Journal: JAMA

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<div><h4>Household Transmission of Influenza A Viruses in 2021-2022.</h4><i>Rolfes MA, Talbot HK, McLean HQ, Stockwell MS, ... Reed C, Grijalva CG</i><br /><b>Importance</b><br />Influenza virus infections declined globally during the COVID-19 pandemic. Loss of natural immunity from lower rates of influenza infection and documented antigenic changes in circulating viruses may have resulted in increased susceptibility to influenza virus infection during the 2021-2022 influenza season.<br /><b>Objective</b><br />To compare the risk of influenza virus infection among household contacts of patients with influenza during the 2021-2022 influenza season with risk of influenza virus infection among household contacts during influenza seasons before the COVID-19 pandemic in the US.<br /><b>Design, setting, and participants</b><br />This prospective study of influenza transmission enrolled households in 2 states before the COVID-19 pandemic (2017-2020) and in 4 US states during the 2021-2022 influenza season. Primary cases were individuals with the earliest laboratory-confirmed influenza A(H3N2) virus infection in a household. Household contacts were people living with the primary cases who self-collected nasal swabs daily for influenza molecular testing and completed symptom diaries daily for 5 to 10 days after enrollment.<br /><b>Exposures</b><br />Household contacts living with a primary case.<br /><b>Main outcomes and measures</b><br />Relative risk of laboratory-confirmed influenza A(H3N2) virus infection in household contacts during the 2021-2022 season compared with prepandemic seasons. Risk estimates were adjusted for age, vaccination status, frequency of interaction with the primary case, and household density. Subgroup analyses by age, vaccination status, and frequency of interaction with the primary case were also conducted.<br /><b>Results</b><br />During the prepandemic seasons, 152 primary cases (median age, 13 years; 3.9% Black; 52.0% female) and 353 household contacts (median age, 33 years; 2.8% Black; 54.1% female) were included and during the 2021-2022 influenza season, 84 primary cases (median age, 10 years; 13.1% Black; 52.4% female) and 186 household contacts (median age, 28.5 years; 14.0% Black; 63.4% female) were included in the analysis. During the prepandemic influenza seasons, 20.1% (71/353) of household contacts were infected with influenza A(H3N2) viruses compared with 50.0% (93/186) of household contacts in 2021-2022. The adjusted relative risk of A(H3N2) virus infection in 2021-2022 was 2.31 (95% CI, 1.86-2.86) compared with prepandemic seasons.<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />Among cohorts in 5 US states, there was a significantly increased risk of household transmission of influenza A(H3N2) in 2021-2022 compared with prepandemic seasons. Additional research is needed to understand reasons for this association.<br /><br /><br /><br /><small>JAMA: 26 Jan 2023; epub ahead of print</small></div>
Rolfes MA, Talbot HK, McLean HQ, Stockwell MS, ... Reed C, Grijalva CG
JAMA: 26 Jan 2023; epub ahead of print | PMID: 36701144
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<div><h4>Organization and Performance of US Health Systems.</h4><i>Beaulieu ND, Chernew ME, McWilliams JM, Landrum MB, ... Hicks AL, Cutler DM</i><br /><b>Importance</b><br />Health systems play a central role in the delivery of health care, but relatively little is known about these organizations and their performance.<br /><b>Objective</b><br />To (1) identify and describe health systems in the United States; (2) assess differences between physicians and hospitals in and outside of health systems; and (3) compare quality and cost of care delivered by physicians and hospitals in and outside of health systems.<br /><b>Evidence review</b><br />Health systems were defined as groups of commonly owned or managed entities that included at least 1 general acute care hospital, 10 primary care physicians, and 50 total physicians located within a single hospital referral region. They were identified using Centers for Medicare & Medicaid Services administrative data, Internal Revenue Service filings, Medicare and commercial claims, and other data. Health systems were categorized as academic, public, large for-profit, large nonprofit, or other private systems. Quality of preventive care, chronic disease management, patient experience, low-value care, mortality, hospital readmissions, and spending were assessed for Medicare beneficiaries attributed to system and nonsystem physicians. Prices for physician and hospital services and total spending were assessed in 2018 commercial claims data. Outcomes were adjusted for patient characteristics and geographic area.<br /><b>Findings</b><br />A total of 580 health systems were identified and varied greatly in size. Systems accounted for 40% of physicians and 84% of general acute care hospital beds and delivered primary care to 41% of traditional Medicare beneficiaries. Academic and large nonprofit systems accounted for a majority of system physicians (80%) and system hospital beds (64%). System hospitals were larger than nonsystem hospitals (67% vs 23% with >100 beds), as were system physician practices (74% vs 12% with >100 physicians). Performance on measures of preventive care, clinical quality, and patient experience was modestly higher for health system physicians and hospitals than for nonsystem physicians and hospitals. Prices paid to health system physicians and hospitals were significantly higher than prices paid to nonsystem physicians and hospitals (12%-26% higher for physician services, 31% for hospital services). Adjusting for practice size attenuated health systems differences on quality measures, but price differences for small and medium practices remained large.<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />In 2018, health system physicians and hospitals delivered a large portion of medical services. Performance on clinical quality and patient experience measures was marginally better in systems but spending and prices were substantially higher. This was especially true for small practices. Small quality differentials combined with large price differentials suggests that health systems have not, on average, realized their potential for better care at equal or lower cost.<br /><br /><br /><br /><small>JAMA: 24 Jan 2023; 329:325-335</small></div>
Beaulieu ND, Chernew ME, McWilliams JM, Landrum MB, ... Hicks AL, Cutler DM
JAMA: 24 Jan 2023; 329:325-335 | PMID: 36692555
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<div><h4>Estimated Prevalence and Clinical Manifestations of UBA1 Variants Associated With VEXAS Syndrome in a Clinical Population.</h4><i>Beck DB, Bodian DL, Shah V, Mirshahi UL, ... Carey DJ, Stewart DR</i><br /><b>Importance</b><br />VEXAS (vacuoles, E1-ubiquitin-activating enzyme, X-linked, autoinflammatory, somatic) syndrome is a disease with rheumatologic and hematologic features caused by somatic variants in UBA1. Pathogenic variants are associated with a broad spectrum of clinical manifestations. Knowledge of prevalence, penetrance, and clinical characteristics of this disease have been limited by ascertainment biases based on known phenotypes.<br /><b>Objective</b><br />To determine the prevalence of pathogenic variants in UBA1 and associated clinical manifestations in an unselected population using a genomic ascertainment approach.<br /><b>Design, setting, and participants</b><br />This retrospective observational study evaluated UBA1 variants in exome data from 163 096 participants within the Geisinger MyCode Community Health Initiative. Clinical phenotypes were determined from Geisinger electronic health record data from January 1, 1996, to January 1, 2022.<br /><b>Exposures</b><br />Exome sequencing was performed.<br /><b>Main outcomes and measures</b><br />Outcome measures included prevalence of somatic UBA1 variation; presence of rheumatologic, hematologic, pulmonary, dermatologic, and other findings in individuals with somatic UBA1 variation on review of the electronic health record; review of laboratory data; bone marrow biopsy pathology analysis; and in vitro enzymatic assays.<br /><b>Results</b><br />In 163 096 participants (mean age, 52.8 years; 94% White; 61% women), 11 individuals harbored likely somatic variants at known pathogenic UBA1 positions, with 11 of 11 (100%) having clinical manifestations consistent with VEXAS syndrome (9 male, 2 female). A total of 5 of 11 individuals (45%) did not meet criteria for rheumatologic and/or hematologic diagnoses previously associated with VEXAS syndrome; however, all individuals had anemia (hemoglobin: mean, 7.8 g/dL; median, 7.5 g/dL), which was mostly macrocytic (10/11 [91%]) with concomitant thrombocytopenia (10/11 [91%]). Among the 11 patients identified, there was a pathogenic variant in 1 male participant prior to onset of VEXAS-related signs or symptoms and 2 female participants had disease with heterozygous variants. A previously unreported UBA1 variant (c.1861A>T; p.Ser621Cys) was found in a symptomatic patient, with in vitro data supporting a catalytic defect and pathogenicity. Together, disease-causing UBA1 variants were found in 1 in 13 591 unrelated individuals (95% CI, 1:7775-1:23 758), 1 in 4269 men older than 50 years (95% CI, 1:2319-1:7859), and 1 in 26 238 women older than 50 years (95% CI, 1:7196-1:147 669).<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />This study provides an estimate of the prevalence and a description of the clinical manifestations of UBA1 variants associated with VEXAS syndrome within a single regional health system in the US. Additional studies are needed in unselected and genetically diverse populations to better define general population prevalence and phenotypic spectrum.<br /><br /><br /><br /><small>JAMA: 24 Jan 2023; 329:318-324</small></div>
Beck DB, Bodian DL, Shah V, Mirshahi UL, ... Carey DJ, Stewart DR
JAMA: 24 Jan 2023; 329:318-324 | PMID: 36692560
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<div><h4>Predictive Accuracy of Stroke Risk Prediction Models Across Black and White Race, Sex, and Age Groups.</h4><i>Hong C, Pencina MJ, Wojdyla DM, Hall JL, ... Kissela B, Henao R</i><br /><b>Importance</b><br />Stroke is the fifth-highest cause of death in the US and a leading cause of serious long-term disability with particularly high risk in Black individuals. Quality risk prediction algorithms, free of bias, are key for comprehensive prevention strategies.<br /><b>Objective</b><br />To compare the performance of stroke-specific algorithms with pooled cohort equations developed for atherosclerotic cardiovascular disease for the prediction of new-onset stroke across different subgroups (race, sex, and age) and to determine the added value of novel machine learning techniques.<br /><b>Design, setting, and participants</b><br />Retrospective cohort study on combined and harmonized data from Black and White participants of the Framingham Offspring, Atherosclerosis Risk in Communities (ARIC), Multi-Ethnic Study for Atherosclerosis (MESA), and Reasons for Geographical and Racial Differences in Stroke (REGARDS) studies (1983-2019) conducted in the US. The 62 482 participants included at baseline were at least 45 years of age and free of stroke or transient ischemic attack.<br /><b>Exposures</b><br />Published stroke-specific algorithms from Framingham and REGARDS (based on self-reported risk factors) as well as pooled cohort equations for atherosclerotic cardiovascular disease plus 2 newly developed machine learning algorithms.<br /><b>Main outcomes and measures</b><br />Models were designed to estimate the 10-year risk of new-onset stroke (ischemic or hemorrhagic). Discrimination concordance index (C index) and calibration ratios of expected vs observed event rates were assessed at 10 years. Analyses were conducted by race, sex, and age groups.<br /><b>Results</b><br />The combined study sample included 62 482 participants (median age, 61 years, 54% women, and 29% Black individuals). Discrimination C indexes were not significantly different for the 2 stroke-specific models (Framingham stroke, 0.72; 95% CI, 0.72-073; REGARDS self-report, 0.73; 95% CI, 0.72-0.74) vs the pooled cohort equations (0.72; 95% CI, 0.71-0.73): differences 0.01 or less (P values >.05) in the combined sample. Significant differences in discrimination were observed by race: the C indexes were 0.76 for all 3 models in White vs 0.69 in Black women (all P values <.001) and between 0.71 and 0.72 in White men and between 0.64 and 0.66 in Black men (all P values ≤.001). When stratified by age, model discrimination was better for younger (<60 years) vs older (≥60 years) adults for both Black and White individuals. The ratios of observed to expected 10-year stroke rates were closest to 1 for the REGARDS self-report model (1.05; 95% CI, 1.00-1.09) and indicated risk overestimation for Framingham stroke (0.86; 95% CI, 0.82-0.89) and pooled cohort equations (0.74; 95% CI, 0.71-0.77). Performance did not significantly improve when novel machine learning algorithms were applied.<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />In this analysis of Black and White individuals without stroke or transient ischemic attack among 4 US cohorts, existing stroke-specific risk prediction models and novel machine learning techniques did not significantly improve discriminative accuracy for new-onset stroke compared with the pooled cohort equations, and the REGARDS self-report model had the best calibration. All algorithms exhibited worse discrimination in Black individuals than in White individuals, indicating the need to expand the pool of risk factors and improve modeling techniques to address observed racial disparities and improve model performance.<br /><br /><br /><br /><small>JAMA: 24 Jan 2023; 329:306-317</small></div>
Hong C, Pencina MJ, Wojdyla DM, Hall JL, ... Kissela B, Henao R
JAMA: 24 Jan 2023; 329:306-317 | PMID: 36692561
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<div><h4>Surgical Site Infection Prevention: A Review.</h4><i>Seidelman JL, Mantyh CR, Anderson DJ</i><br /><b>Importance</b><br />Approximately 0.5% to 3% of patients undergoing surgery will experience infection at or adjacent to the surgical incision site. Compared with patients undergoing surgery who do not have a surgical site infection, those with a surgical site infection are hospitalized approximately 7 to 11 days longer.<br /><b>Observations</b><br />Most surgical site infections can be prevented if appropriate strategies are implemented. These infections are typically caused when bacteria from the patient\'s endogenous flora are inoculated into the surgical site at the time of surgery. Development of an infection depends on various factors such as the health of the patient\'s immune system, presence of foreign material, degree of bacterial wound contamination, and use of antibiotic prophylaxis. Although numerous strategies are recommended by international organizations to decrease surgical site infection, only 6 general strategies are supported by randomized trials. Interventions that are associated with lower rates of infection include avoiding razors for hair removal (4.4% with razors vs 2.5% with clippers); decolonization with intranasal antistaphylococcal agents and antistaphylococcal skin antiseptics for high-risk procedures (0.8% with decolonization vs 2% without); use of chlorhexidine gluconate and alcohol-based skin preparation (4.0% with chlorhexidine gluconate plus alcohol vs 6.5% with povidone iodine plus alcohol); maintaining normothermia with active warming such as warmed intravenous fluids, skin warming, and warm forced air to keep the body temperature warmer than 36 °C (4.7% with active warming vs 13% without); perioperative glycemic control (9.4% with glucose <150 mg/dL vs 16% with glucose >150 mg/dL); and use of negative pressure wound therapy (9.7% with vs 15% without). Guidelines recommend appropriate dosing, timing, and choice of preoperative parenteral antimicrobial prophylaxis.<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />Surgical site infections affect approximately 0.5% to 3% of patients undergoing surgery and are associated with longer hospital stays than patients with no surgical site infections. Avoiding razors for hair removal, maintaining normothermia, use of chlorhexidine gluconate plus alcohol-based skin preparation agents, decolonization with intranasal antistaphylococcal agents and antistaphylococcal skin antiseptics for high-risk procedures, controlling for perioperative glucose concentrations, and using negative pressure wound therapy can reduce the rate of surgical site infections.<br /><br /><br /><br /><small>JAMA: 17 Jan 2023; 329:244-252</small></div>
Seidelman JL, Mantyh CR, Anderson DJ
JAMA: 17 Jan 2023; 329:244-252 | PMID: 36648463
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<div><h4>Effect of Torsemide vs Furosemide After Discharge on All-Cause Mortality in Patients Hospitalized With Heart Failure: The TRANSFORM-HF Randomized Clinical Trial.</h4><i>Mentz RJ, Anstrom KJ, Eisenstein EL, Sapp S, ... Velazquez EJ, TRANSFORM-HF Investigators</i><br /><b>Importance</b><br />Although furosemide is the most commonly used loop diuretic in patients with heart failure, some studies suggest a potential benefit for torsemide.<br /><b>Objective</b><br />To determine whether torsemide results in decreased mortality compared with furosemide among patients hospitalized for heart failure.<br /><b>Design, setting, and participants</b><br />TRANSFORM-HF was an open-label, pragmatic randomized trial that recruited 2859 participants hospitalized with heart failure (regardless of ejection fraction) at 60 hospitals in the United States. Recruitment occurred from June 2018 through March 2022, with follow-up through 30 months for death and 12 months for hospitalizations. The final date for follow-up data collection was July 2022.<br /><b>Interventions</b><br />Loop diuretic strategy of torsemide (n = 1431) or furosemide (n = 1428) with investigator-selected dosage.<br /><b>Main outcomes and measures</b><br />The primary outcome was all-cause mortality in a time-to-event analysis. There were 5 secondary outcomes with all-cause mortality or all-cause hospitalization and total hospitalizations assessed over 12 months being highest in the hierarchy. The prespecified primary hypothesis was that torsemide would reduce all-cause mortality by 20% compared with furosemide.<br /><b>Results</b><br />TRANSFORM-HF randomized 2859 participants with a median age of 65 years (IQR, 56-75), 36.9% were women, and 33.9% were Black. Over a median follow-up of 17.4 months, a total of 113 patients (53 [3.7%] in the torsemide group and 60 [4.2%] in the furosemide group) withdrew consent from the trial prior to completion. Death occurred in 373 of 1431 patients (26.1%) in the torsemide group and 374 of 1428 patients (26.2%) in the furosemide group (hazard ratio, 1.02 [95% CI, 0.89-1.18]). Over 12 months following randomization, all-cause mortality or all-cause hospitalization occurred in 677 patients (47.3%) in the torsemide group and 704 patients (49.3%) in the furosemide group (hazard ratio, 0.92 [95% CI, 0.83-1.02]). There were 940 total hospitalizations among 536 participants in the torsemide group and 987 total hospitalizations among 577 participants in the furosemide group (rate ratio, 0.94 [95% CI, 0.84-1.07]). Results were similar across prespecified subgroups, including among patients with reduced, mildly reduced, or preserved ejection fraction.<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />Among patients discharged after hospitalization for heart failure, torsemide compared with furosemide did not result in a significant difference in all-cause mortality over 12 months. However, interpretation of these findings is limited by loss to follow-up and participant crossover and nonadherence.<br /><b>Trial registration</b><br />ClinicalTrials.gov Identifier: NCT03296813.<br /><br /><br /><br /><small>JAMA: 17 Jan 2023; 329:214-223</small></div>
