Journal: JAMA

Sorted by: date / impact
Abstract

Screening for Syphilis Infection in Nonpregnant Adolescents and Adults: US Preventive Services Task Force Reaffirmation Recommendation Statement.

US Preventive Services Task Force, Mangione CM, Barry MJ, Nicholson WK, ... Stevermer J, Wong JB
Importance
Syphilis is a sexually transmitted infection that can progress through different stages (primary, secondary, latent, and tertiary) and cause serious health problems if left untreated. Reported cases of primary and secondary syphilis in the US increased from a record low of 2.1 cases per 100 000 population in 2000 and 2001 to 11.9 cases per 100 000 population in 2019. Men account for the majority of cases (83% of primary and secondary syphilis cases in 2019), and rates among women nearly tripled from 2015 to 2019.
Objective
To reaffirm its 2016 recommendation, the US Preventive Services Task Force (USPSTF) commissioned a reaffirmation evidence update focusing on targeted key questions evaluating the performance of risk assessment tools and the benefits and harms of screening for syphilis in nonpregnant adolescents and adults.
Population
Asymptomatic, nonpregnant adolescents and adults who have ever been sexually active and are at increased risk for syphilis infection.
Evidence assessment
Using a reaffirmation process, the USPSTF concludes with high certainty that there is a substantial net benefit of screening for syphilis infection in nonpregnant persons who are at increased risk for infection.
Recommendation
The USPSTF recommends screening for syphilis infection in persons who are at increased risk for infection. (A recommendation).



JAMA: 27 Sep 2022; 328:1243-1249
US Preventive Services Task Force, Mangione CM, Barry MJ, Nicholson WK, ... Stevermer J, Wong JB
JAMA: 27 Sep 2022; 328:1243-1249 | PMID: 36166020
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Impact:
Abstract

Effect of First-Line Serplulimab vs Placebo Added to Chemotherapy on Survival in Patients With Extensive-Stage Small Cell Lung Cancer: The ASTRUM-005 Randomized Clinical Trial.

Cheng Y, Han L, Wu L, Chen J, ... Zhu J, ASTRUM-005 Study Group
Importance
Programmed cell death ligand 1 inhibitors combined with chemotherapy has changed the approach to first-line treatment in patients with extensive-stage small cell lung cancer (SCLC). It remained unknown whether adding a programmed cell death 1 (PD-1) inhibitor to chemotherapy provided similar or better benefits in patients with extensive-stage SCLC, which would add evidence on the efficacy of checkpoint inhibitors in the treatment of extensive-stage SCLC.
Objective
To evaluate the efficacy and adverse event profile of the PD-1 inhibitor serplulimab plus chemotherapy compared with placebo plus chemotherapy as first-line treatment in patients with extensive-stage SCLC.
Design, setting, and participants
This international, double-blind, phase 3 randomized clinical trial (ASTRUM-005) enrolled patients at 114 hospital sites in 6 countries between September 12, 2019, and April 27, 2021. Of 894 patients who were screened, 585 with extensive-stage SCLC who had not previously received systemic therapy were randomized. Patients were followed up through October 22, 2021.
Interventions
Patients were randomized 2:1 to receive either 4.5 mg/kg of serplulimab (n = 389) or placebo (n = 196) intravenously every 3 weeks. All patients received intravenous carboplatin and etoposide every 3 weeks for up to 12 weeks.
Main outcomes and measures
The primary outcome was overall survival (prespecified significance threshold at the interim analysis, 2-sided P < .012). There were 13 secondary outcomes, including progression-free survival and adverse events.
Results
Among the 585 patients who were randomized (mean age, 61.1 [SD, 8.67] years; 104 [17.8%] women), 246 (42.1%) completed the trial and 465 (79.5%) discontinued study treatment. All patients received study treatment and were included in the primary analyses. As of the data cutoff (October 22, 2021) for this interim analysis, the median duration of follow-up was 12.3 months (range, 0.2-24.8 months). The median overall survival was significantly longer in the serplulimab group (15.4 months [95% CI, 13.3 months-not evaluable]) than in the placebo group (10.9 months [95% CI, 10.0-14.3 months]) (hazard ratio, 0.63 [95% CI, 0.49-0.82]; P < .001). The median progression-free survival (assessed by an independent radiology review committee) also was longer in the serplulimab group (5.7 months [95% CI, 5.5-6.9 months]) than in the placebo group (4.3 months [95% CI, 4.2-4.5 months]) (hazard ratio, 0.48 [95% CI, 0.38-0.59]). Treatment-related adverse events that were grade 3 or higher occurred in 129 patients (33.2%) in the serplulimab group and in 54 patients (27.6%) in the placebo group.

Conclusions:
and relevance
Among patients with previously untreated extensive-stage SCLC, serplulimab plus chemotherapy significantly improved overall survival compared with chemotherapy alone, supporting the use of serplulimab plus chemotherapy as the first-line treatment for this patient population.
Trial registration
ClinicalTrials.gov Identifier: NCT04063163.



JAMA: 27 Sep 2022; 328:1223-1232
Cheng Y, Han L, Wu L, Chen J, ... Zhu J, ASTRUM-005 Study Group
JAMA: 27 Sep 2022; 328:1223-1232 | PMID: 36166026
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Impact:
Abstract

Effect of High-Flow Nasal Cannula Oxygen vs Standard Oxygen Therapy on Mortality in Patients With Respiratory Failure Due to COVID-19: The SOHO-COVID Randomized Clinical Trial.

Frat JP, Quenot JP, Badie J, Coudroy R, ... Thille AW, SOHO-COVID Study Group and the REVA Network
Importance
The benefit of high-flow nasal cannula oxygen (high-flow oxygen) in terms of intubation and mortality in patients with respiratory failure due to COVID-19 is controversial.
Objective
To determine whether the use of high-flow oxygen, compared with standard oxygen, could reduce the rate of mortality at day 28 in patients with respiratory failure due to COVID-19 admitted in intensive care units (ICUs).
Design, setting, and participants
The SOHO-COVID randomized clinical trial was conducted in 34 ICUs in France and included 711 patients with respiratory failure due to COVID-19 and a ratio of partial pressure of arterial oxygen to fraction of inspired oxygen equal to or below 200 mm Hg. It was an ancillary trial of the ongoing original SOHO randomized clinical trial, which was designed to include patients with acute hypoxemic respiratory failure from all causes. Patients were enrolled from January to December 2021; final follow-up occurred on March 5, 2022.
Interventions
Patients were randomly assigned to receive high-flow oxygen (n = 357) or standard oxygen delivered through a nonrebreathing mask initially set at a 10-L/min minimum (n = 354).
Main outcomes and measures
The primary outcome was mortality at day 28. There were 13 secondary outcomes, including the proportion of patients requiring intubation, number of ventilator-free days at day 28, mortality at day 90, mortality and length of stay in the ICU, and adverse events.
Results
Among the 782 randomized patients, 711 patients with respiratory failure due to COVID-19 were included in the analysis (mean [SD] age, 61 [12] years; 214 women [30%]). The mortality rate at day 28 was 10% (36/357) with high-flow oxygen and 11% (40/354) with standard oxygen (absolute difference, -1.2% [95% CI, -5.8% to 3.4%]; P = .60). Of 13 prespecified secondary outcomes, 12 showed no significant difference including in length of stay and mortality in the ICU and in mortality up until day 90. The intubation rate was significantly lower with high-flow oxygen than with standard oxygen (45% [160/357] vs 53% [186/354]; absolute difference, -7.7% [95% CI, -14.9% to -0.4%]; P = .04). The number of ventilator-free days at day 28 was not significantly different between groups (median, 28 [IQR, 11-28] vs 23 [IQR, 10-28] days; absolute difference, 0.5 days [95% CI, -7.7 to 9.1]; P = .07). The most common adverse events were ventilator-associated pneumonia, occurring in 58% (93/160) in the high-flow oxygen group and 53% (99/186) in the standard oxygen group.

Conclusions:
and relevance
Among patients with respiratory failure due to COVID-19, high-flow nasal cannula oxygen, compared with standard oxygen therapy, did not significantly reduce 28-day mortality.
Trial registration
ClinicalTrials.gov Identifier: NCT04468126.



JAMA: 27 Sep 2022; 328:1212-1222
Frat JP, Quenot JP, Badie J, Coudroy R, ... Thille AW, SOHO-COVID Study Group and the REVA Network
JAMA: 27 Sep 2022; 328:1212-1222 | PMID: 36166027
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Impact:
Abstract

Incidence of Severe COVID-19 Illness Following Vaccination and Booster With BNT162b2, mRNA-1273, and Ad26.COV2.S Vaccines.

Kelly JD, Leonard S, Hoggatt KJ, Boscardin WJ, ... Tien PC, Keyhani S
Importance
Evidence describing the incidence of severe COVID-19 illness following vaccination and booster with BNT162b2, mRNA-1273, and Ad26.COV2.S vaccines is needed, particularly for high-risk populations.
Objective
To describe the incidence of severe COVID-19 illness among a cohort that received vaccination plus a booster vaccine dose.
Design, setting, and participants
Retrospective cohort study of adults receiving care at Veterans Health Administration facilities across the US who received a vaccination series plus 1 booster against SARS-CoV-2, conducted from July 1, 2021, to May 30, 2022. Patients were eligible if they had received a primary care visit in the prior 2 years and had documented receipt of all US Food and Drug Administration-authorized doses of the initial mRNA vaccine or viral vector vaccination series after December 11, 2020, and a subsequent documented booster dose between July 1, 2021, and April 29, 2022. The analytic cohort consisted of 1 610 719 participants.
Exposures
Receipt of any combination of mRNA-1273 (Moderna), BNT162b2 (Pfizer-BioNTech), and Ad26.COV2.S (Janssen/Johnson & Johnson) primary vaccination series and a booster dose.
Main outcomes and measures
Outcomes were breakthrough COVID-19 (symptomatic infection), hospitalization with COVID-19 pneumonia and/or death, and hospitalization with severe COVID-19 pneumonia and/or death. A subgroup analysis of nonoverlapping populations included those aged 65 years or older, those with high-risk comorbid conditions, and those with immunocompromising conditions.
Results
Of 1 610 719 participants, 1 100 280 (68.4%) were aged 65 years or older and 132 243 (8.2%) were female; 1 133 785 (70.4%) had high-risk comorbid conditions, 155 995 (9.6%) had immunocompromising conditions, and 1 467 879 (91.1%) received the same type of mRNA vaccine (initial series and booster). Over 24 weeks, 125.0 (95% CI, 123.3-126.8) per 10 000 persons had breakthrough COVID-19, 8.9 (95% CI, 8.5-9.4) per 10 000 persons were hospitalized with COVID-19 pneumonia or died, and 3.4 (95% CI, 3.1-3.7) per 10 000 persons were hospitalized with severe pneumonia or died. For high-risk populations, incidence of hospitalization with COVID-19 pneumonia or death was as follows: aged 65 years or older, 1.9 (95% CI, 1.4-2.6) per 10 000 persons; high-risk comorbid conditions, 6.7 (95% CI, 6.2-7.2) per 10 000 persons; and immunocompromising conditions, 39.6 (95% CI, 36.6-42.9) per 10 000 persons. Subgroup analyses of patients hospitalized with COVID-19 pneumonia or death by time after booster demonstrated similar incidence estimates among those aged 65 years or older and with high-risk comorbid conditions but not among those with immunocompromising conditions.

