Patient-Centered Prescription Opioid Tapering Methods: A Randomized Clinical Trial: Annals of Internal Medicine: Vol 0, No 0

Background: Evidence is needed on tapering long-term prescription opioids in outpatient settings. Objective: To determine and compare the effectiveness of 3 opioid tapering and pain control strategies (July 2018 to November 2023). Design: Randomized controlled trial. (ClinicalTrials.gov: NCT03445988) Setting: 11 U.S. sites. Participants: Adults with pain for at least 6 months receiving a morphine equivalent daily dose (MEDD) of 10 or higher for at least 3 months without moderate or severe opioid use disorder. Intervention: Patient-centered opioid tapering with close monitoring and electronic supports was administered as taper only, taper plus cognitive behavioral therapy for chronic pain (pain-CBT), or taper plus a chronic pain self-management program (CPSMP). Measurements: Taper success (primary outcome) was either an MEDD decrease of at least 50% with no increased pain or no MEDD increase with decreased pain intensity. Results: A total of 562 participants were randomly assigned (191 taper only, 203 taper plus pain-CBT, 168 taper plus CPSMP). The taper success rate was 50.9% (95% CI, 42.9% to 58.9%) for taper only, 48.6% (CI, 41.0% to 56.2%) for taper plus pain-CBT, and 44.5% (CI, 36.0% to 53.3%) for taper plus CPSMP. Tapering with pain-CBT or CPSMP provided no benefit in taper success over taper only (taper plus pain-CBT vs. taper only, −2.4 percentage points [CI, −11.9 to 7.2 percentage points]; taper plus CPSMP vs. taper only, −5.2 percentage points [CI, −15.3 to 4.8 percentage points]). Study-related adverse event risk (including opioid withdrawal symptoms) was highest in the taper only group (126 of 191 [66%]) compared with taper plus pain-CBT (109 of 203 [54%]) and taper plus CPSMP (108 of 168 [64%]). Limitation: Challenges related to COVID-19 reduced the sample size and made treatment groups imbalanced; low behavioral treatment attendance and losses to follow-up could have limited effectiveness. Conclusion: Adding CBT or self-management to patient-centered opioid tapering did not improve taper success at 12 months, although CBT may reduce adverse effects (including opioid withdrawal symptoms). Primary Funding Source: Patient-Centered Outcomes Research Institute.

Prevention of Recurrent Nephrolithiasis in Adults and Children: A Systematic Review: Annals of Internal Medicine: Vol 179, No 5

Background: Recurrent kidney stones are unpleasant and may lead to kidney damage, sepsis, or invasive procedures. Purpose: To assess benefits and harms of diet, pharmacologic therapy, and surveillance imaging to prevent recurrent nephrolithiasis. Data Sources: PubMed, Cochrane Library, and trial registries through December 2025. Study Selection: Randomized controlled trials (RCTs) or nonrandomized studies of interventions (NRSIs) in nonpregnant adults or children. Data Extraction: One reviewer extracted data, and a second reviewer checked for accuracy. Dual independent assessments of risk of bias and strength of evidence (SOE) were done. Data Synthesis: Among 31 studies (26 RCTs and 5 NRSIs), none evaluated imaging strategies. All but 3 included adults only. For adults with calcium oxalate or phosphate stones, increased water intake; a diet with normal to high calcium, low protein, and low sodium; thiazides; alkali treatment; and allopurinol may reduce stone recurrence (low SOE). There may be no difference between selective and empirical pharmacotherapy (low SOE). Acetohydroxamic acid may reduce stone growth in adults with infection-related stones (low SOE) but had insufficient evidence on prevention of recurrent stones and probably increased adverse events (moderate SOE). There may be increased minor adverse events with lemon juice but no increased harm due to serious adverse events with thiazides and allopurinol (low SOE). Limitation: Studies not published in English or with fewer than 30 participants per group were excluded. Conclusion: Increased fluid intake; a diet with normal to high calcium, low protein, and low sodium; thiazides; alkali therapy; and allopurinol may prevent stone recurrence in adults with calcium oxalate or calcium phosphate stones. Evidence is limited on other interventions, including imaging strategies, in children and on harms and other outcomes. Primary Funding Source: Patient-Centered Outcomes Research Institute and Agency for Healthcare Research and Quality (contract no. 75Q80120D00007/75Q80124F32010). (PROSPERO: CRD42024617257)

The Mediterranean Diet for Irritable Bowel Syndrome: A Randomized Clinical Trial: Annals of Internal Medicine: Vol 178, No 12