Mentz RJ, Anstrom KJ, Eisenstein EL, Sapp S, ... Velazquez EJ, TRANSFORM-HF Investigators
JAMA: 17 Jan 2023; 329:214-223 | PMID: 36648467
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<div><h4>Association of Supernumerary Sex Chromosome Aneuploidies With Venous Thromboembolism.</h4><i>Berry ASF, Finucane BM, Myers SM, Abril A, ... Martin CL, Oetjens MT</i><br /><b>Importance</b><br />An increased risk of venous thromboembolism (VTE) has been reported in men with an additional sex chromosome. The association between other sex chromosome aneuploidies and VTE is not well characterized.<br /><b>Objective</b><br />To determine if sex chromosome aneuploidy is associated with VTE.<br /><b>Design, setting, and participants</b><br />Retrospective cohort study of sex chromosome aneuploidy and VTE, performed by analyzing X- and Y-chromosome dosage and VTE incidence in 642 544 individuals from 2 population-scale biobanks: the US Geisinger MyCode Community Health Initiative (N = 154 519) and the UK Biobank (N = 488 025); analysis was limited to participants self-identified as White because of inadequate sample sizes for other race and ethnicity groups. A total of 108 461 unrelated MyCode participants with electronic health record follow-up ranging from September 1996 to December 2020 and 418 725 unrelated British and Irish UK Biobank participants who attended the baseline assessment between March 2006 and October 2010, with follow-up extending to November 2020, were included in analyses of VTE.<br /><b>Exposures</b><br />Sex chromosome aneuploidies.<br /><b>Main outcomes and measures</b><br />Individuals with 1 primary inpatient VTE diagnosis, 2 primary outpatient VTE diagnoses, or a self-reported VTE diagnosis were defined as VTE cases. P values were adjusted for multiple comparisons.<br /><b>Results</b><br />Identification of sex chromosome aneuploidy was undertaken among 642 544 individuals aged 18 to 90 years. Identification of a diagnosis of VTE was undertaken among 108 461 unrelated MyCode participants (65 565 [60.5%] female; mean age at last visit, 58.0 [SD, 17.6] years; median follow-up, 15.3 [IQR, 9.7] years) and among 418 725 unrelated UK Biobank participants (224 695 [53.7%] female; mean age at baseline interview, 56.9 [SD, 8.0] years; median follow-up, 12.0 [IQR, 1.6] years). Among MyCode participants, during 10 years of follow-up, 17 incident VTE events per 1353 person-years were detected among those with supernumerary sex chromosome aneuploidy (1.3% per person-year) compared with 2060 per 816 682 person-years among those with 46,XX or 46,XY (0.25% per person-year) (hazard ratio, 5.4 [95% CI, 3.4-8.7]; 10-year risk difference, 8.8% [95% CI, 4.2%-14.0%]; P < .001). Among UK Biobank participants, during 10 years of follow-up, 16 incident VTE events per 3803 person-years were detected among those with supernumerary sex chromosome aneuploidy (0.42% per person-year) compared with 4491 per 3 970 467 person-years among those with 46,XX or 46,XY (0.11% per person-year) (hazard ratio, 4.1 [95% CI, 2.5-6.7]; 10-year risk difference, 3.7% [95% CI, 1.4%-5.9%]; P < .001).<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />Adults with supernumerary sex chromosome aneuploidies compared with 2 sex chromosomes had a small but statistically significant increased risk of VTE. Further research is needed to understand the clinical implications of this association.<br /><br /><br /><br /><small>JAMA: 17 Jan 2023; 329:235-243</small></div>
Berry ASF, Finucane BM, Myers SM, Abril A, ... Martin CL, Oetjens MT
JAMA: 17 Jan 2023; 329:235-243 | PMID: 36648468
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<div><h4>Effect of Early High-Flow Nasal Oxygen vs Standard Oxygen Therapy on Length of Hospital Stay in Hospitalized Children With Acute Hypoxemic Respiratory Failure: The PARIS-2 Randomized Clinical Trial.</h4><i>Franklin D, Babl FE, George S, Oakley E, ... Dalziel SR, Schibler A</i><br /><b>Importance</b><br />Nasal high-flow oxygen therapy in infants with bronchiolitis and hypoxia has been shown to reduce the requirement to escalate care. The efficacy of high-flow oxygen therapy in children aged 1 to 4 years with acute hypoxemic respiratory failure without bronchiolitis is unknown.<br /><b>Objective</b><br />To determine the effect of early high-flow oxygen therapy vs standard oxygen therapy in children with acute hypoxemic respiratory failure.<br /><b>Design, setting, and participants</b><br />A multicenter, randomized clinical trial was conducted at 14 metropolitan and tertiary hospitals in Australia and New Zealand, including 1567 children aged 1 to 4 years (randomized between December 18, 2017, and March 18, 2020) requiring hospital admission for acute hypoxemic respiratory failure. The last participant follow-up was completed on March 22, 2020.<br /><b>Interventions</b><br />Enrolled children were randomly allocated 1:1 to high-flow oxygen therapy (n = 753) or standard oxygen therapy (n = 764). The type of oxygen therapy could not be masked, but the investigators remained blinded until the outcome data were locked.<br /><b>Main outcomes and measures</b><br />The primary outcome was length of hospital stay with the hypothesis that high-flow oxygen therapy reduces length of stay. There were 9 secondary outcomes, including length of oxygen therapy and admission to the intensive care unit. Children were analyzed according to their randomization group.<br /><b>Results</b><br />Of the 1567 children who were randomized, 1517 (97%) were included in the primary analysis (median age, 1.9 years [IQR, 1.4-3.0 years]; 732 [46.7%] were female) and all children completed the trial. The length of hospital stay was significantly longer in the high-flow oxygen group with a median of 1.77 days (IQR, 1.03-2.80 days) vs 1.50 days (IQR, 0.85-2.44 days) in the standard oxygen group (adjusted hazard ratio, 0.83 [95% CI, 0.75-0.92]; P < .001). Of the 9 prespecified secondary outcomes, 4 showed no significant difference. The median length of oxygen therapy was 1.07 days (IQR, 0.50-2.06 days) in the high-flow oxygen group vs 0.75 days (IQR, 0.35-1.61 days) in the standard oxygen therapy group (adjusted hazard ratio, 0.78 [95% CI, 0.70-0.86]). In the high-flow oxygen group, there were 94 admissions (12.5%) to the intensive care unit compared with 53 admissions (6.9%) in the standard oxygen group (adjusted odds ratio, 1.93 [95% CI, 1.35-2.75]). There was only 1 death and it occurred in the high-flow oxygen group.<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />Nasal high-flow oxygen used as the initial primary therapy in children aged 1 to 4 years with acute hypoxemic respiratory failure did not significantly reduce the length of hospital stay compared with standard oxygen therapy.<br /><b>Trial registration</b><br />anzctr.org.au Identifier: ACTRN12618000210279.<br /><br /><br /><br /><small>JAMA: 17 Jan 2023; 329:224-234</small></div>
Abstract
<div><h4>Effect of Fluvoxamine vs Placebo on Time to Sustained Recovery in Outpatients With Mild to Moderate COVID-19: A Randomized Clinical Trial.</h4><i>McCarthy MW, Naggie S, Boulware DR, Lindsell CJ, ... Hernandez AF, Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV)-6 Study Group and Investigators</i><br /><b>Importance</b><br />The effectiveness of fluvoxamine to shorten symptom duration or prevent hospitalization among outpatients with mild to moderate symptomatic COVID-19 is unclear.<br /><b>Objective</b><br />To evaluate the efficacy of low-dose fluvoxamine (50 mg twice daily) for 10 days compared with placebo for the treatment of mild to moderate COVID-19 in the US.<br /><b>Design, setting, and participants</b><br />The ongoing Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV-6) platform randomized clinical trial was designed to test repurposed medications in outpatients with mild to moderate COVID-19. A total of 1288 participants aged 30 years or older with test-confirmed SARS-CoV-2 infection and experiencing 2 or more symptoms of acute COVID-19 for 7 days or less were enrolled between August 6, 2021, and May 27, 2022, at 91 sites in the US.<br /><b>Interventions</b><br />Participants were randomized to receive 50 mg of fluvoxamine twice daily for 10 days or placebo.<br /><b>Main outcomes and measures</b><br />The primary outcome was time to sustained recovery (defined as the third day of 3 consecutive days without symptoms). There were 7 secondary outcomes, including a composite outcome of hospitalization, urgent care visit, emergency department visit, or death through day 28.<br /><b>Results</b><br />Among 1331 participants who were randomized (median age, 47 years [IQR, 38-57 years]; 57% were women; and 67% reported receiving ≥2 doses of a SARS-CoV-2 vaccine), 1288 completed the trial (674 in the fluvoxamine group and 614 in the placebo group). The median time to sustained recovery was 12 days (IQR, 11-14 days) in the fluvoxamine group and 13 days (IQR, 12-13 days) in the placebo group (hazard ratio [HR], 0.96 [95% credible interval, 0.86-1.06], posterior P = .21 for the probability of benefit [determined by an HR >1]). For the composite outcome, 26 participants (3.9%) in the fluvoxamine group were hospitalized, had an urgent care visit, had an emergency department visit, or died compared with 23 participants (3.8%) in the placebo group (HR, 1.1 [95% credible interval, 0.5-1.8], posterior P = .35 for the probability of benefit [determined by an HR <1]). One participant in the fluvoxamine group and 2 participants in the placebo group were hospitalized; no deaths occurred in either group. Adverse events were uncommon in both groups.<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />Among outpatients with mild to moderate COVID-19, treatment with 50 mg of fluvoxamine twice daily for 10 days, compared with placebo, did not improve time to sustained recovery. These findings do not support the use of fluvoxamine at this dose and duration in patients with mild to moderate COVID-19.<br /><b>Trial registration</b><br />ClinicalTrials.gov Identifier: NCT04885530.<br /><br /><br /><br /><small>JAMA: 12 Jan 2023; epub ahead of print</small></div>
McCarthy MW, Naggie S, Boulware DR, Lindsell CJ, ... Hernandez AF, Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV)-6 Study Group and Investigators
JAMA: 12 Jan 2023; epub ahead of print | PMID: 36633838
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<div><h4>Autism Spectrum Disorder: A Review.</h4><i>Hirota T, King BH</i><br /><b>Importance</b><br />Autism spectrum disorder (ASD), characterized by deficits in social communication and the presence of restricted, repetitive behaviors or interests, is a neurodevelopmental disorder affecting approximately 2.3% children aged 8 years in the US and approximately 2.2% of adults. This review summarizes evidence on the diagnosis and treatment of ASD.<br /><b>Observations</b><br />The estimated prevalence of ASD has been increasing in the US, from 1.1% in 2008 to 2.3% in 2018, which is likely associated with changes in diagnostic criteria, improved performance of screening and diagnostic tools, and increased public awareness. No biomarkers specific to the diagnosis of ASD have been identified. Common early signs and symptoms of ASD in a child\'s first 2 years of life include no response to name when called, no or limited use of gestures in communication, and lack of imaginative play. The criterion standard for the diagnosis of ASD is a comprehensive evaluation with a multidisciplinary team of clinicians and is based on semistructured direct observation of the child\'s behavior and semistructured caregiver interview focused on the individual\'s development and behaviors using standardized measures, such as the Autism Diagnostic Observation Schedule-Second Edition and the Autism Diagnostic Interview. These diagnostic measures have sensitivity of 91% and 80% and specificity of 76% and 72%, respectively. Compared with people without ASD, individuals with ASD have higher rates of depression (20% vs 7%), anxiety (11% vs 5%), sleep difficulties (13% vs 5%), and epilepsy (21% with co-occurring intellectual disability vs 0.8%). Intensive behavioral interventions, such as the Early Start Denver Model, are beneficial in children 5 years or younger for improvement in language, play, and social communication (small to medium effect size based on standardized mean difference). Pharmacotherapy is indicated for co-occurring psychiatric conditions, such as emotion dysregulation or attention-deficit/hyperactivity disorder. Risperidone and aripiprazole can improve irritability and aggression (standardized mean difference of 1.1, consistent with a large effect size) compared with placebo. Psychostimulants are effective for attention-deficit/hyperactivity disorder (standardized mean difference of 0.6, consistent with a moderate effect size) compared with placebo. These medications are associated with adverse effects including, most commonly, changes in appetite, weight, and sleep.<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />ASD affects approximately 2.3% of children aged 8 years and approximately 2.2% of adults in the US. First-line therapy consists of behavioral interventions, while co-occurring psychiatric conditions, such as anxiety or aggression, may be treated with specific behavioral therapy or medication.<br /><br /><br /><br /><small>JAMA: 10 Jan 2023; 329:157-168</small></div>
Hirota T, King BH
JAMA: 10 Jan 2023; 329:157-168 | PMID: 36625807
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<div><h4>Effect of Catheter Ablation Using Pulmonary Vein Isolation With vs Without Posterior Left Atrial Wall Isolation on Atrial Arrhythmia Recurrence in Patients With Persistent Atrial Fibrillation: The CAPLA Randomized Clinical Trial.</h4><i>Kistler PM, Chieng D, Sugumar H, Ling LH, ... Sanders P, Kalman JM</i><br /><b>Importance</b><br />Pulmonary vein isolation (PVI) alone is less effective in patients with persistent atrial fibrillation (AF) compared with paroxysmal AF. The left atrial posterior wall may contribute to maintenance of persistent AF, and posterior wall isolation (PWI) is a common PVI adjunct. However, PWI has not been subjected to randomized comparison.<br /><b>Objective</b><br />To compare PVI with PWI vs PVI alone in patients with persistent AF undergoing first-time catheter ablation.<br /><b>Design, setting, and participants</b><br />Investigator initiated, multicenter, randomized clinical trial involving 11 centers in 3 countries (Australia, Canada, UK). Symptomatic patients with persistent AF were randomized 1:1 to either PVI with PWI or PVI alone. Patients were enrolled July 2018-March 2021, with 1-year follow-up completed March 2022.<br /><b>Interventions</b><br />The PVI with PWI group (n = 170) underwent wide antral pulmonary vein isolation followed by posterior wall isolation involving linear ablation at the roof and floor to achieve electrical isolation. The PVI-alone group (n = 168) underwent wide antral pulmonary vein isolation alone.<br /><b>Main outcomes and measures</b><br />Primary end point was freedom from any documented atrial arrhythmia of more than 30 seconds without antiarrhythmic medication at 12 months, after a single ablation procedure. The 23 secondary outcomes included freedom from atrial arrhythmia with/without antiarrhythmic medication after multiple procedures, freedom from symptomatic AF with/without antiarrhythmic medication after multiple procedures, AF burden between study groups at 12 months, procedural outcomes, and complications.<br /><b>Results</b><br />Among 338 patients randomized (median age, 65.6 [IQR, 13.1] years; 76.9% men), 330 (97.6%) completed the study. After 12 months, 89 patients (52.4%) assigned to PVI with PWI were free from recurrent atrial arrhythmia without antiarrhythmic medication after a single procedure, compared with 90 (53.6%) assigned to PVI alone (between-group difference, -1.2%; hazard ratio [HR], 0.99 [95% CI, 0.73-1.36]; P = .98). Of the secondary end points, 9 showed no significant difference, including freedom from atrial arrhythmia with/without antiarrhythmic medication after multiple procedures (58.2% for PVI with PWI vs 60.1% for PVI alone; HR, 1.10 [95% CI, 0.79-1.55]; P = .57), freedom from symptomatic AF with/without antiarrhythmic medication after multiple procedures (68.2% vs 72%; HR, 1.20 [95% CI, 0.80-1.78]; P = .36) or AF burden (0% [IQR, 0%-2.3%] vs 0% [IQR, 0%-2.8%], P = .47). Mean procedural times (142 [SD, 69] vs 121 [SD, 57] minutes, P < .001) and ablation times (34 [SD, 21] vs 28 [SD, 12] minutes, P < .001) were significantly shorter for PVI alone. There were 6 complications for PVI with PWI and 4 for PVI alone.<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />In patients undergoing first-time catheter ablation for persistent AF, the addition of PWI to PVI alone did not significantly improve freedom from atrial arrhythmia at 12 months compared with PVI alone. These findings do not support the empirical inclusion of PWI for ablation of persistent AF.<br /><b>Trial registration</b><br />anzctr.org.au Identifier: ACTRN12616001436460.<br /><br /><br /><br /><small>JAMA: 10 Jan 2023; 329:127-135</small></div>
Abstract
<div><h4>Use of Recalled Devices in New Device Authorizations Under the US Food and Drug Administration\'s 510(k) Pathway and Risk of Subsequent Recalls.</h4><i>Kadakia KT, Dhruva SS, Caraballo C, Ross JS, Krumholz HM</i><br /><b>Importance</b><br />In the US, nearly all medical devices progress to market under the 510(k) pathway, which uses previously authorized devices (predicates) to support new authorizations. Current regulations permit manufacturers to use devices subject to a Class I recall-the FDA\'s most serious designation indicating a high probability of adverse health consequences or death-as predicates for new devices. The consequences for patient safety are not known.<br /><b>Objective</b><br />To determine the risk of a future Class I recall associated with using a recalled device as a predicate device in the 510(k) pathway.<br /><b>Design and setting</b><br />In this cross-sectional study, all 510(k) devices subject to Class I recalls from January 2017 through December 2021 (index devices) were identified from the FDA\'s annual recall listings. Information about predicate devices was extracted from the Devices@FDA database. Devices authorized using index devices as predicates (descendants) were identified using a regulatory intelligence platform. A matched cohort of predicates was constructed to assess the future recall risk from using a predicate device with a Class I recall.<br /><b>Main outcomes and measures</b><br />Devices were characterized by their regulatory history and recall history. Risk ratios (RRs) were calculated to compare the risk of future Class I recalls between devices descended from predicates with matched controls.<br /><b>Results</b><br />Of 156 index devices subject to Class I recall from 2017 through 2021, 44 (28.2%) had prior Class I recalls. Predicates were identified for 127 index devices, with 56 (44.1%) using predicates with a Class I recall. One hundred four index devices were also used as predicates to support the authorization of 265 descendant devices, with 50 index devices (48.1%) authorizing a descendant with a Class I recall. Compared with matched controls, devices authorized using predicates with Class I recalls had a higher risk of subsequent Class I recall (6.40 [95% CI, 3.59-11.40]; P<.001).<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />Many 510(k) devices subjected to Class I recalls in the US use predicates with a known history of Class I recalls. These devices have substantially higher risk of a subsequent Class I recall. Safeguards for the 510(k) pathway are needed to prevent problematic predicate selection and ensure patient safety.<br /><br /><br /><br /><small>JAMA: 10 Jan 2023; 329:136-143</small></div>