Conclusions:
and relevance
In a US cohort of patients receiving care at Veterans Health Administration facilities during a period of Delta and Omicron variant predominance, there was a low incidence of hospitalization with COVID-19 pneumonia or death following vaccination and booster with any of BNT162b2, mRNA-1273, or Ad26.COV2.S vaccines.



JAMA: 26 Sep 2022; epub ahead of print
Kelly JD, Leonard S, Hoggatt KJ, Boscardin WJ, ... Tien PC, Keyhani S
JAMA: 26 Sep 2022; epub ahead of print | PMID: 36156706
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Impact:
Abstract

Association of Primary and Booster Vaccination and Prior Infection With SARS-CoV-2 Infection and Severe COVID-19 Outcomes.

Lin DY, Gu Y, Xu Y, Wheeler B, ... Moore Z, Zeng D
Importance
Data about the association of COVID-19 vaccination and prior SARS-CoV-2 infection with risk of SARS-CoV-2 infection and severe COVID-19 outcomes may guide prevention strategies.
Objective
To estimate the time-varying association of primary and booster COVID-19 vaccination and prior SARS-CoV-2 infection with subsequent SARS-CoV-2 infection, hospitalization, and death.
Design, setting, and participants
Cohort study of 10.6 million residents in North Carolina from March 2, 2020, through June 3, 2022.
Exposures
COVID-19 primary vaccine series and boosters and prior SARS-CoV-2 infection.
Main outcomes and measures
Rate ratio (RR) of SARS-CoV-2 infection and hazard ratio (HR) of COVID-19-related hospitalization and death.
Results
The median age among the 10.6 million participants was 39 years; 51.3% were female, 71.5% were White, and 9.9% were Hispanic. As of June 3, 2022, 67% of participants had been vaccinated. There were 2 771 364 SARS-CoV-2 infections, with a hospitalization rate of 6.3% and mortality rate of 1.4%. The adjusted RR of the primary vaccine series compared with being unvaccinated against infection became 0.53 (95% CI, 0.52-0.53) for BNT162b2, 0.52 (95% CI, 0.51-0.53) for mRNA-1273, and 0.51 (95% CI, 0.50-0.53) for Ad26.COV2.S 10 months after the first dose, but the adjusted HR for hospitalization remained at 0.29 (95% CI, 0.24-0.35) for BNT162b2, 0.27 (95% CI, 0.23-0.32) for mRNA-1273, and 0.35 (95% CI, 0.29-0.42) for Ad26.COV2.S and the adjusted HR of death remained at 0.23 (95% CI, 0.17-0.29) for BNT162b2, 0.15 (95% CI, 0.11-0.20) for mRNA-1273, and 0.24 (95% CI, 0.19-0.31) for Ad26.COV2.S. For the BNT162b2 primary series, boosting in December 2021 with BNT162b2 had the adjusted RR relative to primary series of 0.39 (95% CI, 0.38-0.40) and boosting with mRNA-1273 had the adjusted RR of 0.32 (95% CI, 0.30-0.34) against infection after 1 month and boosting with BNT162b2 had the adjusted RR of 0.84 (95% CI, 0.82-0.86) and boosting with mRNA-1273 had the adjusted RR of 0.60 (95% CI, 0.57-0.62) after 3 months. Among all participants, the adjusted RR of Omicron infection compared with no prior infection was estimated at 0.23 (95% CI, 0.22-0.24) against infection, and the adjusted HRs were 0.10 (95% CI, 0.07-0.14) against hospitalization and 0.11 (95% CI, 0.08-0.15) against death after 4 months.

Conclusions:
and relevance
Receipt of primary COVID-19 vaccine series compared with being unvaccinated, receipt of boosters compared with primary vaccination, and prior infection compared with no prior infection were all significantly associated with lower risk of SARS-CoV-2 infection (including Omicron) and resulting hospitalization and death. The associated protection waned over time, especially against infection.



JAMA: 26 Sep 2022; epub ahead of print
Lin DY, Gu Y, Xu Y, Wheeler B, ... Moore Z, Zeng D
JAMA: 26 Sep 2022; epub ahead of print | PMID: 36155617
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Impact:
Abstract

The US Medicaid Program: Coverage, Financing, Reforms, and Implications for Health Equity.

Donohue JM, Cole ES, James CV, Jarlenski M, Michener JD, Roberts ET
Importance
Medicaid is the largest health insurance program by enrollment in the US and has an important role in financing care for eligible low-income adults, children, pregnant persons, older adults, people with disabilities, and people from racial and ethnic minority groups. Medicaid has evolved with policy reform and expansion under the Affordable Care Act and is at a crossroads in balancing its role in addressing health disparities and health inequities against fiscal and political pressures to limit spending.
Objective
To describe Medicaid eligibility, enrollment, and spending and to examine areas of Medicaid policy, including managed care, payment, and delivery system reforms; Medicaid expansion; racial and ethnic health disparities; and the potential to achieve health equity.
Evidence review
Analyses of publicly available data reported from 2010 to 2022 on Medicaid enrollment and program expenditures were performed to describe the structure and financing of Medicaid and characteristics of Medicaid enrollees. A search of PubMed for peer-reviewed literature and online reports from nonprofit and government organizations was conducted between August 1, 2021, and February 1, 2022, to review evidence on Medicaid managed care, delivery system reforms, expansion, and health disparities. Peer-reviewed articles and reports published between January 2003 and February 2022 were included.
Findings
Medicaid covered approximately 80.6 million people (mean per month) in 2022 (24.2% of the US population) and accounted for an estimated $671.2 billion in health spending in 2020, representing 16.3% of US health spending. Medicaid accounted for an estimated 27.2% of total state spending and 7.6% of total federal expenditures in 2021. States enrolled 69.5% of Medicaid beneficiaries in managed care plans in 2019 and adopted 139 delivery system reforms from 2003 to 2019. The 38 states (and Washington, DC) that expanded Medicaid under the Affordable Care Act experienced gains in coverage, increased federal revenues, and improvements in health care access and some health outcomes. Approximately 56.4% of Medicaid beneficiaries were from racial and ethnic minority groups in 2019, and disparities in access, quality, and outcomes are common among these groups within Medicaid. Expanding Medicaid, addressing disparities within Medicaid, and having an explicit focus on equity in managed care and delivery system reforms may represent opportunities for Medicaid to advance health equity.

Conclusions:
and relevance
Medicaid insures a substantial portion of the US population, accounts for a significant amount of total health spending and state expenditures, and has evolved with delivery system reforms, increased managed care enrollment, and state expansions. Additional Medicaid policy reforms are needed to reduce health disparities by race and ethnicity and to help achieve equity in access, quality, and outcomes.



JAMA: 20 Sep 2022; 328:1085-1099
Donohue JM, Cole ES, James CV, Jarlenski M, Michener JD, Roberts ET
JAMA: 20 Sep 2022; 328:1085-1099 | PMID: 36125468
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Impact:
Abstract

Effect of Tocilizumab on Disease Activity in Patients With Active Polymyalgia Rheumatica Receiving Glucocorticoid Therapy: A Randomized Clinical Trial.

Devauchelle-Pensec V, Carvajal-Alegria G, Dernis E, Richez C, ... Nowak E, Saraux A
Importance
Few treatments are available for patients with glucocorticoid-dependent polymyalgia rheumatica. IL-6 antagonists may reduce disease activity in patients with active glucocorticoid-dependent polymyalgia rheumatica.
Objective
To compare the efficacy of tocilizumab vs placebo in patients with glucocorticoid-dependent polymyalgia rheumatica.
Design, setting, and participants
This double-blind, parallel-group, placebo-controlled randomized clinical trial enrolled 101 patients with polymyalgia rheumatica at 17 hospitals in France from February 2017 to October 2019. Final follow-up occurred in November 2020. Inclusion criteria were persistent disease activity (polymyalgia rheumatica activity score computed using the C-reactive protein level [CRP PMR-AS] >10) and prednisone dose greater than or equal to 10 mg per day.
Interventions
Patients were randomly assigned to receive intravenous tocilizumab (8 mg/kg; n = 51) or placebo (n = 50) every 4 weeks for 24 weeks, combined with predefined standardized tapering of oral prednisone.
Main outcomes and measures
The primary efficacy end point was CRP PMR-AS less than 10 (range, 0-100; higher values indicate greater activity; no minimal clinically important difference defined) combined with either prednisone dose less than or equal to 5 mg per day or a decrease in prednisone dose greater than or equal to 10 mg from baseline at week 24. There were 11 secondary outcomes assessed at week 24 included in this report, including disease activity (measured by CRP PMR-AS) and the proportion of patients no longer taking prednisone.
Results
Of the 101 randomized patients (mean age, 67.2 years; 68 [67.3%] women), 100 (99%) received at least 1 infusion and 100 completed the trial. The primary end point was achieved in 67.3% of patients in the tocilizumab group and 31.4% of patients in the placebo group (adjusted difference, 36.0% [95% CI, 19.4%-52.6%]; adjusted relative risk, 2.3 [95% CI, 1.5-3.6]; P < .001). Of 11 reported secondary end points at 24 weeks, 7 showed significant differences favoring tocilizumab, including mean CRP PMR-AS score (7.5 [95% CI, 5.4-9.6] vs 14.9 [95% CI, 11.4-18.4]; adjusted difference, -7.5 [95% CI, -11.2 to -3.8]; P < .001) and the percentage of patients no longer receiving prednisone (49.0% vs 19.6%; adjusted difference, 29.3% [95% CI, 18.9%-39.7%]; adjusted relative risk, 2.5 [95% CI, 1.8-3.5]; P < .001). The most frequent adverse events were infections, experienced by 23 patients (46.9%) in the tocilizumab group and 20 (39.2%) in the placebo group.

Conclusions:
and relevance
Among patients with active polymyalgia rheumatica despite prednisone therapy, tocilizumab, compared with placebo, resulted in a significantly greater percentage of patients with a CRP PMR-AS less than 10 with reduced prednisone requirements at week 24. Further research is needed to confirm efficacy and to determine the balance of potential benefits and harms.
Trial registration
ClinicalTrials.gov Identifier: NCT02908217.



JAMA: 20 Sep 2022; 328:1053-1062
Devauchelle-Pensec V, Carvajal-Alegria G, Dernis E, Richez C, ... Nowak E, Saraux A
JAMA: 20 Sep 2022; 328:1053-1062 | PMID: 36125471
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Impact:
Abstract

Effect of Roflumilast Cream vs Vehicle Cream on Chronic Plaque Psoriasis: The DERMIS-1 and DERMIS-2 Randomized Clinical Trials.