Background: Patients with irritable bowel syndrome (IBS) frequently seek dietary advice, but few evidence-based options exist. Major societal guidelines recommend traditional dietary advice (TDA) as first-line therapy, with the cumbersome and resource-intensive low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) diet reserved as second-line therapy. Recent pilot data suggest that the Mediterranean diet (MD), renowned for its general health benefits, improves IBS symptoms, but whether it can be considered another first-line dietary option is unknown. Objective: To determine if the MD is noninferior to TDA in managing IBS symptoms. Design: Randomized noninferiority clinical trial. (ClinicalTrials.gov: NCT05985018) Setting: Online virtual platform. Participants: 139 persons with IBS from across the United Kingdom. Intervention: 6 weeks of the MD (n = 68) or TDA (n = 71). Measurements: Primary end point was the proportion achieving clinical response, defined as 50-point or greater reduction in IBS Symptom Severity Scale (IBS-SSS). Secondary outcomes included changes in IBS-SSS scores, psychological health, somatic symptom reporting, quality of life, diet satisfaction, and Mediterranean Diet Adherence Screener (MEDAS). Results: Baseline characteristics (mean age, 40.4 years [range, 19 to 65 years]; 80% women) and IBS-SSS (mean, 309 [SD, 90]) were similar between groups. On modified intention-to-treat analysis, the primary end point was met by 62% (95% CI, 50% to 73%) following a MD versus 42% (CI, 31% to 55%) following TDA. The difference in clinical response favored the MD (difference, 20 percentage points [CI, 4 to 36 percentage points]; P = 0.017), demonstrating noninferiority and superiority. There was a greater reduction in the mean IBS-SSS after a MD than TDA (−101.2 vs. −64.5; Δ−36.7 [CI,−70.5 to −2.8]; P = 0.034). No statistically significant differences were seen between the groups with regard to changes in mood, somatic symptoms, quality of life, or diet satisfaction. The MEDAS significantly increased after a MD compared with TDA (P < 0.001). Limitation: No long-term data. Conclusion: The MD showed noninferiority and superiority to TDA in managing IBS symptoms. It represents a viable first-line dietary intervention for IBS. Primary Funding Source: None.

Exposure to Computed Tomography Before Pregnancy and Risk for Pregnancy Loss and Congenital Anomalies: A Population-Based Cohort Study: Annals of Internal Medicine: Vol 178, No 11

Background: Animal studies show ovarian follicle damage and mutagenesis after ionizing radiation exposure. Computed tomography (CT) imaging is commonly done outside pregnancy, but risks to future pregnancy are unknown. Objective: To evaluate the risk for spontaneous pregnancy loss and congenital anomalies in offspring of women exposed to CT ionizing radiation before conception. Design: Population-based observational study. Setting: Ontario, Canada. Participants: 5 142 339 recognized pregnancies and 3 451 968 live births identified between 1992 and 2023. Measurements: The exposure was the cumulative number of CT scans up to 4 weeks before conception. Outcomes were spontaneous pregnancy loss (miscarriage, ectopic pregnancy, or stillbirth) among recognized pregnancies and congenital anomalies diagnosed within the first year of life among live births. Results: Mean maternal age was 29 years. Diabetes, hypertension, obesity, and smoking were more common in those exposed to CT imaging. Among recognized pregnancies, rates of spontaneous pregnancy loss were 101, 117, 130, and 142 per 1000 pregnancies with 0, 1, 2, and 3 or more preconception CT scans, respectively, and adjusted hazard ratios (aHRs) were 1.08 (95% CI, 1.07 to 1.08) for 1 CT scan, 1.14 (CI, 1.12 to 1.16) for 2 CT scans, and 1.19 (CI, 1.16 to 1.21) for 3 or more CT scans. Among live births, rates of congenital anomalies were 62, 84, 96, and 105 per 1000 births in those with 0, 1, 2, and 3 or more CT scans, and aHRs were 1.06 (CI, 1.05 to 1.08) for 1 CT scan, 1.11 (CI, 1.09 to 1.14) for 2 CT scans, and 1.15 (CI, 1.11 to 1.18) for 3 or more CT scans. The risk observed with head CT was not consistently lower than with CT of the abdomen, pelvis, or lower spine. Limitation: Incomplete ascertainment of CT exposure and underlying indication may have contributed to residual confounding. Conclusion: Exposure to preconception CT imaging may be associated with higher risks for spontaneous pregnancy loss and congenital anomalies, but causal mechanisms remain to be elucidated. Alternative imaging methods should be considered when appropriate. Primary Funding Source: Canadian Institutes of Health Research.