Kadakia KT, Dhruva SS, Caraballo C, Ross JS, Krumholz HM
JAMA: 10 Jan 2023; 329:136-143 | PMID: 36625810
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<div><h4>Association Between Regulatory Submission Characteristics and Recalls of Medical Devices Receiving 510(k) Clearance.</h4><i>Everhart AO, Sen S, Stern AD, Zhu Y, Karaca-Mandic P</i><br /><b>Importance</b><br />Most regulated medical devices enter the US market via the 510(k) regulatory submission pathway, wherein manufacturers demonstrate that applicant devices are \"substantially equivalent\" to 1 or more \"predicate\" devices (legally marketed medical devices with similar intended use). Most recalled medical devices are 510(k) devices.<br /><b>Objective</b><br />To examine the association between characteristics of predicate medical devices and recall probability for 510(k) devices.<br /><b>Design, setting, and participants</b><br />In this exploratory cross-sectional analysis of medical devices cleared by the US Food and Drug Administration (FDA) between 2003 and 2018 via the 510(k) regulatory submission pathway, linear probability models were used to examine associations between a 510(k) device\'s recall status and characteristics of its predicate medical devices. Public documents for the 510(k) medical devices were collected using FDA databases. A text extraction algorithm was applied to identify predicate medical devices cited in 510(k) regulatory submissions. Algorithm-derived metadata were combined with 2003-2020 FDA recall data.<br /><b>Exposures</b><br />Citation of predicate medical devices with certain characteristics in 510(k) regulatory submissions, including the total number of predicate medical devices cited by the applicant device, the age of the predicate medical devices, the lack of similarity of the predicate medical devices to the applicant device, and the recall status of the predicate medical devices.<br /><b>Main outcomes and measures</b><br />Class I or class II recall of a 510(k) medical device between its FDA regulatory clearance date and December 31, 2020.<br /><b>Results</b><br />The sample included 35 176 medical devices, of which 4007 (11.4%) were recalled. The applicant devices cited a mean of 2.6 predicate medical devices, with mean ages of 3.6 years and 7.4 years for the newest and oldest, respectively, predicate medical devices. Of the applicant devices, 93.9% cited predicate medical devices with no ongoing recalls, 4.3% cited predicate medical devices with 1 ongoing class I or class II recall, 1.0% cited predicate medical devices with 2 ongoing recalls, and 0.8% cited predicate medical devices with 3 or more ongoing recalls. Applicant devices citing predicate medical devices with 3 or more ongoing recalls were significantly associated with a 9.31-percentage-point increase (95% CI, 2.84-15.77 percentage points) in recall probability compared with devices without ongoing recalls of predicate medical devices, or an 81.2% increase in recall probability relative to the mean recall probability. A 1-SD increase in the total number of predicate medical devices cited by the applicant device was significantly associated with a 1.25-percentage-point increase (95% CI, 0.62-1.87 percentage points) in recall probability, or an 11.0% increase in recall probability relative to the mean recall probability. A 1-SD increase in the newest age of a predicate medical device was significantly associated with a 0.78-percentage-point decrease (95% CI, 1.29-0.30 percentage points) in recall probability, or a 6.8% decrease in recall probability relative to the mean recall probability.<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />This exploratory cross-sectional study of 510(k) medical devices cleared by the FDA between 2003 and 2018 demonstrated significant associations between 510(k) submission characteristics and recalls of medical devices. Further research is needed to understand the implications of these associations.<br /><br /><br /><br /><small>JAMA: 10 Jan 2023; 329:144-156</small></div>
Everhart AO, Sen S, Stern AD, Zhu Y, Karaca-Mandic P
JAMA: 10 Jan 2023; 329:144-156 | PMID: 36625811
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<div><h4>Association of Race and Ethnicity With Initial Prescription of Antiretroviral Therapy Among People With HIV in the US.</h4><i>Zalla LC, Cole SR, Eron JJ, Adimora AA, ... Moore RD, Edwards JK</i><br /><b>Importance</b><br />Integrase strand transfer inhibitor (INSTI)-containing antiretroviral therapy (ART) is currently the guideline-recommended first-line treatment for HIV. Delayed prescription of INSTI-containing ART may amplify differences and inequities in health outcomes.<br /><b>Objectives</b><br />To estimate racial and ethnic differences in the prescription of INSTI-containing ART among adults newly entering HIV care in the US and to examine variation in these differences over time in relation to changes in treatment guidelines.<br /><b>Design, setting, and participants</b><br />Retrospective observational study of 42 841 adults entering HIV care from October 12, 2007, when the first INSTI was approved by the US Food and Drug Administration, to April 30, 2019, at more than 200 clinical sites contributing to the North American AIDS Cohort Collaboration on Research and Design.<br /><b>Exposures</b><br />Combined race and ethnicity as reported in patient medical records.<br /><b>Main outcomes and measures</b><br />Probability of initial prescription of ART within 1 month of care entry and probability of being prescribed INSTI-containing ART. Differences among non-Hispanic Black and Hispanic patients compared with non-Hispanic White patients were estimated by calendar year and time period in relation to changes in national guidelines on the timing of treatment initiation and recommended initial treatment regimens.<br /><b>Results</b><br />Of 41 263 patients with information on race and ethnicity, 19 378 (47%) as non-Hispanic Black, 6798 (16%) identified as Hispanic, and 13 539 (33%) as non-Hispanic White; 36 394 patients (85%) were male, and the median age was 42 years (IQR, 30 to 51). From 2007-2015, when guidelines recommended treatment initiation based on CD4+ cell count, the probability of ART initiation within 1 month of care entry was 45% among White patients, 45% among Black patients (difference, 0% [95% CI, -1% to 1%]), and 51% among Hispanic patients (difference, 5% [95% CI, 4% to 7%]). From 2016-2019, when guidelines strongly recommended treating all patients regardless of CD4+ cell count, this probability increased to 66% among White patients, 68% among Black patients (difference, 2% [95% CI, -1% to 5%]), and 71% among Hispanic patients (difference, 5% [95% CI, 1% to 9%]). INSTIs were prescribed to 22% of White patients and only 17% of Black patients (difference, -5% [95% CI, -7% to -4%]) and 17% of Hispanic patients (difference, -5% [95% CI, -7% to -3%]) from 2009-2014, when INSTIs were approved as initial therapy but were not yet guideline recommended. Significant differences persisted for Black patients (difference, -6% [95% CI, -8% to -4%]) but not for Hispanic patients (difference, -1% [95% CI, -4% to 2%]) compared with White patients from 2014-2017, when INSTI-containing ART was a guideline-recommended option for initial therapy; differences by race and ethnicity were not statistically significant from 2017-2019, when INSTI-containing ART was the single recommended initial therapy for most people with HIV.<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />Among adults entering HIV care within a large US research consortium from 2007-2019, the 1-month probability of ART prescription was not significantly different across most races and ethnicities, although Black and Hispanic patients were significantly less likely than White patients to receive INSTI-containing ART in earlier time periods but not after INSTIs became guideline-recommended initial therapy for most people with HIV. Additional research is needed to understand the underlying racial and ethnic differences and whether the differences in prescribing were associated with clinical outcomes.<br /><br /><br /><br /><small>JAMA: 03 Jan 2023; 329:52-62</small></div>
Zalla LC, Cole SR, Eron JJ, Adimora AA, ... Moore RD, Edwards JK
JAMA: 03 Jan 2023; 329:52-62 | PMID: 36594946
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<div><h4>Effect of Remifentanil vs Neuromuscular Blockers During Rapid Sequence Intubation on Successful Intubation Without Major Complications Among Patients at Risk of Aspiration: A Randomized Clinical Trial.</h4><i>Grillot N, Lebuffe G, Huet O, Lasocki S, ... Roquilly A, Atlanrea Study GroupSociété Française d’Anesthésie Réanimation (SFAR) Research Network</i><br /><b>Importance</b><br />It is uncertain whether a rapid-onset opioid is noninferior to a rapid-onset neuromuscular blocker during rapid sequence intubation when used in conjunction with a hypnotic agent.<br /><b>Objective</b><br />To determine whether remifentanil is noninferior to rapid-onset neuromuscular blockers for rapid sequence intubation.<br /><b>Design, setting, and participants</b><br />Multicenter, randomized, open-label, noninferiority trial among 1150 adults at risk of aspiration (fasting for <6 hours, bowel occlusion, recent trauma, or severe gastroesophageal reflux) who underwent tracheal intubation in the operating room at 15 hospitals in France from October 2019 to April 2021. Follow-up was completed on May 15, 2021.<br /><b>Interventions</b><br />Patients were randomized to receive neuromuscular blockers (1 mg/kg of succinylcholine or rocuronium; n = 575) or remifentanil (3 to 4 μg/kg; n = 575) immediately after injection of a hypnotic.<br /><b>Main outcomes and measures</b><br />The primary outcome was assessed in all randomized patients (as-randomized population) and in all eligible patients who received assigned treatment (per-protocol population). The primary outcome was successful tracheal intubation on the first attempt without major complications, defined as lung aspiration of digestive content, oxygen desaturation, major hemodynamic instability, sustained arrhythmia, cardiac arrest, and severe anaphylactic reaction. The prespecified noninferiority margin was 7.0%.<br /><b>Results</b><br />Among 1150 randomized patients (mean age, 50.7 [SD, 17.4] years; 573 [50%] women), 1130 (98.3%) completed the trial. In the as-randomized population, tracheal intubation on the first attempt without major complications occurred in 374 of 575 patients (66.1%) in the remifentanil group and 408 of 575 (71.6%) in the neuromuscular blocker group (between-group difference adjusted for randomization strata and center, -6.1%; 95% CI, -11.6% to -0.5%; P = .37 for noninferiority), demonstrating inferiority. In the per-protocol population, 374 of 565 patients (66.2%) in the remifentanil group and 403 of 565 (71.3%) in the neuromuscular blocker group had successful intubation without major complications (adjusted difference, -5.7%; 2-sided 95% CI, -11.3% to -0.1%; P = .32 for noninferiority). An adverse event of hemodynamic instability was recorded in 19 of 575 patients (3.3%) with remifentanil and 3 of 575 (0.5%) with neuromuscular blockers (adjusted difference, 2.8%; 95% CI, 1.2%-4.4%).<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />Among adults at risk of aspiration during rapid sequence intubation in the operating room, remifentanil, compared with neuromuscular blockers, did not meet the criterion for noninferiority with regard to successful intubation on first attempt without major complications. Although remifentanil was statistically inferior to neuromuscular blockers, the wide confidence interval around the effect estimate remains compatible with noninferiority and limits conclusions about the clinical relevance of the difference.<br /><b>Trial registration</b><br />ClinicalTrials.gov Identifier: NCT03960801.<br /><br /><br /><br /><small>JAMA: 03 Jan 2023; 329:28-38</small></div>
Grillot N, Lebuffe G, Huet O, Lasocki S, ... Roquilly A, Atlanrea Study GroupSociété Française d’Anesthésie Réanimation (SFAR) Research Network
JAMA: 03 Jan 2023; 329:28-38 | PMID: 36594947
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<div><h4>Anxiety Disorders: A Review.</h4><i>Szuhany KL, Simon NM</i><br /><b>Importance</b><br />Anxiety disorders have a lifetime prevalence of approximately 34% in the US, are often chronic, and significantly impair quality of life and functioning.<br /><b>Observations</b><br />Anxiety disorders are characterized by symptoms that include worry, social and performance fears, unexpected and/or triggered panic attacks, anticipatory anxiety, and avoidance behaviors. Generalized anxiety disorder (6.2% lifetime prevalence), social anxiety disorder (13% lifetime prevalence), and panic disorder (5.2% lifetime prevalence) with or without agoraphobia are common anxiety disorders seen in primary care. Anxiety disorders are associated with physical symptoms, such as palpitations, shortness of breath, and dizziness. Brief screening measures applied in primary care, such as the Generalized Anxiety Disorder-7, can aid in diagnosis of anxiety disorders (sensitivity, 57.6% to 93.9%; specificity, 61% to 97%). Providing information about symptoms, diagnosis, and evidence-based treatments is a first step in helping patients with anxiety. First-line treatments include pharmacotherapy and psychotherapy. Selective serotonin reuptake inhibitors (SSRIs, eg, sertraline) and serotonin-norepinephrine reuptake inhibitors (SNRIs, eg, venlafaxine extended release) remain first-line pharmacotherapy for generalized anxiety disorder, social anxiety disorder, and panic disorder. Meta-analyses suggest that SSRIs and SNRIs are associated with small to medium effect sizes compared with placebo (eg, generalized anxiety disorder: standardized mean difference [SMD], -0.55 [95% CI, -0.64 to -0.46]; social anxiety disorder: SMD, -0.67 [95% CI, -0.76 to -0.58]; panic disorder: SMD, -0.30 [95% CI, -0.37 to -0.23]). Cognitive behavioral therapy is the psychotherapy with the most evidence of efficacy for anxiety disorders compared with psychological or pill placebo (eg, generalized anxiety disorder: Hedges g = 1.01 [large effect size] [95% CI, 0.44 to 1.57]; social anxiety disorder: Hedges g = 0.41 [small to medium effect] [95% CI, 0.25 to 0.57]; panic disorder: Hedges g = 0.39 [small to medium effect[ [95% CI, 0.12 to 0.65]), including in primary care. When selecting treatment, clinicians should consider patient preference, current and prior treatments, medical and psychiatric comorbid illnesses, age, sex, and reproductive planning, as well as cost and access to care.<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />Anxiety disorders affect approximately 34% of adults during their lifetime in the US and are associated with significant distress and impairment. First-line treatments for anxiety disorders include cognitive behavioral therapy, SSRIs such as sertraline, and SNRIs such as venlafaxine extended release.<br /><br /><br /><br /><small>JAMA: 27 Dec 2022; 328:2431-2445</small></div>
Szuhany KL, Simon NM
JAMA: 27 Dec 2022; 328:2431-2445 | PMID: 36573969
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<div><h4>Exome Sequencing of a Clinical Population for Autosomal Dominant Polycystic Kidney Disease.</h4><i>Chang AR, Moore BS, Luo JZ, Sartori G, ... Singh G, Mirshahi T</i><br /><b>Importance</b><br />Most studies of autosomal dominant polycystic kidney disease (ADPKD) genetics have used kidney specialty cohorts, focusing on PKD1 and PKD2. These can lead to biased estimates of population prevalence of ADPKD-associated gene variants and their phenotypic expression.<br /><b>Objective</b><br />To determine the prevalence of ADPKD and contributions of PKD1, PKD2, and other genes related to cystic kidney disease in a large, unselected cohort.<br /><b>Design, setting, and participants</b><br />This retrospective observational study used an unselected health system-based cohort in central and northeast Pennsylvania with exome sequencing (enrolled from 2004 to 2020) and electronic health record data (up to October 2021). The genotype-first approach included the entire cohort and the phenotype-first approach focused on patients with ADPKD diagnosis codes, confirmed by chart and imaging review.<br /><b>Exposures</b><br />Loss-of-function (LOF) variants in PKD1, PKD2, and other genes associated with cystic kidney disease (ie, ALG8, ALG9, DNAJB11, GANAB, HNF1B, IFT140, SEC61B, PKHD1, PRKCSH, SEC63); likely pathogenic missense variants in PKD1 and PKD2.<br /><b>Main outcomes and measures</b><br />Genotype-first analysis: ADPKD diagnosis code (Q61.2, Q61.3, 753.13, 753.12); phenotype-first analysis: presence of a rare variant in PKD1, PKD2, or other genes associated with cystic kidney disease.<br /><b>Results</b><br />Of 174 172 patients (median age, 60 years; 60.6% female; 93% of European ancestry), 303 patients had ADPKD diagnosis codes, including 235 with sufficient chart review data for confirmation. In addition to PKD1 and PKD2, LOF variants in IFT140, GANAB, and HNF1B were associated with ADPKD diagnosis after correction for multiple comparisons. Among patients with LOF variants in PKD1, 66 of 68 (97%) had ADPKD; 43 of 43 patients (100%) with LOF variants in PKD2 had ADPKD. In contrast, only 24 of 77 patients (31.2%) with a PKD1 missense variant previously classified as \"likely pathogenic\" had ADPKD, suggesting misclassification or variable penetrance. Among patients with ADPKD diagnosis confirmed by chart review, 180 of 235 (76.6%) had a potential genetic cause, with the majority being rare variants in PKD1 (127 patients) or PKD2 (34 patients); 19 of 235 (8.1%) had variants in other genes associated with cystic kidney disease. Of these 235 patients with confirmed ADPKD, 150 (63.8%) had a family history of ADPKD. The yield for a genetic determinant of ADPKD was higher for those with a family history of ADPKD compared with those without family history (91.3% [137/150] vs 50.6% [43/85]; difference, 40.7% [95% CI, 29.2%-52.3%]; P < .001). Previously unreported PKD1, PKD2, and GANAB variants were identified with pedigree data suggesting pathogenicity, and several PKD1 missense variants previously reported as likely pathogenic appeared to be benign.<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />This study demonstrates substantial genetic and phenotypic variability in ADPKD among patients within a regional health system in the US.<br /><br /><br /><br /><small>JAMA: 27 Dec 2022; 328:2412-2421</small></div>
