Incremental Health Care Costs of Self-Reported Functional Impairments and Phenotypic Frailty in Community-Dwelling Older Adults: A Prospective Cohort Study: Annals of Internal Medicine: Vol 176, No 4

Background: Health care systems need better strategies to identify older adults at risk for costly care to select target populations for interventions to reduce health care burden. Objective: To determine whether self-reported functional impairments and phenotypic frailty are associated with incremental health care costs after accounting for claims-based predictors. Design: Prospective cohort study. Setting: Index examinations (2002 to 2011) of 4 prospective cohort studies linked with Medicare claims. Participants: 8165 community-dwelling fee-for-service beneficiaries (4318 women, 3847 men). Measurements: Weighted (Centers for Medicare & Medicaid Services Hierarchical Condition Category index) and unweighted (count of conditions) multimorbidity and frailty indicators derived from claims. Self-reported functional impairments (difficulty performing 4 activities of daily living) and frailty phenotype (operationalized using 5 components) derived from cohort data. Health care costs ascertained for 36 months after index examinations. Results: Average annualized costs (2020 U.S. dollars) were $13 906 among women and $14 598 among men. After accounting for claims-based indicators, average incremental costs of functional impairments versus no impairment in women (men) were $3328 ($2354) for 1 impairment increasing to $7330 ($11 760) for 4 impairments; average incremental costs of phenotypic frailty versus robust in women (men) were $8532 ($6172). Mean predicted costs adjusted for claims-based indicators in women (men) varied by both functional impairments and the frailty phenotype ranging from $8124 ($11 831) among robust persons without impairments to $18 792 ($24 713) among frail persons with 4 impairments. Compared with the model with claims-derived indicators alone, this model resulted in more accurate cost prediction for persons with multiple impairments or phenotypic frailty. Limitation: Cost data limited to participants enrolled in the Medicare fee-for-service program. Conclusion: Self-reported functional impairments and phenotypic frailty are associated with higher subsequent health care expenditures in community-dwelling beneficiaries after accounting for several claims-based indicators of costs. Primary Funding Source: National Institutes of Health.

Role of Artificial Intelligence in Colonoscopy Detection of Advanced Neoplasias: A Randomized Trial: Annals of Internal Medicine: Vol 176, No 9

Background: The role of computer-aided detection in identifying advanced colorectal neoplasia is unknown. Objective: To evaluate the contribution of computer-aided detection to colonoscopic detection of advanced colorectal neoplasias as well as adenomas, serrated polyps, and nonpolypoid and right-sided lesions. Design: Multicenter, parallel, randomized controlled trial. (ClinicalTrials.gov: NCT04673136) Setting: Spanish colorectal cancer screening program. Participants: 3213 persons with a positive fecal immunochemical test. Intervention: Enrollees were randomly assigned to colonoscopy with or without computer-aided detection. Measurements: Advanced colorectal neoplasia was defined as advanced adenoma and/or advanced serrated polyp. Results: The 2 comparison groups showed no significant difference in advanced colorectal neoplasia detection rate (34.8% with intervention vs. 34.6% for controls; adjusted risk ratio [aRR], 1.01 [95% CI, 0.92 to 1.10]) or the mean number of advanced colorectal neoplasias detected per colonoscopy (0.54 [SD, 0.95] with intervention vs. 0.52 [SD, 0.95] for controls; adjusted rate ratio, 1.04 [99.9% CI, 0.88 to 1.22]). Adenoma detection rate also did not differ (64.2% with intervention vs. 62.0% for controls; aRR, 1.06 [99.9% CI, 0.91 to 1.23]). Computer-aided detection increased the mean number of nonpolypoid lesions (0.56 [SD, 1.25] vs. 0.47 [SD, 1.18] for controls; adjusted rate ratio, 1.19 [99.9% CI, 1.01 to 1.41]), proximal adenomas (0.94 [SD, 1.62] vs. 0.81 [SD, 1.52] for controls; adjusted rate ratio, 1.17 [99.9% CI, 1.03 to 1.33]), and lesions of 5 mm or smaller (polyps in general and adenomas and serrated lesions in particular) detected per colonoscopy. Limitations: The high adenoma detection rate in the control group may limit the generalizability of the findings to endoscopists with low detection rates. Conclusion: Computer-aided detection did not improve colonoscopic identification of advanced colorectal neoplasias. Primary Funding Source: Medtronic.

