricyclic antidepressants (OR = 2.11, 85% CI 1.10-4.22), selective serotonin reuptake inhibitors (OR = 2.78, 95% CI: 1.24-6.24), venlafaxine (OR = 3.73, 95% CI: 1.33-10.45, number of adults: 4,040), and nortriptyline (OR = 4.60, 95% CI: 1.20-18.40, number of adults: 5,298). CONCLUSIONS: Evidence regarding the risk of QT prolongation in children is sparse.

Comparative Clinical Outcomes of Edoxaban in Adults With Nonvalvular Atrial Fibrillation.

BACKGROUND: A critical appraisal of all pooled evidence regarding novel oral anticoagulants (NOACs) for stroke prevention regardless of publication status or study design has not been conducted yet. Being the latest addition to NOACs, the data on edoxaban are especially scarce. STUDY QUESTION: What are the comparative clinical outcomes of edoxaban versus warfarin and other NOACs apixaban, dabigatran, or rivaroxaban in adults with nonvalvular atrial fibrillation? DATA SOURCES: Randomized controlled trials (RCTs), observational studies, and network meta-analyses were identified in PubMed, EMBASE, the Cochrane Library, Pharmapendium, Elsevier Clinical Pharmacology, and the clinicaltrials.gov trial registry in June 2018. STUDY DESIGN: Rapid review per a priori developed protocol, direct frequentist random-effects meta-analysis of aggregate data, grading the quality of evidence per the Grading of Recommendations Assessment, Development and Evaluation working group approach. RESULTS: Direct 4 RCTs (23,021 patients) suggest that edoxaban is noninferior to warfarin in prevention of stroke and systemic embolism [pooled relative risk (RR): 0.65, 95% confidence interval (CI): 0.23-1.81, 2 RCTs] and reduces the risk of cardiovascular mortality (RR: 0.87, 95% CI: 0.78-0.97, 1 RCT), major cardiovascular morbidity (RR: 0.90, 95% CI: 0.82-0.98, 2 RCTs), and major bleeding events (RR: 0.80, 95% CI: 0.71-0.91, 1 RCT) but increases the risk of gastrointestinal bleeding (RR: 1.21, 95% CI: 1.01-1.46, 1 RCT) and anemia (RR: 1.45, 95% CI: 1.05-1.99, 3 RCTs). Edoxaban is superior to warfarin in patients with increased risk of bleeding with warfarin because of variants in CYP2C9 and VKORC1 genes. Indirect evidence does not allow valid conclusions regarding comparative superiority of NOACs. The quality of evidence was downgraded because of reporting bias, small number of events, and indirectness in comparisons. CONCLUSIONS: Edoxaban is a welcome addition to the NOAC's armamentarium. However, the comparative data with other novel NOACs are mostly nonexisting, and urgently needed for better individual patient assessment.

Does Early Repair of Orbital Fractures Result in Superior Patient Outcomes? A Systematic Review and Meta-Analysis.

PURPOSE: To date, no clear evidence-based guidelines exist pertaining to the ideal timing to perform surgical treatment of orbital fractures. The purpose of this study was to determine if early treatment of orbital fractures resulted in better patient outcomes. MATERIALS AND METHODS: We designed and implemented a systematic review and meta-analysis to test the null hypothesis of no difference in outcomes between different time intervals between orbital injury and surgical intervention. PubMed, Embase, the Cochrane Library, the Elsevier text mining tool database, and clinicaltrials.gov trial registry were queried. The quality of evidence was based on Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. The predictor variable was the timing of operative repair (early vs late). The outcome variable was complete recovery. Other variables of interest were diplopia, enophthalmos, and preoperative motility restriction. Meta-analyses were performed when definitions of active and control interventions and patient outcomes were deemed similar. In addition, χ2 tests were performed to determine differences in clinical outcomes between early and late operative repair. RESULTS: Of the 1,160 articles reviewed, 20 met the inclusion criteria. Surgery performed less than 2 weeks after injury was significantly associated with greater odds of complete recovery of symptoms (odds ratio [OR], 6.9 [95% confidence interval (CI), 1.35-35.06]), as well as a lower incidence of postoperative diplopia (OR, 0.3 [95% CI, 0.1-0.9]) and enophthalmos (OR, 0.2 [95% CI, 0.1-0.9]). Repair performed less than 30 days after injury was associated complete resolution of preoperative motility restriction (OR, 24.6 [95% CI, 1.30-462.34]) as well as diplopia. CONCLUSIONS: Differences in the timing of surgery and definition of patient outcomes, as well as variations in methods of evaluating postoperative outcomes, potentiate the risk of bias and warrant downgrading of the quality of evidence in a study. The timing of repair varied among 2, 4, and 8 weeks after injury. However, a short time to surgical intervention was significantly associated with resolution of vertical dystopia, postoperative enophthalmos, and motility restriction.