Chang AR, Moore BS, Luo JZ, Sartori G, ... Singh G, Mirshahi T
JAMA: 27 Dec 2022; 328:2412-2421 | PMID: 36573973
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<div><h4>Trends in Labor Unionization Among US Health Care Workers, 2009-2021.</h4><i>Ahmed AM, Kadakia K, Ahmed A, Shultz B, Li X</i><br /><b>Importance</b><br />Labor unionization efforts have resurged in the US, and union membership has been shown to improve worker conditions in some industries. However, little is known about labor unionization membership and its economic effects across the health care workforce.<br /><b>Objectives</b><br />To examine the prevalence of labor unionization among health care workers and its associations with pay, noncash benefits, and work hours.<br /><b>Design, setting, and participants</b><br />This cross-sectional study was conducted using data from the Current Population Survey and Annual Social and Economic Supplement from 2009 through 2021. The US nationally representative, population-based household survey allowed for a sample of 14 298 self-identified health care workers (physicians and dentists, advanced practitioners, nurses, therapists, and technicians and support staff).<br /><b>Exposures</b><br />Self-reported membership status or coverage in a labor union.<br /><b>Main outcomes and measures</b><br />Prevalence and trend in labor unionization. Further comparisons included mean weekly pay, noncash benefits (pension or other retirement benefits; employer-sponsored, full premium-covered health insurance; and employer\'s contribution to the worker\'s health insurance plan), and work hours.<br /><b>Results</b><br />The 14 298 respondents (81.5% women; 7.1% Asian, 12.0% Black, 8.5% Hispanic, 70.4% White individuals; mean [SD] age, 41.6 [13.4] years) included 1072 physicians and dentists, 981 advanced practitioners, 4931 nurses, 964 therapists, and 6350 technicians and support staff. After weighting, 13.2% (95% CI, 12.5% to 13.8%) of respondents reported union membership or coverage, with no significant trend from 2009 through 2021 (P = .75). Among health care workers, those who were members of a racial or ethnic minority group (Asian, Black, or Hispanic individuals compared with White individuals) and those living in metropolitan areas were more likely to report being labor unionized. Reported unionization was associated with significantly higher reported weekly earnings ($1165 vs $1042; mean difference, $123 [95% CI, $88 to $157]; P < .001) and higher likelihood of having a pension or other retirement benefits at work (57.9% vs 43.4%; risk ratio [RR], 1.33 [95% CI, 1.26 to 1.41]; P < .001) and having employer-sponsored, full premium-covered health insurance (22.2% vs 16.5%; RR, 1.35 [95% CI, 1.17 to 1.53]; P < .001). Union members reported more work hours (37.4 vs 36.3; mean differences, 1.11 [95% CI, 0.46 to 1.75]; P < .001) per week. White workers reported mean weekly earnings that were significantly more than members of racial and ethnic minority groups among nonunionized workers ($1066 vs $1001; mean difference, $65 [95% CI, $40 to $91]; P < .001), but there was no significant difference between the 2 groups among unionized workers ($1157 vs $1170; mean difference, -$13 [95% CI, -$78 to $52]; P = .70).<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />From 2009 through 2021, labor unionization among US health care workers remained low. Reported union membership or coverage was significantly associated with higher weekly earnings and better noncash benefits but greater number of weekly work hours.<br /><br /><br /><br /><small>JAMA: 27 Dec 2022; 328:2404-2411</small></div>
Ahmed AM, Kadakia K, Ahmed A, Shultz B, Li X
JAMA: 27 Dec 2022; 328:2404-2411 | PMID: 36573974
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<div><h4>Association of Family Income With Morbidity and Mortality Among US Lower-Income Children and Adolescents.</h4><i>Udalova V, Bhatia V, Polyakova M</i><br /><b>Importance</b><br />Family income is known to be associated with children\'s health; the association may be particularly pronounced among lower-income children in the US, who tend to have more limited access to health resources than their higher-income peers.<br /><b>Objective</b><br />To investigate the association of family income with claims-based measures of morbidity and mortality among children and adolescents in lower-income families in the US enrolled in Medicaid or the Children\'s Health Insurance Program.<br /><b>Design, setting, and participants</b><br />This cross-sectional analysis included 795 000 participants aged 5 to 17 years enrolled in Medicaid (Medicaid Analytic eXtract claims, 2011-2012) living in families with income below 200% of the federal poverty threshold (American Community Survey, 2008-2013). Follow-up ended in December 2021.<br /><b>Exposures</b><br />Family income relative to the federal poverty threshold.<br /><b>Main outcomes and measures</b><br />Record of International Classification of Diseases, Ninth Revision codes for an infection, mental health disorder, injury, asthma, anemia, or substance use disorder and death record within 10 years of observation (Social Security Administration death records through 2021).<br /><b>Results</b><br />Among 795 000 individuals in the sample (all statistics weighted: mean [SD] income-to-poverty ratio, 90% [53%]; mean [SD] age, 10.6 [3.9] years; 56% aged 10 to 17 years), 33% had a diagnosed infection, 13% had a mental health disorder, 6% had an injury, 5% had asthma, 2% had anemia, 1% had a substance use disorder, and 0.6% died between 2011 and 2021, with the mean (SD) age at death of 19.8 (4.2) years. For those aged 5 to 9 years, higher family income was associated with lower adjusted prevalence of all outcomes, except mortality: children in families with an additional 100% income relative to the federal poverty threshold had 2.3 (95% CI, 1.8-2.9) percentage points fewer infections, 1.9 (95% CI, 1.5-2.2) percentage points fewer mental health diagnoses, 0.7 (95% CI, 0.5-0.8) percentage points fewer injuries, 0.3 (95% CI, 0.09-0.5) percentage points less asthma, 0.2 (95% CI, 0.08-0.3) percentage points less anemia, and 0.06 (95% CI, 0.03-0.09) percentage points fewer substance use disorder diagnoses. Except for injury and anemia, the associations were more pronounced among those aged 10 to 17 years than those 5 to 9 years (P for interaction <.05). For those aged 10 to 17 years, an additional 100% income relative to the federal poverty threshold was associated with a lower 10-year mortality rate by 0.18 (95% CI, 0.12-0.25) percentage points.<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />Among children and adolescents in the US aged 5 to 17 years with family income under 200% of the federal poverty threshold who accessed health care through Medicaid or the Children\'s Health Insurance Program, higher family income was significantly associated with a lower prevalence of diagnosed infections, mental health disorders, injury, asthma, anemia, and substance use disorders and lower 10-year mortality. Further research is needed to understand whether these associations are causal.<br /><br /><br /><br /><small>JAMA: 27 Dec 2022; 328:2422-2430</small></div>
Udalova V, Bhatia V, Polyakova M
JAMA: 27 Dec 2022; 328:2422-2430 | PMID: 36573975
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<div><h4>Effect of a Biopsychosocial Intervention or Postural Therapy on Disability and Health Care Spending Among Patients With Acute and Subacute Spine Pain: The SPINE CARE Randomized Clinical Trial.</h4><i>Choudhry NK, Fifer S, Fontanet CP, Archer KR, ... Carr AL, MacDonald J</i><br /><b>Importance</b><br />Low back and neck pain are often self-limited, but health care spending remains high.<br /><b>Objective</b><br />To evaluate the effects of 2 interventions that emphasize noninvasive care for spine pain.<br /><b>Design, setting, and participants</b><br />Pragmatic, cluster, randomized clinical trial conducted at 33 centers in the US that enrolled 2971 participants with neck or back pain of 3 months\' duration or less (enrollment, June 2017 to March 2020; final follow-up, March 2021).<br /><b>Interventions</b><br />Participants were randomized at the clinic-level to (1) usual care (n = 992); (2) a risk-stratified, multidisciplinary intervention (the identify, coordinate, and enhance [ICE] care model that combines physical therapy, health coach counseling, and consultation from a specialist in pain medicine or rehabilitation) (n = 829); or (3) individualized postural therapy (IPT), a postural therapy approach that combines physical therapy with building self-efficacy and self-management (n = 1150).<br /><b>Main outcomes and measures</b><br />The primary outcomes were change in Oswestry Disability Index (ODI) score at 3 months (range, 0 [best] to 100 [worst]; minimal clinically important difference, 6) and spine-related health care spending at 1 year. A 2-sided significance threshold of .025 was used to define statistical significance.<br /><b>Results</b><br />Among 2971 participants randomized (mean age, 51.7 years; 1792 women [60.3%]), 2733 (92%) finished the trial. Between baseline and 3-month follow-up, mean ODI scores changed from 31.2 to 15.4 for ICE, from 29.3 to 15.4 for IPT, and from 28.9 to 19.5 for usual care. At 3-month follow-up, absolute differences compared with usual care were -5.8 (95% CI, -7.7 to -3.9; P < .001) for ICE and -4.3 (95% CI, -5.9 to -2.6; P < .001) for IPT. Mean 12-month spending was $1448, $2528, and $1587 in the ICE, IPT, and usual care groups, respectively. Differences in spending compared with usual care were -$139 (risk ratio, 0.93 [95% CI, 0.87 to 0.997]; P = .04) for ICE and $941 (risk ratio, 1.40 [95% CI, 1.35 to 1.45]; P < .001) for IPT.<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />Among patients with acute or subacute spine pain, a multidisciplinary biopsychosocial intervention or an individualized postural therapy intervention, each compared with usual care, resulted in small but statistically significant reductions in pain-related disability at 3 months. However, compared with usual care, the biopsychosocial intervention resulted in no significant difference in spine-related health care spending and the postural therapy intervention resulted in significantly greater spine-related health care spending at 1 year.<br /><b>Trial registration</b><br />ClinicalTrials.gov Identifier: NCT03083886.<br /><br /><br /><br /><small>JAMA: 20 Dec 2022; 328:2334-2344</small></div>
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<div><h4>Effect of Pessary vs Surgery on Patient-Reported Improvement in Patients With Symptomatic Pelvic Organ Prolapse: A Randomized Clinical Trial.</h4><i>van der Vaart LR, Vollebregt A, Milani AL, Lagro-Janssen AL, ... Roovers JWR, van der Vaart CH</i><br /><b>Importance</b><br />Pelvic organ prolapse is a prevalent condition among women that negatively affects their quality of life. With increasing life expectancy, the global need for cost-effective care for women with pelvic organ prolapse will continue to increase.<br /><b>Objective</b><br />To investigate whether treatment with a pessary is noninferior to surgery among patients with symptomatic pelvic organ prolapse.<br /><b>Design, setting, and participants</b><br />The PEOPLE project was a noninferiority randomized clinical trial conducted in 21 participating hospitals in the Netherlands. A total of 1605 women with symptomatic stage 2 or greater pelvic organ prolapse were requested to participate between March 2015 through November 2019; 440 gave informed consent. Final 24-month follow-up ended at June 30, 2022.<br /><b>Interventions</b><br />Two hundred eighteen participants were randomized to receive pessary treatment and 222 to surgery.<br /><b>Main outcomes and measures</b><br />The primary outcome was subjective patient-reported improvement at 24 months, measured with the Patient Global Impression of Improvement scale, a 7-point Likert scale ranging from very much better to very much worse. This scale was dichotomized as successful, defined as much better or very much better, vs nonsuccessful treatment. The noninferiority margin was set at 10 percentage points risk difference. Data of crossover between therapies and adverse events were captured.<br /><b>Results</b><br />Among 440 patients who were randomized (mean [SD] age, 64.7 [9.29] years), 173 (79.3%) in the pessary group and 162 (73.3%) in the surgery group completed the trial at 24 months. In the population, analyzed as randomized, subjective improvement was reported by 132 of 173 (76.3%) in the pessary group vs 132 of 162 (81.5%) in the surgery group (risk difference, -6.1% [1-sided 95% CI, -12.7 to ∞]; P value for noninferiority, .16). The per-protocol analysis showed a similar result for subjective improvement with 52 of 74 (70.3%) in the pessary group vs 125 of 150 (83.3%) in the surgery group (risk difference, -13.1% [1-sided 95% CI, -23.0 to ∞]; P value for noninferiority, .69). Crossover from pessary to surgery occurred among 118 of 218 (54.1%) participants. The most common adverse event among pessary users was discomfort (42.7%) vs urinary tract infection (9%) following surgery.<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />Among patients with symptomatic pelvic organ prolapse, an initial strategy of pessary therapy, compared with surgery, did not meet criteria for noninferiority with regard to patient-reported improvement at 24 months. Interpretation is limited by loss to follow-up and the large amount of participant crossover from pessary therapy to surgery.<br /><b>Trial registration</b><br />Netherlands Trial Register Identifier: NTR4883.<br /><br /><br /><br /><small>JAMA: 20 Dec 2022; 328:2312-2323</small></div>
van der Vaart LR, Vollebregt A, Milani AL, Lagro-Janssen AL, ... Roovers JWR, van der Vaart CH
JAMA: 20 Dec 2022; 328:2312-2323 | PMID: 36538310
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<div><h4>Effect of a Community Health Worker-Delivered Personal Sound Amplification Device on Self-Perceived Communication Function in Older Adults With Hearing Loss: A Randomized Clinical Trial.</h4><i>Nieman CL, Betz J, Garcia Morales EE, Suen JJ, ... Szanton SL, Lin FR</i><br /><b>Importance</b><br />Age-related hearing loss that impairs daily communication is associated with adverse health outcomes, but use of hearing aids by older adults is low and disparities exist.<br /><b>Objective</b><br />To test whether an affordable, accessible hearing care intervention, delivered by community health workers using over-the-counter hearing technology, could improve self-perceived communication function among older adults with hearing loss compared with a wait-list control.<br /><b>Design, setting, and participants</b><br />Open-label randomized clinical trial conducted between April 2018 and October 2019 with 3-month data collection completed in June 2020. The trial took place at 13 community sites, including affordable independent housing complexes (n = 10), senior centers (n = 2), and an older adult social club (n = 1) in Baltimore, Maryland. A total of 151 participants aged 60 years or older with hearing loss were randomized.<br /><b>Interventions</b><br />Participants were randomized to receive a community health worker-delivered hearing care intervention (n = 78) or to a wait-list control group (n = 73). The 2-hour intervention consisted of fitting a low-cost amplification device and instruction.<br /><b>Main outcomes and measures</b><br />The primary outcome was change in self-perceived communication function (Hearing Handicap Inventory for the Elderly-Screening Version [HHIE-S]; score range, 0-40; higher scores indicate poorer function) from baseline to 3 months postrandomization. The average treatment effect was estimated using the doubly robust weighted least squares estimator, which uses an outcome regression model weighted by the inverse probability of attrition to account for baseline covariate imbalance and missing data.<br /><b>Results</b><br />Among 151 participants randomized (mean age, 76.7 [SD, 8.0] years; 101 [67.8%] women; 65 [43%] self-identified as African American; 96 [63.6%] with low income [<$25 000 annual household income]), 136 (90.1%) completed 3-month follow-up for the primary outcome. In the intervention group, 90.5% completed the intervention session and reported at least 1 hour of daily amplification use at 3 months postrandomization. Mean scores for the HHIE-S were 21.7 (SD, 9.4) at baseline and 7.9 (SD, 9.2) at 3 months (change of -13.2 [SD, 10.3]) in the intervention group, and 20.1 (SD, 10.1) at baseline and 21 (SD, 9.1) at 3 months (change of 0.6 [SD, 7.1]) in the control group. Self-perceived communication function significantly improved in the intervention group compared with the control group, with an estimated average treatment effect of the intervention of a -12.98-point HHIE-S change (95% CI, -15.51 to -10.42). No study-related adverse events were reported.<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />Among older adults with hearing loss, a community health worker-delivered personal sound amplification device intervention, compared with a wait-list control, significantly improved self-perceived communication function at 3 months. Findings are limited by the absence of a sham control, and further research is needed to understand effectiveness compared with other types of care delivery models and amplification devices.<br /><b>Trial registration</b><br />ClinicalTrials.gov Identifier: NCT03442296.<br /><br /><br /><br /><small>JAMA: 20 Dec 2022; 328:2324-2333</small></div>
Nieman CL, Betz J, Garcia Morales EE, Suen JJ, ... Szanton SL, Lin FR
JAMA: 20 Dec 2022; 328:2324-2333 | PMID: 36538311
