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Time-Restricted Eating: How Does It Work?

In this episode of Annals On Call, Dr. Centor discusses time-restricted eating as a weight loss strategy with Dr. Nisa Maruthur. First, listen to the podcast. After listening, ACP members can take the CME/MOC quiz for free.

Time Management for Physicians (to support Well-being and Professional Fulfillment)

Assess how you currently spend your time and explore strategies to align your calendar with your priorities.

The Value of Cystatin C Measurement

In this episode of Annals On Call, Dr. Centor discusses the use of use of cystatin C in estimating glomerular filtration rate with Dr. Joel Topf. First, listen to the podcast. After listening, ACP members can take the CME/MOC quiz for free.

The Role of Corticosteroids in Severe Pneumonia

In this episode of Annals On Call, Dr. Centor discusses the role of corticosteroids in the treatment of community-acquired pneumonia with Dr. Michael Klompas.First, listen to the podcast. After listening, ACP members can take the CME/MOC quiz for free.

The Michigan Appropriateness Guide for Intravenous Catheters in Adult Patients With Cancer (MAGIC-ONC): Results From a Multispecialty Panel Using the RAND/UCLA Appropriateness Method

Patients with cancer frequently require vascular access devices (VADs) for systemic chemotherapies and for supportive treatments. However, VADs are associated with serious complications, including bloodstream infection and venous thromboembolism. This special supplement provides guidance for selection and management of VADs in patients with cancer.

The Diagnosis and Pathophysiology of Claudication

The Annals Consult Guys discuss the evaluation and management of patients with claudication, highlighting observations related to the pathophysiology of peripheral vascular disease.

The Challenge of Diagnosing Community-Acquired Pneumonia

In this episode of Annals On Call, Dr. Centor discusses the diagnostic challenges presented by community-acquired pneumonia with Dr. Barbara Jones. First, listen to the podcast. After listening, ACP members can take the CME/MOC quiz for free.

The Case of the Restless Legs

The Annals Consult Guys tackle a case of restless legs from diagnosis to treatment.

The ABCs of Atrial Fibrillation

The Annals Consult Guys return to the topic of atrial fibrillation and review the Atrial fibrillation Better Care (ABC) pathway for integrated care management of atrial fibrillation.

Teaching Diagnostic Reasoning

In this episode of Annals On Call, Dr. Centor discusses teaching diagnostic reasoning with Drs. Rabih Geha and Reza Manesh. First, listen to the podcast. After listening, ACP members can take the CME/MOC quiz for free.

These Annals of Internal Medicine results only contain recent articles.

Effectiveness of Opioid Analgesic Medicines Prescribed in or at Discharge From Emergency Departments for Musculoskeletal Pain: A Systematic Review and Meta-analysis: Annals of Internal Medicine: Vol 175, No 11

Background: The comparative benefits and harms of opioids for musculoskeletal pain in the emergency department (ED) are uncertain. Purpose: To evaluate the comparative effectiveness and harms of opioids for musculoskeletal pain in the ED setting. Data Sources: Electronic databases and registries from inception to 7 February 2022. Study Selection: Randomized controlled trials of any opioid analgesic compared with placebo or a nonopioid analgesic administered or prescribed to adults in or on discharge from the ED. Data Extraction: Pain and disability were rated on a scale of 0 to 100 and pooled using a random-effects model. Certainty of evidence was assessed using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) framework. Data Synthesis: Forty-two articles were included (n = 6128). In the ED, opioids were statistically but not clinically more effective in reducing pain in the short term (about 2 hours) than placebo and paracetamol (acetaminophen) but were not clinically or statistically more effective than nonsteroidal anti-inflammatory drugs (NSAIDs) or local or systemic anesthetics. Opioids may carry higher risk for harms than placebo, paracetamol, or NSAIDs, although evidence is very uncertain. There was no evidence of difference in harms associated with local or systemic anesthetics. Limitations: Low or very low GRADE ratings for some outcomes, unexplained heterogeneity, and little information on long-term outcomes. Conclusion: The risk–benefit balance of opioids versus placebo, paracetamol, NSAIDs, and local or systemic anesthetics is uncertain. Opioids may have equivalent pain outcomes compared with NSAIDs, but evidence on comparisons of harms is very uncertain and heterogeneous. Although factors such as route of administration or dosage may explain some heterogeneity, more work is needed to identify which subgroups will have a more favorable benefit–risk balance for one analgesic over another. Longer-term pain management once dose thresholds are reached is also uncertain. Primary Funding Source: None. (PROSPERO: CRD42021275293)

Nirmatrelvir Plus Ritonavir for Early COVID-19 in a Large U.S. Health System: A Population-Based Cohort Study: Annals of Internal Medicine: Vol 176, No 1