Short-Term Adverse Outcomes After Mifepristone–Misoprostol Versus Procedural Induced Abortion: A Population-Based Propensity-Weighted Study: Annals of Internal Medicine: Vol 176, No 2

Background: Prior studies comparing first-trimester pharmaceutical induced abortion (IA) with procedural IA were prone to selection bias, were underpowered to assess serious adverse events (SAEs), and did not account for confounding by indication. Starting in 2017, mifepristone–misoprostol was dispensed at no cost in outpatient pharmacies across Ontario, Canada. Objective: To compare short-term risk for adverse outcomes after early IA by mifepristone–misoprostol versus by procedural IA. Design: Population-based cohort study. Setting: Ontario, Canada. Patients: All women who had first-trimester IA. Measurements: A total of 39 856 women dispensed mifepristone–misoprostol as outpatients were compared with 65 176 women undergoing procedural IA at 14 weeks' gestation or earlier within nonhospital outpatient clinics (comparison 1). A total of 39 856 women prescribed mifepristone–misoprostol were compared with 8861 women undergoing ambulatory hospital-based procedural IA at an estimated 9 weeks' gestation or less (comparison 2). The primary composite outcome was any SAE within 42 days after IA, including severe maternal morbidity, end-organ damage, intensive care unit admission, or death. A coprimary broader outcome comprised any SAE, hemorrhage, retained products of conception, infection, or transfusion. Stabilized inverse probability of treatment weighting accounted for confounding between exposure groups. Results: Mean age at IA was about 29 years (SD, 7); 33% were primigravidae. Six percent resided in rural areas, and 25% resided in low-income neighborhoods. In comparison 1, SAEs occurred among 133 women after mifepristone–misoprostol IA (3.3 per 1000) versus 114 after procedural IA (1.8 per 1000) (relative risk [RR], 1.87 [95% CI, 1.44 to 2.43]; absolute risk difference [ARD], 1.5 per 1000 [CI, 0.9 to 2.2]). The respective rates of any adverse event were 28.9 versus 12.4 per 1000 (RR, 2.33 [CI, 2.11 to 2.57]; ARD, 16.5 per 1000 [CI, 14.5 to 18.4]). In comparison 2, SAEs occurred among 133 (3.4 per 1000) and 27 (3.3 per 1000) women, respectively (RR, 1.04 [CI, 0.61 to 1.78]). The respective rates of any adverse event were 31.2 versus 24.9 per 1000 (RR, 1.25 [CI, 1.04 to 1.51]). Limitation: A woman prescribed mifepristone–misoprostol may not have taken the medication, and the exact gestational age at IA was not always known. Conclusion: Although rare, short-term adverse events are more likely after mifepristone–misoprostol IA than procedural IA, especially for less serious adverse outcomes. Primary Funding Source: Canadian Institutes of Health Research.

Physician Turnover in the United States

Background: Medical groups, health systems, and professional associations are concerned about potential increases in physician turnover, which may affect patient access and quality of care. Objective: To examine whether turnover has changed over time and whether it is higher for certain types of physicians or practice settings. Design: The authors developed a novel method using 100% of traditional Medicare billing to create national estimates of turnover. Standardized turnover rates were compared by physician, practice, and patient characteristics. Setting: Traditional Medicare, 2010 to 2020. Participants: Physicians billing traditional Medicare. Measurements: Indicators of physician turnover—physicians who stopped practicing and those who moved from one practice to another—and their sum. Results: The annual rate of turnover increased from 5.3% to 7.2% between 2010 and 2014, was stable through 2017, and increased modestly in 2018 to 7.6%. Most of the increase from 2010 to 2014 came from physicians who stopped practicing increasing from 1.6% to 3.1%; physicians moving increased modestly from 3.7% to 4.2%. Modest but statistically significant (P < 0.001) differences existed across rurality, physician sex, specialty, and patient characteristics. In the second and third quarters of 2020, quarterly turnover was slightly lower than in the corresponding quarters of 2019. Limitation: Measurement was based on traditional Medicare claims. Conclusion: Over the past decade, physician turnover rates have had periods of increase and stability. These early data, covering the first 3 quarters of 2020, give no indication yet of the COVID-19 pandemic increasing turnover, although continued tracking of turnover is warranted. This novel method will enable future monitoring and further investigations into turnover. Primary Funding Source: The Physicians Foundation Center for the Study of Physician Practice and Leadership.