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<div><h4>Long-term (180-Day) Outcomes in Critically Ill Patients With COVID-19 in the REMAP-CAP Randomized Clinical Trial.</h4><i>Writing Committee for the REMAP-CAP Investigators, Higgins AM, Berry LR, Lorenzi E, ... Webb SA, Lawler PR</i><br /><b>Importance</b><br />The longer-term effects of therapies for the treatment of critically ill patients with COVID-19 are unknown.<br /><b>Objective</b><br />To determine the effect of multiple interventions for critically ill adults with COVID-19 on longer-term outcomes.<br /><b>Design, setting, and participants</b><br />Prespecified secondary analysis of an ongoing adaptive platform trial (REMAP-CAP) testing interventions within multiple therapeutic domains in which 4869 critically ill adult patients with COVID-19 were enrolled between March 9, 2020, and June 22, 2021, from 197 sites in 14 countries. The final 180-day follow-up was completed on March 2, 2022.<br /><b>Interventions</b><br />Patients were randomized to receive 1 or more interventions within 6 treatment domains: immune modulators (n = 2274), convalescent plasma (n = 2011), antiplatelet therapy (n = 1557), anticoagulation (n = 1033), antivirals (n = 726), and corticosteroids (n = 401).<br /><b>Main outcomes and measures</b><br />The main outcome was survival through day 180, analyzed using a bayesian piecewise exponential model. A hazard ratio (HR) less than 1 represented improved survival (superiority), while an HR greater than 1 represented worsened survival (harm); futility was represented by a relative improvement less than 20% in outcome, shown by an HR greater than 0.83.<br /><b>Results</b><br />Among 4869 randomized patients (mean age, 59.3 years; 1537 [32.1%] women), 4107 (84.3%) had known vital status and 2590 (63.1%) were alive at day 180. IL-6 receptor antagonists had a greater than 99.9% probability of improving 6-month survival (adjusted HR, 0.74 [95% credible interval {CrI}, 0.61-0.90]) and antiplatelet agents had a 95% probability of improving 6-month survival (adjusted HR, 0.85 [95% CrI, 0.71-1.03]) compared with the control, while the probability of trial-defined statistical futility (HR >0.83) was high for therapeutic anticoagulation (99.9%; HR, 1.13 [95% CrI, 0.93-1.42]), convalescent plasma (99.2%; HR, 0.99 [95% CrI, 0.86-1.14]), and lopinavir-ritonavir (96.6%; HR, 1.06 [95% CrI, 0.82-1.38]) and the probabilities of harm from hydroxychloroquine (96.9%; HR, 1.51 [95% CrI, 0.98-2.29]) and the combination of lopinavir-ritonavir and hydroxychloroquine (96.8%; HR, 1.61 [95% CrI, 0.97-2.67]) were high. The corticosteroid domain was stopped early prior to reaching a predefined statistical trigger; there was a 57.1% to 61.6% probability of improving 6-month survival across varying hydrocortisone dosing strategies.<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />Among critically ill patients with COVID-19 randomized to receive 1 or more therapeutic interventions, treatment with an IL-6 receptor antagonist had a greater than 99.9% probability of improved 180-day mortality compared with patients randomized to the control, and treatment with an antiplatelet had a 95.0% probability of improved 180-day mortality compared with patients randomized to the control. Overall, when considered with previously reported short-term results, the findings indicate that initial in-hospital treatment effects were consistent for most therapies through 6 months.<br /><br /><br /><br /><small>JAMA: 16 Dec 2022; epub ahead of print</small></div>
Writing Committee for the REMAP-CAP Investigators, Higgins AM, Berry LR, Lorenzi E, ... Webb SA, Lawler PR
JAMA: 16 Dec 2022; epub ahead of print | PMID: 36525245
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<div><h4>Guidelines for Reporting Outcomes in Trial Protocols: The SPIRIT-Outcomes 2022 Extension.</h4><i>Butcher NJ, Monsour A, Mew EJ, Chan AW, ... Ungar WJ, Offringa M</i><br /><b>Importance</b><br />Complete information in a trial protocol regarding study outcomes is crucial for obtaining regulatory approvals, ensuring standardized trial conduct, reducing research waste, and providing transparency of methods to facilitate trial replication, critical appraisal, accurate reporting and interpretation of trial results, and knowledge synthesis. However, recommendations on what outcome-specific information should be included are diverse and inconsistent. To improve reporting practices promoting transparent and reproducible outcome selection, assessment, and analysis, a need for specific and harmonized guidance as to what outcome-specific information should be addressed in clinical trial protocols exists.<br /><b>Objective</b><br />To develop harmonized, evidence- and consensus-based standards for describing outcomes in clinical trial protocols through integration with the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) 2013 statement.<br /><b>Evidence review</b><br />Using the Enhancing the Quality and Transparency of Health Research (EQUATOR) methodological framework, the SPIRIT-Outcomes 2022 extension of the SPIRIT 2013 statement was developed by (1) generation and evaluation of candidate outcome reporting items via consultation with experts and a scoping review of existing guidance for reporting trial outcomes (published within the 10 years prior to March 19, 2018) identified through expert solicitation, electronic database searches of MEDLINE and the Cochrane Methodology Register, gray literature searches, and reference list searches; (2) a 3-round international Delphi voting process (November 2018-February 2019) completed by 124 panelists from 22 countries to rate and identify additional items; and (3) an in-person consensus meeting (April 9-10, 2019) attended by 25 panelists to identify essential items for outcome-specific reporting to be addressed in clinical trial protocols.<br /><b>Findings</b><br />The scoping review and consultation with experts identified 108 recommendations relevant to outcome-specific reporting to be addressed in trial protocols, the majority (72%) of which were not included in the SPIRIT 2013 statement. All recommendations were consolidated into 56 items for Delphi voting; after the Delphi survey process, 19 items met criteria for further evaluation at the consensus meeting and possible inclusion in the SPIRIT-Outcomes 2022 extension. The discussions during and after the consensus meeting yielded 9 items that elaborate on the SPIRIT 2013 statement checklist items and are related to completely defining and justifying the choice of primary, secondary, and other outcomes (SPIRIT 2013 statement checklist item 12) prospectively in the trial protocol, defining and justifying the target difference between treatment groups for the primary outcome used in the sample size calculations (SPIRIT 2013 statement checklist item 14), describing the responsiveness of the study instruments used to assess the outcome and providing details on the outcome assessors (SPIRIT 2013 statement checklist item 18a), and describing any planned methods to account for multiplicity relating to the analyses or interpretation of the results (SPIRIT 2013 statement checklist item 20a).<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />This SPIRIT-Outcomes 2022 extension of the SPIRIT 2013 statement provides 9 outcome-specific items that should be addressed in all trial protocols and may help increase trial utility, replicability, and transparency and may minimize the risk of selective nonreporting of trial results.<br /><br /><br /><br /><small>JAMA: 13 Dec 2022; epub ahead of print</small></div>
Butcher NJ, Monsour A, Mew EJ, Chan AW, ... Ungar WJ, Offringa M
JAMA: 13 Dec 2022; epub ahead of print | PMID: 36512367
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<div><h4>Guidelines for Reporting Outcomes in Trial Reports: The CONSORT-Outcomes 2022 Extension.</h4><i>Butcher NJ, Monsour A, Mew EJ, Chan AW, ... Ungar WJ, Offringa M</i><br /><b>Importance</b><br />Clinicians, patients, and policy makers rely on published results from clinical trials to help make evidence-informed decisions. To critically evaluate and use trial results, readers require complete and transparent information regarding what was planned, done, and found. Specific and harmonized guidance as to what outcome-specific information should be reported in publications of clinical trials is needed to reduce deficient reporting practices that obscure issues with outcome selection, assessment, and analysis.<br /><b>Objective</b><br />To develop harmonized, evidence- and consensus-based standards for reporting outcomes in clinical trial reports through integration with the Consolidated Standards of Reporting Trials (CONSORT) 2010 statement.<br /><b>Evidence review</b><br />Using the Enhancing the Quality and Transparency of Health Research (EQUATOR) methodological framework, the CONSORT-Outcomes 2022 extension of the CONSORT 2010 statement was developed by (1) generation and evaluation of candidate outcome reporting items via consultation with experts and a scoping review of existing guidance for reporting trial outcomes (published within the 10 years prior to March 19, 2018) identified through expert solicitation, electronic database searches of MEDLINE and the Cochrane Methodology Register, gray literature searches, and reference list searches; (2) a 3-round international Delphi voting process (November 2018-February 2019) completed by 124 panelists from 22 countries to rate and identify additional items; and (3) an in-person consensus meeting (April 9-10, 2019) attended by 25 panelists to identify essential items for the reporting of outcomes in clinical trial reports.<br /><b>Findings</b><br />The scoping review and consultation with experts identified 128 recommendations relevant to reporting outcomes in trial reports, the majority (83%) of which were not included in the CONSORT 2010 statement. All recommendations were consolidated into 64 items for Delphi voting; after the Delphi survey process, 30 items met criteria for further evaluation at the consensus meeting and possible inclusion in the CONSORT-Outcomes 2022 extension. The discussions during and after the consensus meeting yielded 17 items that elaborate on the CONSORT 2010 statement checklist items and are related to completely defining and justifying the trial outcomes, including how and when they were assessed (CONSORT 2010 statement checklist item 6a), defining and justifying the target difference between treatment groups during sample size calculations (CONSORT 2010 statement checklist item 7a), describing the statistical methods used to compare groups for the primary and secondary outcomes (CONSORT 2010 statement checklist item 12a), and describing the prespecified analyses and any outcome analyses not prespecified (CONSORT 2010 statement checklist item 18).<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />This CONSORT-Outcomes 2022 extension of the CONSORT 2010 statement provides 17 outcome-specific items that should be addressed in all published clinical trial reports and may help increase trial utility, replicability, and transparency and may minimize the risk of selective nonreporting of trial results.<br /><br /><br /><br /><small>JAMA: 13 Dec 2022; 328:2252-2264</small></div>
Butcher NJ, Monsour A, Mew EJ, Chan AW, ... Ungar WJ, Offringa M
JAMA: 13 Dec 2022; 328:2252-2264 | PMID: 36511921
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<div><h4>Effect of Diet and Exercise on Knee Pain in Patients With Osteoarthritis and Overweight or Obesity: A Randomized Clinical Trial.</h4><i>Messier SP, Beavers DP, Queen K, Mihalko SL, ... Jordan JM, Callahan LF</i><br /><b>Importance</b><br />Some weight loss and exercise programs that have been successful in academic center-based trials have not been evaluated in community settings.<br /><b>Objective</b><br />To determine whether adaptation of a diet and exercise intervention to community settings resulted in a statistically significant reduction in pain, compared with an attention control group, at 18-month follow-up.<br /><b>Design, setting, and participants</b><br />Assessor-blinded randomized clinical trial conducted in community settings in urban and rural counties in North Carolina. Patients were men and women aged 50 years or older with knee osteoarthritis and overweight or obesity (body mass index ≥27). Enrollment (N = 823) occurred between May 2016 and August 2019, with follow-up ending in April 2021.<br /><b>Interventions</b><br />Patients were randomly assigned to either a diet and exercise intervention (n = 414) or an attention control (n = 409) group for 18 months.<br /><b>Main outcomes and measures</b><br />The primary outcome was the between-group difference in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) knee pain score (range, 0 [none] to 20 [severe]; minimum clinically important difference, 1.6) over 18 months, tested using a repeated-measures mixed linear model with adjustments for covariates. There were 7 secondary outcomes including body weight.<br /><b>Results</b><br />Among the 823 randomized patients (mean age, 64.6 years; 637 [77%] women), 658 (80%) completed the trial. At 18-month follow-up, the adjusted mean WOMAC pain score was 5.0 in the diet and exercise group (n = 329) compared with 5.5 in the attention control group (n = 316) (adjusted difference, -0.6; 95% CI, -1.0 to -0.1; P = .02). Of 7 secondary outcomes, 5 were significantly better in the intervention group compared with control. The mean change in unadjusted 18-month body weight for patients with available data was -7.7 kg (8%) in the diet and exercise group (n = 289) and -1.7 kg (2%) in the attention control group (n = 273) (mean difference, -6.0 kg; 95% CI, -7.3 kg to -4.7 kg). There were 169 serious adverse events; none were definitely related to the study. There were 729 adverse events; 32 (4%) were definitely related to the study, including 10 body injuries (9 in diet and exercise; 1 in attention control), 7 muscle strains (6 in diet and exercise; 1 in attention control), and 6 trip/fall events (all 6 in diet and exercise).<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />Among patients with knee osteoarthritis and overweight or obesity, diet and exercise compared with an attention control led to a statistically significant but small difference in knee pain over 18 months. The magnitude of the difference in pain between groups is of uncertain clinical importance.<br /><b>Trial registration</b><br />ClinicalTrials.gov Identifier: NCT02577549.<br /><br /><br /><br /><small>JAMA: 13 Dec 2022; 328:2242-2251</small></div>
Messier SP, Beavers DP, Queen K, Mihalko SL, ... Jordan JM, Callahan LF
JAMA: 13 Dec 2022; 328:2242-2251 | PMID: 36511925
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<div><h4>Effects of Mindfulness Training and Exercise on Cognitive Function in Older Adults: A Randomized Clinical Trial.</h4><i>Lenze EJ, Voegtle M, Miller JP, Ances BM, ... Yingling MD, Wetherell JL</i><br /><b>Importance</b><br />Episodic memory and executive function are essential aspects of cognitive functioning that decline with aging. This decline may be ameliorable with lifestyle interventions.<br /><b>Objective</b><br />To determine whether mindfulness-based stress reduction (MBSR), exercise, or a combination of both improve cognitive function in older adults.<br /><b>Design, setting, and participants</b><br />This 2 × 2 factorial randomized clinical trial was conducted at 2 US sites (Washington University in St Louis and University of California, San Diego). A total of 585 older adults (aged 65-84 y) with subjective cognitive concerns, but not dementia, were randomized (enrollment from November 19, 2015, to January 23, 2019; final follow-up on March 16, 2020).<br /><b>Interventions</b><br />Participants were randomized to undergo the following interventions: MBSR with a target of 60 minutes daily of meditation (n = 150); exercise with aerobic, strength, and functional components with a target of at least 300 minutes weekly (n = 138); combined MBSR and exercise (n = 144); or a health education control group (n = 153). Interventions lasted 18 months and consisted of group-based classes and home practice.<br /><b>Main outcomes and measures</b><br />The 2 primary outcomes were composites of episodic memory and executive function (standardized to a mean [SD] of 0 [1]; higher composite scores indicate better cognitive performance) from neuropsychological testing; the primary end point was 6 months and the secondary end point was 18 months. There were 5 reported secondary outcomes: hippocampal volume and dorsolateral prefrontal cortex thickness and surface area from structural magnetic resonance imaging and functional cognitive capacity and self-reported cognitive concerns.<br /><b>Results</b><br />Among 585 randomized participants (mean age, 71.5 years; 424 [72.5%] women), 568 (97.1%) completed 6 months in the trial and 475 (81.2%) completed 18 months. At 6 months, there was no significant effect of mindfulness training or exercise on episodic memory (MBSR vs no MBSR: 0.44 vs 0.48; mean difference, -0.04 points [95% CI, -0.15 to 0.07]; P = .50; exercise vs no exercise: 0.49 vs 0.42; difference, 0.07 [95% CI, -0.04 to 0.17]; P = .23) or executive function (MBSR vs no MBSR: 0.39 vs 0.31; mean difference, 0.08 points [95% CI, -0.02 to 0.19]; P = .12; exercise vs no exercise: 0.39 vs 0.32; difference, 0.07 [95% CI, -0.03 to 0.18]; P = .17) and there were no intervention effects at the secondary end point of 18 months. There was no significant interaction between mindfulness training and exercise (P = .93 for memory and P = .29 for executive function) at 6 months. Of the 5 prespecified secondary outcomes, none showed a significant improvement with either intervention compared with those not receiving the intervention.<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />Among older adults with subjective cognitive concerns, mindfulness training, exercise, or both did not result in significant differences in improvement in episodic memory or executive function at 6 months. The findings do not support the use of these interventions for improving cognition in older adults with subjective cognitive concerns.<br /><b>Trial registration</b><br />ClinicalTrials.gov Identifier: NCT02665481.<br /><br /><br /><br /><small>JAMA: 13 Dec 2022; 328:2218-2229</small></div>
Lenze EJ, Voegtle M, Miller JP, Ances BM, ... Yingling MD, Wetherell JL
JAMA: 13 Dec 2022; 328:2218-2229 | PMID: 36511926
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<div><h4>Effect of a Remotely Delivered Self-directed Behavioral Intervention on Body Weight and Physical Health Status Among Adults With Obesity: The D-ELITE Randomized Clinical Trial.</h4><i>Hoerster KD, Hunter-Merrill R, Nguyen T, Rise P, ... Au DH, Ma J</i><br /><b>Importance</b><br />The effectiveness of remotely delivered, self-directed, weight loss programs in routine clinical practice is largely unknown.<br /><b>Objective</b><br />To test whether a self-directed, remotely administered behavioral lifestyle intervention improves weight and self-reported general health status compared with usual care.<br /><b>Design, setting, and participants</b><br />In this randomized clinical trial, 511 adults with a body mass index (BMI) of 30 or more and less than 45 (based on electronic health record [EHR] weight and height), were enrolled from 30 Veterans Health Administration (VHA) sites between February 15, 2018, and December 18, 2018 (final follow-up February 18, 2021).<br /><b>Interventions</b><br />Participants were randomly assigned to the intervention group (n = 254) or the control group (n = 257). Both received usual care. Participants randomized to the intervention received Diabetes Prevention Program-based self-directed videos, handouts, and coaching messages via an online platform or US mail for 12 months.<br /><b>Main outcomes and measures</b><br />Coprimary outcomes were weight measured in primary care and recorded in the EHR and self-reported general health status using the Medical Outcomes Study 12-Item Short Form Health Survey (SF-12) physical component score (PCS; higher scores are better [range, 0-100]) at the 12-month follow-up. The between-group minimal clinically important differences are 3 kg for weight and 5 points for the SF-12 PCS. Linear mixed models used weights and SF-12 PCS measured at either time point, with participants analyzed according to randomization assignment. Statistical significance for each coprimary outcome was based on a 2-sided α level of .025.<br /><b>Results</b><br />Among 511 participants randomized (mean age, 57.4 [SD, 13.9] years; 231 female [45%]), 429 (84.0%) had EHR-based weights and 410 (80.2%) had SF-12 PCS data at 12 months. The unadjusted mean weight at 12 months declined from 102.7 kg to 99.8 kg in the intervention group compared with 101.9 kg to 101.0 kg in the control group (adjusted between-group mean difference, -1.93 [97.5% CI, -3.24 to -0.61]; P = .001). At 12 months, the unadjusted mean SF-12 PCS scores declined from 44.8 to 44.3 among intervention participants compared with 44.5 to 43.2 among control participants (adjusted between-group mean difference, intervention minus control, 0.69 [97.5% CI, -1.11 to 2.49]; P = .39). Cardiovascular events represented the highest percentage of serious adverse events, accounting for 25% of events in the intervention group and 35% in the control group.<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />Among adults with obesity, a remotely delivered self-directed, behavioral lifestyle intervention, compared with usual care, resulted in statistically significantly greater weight loss at 12 months, although the difference was not clinically important. There was no significant difference in self-reported general physical health status at 12 months.<br /><b>Trial registration</b><br />ClinicalTrials.gov Identifier: NCT03260140.<br /><br /><br /><br /><small>JAMA: 13 Dec 2022; 328:2230-2241</small></div>