Lebwohl MG, Kircik LH, Moore AY, Stein Gold L, ... Higham RC, Berk DR
Importance
Once-daily roflumilast cream, 0.3%, a potent phosphodiesterase 4 inhibitor, demonstrated efficacy and was well tolerated in a phase 2b trial of patients with psoriasis.
Objective
To evaluate the efficacy of roflumilast cream, 0.3%, applied once daily for 8 weeks in 2 trials of patients with plaque psoriasis.
Design, setting, and participants
Two phase 3, randomized, double-blind, controlled, multicenter trials (DERMIS-1 [trial 1; n = 439] and DERMIS-2 [trial 2; n = 442]) were conducted at 40 centers (trial 1) and 39 centers (trial 2) in the US and Canada between December 9, 2019, and November 16, 2020, and between December 9, 2019, and November 23, 2020, respectively. Patients aged 2 years or older with plaque psoriasis involving 2% to 20% of body surface area were enrolled. The dates of final follow-up were November 20, 2020, and November 23, 2020, for trial 1 and trial 2, respectively.
Interventions
Patients were randomized 2:1 to receive roflumilast cream, 0.3% (trial 1: n = 286; trial 2: n = 290), or vehicle cream (trial 1: n = 153; trial 2: n = 152) once daily for 8 weeks.
Main outcomes and measures
The primary efficacy end point was Investigator Global Assessment (IGA) success (clear or almost clear status plus ≥2-grade improvement from baseline [score range, 0-4]) at week 8, analyzed using a Cochran-Mantel-Haenszel test stratified by site, baseline IGA score, and intertriginous involvement. There were 9 secondary outcomes, including intertriginous IGA success, 75% reduction in Psoriasis Area and Severity Index (PASI) score, and Worst Itch Numeric Rating Scale score of 4 or higher at baseline achieving 4-point reduction (WI-NRS success) at week 8 (scale: 0 [no itch] to 10 [worst imaginable itch]; minimum clinically important difference, 4 points).
Results
Among 881 participants (mean age, 47.5 years; 320 [36.3%] female), mean IGA scores in trial 1 were 2.9 [SD, 0.52] for roflumilast and 2.9 [SD, 0.45] for vehicle and in trial 2 were 2.9 [SD, 0.48] for roflumilast and 2.9 [SD, 0.47]) for vehicle. Statistically significantly greater percentages of roflumilast-treated patients than vehicle-treated patients had IGA success at week 8 (trial 1: 42.4% vs 6.1%; difference, 39.6% [95% CI, 32.3%-46.9%]; trial 2: 37.5% vs 6.9%; difference, 28.9% [95% CI, 20.8%-36.9%]; P < .001 for both). Of 9 secondary end points, statistically significant differences favoring roflumilast vs vehicle were observed for 8 in trial 1 and 9 in trial 2, including intertriginous IGA success (71.2% vs 13.8%; difference, 66.5% [95% CI, 47.1%-85.8%] and 68.1% vs 18.5%; difference, 51.6% [95% CI, 29.3%-73.8%]; P < .001 for both), 75% reduction in PASI score (41.6% vs 7.6%; difference, 36.1% [95% CI, 28.5%-43.8%] and 39.0% vs 5.3%; difference, 32.4% [95% CI, 24.9%-39.8%]; P < .001 for both), WI-NRS success (67.5% vs 26.8%; difference, 42.6% [95% CI, 31.3%-53.8%] and 69.4% vs 35.6%; difference, 30.2% [95% CI, 18.2%-42.2%]; P < .001 for both). The incidence of treatment-emergent adverse events was 25.2% with roflumilast vs 23.5% with vehicle in trial 1 and 25.9% with roflumilast vs 18.4% with vehicle in trial 2. The incidence of serious adverse events was 0.7% with roflumilast vs 0.7% with vehicle in trial 1 and 0% with roflumilast vs 0.7% with vehicle in trial 2.

Conclusions:
and relevance
Among patients with chronic plaque psoriasis, treatment with roflumilast cream, 0.3%, compared with vehicle cream resulted in better clinical status at 8 weeks. Further research is needed to assess efficacy compared with other active treatments and to assess longer-term efficacy and safety.
Trial registration
ClinicalTrials.gov Identifiers: NCT04211363, NCT04211389.



JAMA: 20 Sep 2022; 328:1073-1084
Lebwohl MG, Kircik LH, Moore AY, Stein Gold L, ... Higham RC, Berk DR
JAMA: 20 Sep 2022; 328:1073-1084 | PMID: 36125472
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Impact:
Abstract

Effect of Helmet Noninvasive Ventilation vs Usual Respiratory Support on Mortality Among Patients With Acute Hypoxemic Respiratory Failure Due to COVID-19: The HELMET-COVID Randomized Clinical Trial.

Arabi YM, Aldekhyl S, Al Qahtani S, Al-Dorzi HM, ... Tlayjeh H, Saudi Critical Care Trials Group
Importance
Helmet noninvasive ventilation has been used in patients with COVID-19 with the premise that helmet interface is more effective than mask interface in delivering prolonged treatments with high positive airway pressure, but data about its effectiveness are limited.
Objective
To evaluate whether helmet noninvasive ventilation compared with usual respiratory support reduces mortality in patients with acute hypoxemic respiratory failure due to COVID-19 pneumonia.
Design, setting, and participants
This was a multicenter, pragmatic, randomized clinical trial that was conducted in 8 sites in Saudi Arabia and Kuwait between February 8, 2021, and November 16, 2021. Adult patients with acute hypoxemic respiratory failure (n = 320) due to suspected or confirmed COVID-19 were included. The final follow-up date for the primary outcome was December 14, 2021.
Interventions
Patients were randomized to receive helmet noninvasive ventilation (n = 159) or usual respiratory support (n = 161), which included mask noninvasive ventilation, high-flow nasal oxygen, and standard oxygen.
Main outcomes and measures
The primary outcome was 28-day all-cause mortality. There were 12 prespecified secondary outcomes, including endotracheal intubation, barotrauma, skin pressure injury, and serious adverse events.
Results
Among 322 patients who were randomized, 320 were included in the primary analysis, all of whom completed the trial. Median age was 58 years, and 187 were men (58.4%). Within 28 days, 43 of 159 patients (27.0%) died in the helmet noninvasive ventilation group compared with 42 of 161 (26.1%) in the usual respiratory support group (risk difference, 1.0% [95% CI, -8.7% to 10.6%]; relative risk, 1.04 [95% CI, 0.72-1.49]; P = .85). Within 28 days, 75 of 159 patients (47.2%) required endotracheal intubation in the helmet noninvasive ventilation group compared with 81 of 161 (50.3%) in the usual respiratory support group (risk difference, -3.1% [95% CI, -14.1% to 7.8%]; relative risk, 0.94 [95% CI, 0.75-1.17]). There were no significant differences between the 2 groups in any of the prespecified secondary end points. Barotrauma occurred in 30 of 159 patients (18.9%) in the helmet noninvasive ventilation group and 25 of 161 (15.5%) in the usual respiratory support group. Skin pressure injury occurred in 5 of 159 patients (3.1%) in the helmet noninvasive ventilation group and 10 of 161 (6.2%) in the usual respiratory support group. There were 2 serious adverse events in the helmet noninvasive ventilation group and 1 in the usual respiratory support group.

Conclusions:
and relevance
Results of this study suggest that helmet noninvasive ventilation did not significantly reduce 28-day mortality compared with usual respiratory support among patients with acute hypoxemic respiratory failure due to COVID-19 pneumonia. However, interpretation of the findings is limited by imprecision in the effect estimate, which does not exclude potentially clinically important benefit or harm.
Trial registration
ClinicalTrials.gov Identifier: NCT04477668.



JAMA: 20 Sep 2022; 328:1063-1072
Arabi YM, Aldekhyl S, Al Qahtani S, Al-Dorzi HM, ... Tlayjeh H, Saudi Critical Care Trials Group
JAMA: 20 Sep 2022; 328:1063-1072 | PMID: 36125473
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Impact:
Abstract

Screening for Prediabetes and Type 2 Diabetes in Children and Adolescents: US Preventive Services Task Force Recommendation Statement.

US Preventive Services Task Force, Mangione CM, Barry MJ, Nicholson WK, ... Tseng CW, Wong JB
Importance
The Centers for Disease Control and Prevention estimates that 210 000 children and adolescents younger than 20 years had diabetes as of 2018; of these, approximately 23 000 had type 2 diabetes. Youth with type 2 diabetes have an increased prevalence of associated chronic comorbid conditions, including hypertension, dyslipidemia, and nonalcoholic fatty liver disease. Data indicate that the incidence of type 2 diabetes is rising; from 2002-2003 to 2014-2015, incidence increased from 9.0 cases per 100 000 children and adolescents to 13.8 cases per 100 000 children and adolescents.
Objective
The US Preventive Services Task Force (USPSTF) commissioned a review of the evidence on screening for prediabetes and type 2 diabetes in asymptomatic, nonpregnant persons younger than 18 years. This is a new recommendation.
Population
Children and adolescents younger than 18 years without known diabetes or prediabetes or symptoms of diabetes or prediabetes.
Evidence assessment
The USPSTF concludes that the evidence is insufficient to assess the balance of benefits and harms of screening for type 2 diabetes in children and adolescents. There is a lack of evidence on the effect of screening for, and early detection and treatment of, type 2 diabetes on health outcomes in youth, and the balance of benefits and harms cannot be determined.
Recommendation
The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for type 2 diabetes in children and adolescents. (I statement).



JAMA: 13 Sep 2022; 328:963-967
US Preventive Services Task Force, Mangione CM, Barry MJ, Nicholson WK, ... Tseng CW, Wong JB
JAMA: 13 Sep 2022; 328:963-967 | PMID: 36098719
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Impact:
Abstract

Screening for Prediabetes and Type 2 Diabetes in Children and Adolescents: Evidence Report and Systematic Review for the US Preventive Services Task Force.