Management of Teeth in the Line of Mandibular Angle Fractures Treated with Open Reduction and Internal Fixation: A Systematic Review and Meta-Analysis.

BACKGROUND: Mandibular angle fractures are common and frequently involve a tooth in the fracture line. Despite trends toward more conservative indications for tooth extraction during open repair, the literature remains heterogeneous. This review aims to ascertain the effect of tooth extraction/retention on patient outcomes following mandible open reduction and internal fixation and to evaluate the evidence surrounding indications for extraction. METHODS: PubMed, EMBASE, the Cochrane Library, Elsevier text mining tool database, and clinicaltrials.gov were queried through March of 2018 for English language publication on adults with traumatic mandibular fractures. The review protocol was not registered online. Quality of evidence was assigned using the Grading of Recommendations Assessment, Development and Evaluation methodology. Meta-analyses were performed when definitions of outcomes were deemed similar. RESULTS: Overall, 26 of 1212 identified studies met inclusion criteria. Indications for tooth extraction and rates of extraction varied considerably across studies. The quality of evidence was low or very low for all outcomes. Tooth retention was associated with lower overall complications (OR, 0.54; 95 percent CI, 0.37 to 0.79), major complications requiring readmission or reoperation (OR, 0.47; 95 percent CI, 0.24 to 0.92), and malocclusion (OR, 0.56; 95 percent CI, 0.32 to 0.97); there was no difference in wound issues or nonunion. Removal of asymptomatic teeth was associated with inferior alveolar nerve injury (39.4 percent versus 16.1 percent). CONCLUSIONS: The literature is limited by retrospective study deign and poor follow-up; however, when indicated, tooth extraction is not associated with an increased risk of infection or nonunion. Removal of asymptomatic teeth was associated with a risk of inferior alveolar nerve injury. Additional high-quality studies are needed to evaluate potentially expanded indications for tooth extraction.

Fixation Points in the Treatment of Traumatic Zygomaticomaxillary Complex Fractures: A Systematic Review and Meta-Analysis.

PURPOSE: Controversy remains regarding the optimal degree of anatomic exposure, reduction, and fixation required during open reduction and internal fixation of zygomaticomaxillary complex (ZMC) fractures. We critically examined the reported data to compare the patient outcomes after various degrees of ZMC reduction and internal fixation. MATERIALS AND METHODS: A systematic review and meta-analysis were designed to test the null hypothesis of no difference in outcomes between different degrees of fixation of ZMC fractures. The PubMed, EMBASE, Cochrane Library, Elsevier text mining tool database, and clinicaltrials.gov trial registries were queried. The quality of evidence was determined using the Grading of Recommendations Assessment, Development, and Evaluation method. RESULTS: Of 1213 screened studies, 13 met the inclusion criteria. Fracture instability at 3 months was greater with 2-point fixation (61.1%) than with 3-point fixation (10.6%; relative risk, 2.5, 95% confidence interval [CI], 1.4 to 3.3). Less vertical orbital dystopia was seen with 3-point fixation than with 2-point fixation (mean difference, 0.9 mm; 95% CI, 0.6 to 1.3 mm). The incidence of infection and malar asymmetry did not differ between the groups. The quality of evidence was very low to low. CONCLUSIONS: The reported data were limited by low quality, retrospective studies. However, the meta-analysis of randomized control trial data suggested a superiority of 3 points of exposure and fixation regarding fracture stability. When 2 points appear to provide stable fixation, the potential benefits of a third point should be weighed against the cost, operative time, and exposure/periosteal stripping on a case-by-case basis.