Background: In the EPIC-HR (Evaluation of Protease Inhibition for Covid-19 in High-Risk Patients) trial, nirmatrelvir plus ritonavir led to an 89% reduction in hospitalization or death among unvaccinated outpatients with early COVID-19. The clinical impact of nirmatrelvir plus ritonavir among vaccinated populations is uncertain. Objective: To assess whether nirmatrelvir plus ritonavir reduces risk for hospitalization or death among outpatients with early COVID-19 in the setting of prevalent SARS-CoV-2 immunity and immune-evasive SARS-CoV-2 lineages. Design: Population-based cohort study analyzed to emulate a clinical trial using inverse probability–weighted models to account for anticipated bias in treatment. Setting: A large health care system providing care for 1.5 million patients in Massachusetts and New Hampshire during the Omicron wave (1 January to 17 July 2022). Patients: 44 551 nonhospitalized adults (90.3% with ≥3 vaccine doses) aged 50 years or older with COVID-19 and no contraindications for nirmatrelvir plus ritonavir. Measurements: The primary outcome was a composite of hospitalization within 14 days or death within 28 days of a COVID-19 diagnosis. Results: During the study period, 12 541 (28.1%) patients were prescribed nirmatrelvir plus ritonavir, and 32 010 (71.9%) were not. Patients prescribed nirmatrelvir plus ritonavir were more likely to be older, have more comorbidities, and be vaccinated. The composite outcome of hospitalization or death occurred in 69 (0.55%) patients who were prescribed nirmatrelvir plus ritonavir and 310 (0.97%) who were not (adjusted risk ratio, 0.56 [95% CI, 0.42 to 0.75]). Recipients of nirmatrelvir plus ritonavir had lower risk for hospitalization (adjusted risk ratio, 0.60 [CI, 0.44 to 0.81]) and death (adjusted risk ratio, 0.29 [CI, 0.12 to 0.71]). Limitation: Potential residual confounding due to differential access to COVID-19 vaccines, diagnostic tests, and treatment. Conclusion: The overall risk for hospitalization or death was already low (1%) after an outpatient diagnosis of COVID-19, but nirmatrelvir plus ritonavir reduced this risk further. Primary Funding Source: National Institutes of Health.

Temporal Improvements in COVID-19 Outcomes for Hospitalized Adults: A Post Hoc Observational Study of Remdesivir Group Participants in the Adaptive COVID-19 Treatment Trial

Background: The COVID-19 standard of care (SOC) evolved rapidly during 2020 and 2021, but its cumulative effect over time is unclear. Objective: To evaluate whether recovery and mortality improved as SOC evolved, using data from ACTT (Adaptive COVID-19 Treatment Trial). Design: ACTT is a series of phase 3, randomized, double-blind, placebo-controlled trials that evaluated COVID-19 therapeutics from February 2020 through May 2021. ACTT-1 compared remdesivir plus SOC to placebo plus SOC, and in ACTT-2 and ACTT-3, remdesivir plus SOC was the control group. This post hoc analysis compared recovery and mortality between these comparable sequential cohorts of patients who received remdesivir plus SOC, adjusting for baseline characteristics with propensity score weighting. The analysis was repeated for participants in ACTT-3 and ACTT-4 who received remdesivir plus dexamethasone plus SOC. Trends in SOC that could explain outcome improvements were analyzed. (ClinicalTrials.gov: NCT04280705 [ACTT-1], NCT04401579 [ACTT-2], NCT04492475 [ACTT-3], and NCT04640168 [ACTT-4]) Setting: 94 hospitals in 10 countries (86% U.S. participants). Participants: Adults hospitalized with COVID-19. Intervention: SOC. Measurements: 28-day mortality and recovery. Results: Although outcomes were better in ACTT-2 than in ACTT-1, adjusted hazard ratios (HRs) were close to 1 (HR for recovery, 1.04 [95% CI, 0.92 to 1.17]; HR for mortality, 0.90 [CI, 0.56 to 1.40]). Comparable patients were less likely to be intubated in ACTT-2 than in ACTT-1 (odds ratio, 0.75 [CI, 0.53 to 0.97]), and hydroxychloroquine use decreased. Outcomes improved from ACTT-2 to ACTT-3 (HR for recovery, 1.43 [CI, 1.24 to 1.64]; HR for mortality, 0.45 [CI, 0.21 to 0.97]). Potential explanatory factors (SOC trends, case surges, and variant trends) were similar between ACTT-2 and ACTT-3, except for increased dexamethasone use (11% to 77%). Outcomes were similar in ACTT-3 and ACTT-4. Antibiotic use decreased gradually across all stages. Limitation: Unmeasured confounding. Conclusion: Changes in patient composition explained improved outcomes from ACTT-1 to ACTT-2 but not from ACTT-2 to ACTT-3, suggesting improved SOC. These results support excluding nonconcurrent controls from analysis of platform trials in rapidly changing therapeutic areas. Primary Funding Source: National Institute of Allergy and Infectious Diseases.