Prevalence and Correlates of Patient Rationing of Insulin in the United States: A National Survey

Symptom and Viral Rebound in Untreated SARS-CoV-2 Infection

Background: Although symptom and viral rebound have been reported after nirmatrelvir–ritonavir treatment, the trajectories of symptoms and viral load during the natural course of COVID-19 have not been well described. Objective: To characterize symptom and viral rebound in untreated outpatients with mild to moderate COVID-19. Design: Retrospective analysis of participants in a randomized, placebo-controlled trial. (ClinicalTrials.gov: NCT04518410) Setting: Multicenter trial. Patients: 563 participants receiving placebo in the ACTIV-2/A5401 (Adaptive Platform Treatment Trial for Outpatients With COVID-19) platform trial. Measurements: Participants recorded the severity of 13 symptoms daily between days 0 and 28. Nasal swabs were collected for SARS-CoV-2 RNA testing on days 0 to 14, 21, and 28. Symptom rebound was defined as a 4-point increase in total symptom score after improvement any time after study entry. Viral rebound was defined as an increase of at least 0.5 log10 RNA copies/mL from the immediately preceding time point to a viral load of 3.0 log10 copies/mL or higher. High-level viral rebound was defined as an increase of at least 0.5 log10 RNA copies/mL to a viral load of 5.0 log10 copies/mL or higher. Results: Symptom rebound was identified in 26% of participants at a median of 11 days after initial symptom onset. Viral rebound was detected in 31% and high-level viral rebound in 13% of participants. Most symptom and viral rebound events were transient, because 89% of symptom rebound and 95% of viral rebound events occurred at only a single time point before improving. The combination of symptom and high-level viral rebound was observed in 3% of participants. Limitation: A largely unvaccinated population infected with pre-Omicron variants was evaluated. Conclusion: Symptom or viral relapse in the absence of antiviral treatment is common, but the combination of symptom and viral rebound is rare. Primary Funding Source: National Institute of Allergy and Infectious Diseases.

Relationship Between Clinician Language and the Success of Behavioral Weight Loss Interventions: A Mixed-Methods Cohort Study: Annals of Internal Medicine: Vol 176, No 11

Background: International guidelines recommend that primary care clinicians recognize obesity and offer treatment opportunistically, but there is little evidence on how clinicians can discuss weight and offer treatment in ways that are well received and effective. Objective: To examine relationships between language used in the clinical visit and patient weight loss. Design: Mixed-methods cohort study. Setting: 38 primary care clinics in England participating in the Brief Intervention for Weight Loss trial. Participants: 246 patients with obesity seen by 87 general practitioners randomly sampled from the intervention group of the randomized clinical trial. Measurements: Conversation analysis of recorded discussions between 246 patients with obesity and 87 clinicians regarding referral to a 12-week behavioral weight management program offered as part of the randomized clinical trial. Clinicians’ interactional approaches were identified and their association with patient weight loss at 12 months (primary outcome) was examined. Secondary outcomes included patients’ agreement to attend weight management, attendance, loss of 5% body weight, actions taken to lose weight, and postvisit satisfaction. Results: Three interactional approaches were identified on the basis of clinicians’ linguistic and paralinguistic practices: creating a sense of referrals as “good news” related to the opportunity of the referral (n = 62); “bad news,” focusing on the harms of obesity (n = 82); or neutral (n = 102). Outcome data were missing from 57 participants, so weighted analyses were done to adjust for missingness. Relative to neutral news, good news was associated with increased agreement to attend the program (adjusted risk difference, 0.25 [95% CI, 0.15 to 0.35]), increased attendance (adjusted risk difference, 0.45 [CI, 0.34 to 0.56]), and weight change (adjusted difference, −3.60 [CI, −6.58 to −0.62]). There was no evidence of differences in mean weight change comparing bad and neutral news, and no evidence of differences in patient satisfaction across all 3 approaches. Limitations: Data were audio only, so body language and nonverbal cues could not be assessed. There is potential for selection bias and residual confounding. Conclusion: When raising the topic of excess weight in clinical visits, presenting weight loss treatment as a positive opportunity is associated with greater uptake of treatment and greater weight loss. Primary Funding Source: National Institute for Health and Care Research School for Primary Care Research and the Foundation for the Sociology of Health and Illness.