Jonas DE, Vander Schaaf EB, Riley S, Allison BA, ... Voisin CE, LeBlanc ES
Importance
Of youths diagnosed with type 2 diabetes, many develop microvascular complications by young adulthood.
Objective
To review the evidence on benefits and harms of screening children and adolescents for prediabetes and type 2 diabetes to inform the US Preventive Services Task Force (USPSTF).
Data sources
PubMed/MEDLINE, Cochrane Library, and trial registries through May 3, 2021; references; experts; literature surveillance through July 22, 2022.
Study selection
English-language controlled studies evaluating screening or interventions for prediabetes or type 2 diabetes that was screen detected or recently diagnosed.
Data extraction and synthesis
Dual review of abstracts, full-text articles, and study quality; qualitative synthesis of findings.
Main outcomes and measures
Mortality, cardiovascular morbidity, diabetes-related morbidity, development of diabetes, quality of life, and harms.
Results
This review included 8 publications (856 participants; mean age, 14 years [range, 10-17 years]). Of those, 6 were from the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study. No eligible studies directly evaluated the benefits or harms of screening. One randomized clinical trial (RCT) (TODAY; n = 699 adolescents with obesity; mean age, 14 years) comparing metformin, metformin plus rosiglitazone, and metformin plus lifestyle intervention reported that 2 youths with recently diagnosed diabetes developed kidney impairment (0 vs 1 vs 1, respectively; P > .99) and 11 developed diabetic ketoacidosis (5 vs 3 vs 3, respectively; P = .70). One RCT of 75 adolescents (mean age, 13 years) with obesity with prediabetes compared an intensive lifestyle intervention with standard care and reported that no participants in either group developed diabetes, although follow-up was only 6 months. Regarding harms of interventions, 2 RCTs assessing different comparisons enrolled youths with recently diagnosed diabetes. Major hypoglycemic events were reported by less than 1% of participants. Minor hypoglycemic events were more common among youths treated with metformin plus rosiglitazone than among those treated with metformin or metformin plus lifestyle intervention in TODAY (8.2% vs 4.3% vs 3.4%, P = .05). In 1 study, gastrointestinal adverse events were more commonly reported by those taking metformin than by those taking placebo (abdominal pain: 25% vs 12%; nausea/vomiting: 17% vs 10%; P not reported).

Conclusions:
and relevance
No eligible studies directly evaluated the benefits or harms of screening for prediabetes and type 2 diabetes in children and adolescents. For youths with prediabetes or recently diagnosed (not screen-detected) diabetes, the only eligible trials reported few health outcomes and found no difference between groups, although evidence was limited by substantial imprecision and a duration of follow-up likely insufficient to assess health outcomes.



JAMA: 13 Sep 2022; 328:968-979
Jonas DE, Vander Schaaf EB, Riley S, Allison BA, ... Voisin CE, LeBlanc ES
JAMA: 13 Sep 2022; 328:968-979 | PMID: 36098720
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Impact:
Abstract

Association of HIV Infection With Cardiovascular Pathology Based on Advanced Cardiovascular Imaging: A Systematic Review.

Hudson JA, Majonga ED, Ferrand RA, Perel P, Alam SR, Shah ASV
Importance
HIV-associated cardiovascular disease is increasing in prevalence, but its mechanisms remain poorly understood.
Objective
To systematically review data from advanced cardiovascular imaging studies evaluating computed tomographic coronary angiography, positron emission tomography (PET), and cardiac magnetic resonance (MR), in people living with HIV compared with uninfected individuals.
Data sources
Three databases and Google Scholar were searched for studies assessing cardiovascular pathology using computed tomographic coronary angiography, cardiac MR, PET, and HIV from inception to February 11, 2022.
Study selection
Two reviewers selected original studies without any restrictions on design, date, or language, investigating HIV and cardiovascular pathology.
Data extraction and synthesis
One investigator extracted data checked by a second investigator. Prevalence ratios (PRs) and differences in inflammation among people living with HIV and uninfected individuals were qualitatively synthesized in terms of cardiovascular pathology. Study quality was assessed using the National Heart, Lung, and Blood Institute quality assessment tool for observational studies.
Main outcomes and measures
Primary outcomes were computed tomographic coronary angiography-defined moderate to severe (≥50%) coronary stenosis, cardiac MR-defined myocardial fibrosis identified by late gadolinium enhancement, and PET-defined vascular and myocardial target to background ratio. Prevalence of moderate to severe coronary disease, as well as myocardial fibrosis, and PRs compared with uninfected individuals were reported alongside difference in vascular target to background ratio.
Results
Forty-five studies including 5218 people living with HIV (mean age, 48.5 years) and 2414 uninfected individuals (mean age, 49.1 years) were identified. Sixteen studies (n = 5107 participants) evaluated computed tomographic coronary angiography; 16 (n = 1698), cardiac MRs; 10 (n = 681), vascular PET scans; and 3 (n = 146), both computed tomographic coronary angiography and vascular PET scans. No studies originated from low-income countries. Regarding risk of bias, 22% were classified as low; 47% moderate; and 31% high. Prevalence of moderate to severe coronary disease among those with vs without HIV ranged from 0% to 52% and 0% to 27%, respectively, with PRs ranging from 0.33 (95% CI, 0.01-15.90) to 5.19 (95% CI, 1.26-21.42). Prevalence of myocardial fibrosis among those with vs without HIV ranged from 5% to 84% and 0% to 68%, respectively, with PRs ranging from 1.01 (95% CI, 0.85-1.21) to 17.35 (95% CI, 1.10-274.28). Differences in vascular target to background ratio among those with vs without HIV ranged from 0.06 (95% CI, 0.01-0.11) to 0.37 (95% CI, 0.02-0.72).

Conclusions:
and relevance
In this systematic review of studies of advanced cardiovascular imaging, the estimates of the associations between HIV and cardiovascular pathologies demonstrated large amounts of heterogeneity. The findings provide a summary of the available data but may not be representative of all individuals living with HIV, including those from low-income countries with higher HIV endemicity.



JAMA: 13 Sep 2022; 328:951-962
Hudson JA, Majonga ED, Ferrand RA, Perel P, Alam SR, Shah ASV
JAMA: 13 Sep 2022; 328:951-962 | PMID: 36098725
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Impact:
Abstract

Five-Year Outcomes in Patients With Fully Magnetically Levitated vs Axial-Flow Left Ventricular Assist Devices in the MOMENTUM 3 Randomized Trial.

Mehra MR, Goldstein DJ, Cleveland JC, Cowger JA, ... Wang A, Uriel N
Importance
Although durable left ventricular assist device (LVAD) therapy has emerged as an important treatment option for patients with advanced heart failure refractory to pharmacological support, outcomes, including survival, beyond 2 years remain poorly characterized.
Objective
To report the composite end point of survival to transplant, recovery, or LVAD support free of debilitating stroke (Modified Rankin Scale score >3) or reoperation to replace the pump 5 years after the implant in participants who received the fully magnetically levitated centrifugal-flow HeartMate 3 or axial-flow HeartMate II LVAD in the MOMENTUM 3 randomized trial and were still receiving LVAD therapy at the 2-year follow-up.
Design, setting, and participants
This observational study was a 5-year follow-up of the MOMENTUM 3 trial, conducted in 69 US centers, that demonstrated superiority of the centrifugal-flow LVAD to the axial-flow pump with respect to survival to transplant, recovery, or LVAD support free of debilitating stroke or reoperation to replace the pump at 2 years. A total of 295 patients were enrolled between June 2019 to April 2021 in the extended-phase study, with 5-year follow-up completed in September 2021.
Exposures
Of 1020 patients in the investigational device exemption per-protocol population, 536 were still receiving LVAD support at 2 years, of whom 289 received the centrifugal-flow pump and 247 received the axial-flow pump.
Main outcomes and measures
There were 10 end points evaluated at 5 years in the per-protocol population, including a composite of survival to transplant, recovery, or LVAD support free of debilitating stroke or reoperation to replace the pump between the centrifugal-flow and axial-flow pump groups and overall survival between the 2 groups.
Results
A total of 477 patients (295 enrolled and 182 provided limited data) of 536 patients still receiving LVAD support at 2 years contributed to the extended-phase analysis (median age, 62 y; 86 [18%] women). The 5-year Kaplan-Meier estimate of survival to transplant, recovery, or LVAD support free of debilitating stroke or reoperation to replace the pump in the centrifugal-flow vs axial-flow group was 54.0% vs 29.7% (hazard ratio, 0.55 [95% CI, 0.45-0.67]; P < .001). Overall Kaplan-Meier survival was 58.4% in the centrifugal-flow group vs 43.7% in the axial-flow group (hazard ratio, 0.72 [95% CI, 0.58-0.89]; P = .003). Serious adverse events of stroke, bleeding, and pump thrombosis were less frequent in the centrifugal-flow pump group.

Conclusions:
and relevance
In this observational follow-up study of patients from the MOMENTUM 3 randomized trial, per-protocol analyses found that receipt of a fully magnetically levitated centrifugal-flow LVAD vs axial-flow LVAD was associated with a better composite outcome and higher likelihood of overall survival at 5 years. These findings support the use of the fully magnetically levitated LVAD.
Trial registration
ClinicalTrials.gov Identifier: NCT02224755 and NCT03982979.



JAMA: 08 Sep 2022; epub ahead of print
Mehra MR, Goldstein DJ, Cleveland JC, Cowger JA, ... Wang A, Uriel N
JAMA: 08 Sep 2022; epub ahead of print | PMID: 36074476
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Impact:
Abstract

Diagnosis and Treatment of Myelodysplastic Syndromes: A Review.

Sekeres MA, Taylor J
Importance
Myelodysplastic neoplasms (MDS), formerly known as myelodysplastic syndromes, are clonal hematopoietic malignancies that cause morphologic bone marrow dysplasia along with anemia, neutropenia, or thrombocytopenia. MDS are associated with an increased risk of acute myeloid leukemia (AML). The yearly incidence of MDS is approximately 4 per 100 000 people in the United States and is higher among patients with advanced age.
Observations
MDS are characterized by reduced numbers of peripheral blood cells, an increased risk of acute myeloid leukemia transformation, and reduced survival. The median age at diagnosis is approximately 70 years, and the yearly incidence rate increases to 25 per 100 000 in people aged 65 years and older. Risk factors associated with MDS include older age and prior exposures to toxins such as chemotherapy or radiation therapy. MDS are more common in men compared with women (with yearly incidence rates of approximately 5.4 vs 2.9 per 100 000). MDS typically has an insidious presentation, consisting of signs and symptoms associated with anemia, thrombocytopenia, and neutropenia. MDS can be categorized into subtypes that are associated with lower or higher risk for acute myeloid leukemia transformation and that help with therapy selection. Patients with lower-risk MDS have a median survival of approximately 3 to 10 years, whereas patients with higher-risk disease have a median survival of less than 3 years. Therapy for lower-risk MDS is selected based on whether the primary clinical characteristic is anemia, thrombocytopenia, or neutropenia. Management focuses on treating symptoms and reducing the number of required transfusions in patients with low-risk disease. For patients with lower-risk MDS, erythropoiesis stimulating agents, such as recombinant humanized erythropoietin or the longer-acting erythropoietin, darbepoetin alfa, can improve anemia in 15% to 40% of patients for a median of 8 to 23 months. For those with higher-risk MDS, hypomethylating agents such as azacitidine, decitabine, or decitabine/cedazuridine are first-line therapy. Hematopoietic cell transplantation is considered for higher-risk patients and represents the only potential cure.

Conclusions:
and relevance
MDS are diagnosed in approximately 4 per 100 000 people in the United States and are associated with a 5-year survival rate of approximately 37%. Treatments are tailored to the patient\'s disease characteristics and comorbidities and range from supportive care with or without erythropoiesis-stimulating agents for patients with low-risk MDS to hypomethylating agents, such as azacitidine or decitabine, for patients with higher-risk MDS. Hematopoietic cell transplantation is potentially curative and should be considered for patients with higher-risk MDS at the time of diagnosis.