Hoerster KD, Hunter-Merrill R, Nguyen T, Rise P, ... Au DH, Ma J
JAMA: 13 Dec 2022; 328:2230-2241 | PMID: 36511927
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<div><h4>Progress and Challenges in Bacterial Meningitis: A Review.</h4><i>Hasbun R</i><br /><b>Importance</b><br />Bacterial meningitis is a worldwide health problem, with incidence rates ranging from approximately 0.9 per 100 000 individuals per year in high-income countries to 80 per 100 000 individuals per year in low-income countries. In low-income countries, bacterial meningitis has a mortality rate of up to 54%. Up to 24% of those who survive develop chronic neurological sequelae, such as hearing loss or focal neurological deficits.<br /><b>Observations</b><br />Streptococcus pneumoniae causes about 72% and Neisseria meningitidis causes about 11% of cases of bacterial meningitis in people older than 16 years. Escherichia coli and Streptococcus agalactiae cause about 35% of cases of early-onset neonatal meningitis. In adults, risk factors for bacterial meningitis include older age and immunosuppressive conditions. The most common symptoms are headache (84%), fever (74%), stiff neck (74%), altered mental status (median [IQR] Glasgow Coma Scale score of 11 [9-14] on a scale ranging from 3-15), and nausea (62%). Brain imaging should be performed before lumbar puncture if patients present with altered mental status, focal neurological deficits, papilledema, or history of immunocompromising conditions or central nervous system disease. Bacterial meningitis should be suspected if any of the following are present on admission: serum leukocytes greater than 10.0 ×109/L, cerebrospinal fluid (CSF) leukocytes greater than 2000/μL, CSF granulocytes greater than 1180/μL, CSF protein greater than 2.2 g/L, CSF glucose less than 34.23 mg/dL, or fever. A positive Gram stain result for bacteria is diagnostic, but the sensitivity of a positive Gram stain result for bacterial meningitis ranges from 50% to 90%. In countries in which the prevalence of ceftriaxone-resistant Streptococcus pneumoniae exceeds 1%, vancomycin and ceftriaxone are the empirical antibiotics of choice, with the addition of ampicillin in neonates, older patients, and immunocompromised patients. Adjunctive dexamethasone should be used in patients with bacterial meningitis but stopped if Listeria monocytogenes is confirmed.<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />Bacterial meningitis affects approximately 0.9 per 100 000 individuals to 80 per 100 000 individuals per year and has a mortality rate as high as 54%. First-line therapy is prompt empirical intravenous antibiotic therapy and adjunctive dexamethasone.<br /><br /><br /><br /><small>JAMA: 06 Dec 2022; 328:2147-2154</small></div>
Hasbun R
JAMA: 06 Dec 2022; 328:2147-2154 | PMID: 36472590
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Abstract
<div><h4>Association of Medicare Advantage vs Traditional Medicare With 30-Day Mortality Among Patients With Acute Myocardial Infarction.</h4><i>Landon BE, Anderson TS, Curto VE, Cram P, ... Zaslavsky AM, Ayanian JZ</i><br /><b>Importance</b><br />Medicare Advantage health plans covered 37% of beneficiaries in 2018, and coverage increased to 48% in 2022. Whether Medicare Advantage plans provide similar care for patients presenting with specific clinical conditions is unknown.<br /><b>Objective</b><br />To compare 30-day mortality and treatment for Medicare Advantage and traditional Medicare patients presenting with acute myocardial infarction (MI) from 2009 to 2018.<br /><b>Design, setting, and participants</b><br />Retrospective cohort study that included 557 309 participants with ST-segment elevation [acute] MI (STEMI) and 1 670 193 with non-ST-segment elevation [acute] MI (NSTEMI) presenting to US hospitals from 2009-2018 (date of final follow up, December 31, 2019).<br /><b>Exposures</b><br />Enrollment in Medicare Advantage vs traditional Medicare.<br /><b>Main outcomes and measures</b><br />The primary outcome was adjusted 30-day mortality. Secondary outcomes included age- and sex-adjusted rates of procedure use (catheterization, revascularization), postdischarge medication prescriptions and adherence, and measures of health system performance (intensive care unit [ICU] admission and 30-day readmissions).<br /><b>Results</b><br />The study included a total of 2 227 502 participants, and the mean age in 2018 ranged from 76.9 years (Medicare Advantage STEMI) to 79.3 years (traditional Medicare NSTEMI), with similar proportions of female patients in Medicare Advantage and traditional Medicare (41.4% vs 41.9% for STEMI in 2018). Enrollment in Medicare Advantage vs traditional Medicare was associated with significantly lower adjusted 30-day mortality rates in 2009 (19.1% vs 20.6% for STEMI; difference, -1.5 percentage points [95% CI, -2.2 to -0.7] and 12.0% vs 12.5% for NSTEMI; difference, -0.5 percentage points [95% CI, -0.9% to -0.1%]). By 2018, mortality had declined in all groups, and there were no longer statically significant differences between Medicare Advantage (17.7%) and traditional Medicare (17.8%) for STEMI (difference, 0.0 percentage points [95% CI, -0.7 to 0.6]) or between Medicare Advantage (10.9%) and traditional Medicare (11.1%) for NSTEMI (difference, -0.2 percentage points [95% CI, -0.4 to 0.1]). By 2018, there was no statistically significant difference in standardized 90-day revascularization rates between Medicare Advantage and traditional Medicare. Rates of guideline-recommended medication prescriptions were significantly higher in Medicare Advantage (91.7%) vs traditional Medicare patients (89.0%) who received a statin prescription (difference, 2.7 percentage points [95% CI, 1.2 to 4.2] for 2018 STEMI). Medicare Advantage patients were significantly less likely to be admitted to an ICU than traditional Medicare patients (for 2018 STEMI, 50.3% vs 51.2%; difference, -0.9 percentage points [95% CI, -1.8 to 0.0]) and significantly more likely to be discharged to home rather than to a postacute facility (for 2018 STEMI, 71.5% vs 70.2%; difference, 1.3 percentage points [95% CI, 0.5 to 2.1]). Adjusted 30-day readmission rates were consistently lower in Medicare Advantage than in traditional Medicare (for 2009 STEMI, 13.8% vs 15.2%; difference, -1.3 percentage points [95% CI, -2.0 to -0.6]; and for 2018 STEMI, 11.2% vs 11.9%; difference, 0.6 percentage points [95% CI, -1.5 to 0.0]).<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />Among Medicare beneficiaries with acute MI, enrollment in Medicare Advantage, compared with traditional Medicare, was significantly associated with modestly lower rates of 30-day mortality in 2009, and the difference was no longer statistically significant by 2018. These findings, considered with other outcomes, may provide insight into differences in treatment and outcomes by Medicare insurance type.<br /><br /><br /><br /><small>JAMA: 06 Dec 2022; 328:2126-2135</small></div>
Landon BE, Anderson TS, Curto VE, Cram P, ... Zaslavsky AM, Ayanian JZ
JAMA: 06 Dec 2022; 328:2126-2135 | PMID: 36472594
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<div><h4>Association Between Individual Primary Care Physician Merit-based Incentive Payment System Score and Measures of Process and Patient Outcomes.</h4><i>Bond AM, Schpero WL, Casalino LP, Zhang M, Khullar D</i><br /><b>Importance</b><br />The Medicare Merit-based Incentive Payment System (MIPS) influences reimbursement for hundreds of thousands of US physicians, but little is known about whether program performance accurately captures the quality of care they provide.<br /><b>Objective</b><br />To examine whether primary care physicians\' MIPS scores are associated with performance on process and outcome measures.<br /><b>Design, setting, and participants</b><br />Cross-sectional study of 80 246 US primary care physicians participating in the MIPS program in 2019.<br /><b>Exposures</b><br />MIPS score.<br /><b>Main outcomes and measures</b><br />The association between physician MIPS scores and performance on 5 unadjusted process measures, 6 adjusted outcome measures, and a composite outcome measure.<br /><b>Results</b><br />The study population included 3.4 million patients attributed to 80 246 primary care physicians, including 4773 physicians with low MIPS scores (≤30), 6151 physicians with medium MIPS scores (>30-75), and 69 322 physicians with high MIPS scores (>75). Compared with physicians with high MIPS scores, physicians with low MIPS scores had significantly worse mean performance on 3 of 5 process measures: diabetic eye examinations (56.1% vs 63.2%; difference, -7.1 percentage points [95% CI, -8.0 to -6.2]; P < .001), diabetic HbA1c screening (84.6% vs 89.4%; difference, -4.8 percentage points [95% CI, -5.4 to -4.2]; P < .001), and mammography screening (58.2% vs 70.4%; difference, -12.2 percentage points [95% CI, -13.1 to -11.4]; P < .001) but significantly better mean performance on rates of influenza vaccination (78.0% vs 76.8%; difference, 1.2 percentage points [95% CI, 0.0 to 2.5]; P = .045] and tobacco screening (95.0% vs 94.1%; difference, 0.9 percentage points [95% CI, 0.3 to 1.5]; P = .001). MIPS scores were inconsistently associated with risk-adjusted patient outcomes: compared with physicians with high MIPS scores, physicians with low MIPS scores had significantly better mean performance on 1 outcome (307.6 vs 316.4 emergency department visits per 1000 patients; difference, -8.9 [95% CI, -13.7 to -4.1]; P < .001), worse performance on 1 outcome (255.4 vs 225.2 all-cause hospitalizations per 1000 patients; difference, 30.2 [95% CI, 24.8 to 35.7]; P < .001), and did not have significantly different performance on 4 ambulatory care-sensitive admission outcomes. Nineteen percent of physicians with low MIPS scores had composite outcomes performance in the top quintile, while 21% of physicians with high MIPS scores had outcomes in the bottom quintile. Physicians with low MIPS scores but superior outcomes cared for more medically complex and socially vulnerable patients, compared with physicians with low MIPS scores and poor outcomes.<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />Among US primary care physicians in 2019, MIPS scores were inconsistently associated with performance on process and outcome measures. These findings suggest that the MIPS program may be ineffective at measuring and incentivizing quality improvement among US physicians.<br /><br /><br /><br /><small>JAMA: 06 Dec 2022; 328:2136-2146</small></div>
Bond AM, Schpero WL, Casalino LP, Zhang M, Khullar D
JAMA: 06 Dec 2022; 328:2136-2146 | PMID: 36472595
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<div><h4>Effect of Timing by Endometrial Receptivity Testing vs Standard Timing of Frozen Embryo Transfer on Live Birth in Patients Undergoing In Vitro Fertilization: A Randomized Clinical Trial.</h4><i>Doyle N, Jahandideh S, Hill MJ, Widra EA, Levy M, Devine K</i><br /><b>Importance</b><br />Endometrial receptivity testing is purported to improve live birth following frozen embryo transfer by identifying the optimal embryo transfer time for an individual patient; however, data are conflicting.<br /><b>Objective</b><br />To compare live birth from single euploid frozen embryo transfer according to endometrial receptivity testing vs standardized timing.<br /><b>Design, setting, and participants</b><br />Double-blind, randomized clinical trial at 30 sites within a multicenter private fertility practice in the Eastern US. Enrollment was from May 2018 to September 2020; follow-up concluded in August 2021. Participants underwent in vitro fertilization, preimplantation genetic testing for aneuploidy, endometrial receptivity testing, and frozen embryo transfer. Those with euploid blastocyst(s) and an informative receptivity result were randomized. Exclusion criteria included recurrent pregnancy loss, recurrent implantation failure, surgically aspirated sperm, donor egg(s), and unmitigated anatomic uterine cavity defects.<br /><b>Interventions</b><br />The intervention group (n = 381) underwent receptivity-timed frozen embryo transfer, with adjusted duration of progesterone exposure prior to transfer, if indicated by receptivity testing. The control group (n = 386) underwent transfer at standard timing, regardless of receptivity test results.<br /><b>Main outcomes and measures</b><br />The primary outcome was live birth. There were 3 secondary outcomes, including biochemical pregnancy and clinical pregnancy.<br /><b>Results</b><br />Among 767 participants who were randomized (mean age, 35 years), 755 (98%) completed the trial. All randomized participants were analyzed. The primary outcome of live birth occurred in 58.5% of transfers (223 of 381) in the intervention group vs 61.9% of transfers (239 of 386) in the control group (difference, -3.4% [95% CI, -10.3% to 3.5%]; rate ratio [RR], 0.95 [95% CI, 0.79 to 1.13]; P = .38). There were no significant differences in the intervention vs the control group for the prespecified secondary outcomes, including biochemical pregnancy rate (77.2% vs 79.5%, respectively; difference, -2.3% [95% CI, -8.2% to 3.5%]; RR, 0.97 [95% CI, 0.83 to 1.14]; P = .48) and clinical pregnancy rate (68.8% vs 72.8%, respectively; difference, -4.0% [95% CI, -10.4% to 2.4%]; RR, 0.94 [95% CI, 0.80 to 1.12]; P = .25). There were no reported adverse events.<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />Among patients for whom in vitro fertilization yielded a euploid blastocyst, the use of receptivity testing to guide the timing of frozen embryo transfer, compared with standard timing for transfer, did not significantly improve the rate of live birth. The findings do not support routine use of receptivity testing to guide the timing of embryo transfer during in vitro fertilization.<br /><b>Trial registration</b><br />ClinicalTrials.gov Identifier: NCT03558399.<br /><br /><br /><br /><small>JAMA: 06 Dec 2022; 328:2117-2125</small></div>
Abstract
<div><h4>Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults: 2022 Recommendations of the International Antiviral Society-USA Panel.</h4><i>Gandhi RT, Bedimo R, Hoy JF, Landovitz RJ, ... Jacobsen DM, Saag MS</i><br /><b>Importance</b><br />Recent advances in treatment and prevention of HIV warrant updated recommendations to guide optimal practice.<br /><b>Objective</b><br />Based on a critical evaluation of new data, to provide clinicians with recommendations on use of antiretroviral drugs for the treatment and prevention of HIV, laboratory monitoring, care of people aging with HIV, substance use disorder and HIV, and new challenges in people with HIV, including COVID-19 and monkeypox virus infection.<br /><b>Evidence review</b><br />A panel of volunteer expert physician scientists were appointed to update the 2020 consensus recommendations. Relevant evidence in the literature (PubMed and Embase searches, which initially yielded 7891 unique citations, of which 834 were considered relevant) and studies presented at peer-reviewed scientific conferences between January 2020 and October 2022 were considered.<br /><b>Findings</b><br />Initiation of antiretroviral therapy (ART) is recommended as soon as possible after diagnosis of HIV. Barriers to care should be addressed, including ensuring access to ART and adherence support. Integrase strand transfer inhibitor-containing regimens remain the mainstay of initial therapy. For people who have achieved viral suppression with a daily oral regimen, long-acting injectable therapy with cabotegravir plus rilpivirine given as infrequently as every 2 months is now an option. Weight gain and metabolic complications have been linked to certain antiretroviral medications; novel strategies to ameliorate these complications are needed. Management of comorbidities throughout the life span is increasingly important, because people with HIV are living longer and confronting the health challenges of aging. In addition, management of substance use disorder in people with HIV requires an evidence-based, integrated approach. Options for preexposure prophylaxis include oral medications (tenofovir disoproxil fumarate or tenofovir alafenamide plus emtricitabine) and, for the first time, a long-acting injectable agent, cabotegravir. Recent global health emergencies, like the SARS-CoV-2 pandemic and monkeypox virus outbreak, continue to have a major effect on people with HIV and the delivery of services. To address these and other challenges, an equity-based approach is essential.<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />Advances in treatment and prevention of HIV continue to improve outcomes, but challenges and opportunities remain.<br /><br /><br /><br /><small>JAMA: 01 Dec 2022; epub ahead of print</small></div>
Gandhi RT, Bedimo R, Hoy JF, Landovitz RJ, ... Jacobsen DM, Saag MS
JAMA: 01 Dec 2022; epub ahead of print | PMID: 36454551