Effects of Dapagliflozin on Hospitalizations in Patients With Chronic Kidney Disease: A Post Hoc Analysis of DAPA-CKD: Annals of Internal Medicine: Vol 176, No 1

Background: Acute hospitalizations are common in patients with chronic kidney disease (CKD) and often lead to decreases in health-related quality of life and increased care costs. Objective: To determine the effects of dapagliflozin on first hospitalizations and all (first and subsequent) hospitalizations and to explore effects on cause-specific hospitalizations. Design: Post hoc analysis of a randomized, double-blind, placebo-controlled clinical trial. (ClinicalTrials.gov: NCT03036150) Setting: 386 ambulatory practice sites in 21 countries from 2 February 2017 through 12 June 2020. Participants: Adults with an estimated glomerular filtration rate of 25 to 75 mL/min/1.73 m2 and a urinary albumin–creatinine ratio of 200 to 5000 mg/g, with and without type 2 diabetes. Intervention: Dapagliflozin, 10 mg once daily, or matching placebo (1:1 ratio). Measurements: The effects of dapagliflozin on first hospitalizations for any cause, all hospitalizations, and cause-specific (first and recurrent) hospitalizations were determined. The reported system organ class was used to evaluate reasons for admission. Hospitalizations were analyzed using Cox proportional hazards regression models (first hospitalization), the Lin–Wei–Yang–Ying method (all hospitalizations or death), and negative binomial models (cause-specific hospitalizations). Results: The study included 4304 patients (mean age, 61.8 years; 33.1% women). During a median follow-up of 2.4 years, 2072 hospitalizations were reported among 1224 (28.4%) participants. Compared with placebo, dapagliflozin reduced risk for a first hospitalization (hazard ratio, 0.84 [95% CI, 0.75 to 0.94]) and all hospitalizations or death (rate ratio, 0.79 [CI, 0.70 to 0.89]). There was no evidence that the effects of dapagliflozin on first and all hospitalizations varied by baseline presence of type 2 diabetes (P for interaction = 0.60 for each). Compared with placebo, dapagliflozin reduced the rate of admissions due to cardiac disorders, renal and urinary disorders, metabolism and nutrition disorders, and neoplasms. Limitations: This was a post hoc analysis and should be viewed as hypothesis-generating. Hospitalizations and causes were reported by site investigators and were not centrally adjudicated. Conclusion: Dapagliflozin reduced the risk for hospitalization for any cause in patients with CKD with and without type 2 diabetes. Primary Funding Source: AstraZeneca.

Total Ankle Replacement Versus Arthrodesis for End-Stage Ankle Osteoarthritis: A Randomized Controlled Trial: Annals of Internal Medicine: Vol 175, No 12

Background: End-stage ankle osteoarthritis causes severe pain and disability. There are no randomized trials comparing the 2 main surgical treatments: total ankle replacement (TAR) and ankle fusion (AF). Objective: To determine which treatment is superior in terms of clinical scores and adverse events. Design: A multicenter, parallel-group, open-label randomized trial. (ISRCTN registry number: 60672307) Setting: 17 National Health Service trusts across the United Kingdom. Patients: Patients with end-stage ankle osteoarthritis, aged 50 to 85 years, and suitable for either procedure. Intervention: Patients were randomly assigned to TAR or AF surgical treatment. Measurements: The primary outcome was change in Manchester–Oxford Foot Questionnaire walking/standing (MOXFQ-W/S) domain scores between baseline and 52 weeks after surgery. No blinding was possible. Results: Between 6 March 2015 and 10 January 2019, a total of 303 patients were randomly assigned; mean age was 68 years, and 71% were men. Twenty-one patients withdrew before surgery, and 281 clinical scores were analyzed. At 52 weeks, the mean MOXFQ-W/S scores improved for both groups. The adjusted difference in the change in MOXFQ-W/S scores from baseline was −5.6 (95% CI, −12.5 to 1.4), showing that TAR improved more than AF, but the difference was not considered clinically or statistically significant. The number of adverse events was similar between groups (109 vs. 104), but there were more wound healing issues in the TAR group and more thromboembolic events and nonunion in the AF group. The symptomatic nonunion rate for AF was 7%. A post hoc analysis suggested superiority of fixed-bearing TAR over AF (−11.1 [CI, −19.3 to −2.9]). Limitation: Only 52-week data; pragmatic design creates heterogeneity of implants and surgical techniques. Conclusion: Both TAR and AF improve MOXFQ-W/S and had similar clinical scores and number of harms. Total ankle replacement had greater wound healing complications and nerve injuries, whereas AF had greater thromboembolism and nonunion, with a symptomatic nonunion rate of 7%. Primary Funding Source: National Institute for Health and Care Research Heath Technology Assessment Programme.