Diet and Risk for Incident Diverticulitis in Women: A Prospective Cohort Study: Annals of Internal Medicine: Vol 178, No 6

Background: Patients with diverticulitis often attempt to control their diet with a particular focus on avoiding nuts and seeds. However, whether dietary patterns or dietary intake of nuts and seeds are associated with diverticulitis risk is poorly studied, particularly in women. Objective: To determine whether select diets affect incident diverticulitis risk in women. Design: Prospective cohort study. Setting: Cohort study in the United States and Puerto Rico. Participants: Women aged 35 to 74 years at enrollment who responded to food frequency and diverticulitis questionnaires and had no history of inflammatory bowel disease, cancer, or diverticulitis (n = 29 916). Intervention: Food frequency questionnaires were used to calculate dietary index scores and to assess intake of nuts, seeds, and corn. Measurements: Cox proportional hazards regression was used to estimate adjusted hazard ratios (aHRs) and 95% CIs for the associations between each dietary component or dietary index and diverticulitis risk. Results: 1531 cases of incident diverticulitis for 415 103 person-years of follow-up were identified. Intake of peanuts, nuts, and seeds (aHR,1.07 [95% CI, 0.91 to 1.25]) and fresh fruits with edible seeds (aHR,1.06 [CI, 0.90 to 1.24]) was not associated with incident diverticulitis. There was a reduced risk for incident diverticulitis in women in the highest quartile of healthy diets compared with the lowest quartile: the Dietary Approaches to Stop Hypertension diet (aHR, 0.77 [CI, 0.65 to 0.90]), the Healthy Eating Index (aHR, 0.78 [CI, 0.66 to 0.91]), the Alternative Healthy Eating Index (aHR, 0.81 [CI, 0.69 to 0.95]), and the Alternative Mediterranean diet (aHR, 0.91 [CI, 0.78 to 1.06]). Limitation: Confounding, selection bias, and measurement bias are possible. Conclusion: Healthy diets were associated with a reduced risk for incident diverticulitis in women. Consumption of nuts and seeds was not associated with diverticulitis risk. Primary Funding Source: National Institutes of Health.

Fecal Microbiota Transplantation Versus Vancomycin for Primary Clostridioides difficile Infection: A Randomized Controlled Trial: Annals of Internal Medicine: Vol 178, No 7

Background: Fecal microbiota transplantation (FMT) is recommended for recurrent Clostridioides difficile infection (CDI), but its role in primary CDI is unclear. Objective: To investigate the efficacy and safety of FMT in primary CDI. Design: Randomized, open-label, noninferiority, multicenter trial. (ClinicalTrials.gov: NCT03796650) Setting: Hospitals and primary care facilities in Norway. Patients: Adults with CDI (C difficile toxin in stool and ≥3 loose stools daily) and no previous CDI within 365 days before enrollment. Intervention: FMT without antibiotic pretreatment versus oral vancomycin, 125 mg 4 times daily for 10 days. Measurements: The primary end point was clinical cure (firm stools or <3 bowel movements daily) at day 14 and no disease recurrence within 60 days with the assigned treatment alone. Results: Of 104 randomly assigned patients, 100 received FMT or the first dose of vancomycin and were eligible for analysis. Clinical cure and no disease recurrence within 60 days without additional treatment was observed in 34 of 51 patients (66.7%) with FMT versus 30 of 49 (61.2%) with vancomycin (difference, 5.4 percentage points [95.2% CI, −13.5 to 24.4 percentage points]; P for noninferiority < 0.001, rejecting the hypothesis that response to FMT is 25 percentage points lower than response to vancomycin). Eleven patients in the FMT group and 4 in the vancomycin group had additional C difficile treatment. Clinical cure at day 14 and no recurrence with or without additional treatment was observed in 40 of 51 patients (78.4%) with FMT and 30 of 49 (61.2%) with vancomycin (difference, 17.2 percentage points [95.2% CI, −0.7 to 35.1 percentage points]). No significant differences in adverse events were observed between groups. Limitations: Open-label design and reliance on clinical end points. Conclusion: FMT may be considered as first-line therapy in primary CDI. Primary Funding Source: South-East Norway Health Trust.