Exercise for Preventing Hospitalization and Readmission in Adults With Congestive Heart Failure.

We critically appraised all available evidence regarding exercise interventions for improving patient survival and reducing hospital admissions in adults with chronic heart failure (HF). We searched 4 databases up to April 2018 and graded the quality of evidence according to the Grading of Recommendations Assessment, Development and Evaluation working group approach. We reviewed 7 meta-analyses and the publications of 48 randomized controlled trials (RCTs). In HF with reduced ejection fraction, low-quality evidence suggests that exercise prevents all-cause hospitalizations [Relative risk (RR), 0.77; 95% confidence interval (CI), 0.63 to 0.93; 1328 patients in 15 RCTs] and hospitalizations due to HF (RR, 0.57; 95% CI, 0.37 to 0.88; 1073 patients in 13 RCTs) and improves quality of life (standardized mean difference, -0.37; 95% CI, -0.60 to -0.14; 1270 patients in 25 RCTs) but has no effect on mortality. In HF with preserved ejection fraction, low-quality evidence suggests that exercise improves peak oxygen uptake (mean difference, 2.36; 95% CI, 1.16 to 3.57; 171 patients in 3 RCTs) and quality of life (mean difference, -4.65; 95% CI, -8.46 to -0.83; 203 patients in 4 RCTs). In patients after heart transplantation, low-quality evidence suggests that exercise improves peak oxygen uptake (standardized mean difference, 0.68; 95% CI, 0.43 to 0.93; 284 patients in 9 RCTs) but does not improve quality of life. In order to reduce hospitalization and improve quality of life for adults with HF and reduced ejection fraction, clinicians should recommend exercise interventions. For adults with HF and preserved ejection fraction and in those undergoing heart transplantation, clinicians may recommend exercise interventions in order to improve peak oxygen uptake.

Comparative Effectiveness and Safety of Rivaroxaban in Adults With Nonvalvular Atrial Fibrillation.

BACKGROUND: All evidence regarding benefits and harms of rivaroxaban for stroke prevention has not been appraised yet. STUDY QUESTION: What are the comparative effectiveness and safety of rivaroxaban in adults with nonvalvular atrial fibrillation? DATA SOURCES: Randomized controlled trials (RCTs), meta-analyses, and observational studies were identified in several databases in October 2018. STUDY DESIGN: Rapid review with evidence appraisal using the Grading of Recommendations Assessment, Development and Evaluation working group approach. RESULTS: Two direct RCTs (23,021 patients) suggest that rivaroxaban is noninferior to warfarin in the prevention of stroke and systemic embolism (pooled relative risk [RR] 0.73, 95% confidence interval [CI], 0.43-1.24), reduces risk of hemorrhagic stroke (RR 0.59, 95% CI, 0.38-0.92), fatal bleeding (RR 0.49, 95% CI, 0.31-0.76), and cardiac arrest (RR 0.45, 95% CI, 0.25-0.82, 2 RCTs), but increases risk of major gastrointestinal bleeding (RR 1.46, 95% CI, 1.19-1.78). In observational studies, rivaroxaban is associated with lower risk of ischemic stroke (RR 0.87, 95% CI, 0.77-0.99, 222,750 patients), acute myocardial infarction (RR 0.61, 95% CI, 0.48-0.78, 73,739 patients), and intracranial hemorrhage (RR 0.64, 95% CI, 0.45-0.92, 197,506 patients) but higher risk of gastrointestinal bleeding (RR 1.30, 95% CI, 1.19-1.42, 188,968 patients) and higher risk of mortality when compared with warfarin in European studies (RR 1.19, 103,270 patients in the UK; RR 2.02, 22,358 patients in Denmark) but lower risk of mortality in Taiwan (RR 0.58, 40,000 patients). Network meta-analyses and observational studies suggest that rivaroxaban is associated with higher risk of bleeding when compared with apixaban (RR 2.14, 72,586 patients), dabigatran (RR 1.24, 67,102 patients), and edoxaban (RR 1.32, 71,683 patients). CONCLUSIONS: Research on the long-term comparative effectiveness, safety, and effects on quality of life between rivaroxaban and other novel oral anticoagulants is urgently needed.

