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).

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.

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.

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.

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.

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.

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.

Preventive pharmacologic treatments for episodic migraine in adults.

OBJECTIVES: Systematic review of preventive pharmacologic treatments for community-dwelling adults with episodic migraine. DATA SOURCES: Electronic databases through May 20, 2012. ELIGIBILITY CRITERIA: English-language randomized controlled trials (RCTs) of preventive drugs compared to placebo or active treatments examining rates of ≥50 % reduction in monthly migraine frequency or improvement in quality of life. STUDY APPRAISAL AND SYNTHESIS METHODS: We assessed risk of bias and strength of evidence and conducted random effects meta-analyses of absolute risk differences and Bayesian network meta-analysis. RESULTS: Of 5,244 retrieved references, 215 publications of RCTs provided mostly low-strength evidence because of the risk of bias and imprecision. RCTs examined 59 drugs from 14 drug classes. All approved drugs, including topiramate (9 RCTs), divalproex (3 RCTs), timolol (3 RCTs), and propranolol (4 RCTs); off-label beta blockers metoprolol (4 RCTs), atenolol (1 RCT), nadolol (1 RCT), and acebutolol (1 RCT); angiotensin-converting enzyme inhibitors captopril (1 RCT) and lisinopril (1 RCT); and angiotensin II receptor blocker candesartan (1 RCT), outperformed placebo in reducing monthly migraine frequency by ≥50 % in 200-400 patients per 1,000 treated. Adverse effects leading to treatment discontinuation (68 RCTs) were greater with topiramate, off-label antiepileptics, and antidepressants than with placebo. Limited direct evidence as well as frequentist and exploratory network Bayesian meta-analysis showed no statistically significant differences in benefits between approved drugs. Off-label angiotensin-inhibiting drugs and beta-blockers were most effective and tolerable for episodic migraine prevention. LIMITATIONS: We did not quantify reporting bias or contact principal investigators regarding unpublished trials. CONCLUSIONS: Approved drugs prevented episodic migraine frequency by ≥50 % with no statistically significant difference between them. Exploratory network meta-analysis suggested that off-label angiotensin-inhibiting drugs and beta-blockers had favorable benefit-to-harm ratios. Evidence is lacking for long-term effects of drug treatments (i.e., trials of more than 3 months duration), especially for quality of life.

Benefits and harms of pharmacologic treatment for urinary incontinence in women: a systematic review.

BACKGROUND: Urinary incontinence (UI) in women adversely affects quality of life. PURPOSE: To conduct a systematic literature review of drugs for urgency UI in women. DATA SOURCES: MEDLINE, the Cochrane Central Register of Controlled Trials, SCIRUS, and Google Scholar were searched for articles published from 1966 to November 2011. STUDY SELECTION: Randomized, controlled trials (RCTs) reported in English. DATA EXTRACTION: Rates of outcomes and risk of bias were extracted by using a standardized form to pool absolute risk differences and calculate the number of attributable events per 1000 patients treated, with 95% CIs. DATA SYNTHESIS: 94 RCTs were eligible. Pooled analyses showed that among drugs for urgency UI, per 1000 treated women, continence was restored in 130 with fesoterodine (CI, 58 to 202), 85 with tolterodine (CI, 40 to 129), 114 with oxybutynin (CI, 64 to 163), 107 with solifenacin (CI, 58 to 156), and 114 with trospium (CI, 83 to 144). Rates of treatment discontinuation due to adverse effects were 31 per 1000 treated with fesoterodine (CI, 10 to 56), 63 with oxybutynin (CI, 12 to 127), 18 with trospium (CI, 4 to 33), and 13 with solifenacin (CI, 1 to 26). The studies' inconsistent definitions of reduction in UI and quality of life hampered synthesis of evidence. LIMITATION: Evidence for quality-of-life improvements and comparative effectiveness with drugs was limited, and evidence for the effects of race, baseline severity of UI, and comorbid conditions on treatment success was insufficient. CONCLUSION: Overall, drugs for urgency UI showed similar small benefit. Therapeutic choices should consider the harms profile. Evidence for long-term adherence and safety of treatments is lacking.

Physical therapy interventions for knee pain secondary to osteoarthritis: a systematic review.