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<div><h4>Effect of Regular, Low-Dose, Extended-release Morphine on Chronic Breathlessness in Chronic Obstructive Pulmonary Disease: The BEAMS Randomized Clinical Trial.</h4><i>Ekström M, Ferreira D, Chang S, Louw S, ... Currow DC, Australian National Palliative Care Clinical Studies Collaborative</i><br /><b>Importance</b><br />Chronic breathlessness is common in people with chronic obstructive pulmonary disease (COPD). Regular, low-dose, extended-release morphine may relieve breathlessness, but evidence about its efficacy and dosing is needed.<br /><b>Objective</b><br />To determine the effect of different doses of extended-release morphine on worst breathlessness in people with COPD after 1 week of treatment.<br /><b>Design, setting, and participants</b><br />Multicenter, double-blind, placebo-controlled randomized clinical trial including people with COPD and chronic breathlessness (defined as a modified Medical Research Council score of 3 to 4) conducted at 20 centers in Australia. People were enrolled between September 1, 2016, and November 20, 2019, and followed up through December 26, 2019.<br /><b>Interventions</b><br />People were randomized 1:1:1 to 8 mg/d or 16 mg/d of oral extended-release morphine or placebo during week 1. At the start of weeks 2 and 3, people were randomized 1:1 to 8 mg/d of extended-release morphine, which was added to the prior week\'s dose, or placebo.<br /><b>Main outcomes and measures</b><br />The primary outcome was change in the intensity of worst breathlessness on a numerical rating scale (score range, 0 [none] to 10 [being worst or most intense]) using the mean score at baseline (from days -3 to -1) to the mean score after week 1 of treatment (from days 5 to 7) in the 8 mg/d and 16 mg/d of extended-release morphine groups vs the placebo group. Secondary outcomes included change in daily step count measured using an actigraphy device from baseline (day -1) to the mean step count from week 3 (from days 19 to 21).<br /><b>Results</b><br />Among the 160 people randomized, 156 were included in the primary analyses (median age, 72 years [IQR, 67 to 78 years]; 48% were women) and 138 (88%) completed treatment at week 1 (48 in the 8 mg/d of morphine group, 43 in the 16 mg/d of morphine group, and 47 in the placebo group). The change in the intensity of worst breathlessness at week 1 was not significantly different between the 8 mg/d of morphine group and the placebo group (mean difference, -0.3 [95% CI, -0.9 to 0.4]) or between the 16 mg/d of morphine group and the placebo group (mean difference, -0.3 [95%, CI, -1.0 to 0.4]). At week 3, the secondary outcome of change in mean daily step count was not significantly different between the 8 mg/d of morphine group and the placebo group (mean difference, -1453 [95% CI, -3310 to 405]), between the 16 mg/d of morphine group and the placebo group (mean difference, -1312 [95% CI, -3220 to 596]), between the 24 mg/d of morphine group and the placebo group (mean difference, -692 [95% CI, -2553 to 1170]), or between the 32 mg/d of morphine group and the placebo group (mean difference, -1924 [95% CI, -47 699 to 921]).<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />Among people with COPD and severe chronic breathlessness, daily low-dose, extended-release morphine did not significantly reduce the intensity of worst breathlessness after 1 week of treatment. These findings do not support the use of these doses of extended-release morphine to relieve breathlessness.<br /><b>Trial registration</b><br />ClinicalTrials.gov Identifier: NCT02720822.<br /><br /><br /><br /><small>JAMA: 22 Nov 2022; 328:2022-2032</small></div>
Ekström M, Ferreira D, Chang S, Louw S, ... Currow DC, Australian National Palliative Care Clinical Studies Collaborative
JAMA: 22 Nov 2022; 328:2022-2032 | PMID: 36413230
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<div><h4>Screening for Obstructive Sleep Apnea in Adults: US Preventive Services Task Force Recommendation Statement.</h4><i>US Preventive Services Task Force, Mangione CM, Barry MJ, Nicholson WK, ... Stevermer J, Wong JB</i><br /><b>Importance</b><br />Current prevalence of obstructive sleep apnea (OSA) in the US is not well established; however, based on cohort and survey data, in 2007-2010 the estimated prevalence of at least mild OSA (defined as an apnea-hypoxia index [AHI] ≥5) plus symptoms of daytime sleepiness among adults aged 30 to 70 years was 14% for men and 5% for women, and the estimated prevalence of moderate to severe OSA (defined as AHI ≥15) was 13% for men and 6% for women. Severe OSA is associated with increased all-cause mortality. Other adverse health outcomes associated with untreated OSA include cardiovascular disease and cerebrovascular events, type 2 diabetes, cognitive impairment, decreased quality of life, and motor vehicle crashes.<br /><b>Objective</b><br />To update its 2017 recommendation, the US Preventive Services Task Force (USPSTF) commissioned a systematic review to evaluate the benefits and harms of screening for OSA in adults.<br /><b>Population</b><br />Asymptomatic adults (18 years or older) and adults with unrecognized symptoms of OSA.<br /><b>Evidence assessment</b><br />The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for OSA in the general adult population.<br /><b>Recommendation</b><br />The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for OSA in the general adult population. (I statement).<br /><br /><br /><br /><small>JAMA: 15 Nov 2022; 328:1945-1950</small></div>
US Preventive Services Task Force, Mangione CM, Barry MJ, Nicholson WK, ... Stevermer J, Wong JB
JAMA: 15 Nov 2022; 328:1945-1950 | PMID: 36378202
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<div><h4>Screening for Obstructive Sleep Apnea in Adults: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.</h4><i>Feltner C, Wallace IF, Aymes S, Cook Middleton J, ... Voisin CE, Jonas DE</i><br /><b>Importance</b><br />Obstructive sleep apnea (OSA) is associated with adverse health outcomes.<br /><b>Objective</b><br />To review the evidence on screening for OSA in asymptomatic adults or those with unrecognized OSA symptoms to inform the US Preventive Services Task Force.<br /><b>Data sources</b><br />PubMed/MEDLINE, Cochrane Library, Embase, and trial registries through August 23, 2021; surveillance through September 23, 2022.<br /><b>Study selection</b><br />English-language studies of screening test accuracy, randomized clinical trials (RCTs) of screening or treatment of OSA reporting health outcomes or harms, and systematic reviews of treatment reporting changes in blood pressure and apnea-hypopnea index (AHI) scores.<br /><b>Data extraction and synthesis</b><br />Dual review of abstracts, full-text articles, and study quality. Meta-analysis of intervention trials.<br /><b>Main outcomes and measures</b><br />Test accuracy, excessive daytime sleepiness, sleep-related and general health-related quality of life (QOL), and harms.<br /><b>Results</b><br />Eighty-six studies were included (N = 11 051). No study directly compared screening with no screening. Screening accuracy of the Multivariable Apnea Prediction score followed by unattended home sleep testing for detecting severe OSA syndrome (AHI ≥30 and Epworth Sleepiness Scale [ESS] score >10) measured as the area under the curve in 2 studies (n = 702) was 0.80 (95% CI, 0.78 to 0.82) and 0.83 (95% CI, 0.77 to 0.90). Five studies assessing the accuracy of other screening tools were heterogeneous and results were inconsistent. Compared with inactive control, positive airway pressure was associated with a significant improvement in ESS score from baseline (pooled mean difference, -2.33 [95% CI, -2.75 to -1.90]; 47 trials; n = 7024), sleep-related QOL (standardized mean difference, 0.30 [95% CI, 0.19 to 0.42]; 17 trials; n = 3083), and general health-related QOL measured by the 36-Item Short Form Health Survey (SF-36) mental health component summary score change (pooled mean difference, 2.20 [95% CI, 0.95 to 3.44]; 15 trials; n = 2345) and SF-36 physical health component summary score change (pooled mean difference, 1.53 [95% CI, 0.29 to 2.77]; 13 trials; n = 2031). Use of mandibular advancement devices was also associated with a significantly larger ESS score change compared with controls (pooled mean difference, -1.67 [95% CI, 2.09 to -1.25]; 10 trials; n = 1540). Reporting of other health outcomes was sparse; no included trial found significant benefit associated with treatment on mortality, cardiovascular events, or motor vehicle crashes. In 3 systematic reviews, positive airway pressure was significantly associated with reduced blood pressure; however, the difference was relatively small (2-3 mm Hg).<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />The accuracy and clinical utility of OSA screening tools that could be used in primary care settings were uncertain. Positive airway pressure and mandibular advancement devices reduced ESS score. Trials of positive airway pressure found modest improvement in sleep-related and general health-related QOL but have not established whether treatment reduces mortality or improves most other health outcomes.<br /><br /><br /><br /><small>JAMA: 15 Nov 2022; 328:1951-1971</small></div>
Feltner C, Wallace IF, Aymes S, Cook Middleton J, ... Voisin CE, Jonas DE
JAMA: 15 Nov 2022; 328:1951-1971 | PMID: 36378203
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<div><h4>Development of a Prediction Model for Ascending Aortic Diameter Among Asymptomatic Individuals.</h4><i>Pirruccello JP, Lin H, Khurshid S, Nekoui M, ... Lindsay ME, Ellinor PT</i><br /><b>Importance</b><br />Ascending thoracic aortic disease is an important cause of sudden death in the US, yet most aortic aneurysms are identified incidentally.<br /><b>Objective</b><br />To develop and validate a clinical score to estimate ascending aortic diameter.<br /><b>Design, setting, and participants</b><br />Using an ongoing magnetic resonance imaging substudy of the UK Biobank cohort study, which had enrolled participants from 2006 through 2010, score derivation was performed in 30 018 participants and internal validation in an additional 6681. External validation was performed in 1367 participants from the Framingham Heart Study (FHS) offspring cohort who had undergone computed tomography from 2002 through 2005, and in 50 768 individuals who had undergone transthoracic echocardiography in the Community Care Cohort Project, a retrospective hospital-based cohort of longitudinal primary care patients in the Mass General Brigham (MGB) network between 2001-2018.<br /><b>Exposures</b><br />Demographic and clinical variables (11 covariates that would not independently prompt thoracic imaging).<br /><b>Main outcomes and measures</b><br />Ascending aortic diameter was modeled with hierarchical group least absolute shrinkage and selection operator (LASSO) regression. Correlation between estimated and measured diameter and performance for identifying diameter 4.0 cm or greater were assessed.<br /><b>Results</b><br />The 30 018-participant training cohort (52% women), were a median age of 65.1 years (IQR, 58.6-70.6 years). The mean (SD) ascending aortic diameter was 3.04 (0.31) cm for women and 3.32 (0.34) cm for men. A score to estimate ascending aortic diameter explained 28.2% of the variance in aortic diameter in the UK Biobank validation cohort (95% CI, 26.4%-30.0%), 30.8% in the FHS cohort (95% CI, 26.8%-34.9%), and 32.6% in the MGB cohort (95% CI, 31.9%-33.2%). For detecting individuals with an ascending aortic diameter of 4 cm or greater, the score had an area under the receiver operator characteristic curve of 0.770 (95% CI, 0.737-0.803) in the UK Biobank, 0.813 (95% CI, 0.772-0.854) in the FHS, and 0.766 (95% CI, 0.757-0.774) in the MGB cohorts, although the model significantly overestimated or underestimated aortic diameter in external validation. Using a fixed-score threshold of 3.537, 9.7 people in UK Biobank, 1.8 in the FHS, and 4.6 in the MGB cohorts would need imaging to confirm 1 individual with an ascending aortic diameter of 4 cm or greater. The sensitivity at that threshold was 8.9% in the UK Biobank, 11.3% in the FHS, and 18.8% in the MGB cohorts, with specificities of 98.1%, 99.2%, and 96.2%, respectively.<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />A prediction model based on common clinically available data was derived and validated to predict ascending aortic diameter. Further research is needed to optimize the prediction model and to determine whether its use is associated with improved outcomes.<br /><br /><br /><br /><small>JAMA: 15 Nov 2022; 328:1935-1944</small></div>
Pirruccello JP, Lin H, Khurshid S, Nekoui M, ... Lindsay ME, Ellinor PT
JAMA: 15 Nov 2022; 328:1935-1944 | PMID: 36378208
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<div><h4>Treatment of Hypertension: A Review.</h4><i>Carey RM, Moran AE, Whelton PK</i><br /><b>Importance</b><br />Hypertension, defined as persistent systolic blood pressure (SBP) at least 130 mm Hg or diastolic BP (DBP) at least 80 mm Hg, affects approximately 116 million adults in the US and more than 1 billion adults worldwide. Hypertension is associated with increased risk of cardiovascular disease (CVD) events (coronary heart disease, heart failure, and stroke) and death.<br /><b>Observations</b><br />First-line therapy for hypertension is lifestyle modification, including weight loss, healthy dietary pattern that includes low sodium and high potassium intake, physical activity, and moderation or elimination of alcohol consumption. The BP-lowering effects of individual lifestyle components are partially additive and enhance the efficacy of pharmacologic therapy. The decision to initiate antihypertensive medication should be based on the level of BP and the presence of high atherosclerotic CVD risk. First-line drug therapy for hypertension consists of a thiazide or thiazidelike diuretic such as hydrochlorothiazide or chlorthalidone, an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker such as enalapril or candesartan, and a calcium channel blocker such as amlodipine and should be titrated according to office and home SBP/DBP levels to achieve in most people an SBP/DBP target (<130/80 mm Hg for adults <65 years and SBP <130 mm Hg in adults ≥65 years). Randomized clinical trials have established the efficacy of BP lowering to reduce the risk of CVD morbidity and mortality. An SBP reduction of 10 mm Hg decreases risk of CVD events by approximately 20% to 30%. Despite the benefits of BP control, only 44% of US adults with hypertension have their SBP/DBP controlled to less than 140/90 mm Hg.<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />Hypertension affects approximately 116 million adults in the US and more than 1 billion adults worldwide and is a leading cause of CVD morbidity and mortality. First-line therapy for hypertension is lifestyle modification, consisting of weight loss, dietary sodium reduction and potassium supplementation, healthy dietary pattern, physical activity, and limited alcohol consumption. When drug therapy is required, first-line therapies are thiazide or thiazidelike diuretics, angiotensin-converting enzyme inhibitor or angiotensin receptor blockers, and calcium channel blockers.<br /><br /><br /><br /><small>JAMA: 08 Nov 2022; 328:1849-1861</small></div>
Carey RM, Moran AE, Whelton PK
JAMA: 08 Nov 2022; 328:1849-1861 | PMID: 36346411
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Abstract
<div><h4>Treatment Time and In-Hospital Mortality Among Patients With ST-Segment Elevation Myocardial Infarction, 2018-2021.</h4><i>Jollis JG, Granger CB, Zègre-Hemsey JK, Henry TD, ... Stone RH, Jacobs AK</i><br /><b>Importance</b><br />Recognizing the association between timely treatment and less myocardial injury for patients with ST-segment elevation myocardial infarction (STEMI), US national guidelines recommend specific treatment-time goals.<br /><b>Objective</b><br />To describe these process measures and outcomes for a recent cohort of patients.<br /><b>Design, setting, and participants</b><br />Cross-sectional study of a diagnosis-based registry between the second quarter of 2018 and the third quarter of 2021 for 114 871 patients with STEMI treated at 648 hospitals in the Get With The Guidelines-Coronary Artery Disease registry.<br /><b>Exposures</b><br />STEMI or STEMI equivalent.<br /><b>Main outcomes and measures</b><br />Treatment times, in-hospital mortality, and adherence to system goals (75% treated ≤90 minutes of first medical contact if the first hospital is percutaneous coronary intervention [PCI]-capable and ≤120 minutes if patients require transfer to a PCI-capable hospital).<br /><b>Results</b><br />In the study population, median age was 63 (IQR, 54-72) years, 71% were men, and 29% were women. Median time from symptom onset to PCI was 148 minutes (IQR, 111-226) for patients presenting to PCI-capable hospitals by emergency medical service, 195 minutes (IQR, 127-349) for patients walking in, and 240 minutes (IQR, 166-402) for patients transferred from another hospital. Adjusted in-hospital mortality was lower for those treated within target times vs beyond time goals for patients transported via emergency medical services (first medical contact to laboratory activation ≤20 minutes [in-hospital mortality, 3.6 vs 9.2] adjusted OR, 0.54 [95% CI, 0.48-0.60], and first medical contact to device ≤90 minutes [in-hospital mortality, 3.3 vs 12.1] adjusted OR, 0.40 [95% CI, 0.36-0.44]), walk-in patients (hospital arrival to device ≤90 minutes [in-hospital mortality, 1.8 vs 4.7] adjusted OR, 0.47 [95% CI, 0.40-0.55]), and transferred patients (door-in to door-out time <30 minutes [in-hospital mortality, 2.9 vs 6.4] adjusted OR, 0.51 [95% CI, 0.32-0.78], and first hospital arrival to device ≤120 minutes [in-hospital mortality, 4.3 vs 14.2] adjusted OR, 0.44 [95% CI, 0.26-0.71]). Regardless of mode of presentation, system goals were not met in most quarters, with the most delayed system performance among patients requiring interhospital transfer (17% treated ≤120 minutes).<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />This study of patients with STEMI included in a US national registry provides information on changes in process and outcomes between 2018 and 2021.<br /><br /><br /><br /><small>JAMA: 06 Nov 2022; epub ahead of print</small></div>
Jollis JG, Granger CB, Zègre-Hemsey JK, Henry TD, ... Stone RH, Jacobs AK
JAMA: 06 Nov 2022; epub ahead of print | PMID: 36335474