JAMA: 06 Sep 2022; 328:872-880
Sekeres MA, Taylor J
JAMA: 06 Sep 2022; 328:872-880 | PMID: 36066514
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Impact:
Abstract

Effect of an Individualized Audit and Feedback Intervention on Rates of Musculoskeletal Diagnostic Imaging Requests by Australian General Practitioners: A Randomized Clinical Trial.

O\'Connor DA, Glasziou P, Maher CG, McCaffery KJ, ... Clark B, Buchbinder R
Importance
Audit and feedback can improve professional practice, but few trials have evaluated its effectiveness in reducing potential overuse of musculoskeletal diagnostic imaging in general practice.
Objective
To evaluate the effectiveness of audit and feedback for reducing musculoskeletal imaging by high-requesting Australian general practitioners (GPs).
Design, setting, and participants
This factorial cluster-randomized clinical trial included 2271 general practices with at least 1 GP who was in the top 20% of referrers for 11 imaging tests (of the lumbosacral or cervical spine, shoulder, hip, knee, and ankle/hind foot) and for at least 4 individual tests between January and December 2018. Only high-requesting GPs within participating practices were included. The trial was conducted between November 2019 and May 2021, with final follow-up on May 8, 2021.
Interventions
Eligible practices were randomized in a 1:1:1:1:1 ratio to 1 of 4 different individualized written audit and feedback interventions (n = 3055 GPs) that varied factorially by (1) frequency of feedback (once vs twice) and (2) visual display (standard vs enhanced display highlighting highly requested tests) or to a control condition of no intervention (n = 764 GPs). Participants were not masked.
Main outcomes and measures
The primary outcome was the overall rate of requests for the 11 targeted imaging tests per 1000 patient consultations over 12 months, assessed using routinely collected administrative data. Primary analyses included all randomized GPs who had at least 1 patient consultation during the study period and were performed by statisticians masked to group allocation.
Results
A total of 3819 high-requesting GPs from 2271 practices were randomized, and 3660 GPs (95.8%; n = 727 control, n = 2933 intervention) were included in the primary analysis. Audit and feedback led to a statistically significant reduction in the overall rate of imaging requests per 1000 consultations compared with control over 12 months (adjusted mean, 27.7 [95% CI, 27.5-28.0] vs 30.4 [95% CI, 29.8-30.9], respectively; adjusted mean difference, -2.66 [95% CI, -3.24 to -2.07]; P < .001).

Conclusions:
and relevance
Among Australian general practitioners known to frequently request musculoskeletal diagnostic imaging, an individualized audit and feedback intervention, compared with no intervention, significantly decreased the rate of targeted musculoskeletal imaging tests ordered over 12 months.
Trial registration
ANZCTR Identifier: ACTRN12619001503112.



JAMA: 06 Sep 2022; 328:850-860
O'Connor DA, Glasziou P, Maher CG, McCaffery KJ, ... Clark B, Buchbinder R
JAMA: 06 Sep 2022; 328:850-860 | PMID: 36066518
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Impact:
Abstract

Association of Race and Ethnicity With Prescription of SGLT2 Inhibitors and GLP1 Receptor Agonists Among Patients With Type 2 Diabetes in the Veterans Health Administration System.

Lamprea-Montealegre JA, Madden E, Tummalapalli SL, Peralta C, ... Shlipak MG, Estrella MM
Importance
Novel therapies for type 2 diabetes can reduce the risk of cardiovascular disease and chronic kidney disease progression. The equitability of these agents\' prescription across racial and ethnic groups has not been well-evaluated.
Objective
To investigate differences in the prescription of sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA) among adult patients with type 2 diabetes by racial and ethnic groups.
Design, setting, and participants
Cross-sectional analysis of data from the US Veterans Health Administration\'s Corporate Data Warehouse. The sample included adult patients with type 2 diabetes and at least 2 primary care clinic visits from January 1, 2019, to December 31, 2020.
Exposures
Self-identified race and self-identified ethnicity.
Main outcomes and measures
The primary outcomes were prevalent SGLT2i or GLP-1 RA prescription, defined as any active prescription during the study period.
Results
Among 1 197 914 patients (mean age, 68 years; 96% men; 1% American Indian or Alaska Native, 2% Asian, Native Hawaiian, or Other Pacific Islander, 20% Black or African American, 71% White, and 7% of Hispanic or Latino ethnicity), 10.7% and 7.7% were prescribed an SGLT2i or a GLP-1 RA, respectively. Prescription rates for SGLT2i and GLP-1 RA, respectively, were 11% and 8.4% among American Indian or Alaska Native patients; 11.8% and 8% among Asian, Native Hawaiian, or Other Pacific Islander patients; 8.8% and 6.1% among Black or African American patients; and 11.3% and 8.2% among White patients, respectively. Prescription rates for SGLT2i and GLP-1 RA, respectively, were 11% and 7.1% among Hispanic or Latino patients and 10.7% and 7.8% among non-Hispanic or Latino patients. After accounting for patient- and system-level factors, all racial groups had significantly lower odds of SGLT2i and GLP-1 RA prescription compared with White patients. Black patients had the lowest odds of prescription compared with White patients (adjusted odds ratio, 0.72 [95% CI, 0.71-0.74] for SGLT2i and 0.64 [95% CI, 0.63-0.66] for GLP-1 RA). Patients of Hispanic or Latino ethnicity had significantly lower odds of prescription (0.90 [95% CI, 0.88-0.93] for SGLT2i and 0.88 [95% CI, 0.85-0.91] for GLP-1 RA) compared with non-Hispanic or Latino patients.

Conclusions:
and relevance
Among patients with type 2 diabetes in the Veterans Health Administration system during 2019 and 2020, prescription rates of SGLT2i and GLP-1 RA medications were low, and individuals of several different racial groups and those of Hispanic ethnicity had statistically significantly lower odds of receiving prescriptions for these medications compared with individuals of White race and non-Hispanic ethnicity. Further research is needed to understand the mechanisms underlying these differences in rates of prescribing and the potential relationship with differences in clinical outcomes.



JAMA: 06 Sep 2022; 328:861-871
Lamprea-Montealegre JA, Madden E, Tummalapalli SL, Peralta C, ... Shlipak MG, Estrella MM
JAMA: 06 Sep 2022; 328:861-871 | PMID: 36066519
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Impact:
Abstract

Effect of Clinical Decision Support With Audit and Feedback on Prevention of Acute Kidney Injury in Patients Undergoing Coronary Angiography: A Randomized Clinical Trial.

James MT, Har BJ, Tyrrell BD, Faris PD, ... Klarenbach SW, Graham MM
Importance
Contrast-associated acute kidney injury (AKI) is a common complication of coronary angiography and percutaneous coronary intervention (PCI) that has been associated with high costs and adverse long-term outcomes.
Objective
To determine whether a multifaceted intervention is effective for the prevention of AKI after coronary angiography or PCI.
Design, setting, and participants
A stepped-wedge, cluster randomized clinical trial was conducted in Alberta, Canada, that included all invasive cardiologists at 3 cardiac catheterization laboratories who were randomized to various start dates for the intervention between January 2018 and September 2019. Eligible patients were aged 18 years or older who underwent nonemergency coronary angiography, PCI, or both; who were not undergoing dialysis; and who had a predicted AKI risk of greater than 5%. Thirty-four physicians performed 7820 procedures among 7106 patients who met the inclusion criteria. Participant follow-up ended in November 2020.
Interventions
During the intervention period, cardiologists received educational outreach, computerized clinical decision support on contrast volume and hemodynamic-guided intravenous fluid targets, and audit and feedback. During the control (preintervention) period, cardiologists provided usual care and did not receive the intervention.
Main outcomes and measures
The primary outcome was AKI. There were 12 secondary outcomes, including contrast volume, intravenous fluid administration, and major adverse cardiovascular and kidney events. The analyses were conducted using time-adjusted models.
Results
Of the 34 participating cardiologists who were divided into 8 clusters by practice group and center, the intervention group included 31 who performed 4327 procedures among 4032 patients (mean age, 70.3 [SD, 10.7] years; 1384 were women [32.0%]) and the control group included 34 who performed 3493 procedures among 3251 patients (mean age, 70.2 [SD, 10.8] years; 1151 were women [33.0%]). The incidence of AKI was 7.2% (310 events after 4327 procedures) during the intervention period and 8.6% (299 events after 3493 procedures) during the control period (between-group difference, -2.3% [95% CI, -0.6% to -4.1%]; odds ratio [OR], 0.72 [95% CI, 0.56 to 0.93]; P = .01). Of 12 prespecified secondary outcomes, 8 showed no significant difference. The proportion of procedures in which excessive contrast volumes were used was reduced to 38.1% during the intervention period from 51.7% during the control period (between-group difference, -12.0% [95% CI, -14.4% to -9.4%]; OR, 0.77 [95% CI, 0.65 to 0.90]; P = .002). The proportion of procedures in eligible patients in whom insufficient intravenous fluid was given was reduced to 60.8% during the intervention period from 75.1% during the control period (between-group difference, -15.8% [95% CI, -19.7% to -12.0%]; OR, 0.68 [95% CI, 0.53 to 0.87]; P = .002). There were no significant between-group differences in major adverse cardiovascular events or major adverse kidney events.

Conclusions:
and relevance
Among cardiologists randomized to an intervention including clinical decision support with audit and feedback, patients undergoing coronary procedures during the intervention period were less likely to develop AKI compared with those treated during the control period, with a time-adjusted absolute risk reduction of 2.3%. Whether this intervention would show efficacy outside this study setting requires further investigation.
Trial registration
ClinicalTrials.gov Identifier: NCT03453996.



JAMA: 06 Sep 2022; 328:839-849
James MT, Har BJ, Tyrrell BD, Faris PD, ... Klarenbach SW, Graham MM
JAMA: 06 Sep 2022; 328:839-849 | PMID: 36066520
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Impact:
Abstract

Changes in Health and Quality of Life in US Skilled Nursing Facilities by COVID-19 Exposure Status in 2020.

