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Cardiac Arrest During Delivery Hospitalization: A Cohort Study: Annals of Internal Medicine: Vol 176, No 4
Background: Estimates of cardiac arrest occurring during delivery guide evidence-based strategies to reduce pregnancy-related death. Objective: To investigate rate of, maternal characteristics associated with, and survival after cardiac arrest during delivery hospitalization. Design: Retrospective cohort study. Setting: U.S. acute care hospitals, 2017 to 2019. Participants: Delivery hospitalizations among women aged 12 to 55 years included in the National Inpatient Sample database. Measurements: Delivery hospitalizations, cardiac arrest, underlying medical conditions, obstetric outcomes, and severe maternal complications were identified using codes from the International Classification of Diseases, 10th Revision, Clinical Modification. Survival to hospital discharge was based on discharge disposition. Results: Among 10 921 784 U.S. delivery hospitalizations, the cardiac arrest rate was 13.4 per 100 000. Of the 1465 patients who had cardiac arrest, 68.6% (95% CI, 63.2% to 74.0%) survived to hospital discharge. Cardiac arrest was more common among patients who were older, were non-Hispanic Black, had Medicare or Medicaid, or had underlying medical conditions. Acute respiratory distress syndrome was the most common co-occurring diagnosis (56.0% [CI, 50.2% to 61.7%]). Among co-occurring procedures or interventions examined, mechanical ventilation was the most common (53.2% [CI, 47.5% to 59.0%]). The rate of survival to hospital discharge after cardiac arrest was lower with co-occurring disseminated intravascular coagulation (DIC) without or with transfusion (50.0% [CI, 35.8% to 64.2%] or 54.3% [CI, 39.2% to 69.5%], respectively). Limitations: Cardiac arrests occurring outside delivery hospitalizations were not included. The temporality of arrest relative to the delivery or other maternal complications is unknown. Data do not distinguish cause of cardiac arrest, such as pregnancy-related complications or other underlying causes among pregnant women. Conclusion: Cardiac arrest was observed in approximately 1 in 9000 delivery hospitalizations, among which nearly 7 in 10 women survived to hospital discharge. Survival was lowest during hospitalizations with co-occurring DIC. Primary Funding Source: None.
Planning for Mpox on a College Campus: A Model-Based Decision-Support Tool
Background: In spring and summer 2022, an outbreak of mpox occurred worldwide, largely confined to men who have sex with men (MSM). There was concern that mpox could break swiftly into congregate settings and populations with high levels of regular frequent physical contact, like university campus communities. Objective: To estimate the likelihood of an mpox outbreak and the potential effect of mitigation measures in a residential college setting. Design: A stochastic dynamic SEIR (susceptible, exposed but not infectious, infectious, or recovered) model of mpox transmission in a study population was developed, composed of: a high-risk group representative of the population of MSM with a basic reproductive number (R 0) of 2.4 and a low-risk group with an R 0 of 0.8. Base input assumptions included an incubation time of 7.6 days and time to recovery of 21 days. Setting: U.S. residential college campus. Participants: Hypothetical cohort of 6500 students. Intervention: Isolation, quarantine, and vaccination of close contacts. Measurements: Proportion of 1000 simulations producing sustained transmission; mean cases given sustained transmission; maximum students isolated, quarantined, and vaccinated. All projections are estimated over a planning horizon of 100 days. Results: Without mitigation measures, the model estimated an 83% likelihood of sustained transmission, leading to an average of 183 cases. With detection and isolation of 20%, 50%, and 80% of cases, the average infections would fall to 117, 37, and 8, respectively. Reactive vaccination of contacts of detected cases (assuming 50% detection and isolation) reduced mean cases from 37 to 17, assuming 20 vaccinated contacts per detected case. Preemptive vaccination of 50% of the high-risk population before outbreak reduced cases from 37 to 14, assuming 50% detection and isolation. Limitation: A model is a stylized portrayal of behavior and transmission on a university campus. Conclusion: Based on our current understanding of mpox epidemiology among MSM in the United States, this model-based analysis suggests that future outbreaks of mpox on college campuses may be controlled with timely detection and isolation of symptomatic cases. Primary Funding Source: National Institutes of Health National Institute on Drug Abuse and National Institute of Allergy and Infectious Diseases.