BACKGROUND: Osteoarthritis is a leading cause of disability. Nonsurgical treatment is a key first step. PURPOSE: Systematic literature review of physical therapy (PT) interventions for community-dwelling adults with knee osteoarthritis. DATA SOURCES: MEDLINE, the Cochrane Library, the Physiotherapy Evidence Database, Scirus, Allied and Complementary Medicine, and the Health and Psychosocial Instruments bibliography database. STUDY SELECTION: 193 randomized, controlled trials (RCTs) published in English from 1970 to 29 February 2012. DATA EXTRACTION: Means of outcomes, PT interventions, and risk of bias were extracted to pool standardized mean differences. Disagreements between reviewers abstracting and checking data were resolved through discussion. DATA SYNTHESIS: Meta-analyses of 84 RCTs provided evidence for 13 PT interventions on pain (58 RCTs), physical function (36 RCTs), and disability (29 RCTs). Meta-analyses provided low-strength evidence that aerobic (11 RCTs) and aquatic (3 RCTs) exercise improved disability and that aerobic exercise (19 RCTs), strengthening exercise (17 RCTs), and ultrasonography (6 RCTs) reduced pain and improved function. Several individual RCTs demonstrated clinically important improvements in pain and disability with aerobic exercise. Other PT interventions demonstrated no sustained benefit. Individual RCTs showed similar benefits with aerobic, aquatic, and strengthening exercise. Adverse events were uncommon and did not deter participants from continuing treatment. LIMITATION: Variability in PT interventions and outcomes measures hampered synthesis of evidence. CONCLUSION: Low-strength evidence suggested that only a few PT interventions were effective. Future studies should compare combined PT interventions (which is how PT is generally administered for pain associated with knee osteoarthritis). PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

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.

Results availability from clinical research of female urinary incontinence.

AIMS: To ascertain possible publication bias by examining the completeness and publication of studies on nonsurgical treatments for female urinary incontinence (UI). METHODS: We analyzed information about studies from several trial registries through May 2010. We searched Medline using study registration identifiers to determine publication status, and compared percentages of completed and published studies by study and subject characteristics. RESULTS: Among the 166 closed studies, we found 120 completed (73%), 12 terminated (7%), 3 withdrawn (2%), and 4 (2%) that provided no reasons for noncompletion. Only 17% of closed registered studies (28/166 studies) were published in peer-reviewed journals; publication that did occur was an average of 2.2 years after study completion. The proportion of studies published did not increase over time. Studies sponsored by industry were published less often than those funded by NIH (OR = 0.04; 95%CI: 0.004-0.38). Drug studies were published less often than studies of other interventions (OR = 0.22; 95%CI: 0.05-0.96). Of the 166 closed studies, 7 (4%) posted results on the ClinicalTrials.gov website. Of Phases III and IV trials, 7% and 3% posted results, respectively. CONCLUSIONS: The absence of results from a substantial proportion of conducted studies suggests that treatment decisions for women with UI are based on selected rather than comprehensive evidence of benefits and harms. Regulatory policy for clinical research should guarantee availability of the outcomes for the public, clinicians, and policymakers.

Whole-body vibration therapy for osteoporosis: state of the science.

Clinical guidelines for osteoporosis recommend dietary and pharmacologic interventions and weight-bearing exercise to prevent bone fractures. These interventions sometimes have low adherence and can cause adverse effects. A proposed alternative or adjunctive treatment is whole-body vibration therapy (WBV), in which energy produced by a forced oscillation is transferred to an individual from a mechanical vibration platform. Whole-body vibration platforms are not approved by the U.S. Food and Drug Administration for medical purposes. This review provides a broad overview of important issues related to WBV therapy for prevention and treatment of osteoporosis. Relying on key informants and a search of the gray and published literature from January 2000 to August 2011, the investigators found that the designs of WBV platforms and protocols for their use vary widely. The optimal target population for the therapy is not defined. Although WBV has some theoretical advantages, key informants have voiced several concerns, including uncertain safety and potential consumer confusion between low-intensity vibration platforms intended for osteoporosis therapy and high-intensity platforms intended for exercise. Finally, the scant literature did not establish whether WBV therapy leads to clinically important increases in bone mineral density or reduces risk for fracture.

Tumor characteristics as predictors of local recurrence after treatment of ductal carcinoma in situ: a meta-analysis.

While ductal carcinoma in situ (DCIS) is seldom life threatening, the management of DCIS remains a dilemma for patients and their physicians. Aggressive treatment reduces the risk of ipsilateral breast tumor recurrence (IBTR), but has never been proven to improve survival. There is interest in identifying the prognostic factors for determining low-risk DCIS patients, but a comprehensive review of high-quality evidence on tumor characteristics in predicting local recurrence has never been carried out. We examined the following tumor characteristics: biomarkers, comedonecrosis, focality, surgical margin, method of detection, tumor grade, and tumor size. For this systematic review we restricted the analyses to the results of subgroup analyses from randomized controlled trials (RCTs) and multivariate analyses from RCTs and observational studies. We identified 44 eligible articles. The pooled random-effects risk estimates for IBTR are comedonecrosis 1.71(95% CI, 1.36-2.16), focality 1.95(95% CI, 1.59-2.40), margin 2.25(95% CI, 1.77-2.86), method of detection 1.35(95% CI, 1.12-1.62), tumor grade 1.81(95% CI, 1.53-2.13), and tumor size 1.63(95% CI, 1.30-2.06). Limited evidence indicated that women whose DCIS is ER-negative, PR-negative, or HER2/neu receptor positive have an IBTR higher than those whose DCIS is ER-positive, PR-positive, and HER2/neu receptor negative. A variety of tumor characteristics are significant predictors for IBTR. These results are important for both clinicians and patients to interpret the risk of local recurrence and to decide on a course of treatment.