Barnett ML, Waken RJ, Zheng J, Orav EJ, ... Grabowski DC, Joynt Maddox KE
Importance
During the COVID-19 pandemic, the US federal government required that skilled nursing facilities (SNFs) close to visitors and eliminate communal activities. Although these policies were intended to protect residents, they may have had unintended negative effects.
Objective
To assess health outcomes among SNFs with and without known COVID-19 cases.
Design, setting, and participants
This retrospective observational study used US Medicare claims and Minimum Data Set 3.0 for January through November in each year beginning in 2018 and ending in 2020 including 15 477 US SNFs with 2 985 864 resident-years.
Exposures
January through November of calendar years 2018, 2019, and 2020. COVID-19 diagnoses were used to assign SNFs into 2 mutually exclusive groups with varying membership by month in 2020: active COVID-19 (≥1 COVID-19 diagnosis in the current or past month) or no-known COVID-19 (no observed diagnosis by that month).
Main outcomes and measures
Monthly rates of mortality, hospitalization, emergency department (ED) visits, and monthly changes in activities of daily living (ADLs), body weight, and depressive symptoms. Each SNF in 2018 and 2019 served as its own control for 2020.
Results
In 2018-2019, mean monthly mortality was 2.2%, hospitalization 3.0%, and ED visit rate 2.9% overall. In 2020, among active COVID-19 SNFs compared with their own 2018-2019 baseline, mortality increased by 1.60% (95% CI, 1.58% to 1.62%), hospitalizations decreased by 0.10% (95% CI, -0.12% to -0.09%), and ED visit rates decreased by 0.57% (95% CI, -0.59% to -0.55%). Among no-known COVID-19 SNFs, mortality decreased by 0.15% (95% CI, -0.16% to -0.13%), hospitalizations by 0.83% (95% CI, -0.85% to -0.81%), and ED visits by 0.79% (95% CI, -0.81% to -0.77%). All changes were statistically significant. In 2018-2019, across all SNFs, residents required assistance with an additional 0.89 ADLs between January and November, and lost 1.9 lb; 27.1% had worsened depressive symptoms. In 2020, residents in active COVID-19 SNFs required assistance with an additional 0.36 ADLs (95% CI, 0.34 to 0.38), lost 3.1 lb (95% CI, -3.2 to -3.0 lb) more weight, and were 4.4% (95% CI, 4.1% to 4.7%) more likely to have worsened depressive symptoms, all statistically significant changes. In 2020, residents in no-known COVID-19 SNFs had no significant change in ADLs (-0.06 [95% CI, -0.12 to 0.01]), but lost 1.8 lb (95% CI, -2.1 to -1.5 lb) more weight and were 3.2% more likely (95% CI, 2.3% to 4.1%) to have worsened depressive symptoms, both statistically significant changes.

Conclusions:
and relevance
Among skilled nursing facilities in the US during the first year of the COVID-19 pandemic and prior to the availability of COVID-19 vaccination, mortality and functional decline significantly increased at facilities with active COVID-19 cases compared with the prepandemic period, while a modest statistically significant decrease in mortality was observed at facilities that had never had a known COVID-19 case. Weight loss and depressive symptoms significantly increased in skilled nursing facilities in the first year of the pandemic, regardless of COVID-19 status.



JAMA: 29 Aug 2022; epub ahead of print
Barnett ML, Waken RJ, Zheng J, Orav EJ, ... Grabowski DC, Joynt Maddox KE
JAMA: 29 Aug 2022; epub ahead of print | PMID: 36036916
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Impact:
Abstract

Concordance of SARS-CoV-2 Results in Self-collected Nasal Swabs vs Swabs Collected by Health Care Workers in Children and Adolescents.

Waggoner JJ, Vos MB, Tyburski EA, Nguyen PV, ... Martin GS, Lam WA
Importance
Despite the expansion of SARS-CoV-2 testing, available tests have not received Emergency Use Authorization for performance with self-collected anterior nares (nasal) swabs from children younger than 14 years because the effect of pediatric self-swabbing on SARS-CoV-2 test sensitivity is unknown.
Objective
To characterize the ability of school-aged children to self-collect nasal swabs for SARS-CoV-2 testing compared with collection by health care workers.
Design, setting, and participants
Cross-sectional study of 197 symptomatic children and adolescents aged 4 to 14 years old. Individuals were recruited based on results of testing in the Children\'s Healthcare of Atlanta system from July to August 2021.
Exposures
Children and adolescents were given instructional material consisting of a short instructional video and a handout with written and visual steps for self-swab collection. Participants first provided a self-collected nasal swab. Health care workers then collected a second specimen.
Main outcomes and measures
The primary outcome was SARS-CoV-2 detection and relative quantitation by cycle threshold (Ct) in self- vs health care worker-collected nasal swabs when tested with a real-time reverse transcriptase-polymerase chain reaction test with Emergency Use Authorization.
Results
Among the study participants, 108 of 194 (55.7%) were male and the median age was 9 years (IQR, 6-11). Of the 196 participants, 87 (44.4%) tested positive for SARS-CoV-2 and 105 (53.6%) tested negative by both self- and health care worker-collected swabs. Two children tested positive by self- or health care worker-collected swab alone; 1 child had an invalid health care worker swab. Compared with health care worker-collected swabs, self-collected swabs had 97.8% (95% CI, 94.7%-100.0%) and 98.1% (95% CI, 95.6%-100.0%) positive and negative percent agreement, respectively, and SARS-CoV-2 Ct values did not differ significantly between groups (mean [SD] Ct, self-swab: 26.7 [5.4] vs health care worker swab: 26.3 [6.0]; P = .65).

Conclusions:
and relevance
After hearing and seeing simple instructional materials, children and adolescents aged 4 to 14 years self-collected nasal swabs that closely agreed on SARS-CoV-2 detection with swabs collected by health care workers.



JAMA: 26 Aug 2022; epub ahead of print
Waggoner JJ, Vos MB, Tyburski EA, Nguyen PV, ... Martin GS, Lam WA
JAMA: 26 Aug 2022; epub ahead of print | PMID: 36018570
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Impact:
Abstract

Statin Use for the Primary Prevention of Cardiovascular Disease in Adults: US Preventive Services Task Force Recommendation Statement.

US Preventive Services Task Force, Mangione CM, Barry MJ, Nicholson WK, ... Stevermer J, Wong JB
Importance
Cardiovascular disease (CVD) is the leading cause of morbidity and death in the US and is the cause of more than 1 of every 4 deaths. Coronary heart disease is the single leading cause of death and accounts for 43% of deaths attributable to CVD in the US. In 2019, an estimated 558 000 deaths were caused by coronary heart disease and 109 000 deaths were caused by ischemic stroke.
Objective
To update its 2016 recommendation, the US Preventive Services Task Force (USPSTF) commissioned a review of the evidence on the benefits and harms of statins for reducing CVD-related morbidity or mortality or all-cause mortality.
Population
Adults 40 years or older without a history of known CVD and who do not have signs and symptoms of CVD.
Evidence assessment
The USPSTF concludes with moderate certainty that statin use for the prevention of CVD events and all-cause mortality in adults aged 40 to 75 years with no history of CVD and who have 1 or more CVD risk factors (ie, dyslipidemia, diabetes, hypertension, or smoking) and an estimated 10-year CVD event risk of 10% or greater has at least a moderate net benefit. The USPSTF concludes with moderate certainty that statin use for the prevention of CVD events and all-cause mortality in adults aged 40 to 75 years with no history of CVD and who have 1 or more of these CVD risk factors and an estimated 10-year CVD event risk of 7.5% to less than 10% has at least a small net benefit. The USPSTF concludes that the evidence is insufficient to determine the balance of benefits and harms of statin use for the primary prevention of CVD events and mortality in adults 76 years or older with no history of CVD.
Recommendation
The USPSTF recommends that clinicians prescribe a statin for the primary prevention of CVD for adults aged 40 to 75 years who have 1 or more CVD risk factors (ie, dyslipidemia, diabetes, hypertension, or smoking) and an estimated 10-year CVD risk of 10% or greater. (B recommendation) The USPSTF recommends that clinicians selectively offer a statin for the primary prevention of CVD for adults aged 40 to 75 years who have 1 or more of these CVD risk factors and an estimated 10-year CVD risk of 7.5% to less than 10%. The likelihood of benefit is smaller in this group than in persons with a 10-year risk of 10% or greater. (C recommendation) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of initiating a statin for the primary prevention of CVD events and mortality in adults 76 years or older. (I statement).



JAMA: 23 Aug 2022; 328:746-753
US Preventive Services Task Force, Mangione CM, Barry MJ, Nicholson WK, ... Stevermer J, Wong JB
JAMA: 23 Aug 2022; 328:746-753 | PMID: 35997723
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Impact:
Abstract

Statin Use for the Primary Prevention of Cardiovascular Disease in Adults: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Chou R, Cantor A, Dana T, Wagner J, ... Fu R, Ferencik M
Importance
A 2016 review for the US Preventive Services Task Force (USPSTF) found use of statins for primary prevention of cardiovascular disease (CVD) was associated with reduced mortality and cardiovascular outcomes.
Objective
To update the 2016 review on statins for primary prevention of CVD to inform the USPSTF.
Data sources
Ovid MEDLINE, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews (to November 2021); surveillance through May 20, 2022.
Study selection
Randomized clinical trials on statins vs placebo or no statin and statin intensity in adults without prior cardiovascular events; large cohort studies on harms.
Data extraction and synthesis
One investigator abstracted data; a second checked accuracy. Two investigators independently rated study quality.
Main outcomes and measures
All-cause and cardiovascular mortality, myocardial infarction, stroke, composite cardiovascular outcomes, and adverse events.
Results
Twenty-six studies were included: 22 trials (N = 90 624) with 6 months to 6 years of follow-up compared statins vs placebo or no statin, 1 trial (n = 5144) compared statin intensities, and 3 observational studies (n = 417 523) reported harms. Statins were significantly associated with decreased risk of all-cause mortality (risk ratio [RR], 0.92 [95% CI, 0.87 to 0.98]; absolute risk difference [ARD], -0.35% [95% CI, -0.57% to -0.14%]), stroke (RR, 0.78 [95% CI, 0.68 to 0.90]; ARD, -0.39% [95% CI, -0.54% to -0.25%]), myocardial infarction (RR, 0.67 [95% CI, 0.60 to 0.75]; ARD, -0.85% [95% CI, -1.22% to -0.47%]), and composite cardiovascular outcomes (RR, 0.72 [95% CI, 0.64 to 0.81]; ARD, -1.28% [95% CI, -1.61% to -0.95%]); the association with cardiovascular mortality was not statistically significant (RR, 0.91 [95% CI, 0.81 to 1.02]; ARD, -0.13%). Relative benefits were consistent in groups defined by demographic and clinical characteristics, although data for persons older than 75 years were sparse. Statin therapy was not significantly associated with increased risk of serious adverse events (RR, 0.97 [95% CI, 0.93 to 1.01]), myalgias (RR, 0.98 [95% CI, 0.86 to 1.11]), or elevated alanine aminotransferase level (RR, 0.94 [95% CI, 0.78 to 1.13]). Statin therapy was not significantly associated with increased diabetes risk overall (RR, 1.04 [95% CI, 0.92 to 1.19]), although 1 trial found high-intensity statin therapy was significantly associated with increased risk (RR, 1.25 [95% CI, 1.05 to 1.49]). Otherwise, there were no clear differences in outcomes based on statin intensity.

Conclusions:
and relevance
In adults at increased CVD risk but without prior CVD events, statin therapy for primary prevention of CVD was associated with reduced risk of all-cause mortality and CVD events. Benefits of statin therapy appear to be present across diverse demographic and clinical populations, with consistent relative benefits in groups defined by demographic and clinical characteristics.