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<div><h4>Association Between Preoperative Hemodialysis Timing and Postoperative Mortality in Patients With End-stage Kidney Disease.</h4><i>Fielding-Singh V, Vanneman MW, Grogan T, Neelankavil JP, ... Liu VX, Lin E</i><br /><b>Importance</b><br />For patients with end-stage kidney disease treated with hemodialysis, the optimal timing of hemodialysis prior to elective surgical procedures is unknown.<br /><b>Objective</b><br />To assess whether a longer interval between hemodialysis and subsequent surgery is associated with higher postoperative mortality in patients with end-stage kidney disease treated with hemodialysis.<br /><b>Design, setting, and participants</b><br />Retrospective cohort study of 1 147 846 procedures among 346 828 Medicare beneficiaries with end-stage kidney disease treated with hemodialysis who underwent surgical procedures between January 1, 2011, and September 30, 2018. Follow-up ended on December 31, 2018.<br /><b>Exposures</b><br />One-, two-, or three-day intervals between the most recent hemodialysis treatment and the surgical procedure. Hemodialysis on the day of the surgical procedure vs no hemodialysis on the day of the surgical procedure.<br /><b>Main outcomes and measures</b><br />The primary outcome was 90-day postoperative mortality. The relationship between the dialysis-to-procedure interval and the primary outcome was modeled using a Cox proportional hazards model.<br /><b>Results</b><br />Of the 1 147 846 surgical procedures among 346 828 patients (median age, 65 years [IQR, 56-73 years]; 495 126 procedures [43.1%] in female patients), 750 163 (65.4%) were performed when the last hemodialysis session occurred 1 day prior to surgery, 285 939 (24.9%) when the last hemodialysis session occurred 2 days prior to surgery, and 111 744 (9.7%) when the last hemodialysis session occurred 3 days prior to surgery. Hemodialysis was also performed on the day of surgery for 193 277 procedures (16.8%). Ninety-day postoperative mortality occurred after 34 944 procedures (3.0%). Longer intervals between the last hemodialysis session and surgery were significantly associated with higher risk of 90-day mortality in a dose-dependent manner (2 days vs 1 day: absolute risk, 4.7% vs 4.2%, absolute risk difference, 0.6% [95% CI, 0.4% to 0.8%], adjusted hazard ratio [HR], 1.14 [95% CI, 1.10 to 1.18]; 3 days vs 1 day: absolute risk, 5.2% vs 4.2%, absolute risk difference, 1.0% [95% CI, 0.8% to 1.2%], adjusted HR, 1.25 [95% CI, 1.19 to 1.31]; and 3 days vs 2 days: absolute risk, 5.2% vs 4.7%, absolute risk difference, 0.4% [95% CI, 0.2% to 0.6%], adjusted HR, 1.09 [95% CI, 1.04 to 1.13]). Undergoing hemodialysis on the same day as surgery was associated with a significantly lower hazard of mortality vs no same-day hemodialysis (absolute risk, 4.0% for same-day hemodialysis vs 4.5% for no same-day hemodialysis; absolute risk difference, -0.5% [95% CI, -0.7% to -0.3%]; adjusted HR, 0.88 [95% CI, 0.84-0.91]). In the analyses that evaluated the interaction between the hemodialysis-to-procedure interval and same-day hemodialysis, undergoing hemodialysis on the day of the procedure significantly attenuated the risk associated with a longer hemodialysis-to-procedure interval (P<.001 for interaction).<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />Among Medicare beneficiaries with end-stage kidney disease, longer intervals between hemodialysis and surgery were significantly associated with higher risk of postoperative mortality, mainly among those who did not receive hemodialysis on the day of surgery. However, the magnitude of the absolute risk differences was small, and the findings are susceptible to residual confounding.<br /><br /><br /><br /><small>JAMA: 03 Nov 2022; epub ahead of print</small></div>
Fielding-Singh V, Vanneman MW, Grogan T, Neelankavil JP, ... Liu VX, Lin E
JAMA: 03 Nov 2022; epub ahead of print | PMID: 36326747
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<div><h4>Hormone Therapy for the Primary Prevention of Chronic Conditions in Postmenopausal Persons: US Preventive Services Task Force Recommendation Statement.</h4><i>US Preventive Services Task Force, Mangione CM, Barry MJ, Nicholson WK, ... Stevermer J, Wong JB</i><br /><b>Importance</b><br />Menopause is defined as the cessation of a person\'s menstrual cycle. It is defined retrospectively, 12 months after the final menstrual period. Perimenopause, or the menopausal transition, is the few-year time period preceding a person\'s final menstrual period and is characterized by increasing menstrual cycle length variability and periods of amenorrhea, and often symptoms such as vasomotor dysfunction. The prevalence and incidence of most chronic diseases (eg, cardiovascular disease, cancer, osteoporosis, and fracture) increase with age, and US persons who reach menopause are expected on average to live more than another 30 years.<br /><b>Objective</b><br />To update its 2017 recommendation, the US Preventive Services Task Force (USPSTF) commissioned a systematic review to evaluate the benefits and harms of systemic (ie, oral or transdermal) hormone therapy for the prevention of chronic conditions in postmenopausal persons and whether outcomes vary by age or by timing of intervention after menopause.<br /><b>Population</b><br />Asymptomatic postmenopausal persons who are considering hormone therapy for the primary prevention of chronic medical conditions.<br /><b>Evidence assessment</b><br />The USPSTF concludes with moderate certainty that the use of combined estrogen and progestin for the primary prevention of chronic conditions in postmenopausal persons with an intact uterus has no net benefit. The USPSTF concludes with moderate certainty that the use of estrogen alone for the primary prevention of chronic conditions in postmenopausal persons who have had a hysterectomy has no net benefit.<br /><b>Recommendation</b><br />The USPSTF recommends against the use of combined estrogen and progestin for the primary prevention of chronic conditions in postmenopausal persons. (D recommendation) The USPSTF recommends against the use of estrogen alone for the primary prevention of chronic conditions in postmenopausal persons who have had a hysterectomy. (D recommendation).<br /><br /><br /><br /><small>JAMA: 01 Nov 2022; 328:1740-1746</small></div>
US Preventive Services Task Force, Mangione CM, Barry MJ, Nicholson WK, ... Stevermer J, Wong JB
JAMA: 01 Nov 2022; 328:1740-1746 | PMID: 36318127
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<div><h4>Hormone Therapy for the Primary Prevention of Chronic Conditions in Postmenopausal Persons: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.</h4><i>Gartlehner G, Patel SV, Reddy S, Rains C, Schwimmer M, Kahwati L</i><br /><b>Importance</b><br />It is uncertain whether hormone therapy should be used for the primary prevention of chronic conditions such as heart disease, osteoporosis, or some types of cancers.<br /><b>Objective</b><br />To update evidence for the US Preventive Services Task Force on the benefits and harms of hormone therapy in reducing risks for chronic conditions.<br /><b>Data sources</b><br />PubMed/MEDLINE, Cochrane Library, EMBASE, and trial registries from January 1, 2016, through October 12, 2021; surveillance through July 2022.<br /><b>Study selection</b><br />English-language randomized clinical trials and prospective cohort studies of fair or good quality.<br /><b>Data extraction and synthesis</b><br />Dual review of abstracts, full-text articles, and study quality; meta-analyses when at least 3 similar studies were available.<br /><b>Main outcomes and measures</b><br />Morbidity and mortality related to chronic conditions; health-related quality of life.<br /><b>Results</b><br />Twenty trials (N = 39 145) and 3 cohort studies (N = 1 155 410) were included. Participants using estrogen only compared with placebo had significantly lower risks for diabetes over 7.1 years (1050 vs 903 cases; 134 fewer [95% CI, 18-237]) and fractures over 7.2 years (1024 vs 1413 cases; 388 fewer [95% CI, 277-489]) per 10 000 persons. Risks per 10 000 persons were statistically significantly increased for gallbladder disease over 7.1 years (1113 vs 737 cases; 377 more [95% CI, 234-540]), stroke over 7.2 years (318 vs 239 cases; 79 more [95% CI, 15-159]), venous thromboembolism over 7.2 years (258 vs 181 cases; 77 more [95% CI, 19-153]), and urinary incontinence over 1 year (2331 vs 1446 cases; 885 more [95% CI, 659-1135]). Participants using estrogen plus progestin compared with placebo experienced significantly lower risks, per 10 000 persons, for colorectal cancer over 5.6 years (59 vs 93 cases; 34 fewer [95% CI, 9-51]), diabetes over 5.6 years (403 vs 482 cases; 78 fewer [95% CI, 15-133]), and fractures over 5 years (864 vs 1094 cases; 230 fewer [95% CI, 66-372]). Risks, per 10 000 persons, were significantly increased for invasive breast cancer (242 vs 191 cases; 51 more [95% CI, 6-106]), gallbladder disease (723 vs 463 cases; 260 more [95% CI, 169-364]), stroke (187 vs 135 cases; 52 more [95% CI, 12-104]), and venous thromboembolism (246 vs 126 cases; 120 more [95% CI, 68-185]) over 5.6 years; probable dementia (179 vs 91 cases; 88 more [95% CI, 15-212]) over 4.0 years; and urinary incontinence (1707 vs 1145 cases; 562 more [95% CI, 412-726]) over 1 year.<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />Use of hormone therapy in postmenopausal persons for the primary prevention of chronic conditions was associated with some benefits but also with an increased risk of harms.<br /><br /><br /><br /><small>JAMA: 01 Nov 2022; 328:1747-1765</small></div>
Gartlehner G, Patel SV, Reddy S, Rains C, Schwimmer M, Kahwati L
JAMA: 01 Nov 2022; 328:1747-1765 | PMID: 36318128
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<div><h4>Associations of Unintended Pregnancy With Maternal and Infant Health Outcomes: A Systematic Review and Meta-analysis.</h4><i>Nelson HD, Darney BG, Ahrens K, Burgess A, ... Goueth R, Fu R</i><br /><b>Importance</b><br />Unintended pregnancy is common in the US and is associated with adverse maternal and infant health outcomes; however, estimates of these associations specific to current US populations are lacking.<br /><b>Objective</b><br />To evaluate associations of unintended pregnancy with maternal and infant health outcomes during pregnancy and post partum with studies relevant to current clinical practice and public health in the US.<br /><b>Data sources</b><br />Cochrane Central Register of Controlled Trials and Database of Systematic Reviews, PsycINFO, SocINDEX, and MEDLINE databases (January 1, 2000, to June 15, 2022) and manual review of reference lists.<br /><b>Study selection</b><br />Epidemiologic studies relevant to US populations that compared key maternal and infant health outcomes for unintended vs intended pregnancies and met prespecified eligibility criteria were included after investigators\' independent dual review of abstracts and full-text articles.<br /><b>Data extraction and synthesis</b><br />Investigators abstracted data from publications on study methods, participant characteristics, settings, pregnancy intention, comparators, confounders, and outcomes; data were validated by a second investigator. Risk of bias was independently dual rated by investigators using criteria developed by the US Preventive Services Task Force. Results of studies controlling for confounders were combined by using a profile likelihood random-effects model.<br /><b>Main outcomes and measures</b><br />Prenatal depression, postpartum depression, maternal experience of interpersonal violence, preterm birth, and infant low birth weight.<br /><b>Results</b><br />Thirty-six studies (N = 524 522 participants) were included (14 cohort studies rated good or fair quality; 22 cross-sectional studies); 12 studies used large population-based data sources. Compared with intended pregnancy, unintended pregnancy was significantly associated with higher odds of depression during pregnancy (23.3% vs 13.9%; adjusted odds ratio [aOR], 1.59 [95% CI, 1.35-1.92]; I2 = 85.0%; 15 studies [n = 41 054]) and post partum (15.7% vs 9.6%; aOR, 1.51 [95% CI, 1.40-1.70]; I2 = 7.1%; 10 studies [n = 82 673]), interpersonal violence (14.6% vs 5.5%; aOR, 2.22 [95% CI, 1.41-2.91]; I2 = 64.1%; 5 studies [n = 42 306]), preterm birth (9.4% vs 7.7%; aOR, 1.21 [95% CI, 1.12-1.31]; I2 = 1.7%; 10 studies [n = 94 351]), and infant low birth weight (7.3% vs 5.2%; aOR, 1.09 [95% CI, 1.02-1.21]; I2 = 0.0%; 8 studies [n = 87 547]). Results were similar in sensitivity analyses based on controlling for history of depression for prenatal and postpartum depression and on study design and definition of unintended pregnancy for relevant outcomes. Studies provided limited sociodemographic data and measurement of confounders and outcomes varied.<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />In this systematic review and meta-analysis of epidemiologic observational studies relevant to US populations, unintended pregnancy, compared with intended pregnancy, was significantly associated with adverse maternal and infant outcomes.<br /><b>Trial registration</b><br />PROSPERO Identifier: CRD42020192981.<br /><br /><br /><br /><small>JAMA: 01 Nov 2022; 328:1714-1729</small></div>
Nelson HD, Darney BG, Ahrens K, Burgess A, ... Goueth R, Fu R
JAMA: 01 Nov 2022; 328:1714-1729 | PMID: 36318133
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<div><h4>Estimated Travel Time and Spatial Access to Abortion Facilities in the US Before and After the Dobbs v Jackson Women\'s Health Decision.</h4><i>Rader B, Upadhyay UD, Sehgal NKR, Reis BY, Brownstein JS, Hswen Y</i><br /><b>Importance</b><br />Abortion facility closures resulted in a substantial decrease in access to abortion care in the US.<br /><b>Objectives</b><br />To investigate the changes in travel time to the nearest abortion facility after the Dobbs v Jackson Women\'s Health Organization (referred to hereafter as Dobbs) US Supreme Court decision.<br /><b>Design, setting, and participants</b><br />Repeated cross-sectional spatial analysis of travel time from each census tract in the contiguous US (n = 82 993) to the nearest abortion facility (n = 1134) listed in the Advancing New Standards in Reproductive Health database. Census tract boundaries and demographics were defined by the 2020 American Community Survey. The spatial analysis compared access during the pre-Dobbs period (January-December 2021) with the post-Dobbs period (September 2022) for the estimated 63 718 431 females aged 15 to 44 years (reproductive age for this analysis) in the US (excluding Alaska and Hawaii).<br /><b>Exposures</b><br />The Dobbs ruling and subsequent state laws restricting abortion procedures. The pre-Dobbs period measured abortion access to all facilities providing abortions in 2021. Post-Dobbs abortion access was measured by simulating the closure of all facilities in the 15 states with existing total or 6-week abortion bans in effect as of September 30, 2022.<br /><b>Main outcomes and measures</b><br />Median and mean changes in surface travel time (eg, car, public transportation) to an abortion facility in the post-Dobbs period compared with the pre-Dobbs period and the total percentage of females of reproductive age living more than 60 minutes from abortion facilities during the pre- and post-Dobbs periods.<br /><b>Results</b><br />Of 1134 abortion facilities in the US (at least 1 in every state; 8 in Alaska and Hawaii excluded), 749 were considered active during the pre-Dobbs period and 671 were considered active during a simulated post-Dobbs period. Median (IQR) and mean (SD) travel times to pre-Dobbs abortion facilities were estimated to be 10.9 (4.3-32.4) and 27.8 (42.0) minutes. Travel time to abortion facilities in the post-Dobbs period significantly increased (paired sample t test P <.001) to an estimated median (IQR) of 17.0 (4.9-124.5) minutes and a mean (SD) of and 100.4 (161.5) minutes. In the post-Dobbs period, an estimated 33.3% (sensitivity interval, 32.3%-34.8%) of females of reproductive age lived in a census tract more than 60 minutes from an abortion facility compared with 14.6.% (sensitivity interval, 13.0%-16.9%) of females of reproductive age in the pre-Dobbs period.<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />In this repeated cross-sectional spatial analysis, estimated travel time to abortion facilities in the US was significantly greater in the post-Dobbs period after accounting for the closure of abortion facilities in states with total or 6-week abortion bans compared with the pre-Dobbs period, during which all facilities providing abortions in 2021 were considered active.<br /><br /><br /><br /><small>JAMA: 01 Nov 2022; epub ahead of print</small></div>
Rader B, Upadhyay UD, Sehgal NKR, Reis BY, Brownstein JS, Hswen Y
JAMA: 01 Nov 2022; epub ahead of print | PMID: 36318194
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<div><h4>Association of Texas\' 2021 Ban on Abortion in Early Pregnancy With the Number of Facility-Based Abortions in Texas and Surrounding States.</h4><i>White K, Sierra G, Lerma K, Beasley A, ... Potter JE, Dickman SL</i><br /><b>Importance</b><br />Texas\' 2021 ban on abortion in early pregnancy may demonstrate how patterns of abortion might change following the US Supreme Court\'s June 2022 decision overturning Roe v Wade.<br /><b>Objective</b><br />To assess changes in the number of abortions and changes in the percentage of out-of-state abortions among Texas residents performed at 12 or more weeks of gestation in the first 6 months following implementation of Texas Senate Bill 8 (SB 8), which prohibited abortions after detection of embryonic cardiac activity.<br /><b>Design, setting, and participants</b><br />Retrospective study of a sample of 50 Texas and out-of-state abortion facilities using an interrupted time series analysis to assess changes in the number of abortions, and Poisson regression to assess changes in abortions at 12 or more weeks of gestation. Data included 68 820 Texas facility-based abortions and 11 287 out-of-state abortions among Texas residents during the study period from September 1, 2020, to February 28, 2022.<br /><b>Exposures</b><br />Abortion care obtained after (September 2021-February 2022) vs before (September 2020-August 2021) implementation of SB 8.<br /><b>Main outcomes and measures</b><br />Primary outcomes were changes in the number of facility-based abortions for Texas residents, in Texas and out of state, in the month after implementation of SB 8 compared with the month before. The secondary outcome was the change in the percentage of out-of-state abortions among Texas residents obtained at 12 or more weeks of gestation during the 6-month period after the law\'s implementation.<br /><b>Results</b><br />Between September 2020 and August 2021, there were 55 018 abortions in Texas and 2547 out-of-state abortions among Texas residents. During the 6 months after SB 8, there were 13 802 abortions in Texas and 8740 out-of-state abortions among Texas residents. Compared with the month before implementation of SB 8, the number of Texas facility-based abortions significantly decreased from 5451 to 2169 (difference, -3282 [95% CI, -3171 to -3396]; incidence rate ratio [IRR], 0.43 [95% CI, 0.36-0.51]) in the month after SB 8 was implemented. The number of out-of-state abortions among Texas residents significantly increased from 222 to 1332 (difference, 1110 [95% CI, 1047-1177]; IRR, 5.38 [95% CI, 4.19-6.91]). Overall, the total documented number of Texas facility-based and out-of-state abortions among Texas residents significantly decreased from 5673 to 3501 (absolute change, -2172 [95% CI, -2083 to -2265]; IRR, 0.67 [95% CI, 0.56-0.79]) in the first month after SB 8 was implemented compared with the previous month. Out-of-state abortions among Texas residents obtained at 12 or more weeks of gestation increased from 17.1% (221/1291) to 31.0% (399/1289) (difference, 178 [95% CI, 153-206]) during the period between September 2021 and February 2022 (P < .001 for trend).<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />Among a sample of abortion facilities, the 2021 Texas law banning abortion in early pregnancy (SB 8) was significantly associated with a decrease in the documented total of facility-based abortions in Texas and obtained by Texas residents in surrounding states in the first month after implementation compared with the previous month. Over the 6 months following SB 8 implementation, the percentage of out-of-state abortions among Texas residents obtained at 12 or more weeks of gestation significantly increased.<br /><br /><br /><br /><small>JAMA: 01 Nov 2022; epub ahead of print</small></div>
White K, Sierra G, Lerma K, Beasley A, ... Potter JE, Dickman SL
JAMA: 01 Nov 2022; epub ahead of print | PMID: 36318197
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This program is still in alpha version.