Contact Tracing and Exposure Investigation in Response to the First Case of Monkeypox Virus Infection in the United States During the 2022 Global Monkeypox Outbreak
Background: In May 2022, the first case of monkeypox virus (MPXV) infection in the United States in the current global outbreak was identified. As part of the public health and health care facility response, a contact tracing and exposure investigation was done. Objective: To describe the contact tracing, exposure identification, risk stratification, administration of postexposure prophylaxis (PEP), and exposure period monitoring for contacts of the index patient, including evaluation of persons who developed symptoms possibly consistent with MPXV infection. Design: Contact tracing and exposure investigation. Setting: Multiple health care facilities and community settings in Massachusetts. Participants: Persons identified as contacts of the index patient. Intervention: Contact notification, risk stratification, and symptom monitoring; PEP administration in a subset of contacts. Measurements: Epidemiologic and clinical data collected through standard surveillance procedures at each facility and then aggregated and analyzed. Results: There were 37 community and 129 health care contacts identified, with 4 at high risk, 49 at intermediate risk, and 113 at low or uncertain risk. Fifteen health care contacts developed symptoms during the monitoring period. Three met criteria for MPXV testing, with negative results. Two community contacts developed symptoms. Neither met criteria for MPXV testing, and neither showed disease progression consistent with monkeypox. Among 4 persons with high-risk exposures offered PEP, 3 elected to receive PEP. Among 10 HCP with intermediate-risk exposures for which PEP was offered as part of informed clinical decision making, 2 elected to receive PEP. No transmissions were identified at the conclusion of the 21-day monitoring period, despite the delay in recognition of monkeypox in the index patient. Limitation: Descriptions of exposures are subject to recall bias, which affects risk stratification. Conclusion: In a contact tracing investigation involving 166 community and health care contacts of a patient with monkeypox, no secondary cases were identified. Primary Funding Source: None.
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.
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.
Risk Model–Based Lung Cancer Screening: A Cost-Effectiveness Analysis: Annals of Internal Medicine: Vol 176, No 3
Background: In their 2021 lung cancer screening recommendation update, the U.S. Preventive Services Task Force (USPSTF) evaluated strategies that select people based on their personal lung cancer risk (risk model–based strategies), highlighting the need for further research on the benefits and harms of risk model–based screening. Objective: To evaluate and compare the cost-effectiveness of risk model–based lung cancer screening strategies versus the USPSTF recommendation and to explore optimal risk thresholds. Design: Comparative modeling analysis. Data Sources: National Lung Screening Trial; Surveillance, Epidemiology, and End Results program; U.S. Smoking History Generator. Target Population: 1960 U.S. birth cohort. Time Horizon: 45 years. Perspective: U.S. health care sector. Intervention: Annual low-dose computed tomography in risk model–based strategies that start screening at age 50 or 55 years, stop screening at age 80 years, with 6-year risk thresholds between 0.5% and 2.2% using the PLCOm2012 model. Outcome Measures: Incremental cost-effectiveness ratio (ICER) and cost-effectiveness efficiency frontier connecting strategies with the highest health benefit at a given cost. Results of Base-Case Analysis: Risk model–based screening strategies were more cost-effective than the USPSTF recommendation and exclusively comprised the cost-effectiveness efficiency frontier. Among the strategies on the efficiency frontier, those with a 6-year risk threshold of 1.2% or greater were cost-effective with an ICER less than $100 000 per quality-adjusted life-year (QALY). Specifically, the strategy with a 1.2% risk threshold had an ICER of $94 659 (model range, $72 639 to $156 774), yielding more QALYs for less cost than the USPSTF recommendation, while having a similar level of screening coverage (person ever-screened 21.7% vs. USPSTF's 22.6%). Results of Sensitivity Analyses: Risk model–based strategies were robustly more cost-effective than the 2021 USPSTF recommendation under varying modeling assumptions. Limitation: Risk models were restricted to age, sex, and smoking-related risk predictors. Conclusion: Risk model–based screening is more cost-effective than the USPSTF recommendation, thus warranting further consideration. Primary Funding Source: National Cancer Institute (NCI).
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.