JAMA: 23 Aug 2022; 328:754-771
Chou R, Cantor A, Dana T, Wagner J, ... Fu R, Ferencik M
JAMA: 23 Aug 2022; 328:754-771 | PMID: 35997724
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Impact:
Abstract

Effect of Radiotherapy Alone vs Radiotherapy With Concurrent Chemoradiotherapy on Survival Without Disease Relapse in Patients With Low-risk Nasopharyngeal Carcinoma: A Randomized Clinical Trial.

Tang LL, Guo R, Zhang N, Deng B, ... Sun Y, Ma J
Importance
Concurrent chemoradiotherapy has been the standard treatment for stage II nasopharyngeal carcinoma (NPC) based on data using 2-dimensional conventional radiotherapy. There is limited evidence for the role of chemotherapy with use of intensity-modulated radiation therapy (IMRT).
Objective
To assess whether concurrent chemotherapy can be safely omitted for patients with low-risk stage II/T3N0 NPC treated with IMRT.
Design, setting, and participants
This multicenter, open-label, randomized, phase 3, noninferiority clinical trial was conducted at 5 Chinese hospitals, including 341 adult patients with low-risk NPC, defined as stage II/T3N0M0 without adverse features (all nodes <3 cm, no level IV/Vb nodes; no extranodal extension; Epstein-Barr virus DNA <4000 copies/mL), with enrollment between November 2015 and August 2020. The final date of follow-up was March 15, 2022.
Interventions
Patients were randomly assigned to receive IMRT alone (n = 172) or concurrent chemoradiotherapy (IMRT with cisplatin, 100 mg/m2 every 3 weeks for 3 cycles [n = 169]).
Main outcomes and measures
The primary end point was 3-year failure-free survival (time from randomization to any disease relapse or death), with a noninferiority margin of 10%. Secondary end points comprised overall survival, locoregional relapse-free survival, distant metastasis-free survival, adverse events, and health-related quality of life (QOL) measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30; range, 0-100 points; minimum clinically important difference ≥10 for physical function, symptom control, or health-related QOL; higher score indicates better functioning and global health status or worse symptoms).
Results
Among 341 randomized patients (mean [SD] age, 48 [10] years; 30% women), 334 (98.0%) completed the trial. Median follow-up was 46 months (IQR, 34-58). Three-year failure-free survival was 90.5% for the IMRT-alone group vs 91.9% for the concurrent chemoradiotherapy group (difference, -1.4%; 1-sided 95% CI, -7.4% to ∞; P value for noninferiority, <.001). No significant differences were observed between groups in overall survival, locoregional relapse, or distant metastasis. The IMRT-alone group experienced a significantly lower incidence of grade 3 to 4 adverse events (17% vs 46%; difference, -29% [95% CI, -39% to -20%]), including hematologic toxicities (leukopenia, neutropenia) and nonhematologic toxicities (nausea, vomiting, anorexia, weight loss, mucositis). The IMRT-alone group had significantly better QOL scores during radiotherapy including the domains of global health status, social functioning, fatigue, nausea and vomiting, pain, insomnia, appetite loss, and constipation.

Conclusions:
and relevance
Among patients with low-risk NPC, treatment with IMRT alone resulted in 3-year failure-free survival that was not inferior to concurrent chemoradiotherapy.
Trial registration
ClinicalTrials.gov Identifier: NCT02633202.



JAMA: 23 Aug 2022; 328:728-736
Tang LL, Guo R, Zhang N, Deng B, ... Sun Y, Ma J
JAMA: 23 Aug 2022; 328:728-736 | PMID: 35997729
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Impact:
Abstract

Effect of Aspirin vs Enoxaparin on Symptomatic Venous Thromboembolism in Patients Undergoing Hip or Knee Arthroplasty: The CRISTAL Randomized Trial.

CRISTAL Study Group, Sidhu VS, Kelly TL, Pratt N, ... Wysocki D, Harris IA
Importance
There remains a lack of randomized trials investigating aspirin monotherapy for symptomatic venous thromboembolism (VTE) prophylaxis following total hip arthroplasty (THA) or total knee arthroplasty (TKA).
Objective
To determine whether aspirin was noninferior to enoxaparin in preventing symptomatic VTE after THA or TKA.
Design, setting, and participants
Cluster-randomized, crossover, registry-nested trial across 31 hospitals in Australia. Clusters were hospitals performing greater than 250 THA or TKA procedures annually. Patients (aged ≥18 years) undergoing hip or knee arthroplasty procedures were enrolled at each hospital. Patients receiving preoperative anticoagulation or who had a medical contraindication to either study drug were excluded. A total of 9711 eligible patients were enrolled (5675 in the aspirin group and 4036 in the enoxaparin group) between April 20, 2019, and December 18, 2020. Final follow-up occurred on August 14, 2021.
Interventions
Hospitals were randomized to administer aspirin (100 mg/d) or enoxaparin (40 mg/d) for 35 days after THA and for 14 days after TKA. Crossover occurred after the patient enrollment target had been met for the first group. All 31 hospitals were initially randomized and 16 crossed over prior to trial cessation.
Main outcomes and measures
The primary outcome was symptomatic VTE within 90 days, including pulmonary embolism and deep venous thrombosis (DVT) (above or below the knee). The noninferiority margin was 1%. Six secondary outcomes are reported, including death and major bleeding within 90 days. Analyses were performed by randomization group.
Results
Enrollment was stopped after an interim analysis determined the stopping rule was met, with 9711 patients (median age, 68 years; 56.8% female) of the prespecified 15 562 enrolled (62%). Of these, 9203 (95%) completed the trial. Within 90 days of surgery, symptomatic VTE occurred in 256 patients, including pulmonary embolism (79 cases), above-knee DVT (18 cases), and below-knee DVT (174 cases). The symptomatic VTE rate in the aspirin group was 3.45% and in the enoxaparin group was 1.82% (estimated difference, 1.97%; 95% CI, 0.54%-3.41%). This failed to meet the criterion for noninferiority for aspirin and was significantly superior for enoxaparin (P = .007). Of 6 secondary outcomes, none were significantly better in the enoxaparin group compared with the aspirin group.

Conclusions:
and relevance
Among patients undergoing hip or knee arthroplasty for osteoarthritis, aspirin compared with enoxaparin resulted in a significantly higher rate of symptomatic VTE within 90 days, defined as below- or above-knee DVT or pulmonary embolism. These findings may be informed by a cost-effectiveness analysis.
Trial registration
ANZCTR Identifier: ACTRN12618001879257.



JAMA: 23 Aug 2022; 328:719-727
CRISTAL Study Group, Sidhu VS, Kelly TL, Pratt N, ... Wysocki D, Harris IA
JAMA: 23 Aug 2022; 328:719-727 | PMID: 35997730
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Impact:
Abstract

Trends in Lipid Concentrations and Lipid Control Among US Adults, 2007-2018.

Aggarwal R, Bhatt DL, Rodriguez F, Yeh RW, Wadhera RK
Importance
High lipid concentrations are a modifiable risk factor for cardiovascular disease. Little is known about how population-level lipid concentrations, as well as trends in lipid control, have changed over the past decade among US adults.
Objective
To determine whether lipid concentrations and rates of lipid control changed among US adults and whether these trends differed by sex and race and ethnicity, from 2007 to 2018.
Design, setting, and participants
Serial cross-sectional analysis of 33 040 US adults aged 20 years or older, weighted to be nationally representative, from the National Health and Nutrition Examination Surveys (2007-2008 to 2017-2018).
Main outcomes and measures
Lipid concentrations among US adults and rates of lipid control among adults receiving statin therapy. Lipid control was defined as a total cholesterol concentration of 200 mg/dL or less.
Results
The mean age of the study population was 47.4 years, and 51.4% were women; of the 33 040 participants, 12.0% were non-Hispanic Black; 10.3%, Mexican American; 6.4%, other Hispanic American; 62.7%, non-Hispanic White; and 8.5%, other race and ethnicities (including non-Hispanic Asian. Among all US adults, age-adjusted total cholesterol improved significantly in the overall population from 197 mg/dL in 2007-2008 to 189 mg/dL in 2017-2018 (difference, -8.6 mg/dL [95% CI, -12.2 to -4.9 mg/dL]; P for trend <.001), with similar patterns for men and women. Black, Mexican American, other Hispanic, and White adults experienced significant improvements in total cholesterol, but no significant change was observed for Asian adults. Among adults receiving statin therapy, age-adjusted lipid control rates did not significantly change from 78.5% in 2007-2008 to 79.5% in 2017-2018 (difference, 1.1% [95% CI, -3.7% to 5.8%]; P for trend = .27), and these patterns were similar for men and women. Across all racial and ethnic groups, only Mexican Americans experienced a significant improvement in age-adjusted lipid control (P for trend = .008). In 2015-2018, age-adjusted rates of lipid control were significantly lower for women than for men (OR, 0.54 [95% CI, 0.40 to 0.72]). In addition, when compared with White adults, rates of lipid control while taking statins were significantly lower among Black adults (OR, 0.66 [95% CI, 0.47 to 0.94]) and other Hispanic adults (OR, 0.59 [95% CI, 0.37 to 0.95]); no significant differences were observed for other racial and ethnic groups.

Conclusions:
and relevance
In this serial cross-sectional study, lipid concentrations improved in the US adult population from 2007-2008 through 2017-2018. These patterns were observed across all racial and ethnic subgroups, with the exception of non-Hispanic Asian adults.



JAMA: 23 Aug 2022; 328:737-745
Aggarwal R, Bhatt DL, Rodriguez F, Yeh RW, Wadhera RK
JAMA: 23 Aug 2022; 328:737-745 | PMID: 35997731
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Impact:
Abstract

Barrett Esophagus: A Review.

Sharma P
Importance
Barrett esophagus is characterized by the replacement of normal esophageal squamous cell epithelium with columnar metaplasia and affects approximately 5% of people in the US and approximately 1% worldwide. Approximately 3% to 5% of patients with Barrett esophagus will be diagnosed with esophageal adenocarcinoma in their lifetime.
Observations
Barrett esophagus affects approximately 2.3% to 8.3% of people with gastroesophageal reflux disease (GERD) and approximately 1.2% to 5.6% of people without GERD. Characteristics associated with Barrett esophagus include older age (prevalence of approximately 1.1% in individuals older than 50 years compared with 0.3% in those 50 years or younger), male sex, and smoking (prevalence of approximately 12% in people who smoke cigarettes compared with 1.1% in those who do not smoke cigarettes). The histopathology of Barrett esophagus progresses from metaplasia to dysplasia and, without treatment, can progress to adenocarcinoma. People with Barrett esophagus have approximately a 0.2% to 0.5% annual rate of developing esophageal adenocarcinoma. Management of Barrett esophagus primarily consists of acid-suppressive medications to reduce underlying GERD symptoms and surveillance endoscopy every 3 to 5 years. In patients with Barrett esophagus and dysplasia or early cancer, endoscopic therapy consisting of resection and ablation successfully treats 80% to 90% of patients.