Risk for Stroke After Newly Diagnosed Atrial Fibrillation During Hospitalization for Other Primary Diagnoses: A Retrospective Cohort Study: Annals of Internal Medicine: Vol 178, No 6

Background: Atrial fibrillation (AF) that is first diagnosed during hospitalization for other causes can subside with resolution of the inciting stressor. Objective: To describe the risk for stroke after newly diagnosed AF during hospitalization for other causes. Design: Population-based retrospective cohort study. Setting: Ontario, Canada. Participants: Patients aged 66 years or older discharged alive from the hospital between April 2013 and March 2023 with a first diagnosis of AF. Intervention: Newly diagnosed AF during hospitalization for other causes, categorized into cardiac medical, noncardiac medical, cardiac surgical, and noncardiac surgical. Measurements: The primary outcome was hospitalization for stroke. The cumulative incidence function was used to estimate crude incidence, censoring on anticoagulant dispensation. Inverse probability of censoring weights were used to account for informative censoring. Results: Atrial fibrillation was diagnosed in 20 639 patients (mean age, 77.1 years; 58.1% male) while hospitalized for other causes: 8340 (40.4%) for noncardiac medical, 7097 (34.4%) for cardiac surgical, 3553 (17.2%) for noncardiac surgical, and 1649 (8.0%) for cardiac medical diagnoses. At 1 year, anticoagulants were being dispensed to 26.4% of patients with CHA2DS2-VA scores of 1 to 4 and 35.2% of those with CHA2DS2-VA scores of 5 to 8. The 1-year risk for stroke without anticoagulation was 1.3% (95% CI, 0.7% to 2.3%) for cardiac medical, 1.2% (CI, 0.9% to 1.5%) for noncardiac medical, 1.1% (CI, 0.8% to 1.7%) for noncardiac surgical, and 1.0% (CI, 0.7% to 1.3%) for cardiac surgical patients. Patients with CHA2DS2-VA scores of 1 to 4 had a 1-year stroke risk of 0.7% (CI, 0.6% to 1.0%) without anticoagulation, compared with 1.8% (CI, 1.4% to 2.2%) at CHA2DS2-VA scores of 5 to 8. Limitation: Long-standing AF may have been misclassified as newly diagnosed, leading to overestimation of stroke risk. Conclusion: Among patients with newly diagnosed AF during hospitalization for other causes, a substantial proportion with low CHA2DS2-VA scores receive anticoagulation, with modest increases in this proportion at higher scores. The stroke risk in patients with CHA2DS2-VA scores greater than 4 approximated the 2% threshold commonly used to initiate anticoagulation in AF. Primary Funding Source: Canadian Cardiovascular Society.

Peer Review: Insights Gleaned From Observing the Editorial Process at Annals of Internal Medicine

The Past, Present, and Future of Restrictive Covenants in Medicine in the United States: A Narrative Review: Annals of Internal Medicine: Vol 178, No 1

Restrictive covenants (RCs) are clauses placed into employment agreements across various industries, and they are frequently used in health care—specifically within physician contracts. Given the most recent guidance and rule determined by the Federal Trade Commission in April 2024, the relevancy of RCs in health care has come under even more scrutiny in the latter half of 2024. This review will focus on the history of RC law and review the value of these clauses from the perspectives of the employer, practicing physician, and patient. We also provide the stakeholder responses to both the ban and the subsequent blockage of enforcement by a Texas federal court in August of 2024.

Physician Humility: A Review and Call to Revive Virtue in Medicine

Physician virtues, including humility, are crucial for shaping a physician's identity and practice. The health care literature offers varied views on humility, and the rising call for discussing virtues as a framing for professional identity formation underscores the need for a clearer understanding of physician humility. This review aimed to develop a cohesive conceptualization of physician humility and to define how it functions in medical practice. To achieve this, a comprehensive search was done across PubMed, Ovid MEDLINE, Web of Science, Embase, ERIC, and PsycInfo, covering all records up to 30 October 2023. Articles were included if they discussed physician humility and excluded if they were unrelated to physician humility, focused on nonphysician health professionals, lacked conceptual depth, or focused solely on cultural humility. An applied thematic analysis was conducted. The results provide a synthesized conceptualization of physician humility across stances toward self, others, and the profession. The included articles identified the pivotal role of physician humility within the following 5 domains of medical practice: learning and professional growth, navigating error, uncertainty tolerance, trust and entrustment, and teamwork and communication. The authors highlight some of the intrapersonal, interpersonal, and sociocontextual challenges to cultivating and practicing physician humility. These findings highlight the importance of promoting humility in shaping physicians’ actions, thoughts, and relationships with patients, colleagues, and their profession. Integrating such virtues as humility into medical education is essential for upholding the ideals of the medical profession and cultivating moral agents who engage in self-reflection and embody the principles of exemplary physicians.