Blood pressure targets for hypertension in patients with type 2 diabetes.

BACKGROUND: Clinical guidelines vary in determining optimal blood pressure targets in adults with diabetes mellitus. METHODS: We systematically searched PubMed, EMBASE, Cochrane Library, and clinicaltrials.gov in March 2018; conducted random effects frequentist meta-analyses of direct aggregate data; and appraised the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. RESULTS: From eligible 14 meta-analyses and 95 publications of randomized controlled trials (RCT), only 6 RCTs directly compared lower versus higher blood pressure targets; remaining RCTs aimed at comparative effectiveness of hypotensive drugs. In adults with diabetes mellitus and elevated systolic blood pressure (SBP), direct evidence (2 RCTs) suggests that intensive target SBP <120-140 mmHg decreases the risk of diabetes-related mortality [relative risk (RR) =0.68; 95% confidence interval (CI), 0.50-0.92], fatal (RR =0.41; 95% CI, 0.20-0.84) or nonfatal stroke (RR =0.60; 95% CI, 0.43-0.83), prevalence of left ventricular hypertrophy and electrocardiogram (ECG) abnormalities, macroalbuminuria, and non-spine bone fractures, with no differences in all-cause or cardiovascular mortality or falls. In adults with diabetes mellitus and elevated diastolic blood pressure (DBP) ≥90 mmHg, direct evidence (2 RCTs) suggests that intensive DBP target ≤80 versus 80-90 mmHg decreases the risk of major cardiovascular events. Published meta-analyses of aggregate data suggested a significant association between lower baseline and attained blood pressure and increased cardiovascular mortality. CONCLUSIONS: We concluded that in adults with diabetes mellitus and arterial hypertension, in order to reduce the risk of stroke, clinicians should target blood pressure at 120-130/80 mmHg, with close monitoring for all drug-related harms.

Effects of atypical antipsychotic drugs on QT interval in patients with mental disorders.

BACKGROUND: Drug-induced QT prolongation is associated with higher risk of cardiac arrhythmias and cardiovascular mortality. We investigated the effects of atypical antipsychotic drugs on QT interval in children and adults with mental disorders. METHODS: We conducted random-effects direct frequentist meta-analyses of aggregate data from randomized controlled trials (RCT) and appraised the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. Our search in PubMed, EMBASE, the Cochrane Library, clinicaltrials.gov, and PharmaPendium up to October 2017 identified studies that examined aripiprazole, quetiapine, risperidone, olanzapine, ziprasidone and brexpiprazole. RESULTS: Low quality evidence suggests that aripiprazole (four meta-analyses and twelve RCTs), brexpiprazole (one systematic review and four RCTs) or olanzapine (five meta-analyses and twenty RCTs) do not increase QT interval. Low quality evidence suggests that ziprasidone (five meta-analyses and 11 RCTs) increases QT interval and the rates of QT prolongation while risperidone (four meta-analyses, 70 RCTs) and quetiapine (two meta-analyses and seven RCTs) are associated with QT prolongation and greater odds of torsades de pointes ventricular tachycardia especially in cases of drug overdose. CONCLUSIONS: The main conclusion of our study is that in people with mental disorders and under treatment with atypical antipsychotic drugs, in order to avoid QT prolongation and reduce the risk of ventricular tachycardia clinicians may recommend aripiprazole, brexpiprazole or olanzapine in licensed doses. Long-term comparative safety needs to be established.