Second-Line Chimeric Antigen Receptor T-Cell Therapy in Diffuse Large B-Cell Lymphoma: A Cost-Effectiveness Analysis: Annals of Internal Medicine: Vol 176, No 12

Background: First-line treatment of diffuse large B-cell lymphoma (DLBCL) achieves durable remission in approximately 60% of patients. In relapsed or refractory disease, only about 20% achieve durable remission with salvage chemoimmunotherapy and consolidative autologous stem cell transplantation (ASCT). The ZUMA-7 (axicabtagene ciloleucel [axi-cel]) and TRANSFORM (lisocabtagene maraleucel [liso-cel]) trials demonstrated superior event-free survival (and, in ZUMA-7, overall survival) in primary-refractory or early-relapsed (high-risk) DLBCL with chimeric antigen receptor T-cell therapy (CAR-T) compared with salvage chemoimmunotherapy and consolidative ASCT; however, list prices for CAR-T exceed $400 000 per infusion. Objective: To determine the cost-effectiveness of second-line CAR-T versus salvage chemoimmunotherapy and consolidative ASCT. Design: State-transition microsimulation model. Data Sources: ZUMA-7, TRANSFORM, other trials, and observational data. Target Population: “High-risk” patients with DLBCL. Time Horizon: Lifetime. Perspective: Health care sector. Intervention: Axi-cel or liso-cel versus ASCT. Outcome Measures: Incremental cost-effectiveness ratio (ICER) and incremental net monetary benefit (iNMB) in 2022 U.S. dollars per quality-adjusted life-year (QALY) for a willingness-to-pay (WTP) threshold of $200 000 per QALY. Results of Base-Case Analysis: The increase in median overall survival was 4 months for axi-cel and 1 month for liso-cel. For axi-cel, the ICER was $684 225 per QALY and the iNMB was −$107 642. For liso-cel, the ICER was $1 171 909 per QALY and the iNMB was −$102 477. Results of Sensitivity Analysis: To be cost-effective with a WTP of $200 000, the cost of CAR-T would have to be reduced to $321 123 for axi-cel and $313 730 for liso-cel. Implementation in high-risk patients would increase U.S. health care spending by approximately $6.8 billion over a 5-year period. Limitation: Differences in preinfusion bridging therapies precluded cross-trial comparisons. Conclusion: Neither second-line axi-cel nor liso-cel was cost-effective at a WTP of $200 000 per QALY. Clinical outcomes improved incrementally, but costs of CAR-T must be lowered substantially to enable cost-effectiveness. Primary Funding Source: No research-specific funding.

Cold Versus Hot Snare Polypectomy for Small Colorectal Polyps: A Pragmatic Randomized Controlled Trial: Annals of Internal Medicine: Vol 176, No 3

Background: Although cold snare polypectomy (CSP) is considered effective in reducing delayed postpolypectomy bleeding risk, direct evidence supporting its safety in the general population remains lacking. Objective: To clarify whether CSP would reduce delayed bleeding risk after polypectomy compared with hot snare polypectomy (HSP) in the general population. Design: Multicenter randomized controlled study. (ClinicalTrials.gov: NCT03373136) Setting: 6 sites in Taiwan, July 2018 through July 2020. Participants: Participants aged 40 years or older with polyps of 4 to 10 mm. Intervention: CSP or HSP to remove polyps of 4 to 10 mm. Measurements: The primary outcome was the delayed bleeding rate within 14 days after polypectomy. Severe bleeding was defined as a decrease in hemoglobin concentration of 20 g/L or more, requiring transfusion or hemostasis. Secondary outcomes included mean polypectomy time, successful tissue retrieval, en bloc resection, complete histologic resection, and emergency service visits. Results: A total of 4270 participants were randomly assigned (2137 to CSP and 2133 to HSP). Eight patients (0.4%) in the CSP group and 31 (1.5%) in the HSP group had delayed bleeding (risk difference, −1.1% [95% CI, −1.7% to −0.5%]). Severe delayed bleeding was also lower in the CSP group (1 [0.05%] vs. 8 [0.4%] events; risk difference, −0.3% [CI, −0.6% to −0.05%]). Mean polypectomy time (119.0 vs. 162.9 seconds; difference in mean, −44.0 seconds [CI, −53.1 to −34.9 seconds]) was shorter in the CSP group, although successful tissue retrieval, en bloc resection, and complete histologic resection did not differ. The CSP group had fewer emergency service visits than the HSP group (4 [0.2%] vs. 13 [0.6%] visits; risk difference, −0.4% [CI, −0.8% to −0.04%]). Limitation: An open-label, single-blind trial. Conclusion: Compared with HSP, CSP for small colorectal polyps significantly reduces the risk for delayed postpolypectomy bleeding, including severe events. Primary Funding Source: Boston Scientific Corporation.

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)