Conclusions:
and relevance
Barrett esophagus affects approximately 5% of people in the US and approximately 1% worldwide and is associated with an increased risk of esophageal adenocarcinoma. First-line therapy for Barrett esophagus consists of proton-pump inhibitors for control of reflux symptoms, but their role in chemoprevention is unclear. Surveillance with upper endoscopy is recommended by practice guidelines to monitor for progression to esophageal adenocarcinoma, but randomized clinical trials are lacking.



JAMA: 16 Aug 2022; 328:663-671
Sharma P
JAMA: 16 Aug 2022; 328:663-671 | PMID: 35972481
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Impact:
Abstract

Effect of Remote Ischemic Conditioning vs Usual Care on Neurologic Function in Patients With Acute Moderate Ischemic Stroke: The RICAMIS Randomized Clinical Trial.

Chen HS, Cui Y, Li XQ, Wang XH, ... Wang DL, RICAMIS Investigators
Importance
Preclinical and clinical studies have suggested a neuroprotective effect of remote ischemic conditioning (RIC), which involves repeated occlusion/release cycles on bilateral upper limb arteries; however, robust evidence in patients with ischemic stroke is lacking.
Objective
To assess the efficacy of RIC for acute moderate ischemic stroke.
Design, setting, and participants
This multicenter, open-label, blinded-end point, randomized clinical trial including 1893 patients with acute moderate ischemic stroke was conducted at 55 hospitals in China from December 26, 2018, through January 19, 2021, and the date of final follow-up was April 19, 2021.
Interventions
Eligible patients were randomly assigned within 48 hours after symptom onset to receive treatment with RIC (using a pneumatic electronic device and consisting of 5 cycles of cuff inflation for 5 minutes and deflation for 5 minutes to the bilateral upper limbs to 200 mm Hg) for 10 to 14 days as an adjunct to guideline-based treatment (n = 922) or guideline-based treatment alone (n = 971).
Main outcomes and measures
The primary end point was excellent functional outcome at 90 days, defined as a modified Rankin Scale score of 0 to 1. All end points had blinded assessment and were analyzed on a full analysis set.
Results
Among 1893 eligible patients with acute moderate ischemic stroke who were randomized (mean [SD] age, 65 [10.3] years; 606 women [34.1%]), 1776 (93.8%) completed the trial. The number with excellent functional outcome at 90 days was 582 (67.4%) in the RIC group and 566 (62.0%) in the control group (risk difference, 5.4% [95% CI, 1.0%-9.9%]; odds ratio, 1.27 [95% CI, 1.05-1.54]; P = .02). The proportion of patients with any adverse events was 6.8% (59/863) in the RIC group and 5.6% (51/913) in the control group.

Conclusions:
and relevance
Among adults with acute moderate ischemic stroke, treatment with remote ischemic conditioning compared with usual care significantly increased the likelihood of excellent neurologic function at 90 days. However, these findings require replication in another trial before concluding efficacy for this intervention.
Trial registration
ClinicalTrials.gov Identifier: NCT03740971.



JAMA: 16 Aug 2022; 328:627-636
Chen HS, Cui Y, Li XQ, Wang XH, ... Wang DL, RICAMIS Investigators
JAMA: 16 Aug 2022; 328:627-636 | PMID: 35972485
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Impact:
Abstract

Association of COVID-19 vs Influenza With Risk of Arterial and Venous Thrombotic Events Among Hospitalized Patients.

Lo Re V, Dutcher SK, Connolly JG, Perez-Vilar S, ... Zhou Y, Cocoros NM
Importance
The incidence of arterial thromboembolism and venous thromboembolism in persons with COVID-19 remains unclear.
Objective
To measure the 90-day risk of arterial thromboembolism and venous thromboembolism in patients hospitalized with COVID-19 before or during COVID-19 vaccine availability vs patients hospitalized with influenza.
Design, setting, and participants
Retrospective cohort study of 41 443 patients hospitalized with COVID-19 before vaccine availability (April-November 2020), 44 194 patients hospitalized with COVID-19 during vaccine availability (December 2020-May 2021), and 8269 patients hospitalized with influenza (October 2018-April 2019) in the US Food and Drug Administration Sentinel System (data from 2 national health insurers and 4 regional integrated health systems).
Exposures
COVID-19 or influenza (identified by hospital diagnosis or nucleic acid test).
Main outcomes and measures
Hospital diagnosis of arterial thromboembolism (acute myocardial infarction or ischemic stroke) and venous thromboembolism (deep vein thrombosis or pulmonary embolism) within 90 days. Outcomes were ascertained through July 2019 for patients with influenza and through August 2021 for patients with COVID-19. Propensity scores with fine stratification were developed to account for differences between the influenza and COVID-19 cohorts. Weighted Cox regression was used to estimate the adjusted hazard ratios (HRs) for outcomes during each COVID-19 vaccine availability period vs the influenza period.
Results
A total of 85 637 patients with COVID-19 (mean age, 72 [SD, 13.0] years; 50.5% were male) and 8269 with influenza (mean age, 72 [SD, 13.3] years; 45.0% were male) were included. The 90-day absolute risk of arterial thromboembolism was 14.4% (95% CI, 13.6%-15.2%) in patients with influenza vs 15.8% (95% CI, 15.5%-16.2%) in patients with COVID-19 before vaccine availability (risk difference, 1.4% [95% CI, 1.0%-2.3%]) and 16.3% (95% CI, 16.0%-16.6%) in patients with COVID-19 during vaccine availability (risk difference, 1.9% [95% CI, 1.1%-2.7%]). Compared with patients with influenza, the risk of arterial thromboembolism was not significantly higher among patients with COVID-19 before vaccine availability (adjusted HR, 1.04 [95% CI, 0.97-1.11]) or during vaccine availability (adjusted HR, 1.07 [95% CI, 1.00-1.14]). The 90-day absolute risk of venous thromboembolism was 5.3% (95% CI, 4.9%-5.8%) in patients with influenza vs 9.5% (95% CI, 9.2%-9.7%) in patients with COVID-19 before vaccine availability (risk difference, 4.1% [95% CI, 3.6%-4.7%]) and 10.9% (95% CI, 10.6%-11.1%) in patients with COVID-19 during vaccine availability (risk difference, 5.5% [95% CI, 5.0%-6.1%]). Compared with patients with influenza, the risk of venous thromboembolism was significantly higher among patients with COVID-19 before vaccine availability (adjusted HR, 1.60 [95% CI, 1.43-1.79]) and during vaccine availability (adjusted HR, 1.89 [95% CI, 1.68-2.12]).

Conclusions:
and relevance
Based on data from a US public health surveillance system, hospitalization with COVID-19 before and during vaccine availability, vs hospitalization with influenza in 2018-2019, was significantly associated with a higher risk of venous thromboembolism within 90 days, but there was no significant difference in the risk of arterial thromboembolism within 90 days.



JAMA: 16 Aug 2022; 328:637-651
Lo Re V, Dutcher SK, Connolly JG, Perez-Vilar S, ... Zhou Y, Cocoros NM
JAMA: 16 Aug 2022; 328:637-651 | PMID: 35972486
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Impact:
Abstract

Trends in Active Treatment of Live-born Neonates Between 22 Weeks 0 Days and 25 Weeks 6 Days by Gestational Age and Maternal Race and Ethnicity in the US, 2014 to 2020.

Venkatesh KK, Lynch CD, Costantine MM, Backes CH, ... Khan SS, Grobman WA
Importance
Birth in the periviable period between 22 weeks 0 days and 25 weeks 6 days\' gestation is a major source of neonatal morbidity and mortality, and the decision to initiate active life-saving treatment is challenging.
Objective
To assess whether the frequency of active treatment among live-born neonates in the periviable period has changed over time and whether active treatment differed by gestational age at birth and race and ethnicity.
Design, setting, and participants
Serial cross-sectional descriptive study using National Center for Health Statistics natality data from 2014 to 2020 for 61 908 singleton live births without clinical anomalies between 22 weeks 0 days and 25 weeks 6 days in the US.
Exposures
Year of delivery, gestational age at birth, and race and ethnicity of the pregnant individual, stratified as non-Hispanic Asian/Pacific Islander, non-Hispanic Black, Hispanic/Latina, and non-Hispanic White.
Main outcomes and measures
Active treatment, determined by whether there was an attempt to treat the neonate and defined as a composite of surfactant therapy, immediate assisted ventilation at birth, assisted ventilation more than 6 hours in duration, and/or antibiotic therapy. Frequencies, mean annual percent change (APC), and adjusted risk ratios (aRRs) were estimated.
Results
Of 26 986 716 live births, 61 908 (0.2%) were periviable live births included in this study: 5% were Asian/Pacific Islander, 37% Black, 24% Hispanic, and 34% White; and 14% were born at 22 weeks, 21% at 23 weeks, 30% at 24 weeks, and 34% at 25 weeks. Fifty-two percent of neonates received active treatment. From 2014 to 2020, the overall frequency (mean APC per year) of active treatment increased significantly (3.9% [95% CI, 3.0% to 4.9%]), as well as among all racial and ethnic subgroups (Asian/Pacific Islander: 3.4% [95% CI, 0.8% to 6.0%]); Black: 4.7% [95% CI, 3.4% to 5.9%]; Hispanic: 4.7% [95% CI, 3.4% to 5.9%]; and White: 3.1% [95% CI, 1.1% to 4.4%]) and among each gestational age range (22 weeks: 14.4% [95% CI, 11.1% to 17.7%] and 25 weeks: 2.9% [95% CI, 1.5% to 4.2%]). Compared with neonates born to White individuals (57.0%), neonates born to Asian/Pacific Islander (46.2%; risk difference [RD], -10.81 [95% CI, -12.75 to -8.88]; aRR, 0.82 [95% CI, [0.79-0.86]), Black (51.6%; RD, -5.42 [95% CI, -6.36 to -4.50]; aRR, 0.90 [95% CI, 0.89 to 0.92]), and Hispanic (48.0%; RD, -9.03 [95% CI, -10.07 to -7.99]; aRR, 0.83 [95% CI, 0.81 to 0.85]) individuals were significantly less likely to receive active treatment.

Conclusions:
and relevance
From 2014 to 2020 in the US, the frequency of active treatment among neonates born alive between 22 weeks 0 days and 25 weeks 6 days significantly increased, and there were differences in rates of active treatment by race and ethnicity.



JAMA: 16 Aug 2022; 328:652-662
Venkatesh KK, Lynch CD, Costantine MM, Backes CH, ... Khan SS, Grobman WA
JAMA: 16 Aug 2022; 328:652-662 | PMID: 35972487
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Impact:
Abstract

Association of Younger vs Older Ages With Changes in Incidence of Stroke and Other Vascular Events, 2002-2018.

Li L, Scott CA, Rothwell PM
Importance
Some studies have reported increasing stroke incidence at younger ages (<55 years) but have often relied only on administrative data, and more population-based studies of adjudicated stroke are required. An understanding of the drivers of any increase in incidence of young stroke also requires comparisons with stroke trends at older ages and with trends in incidence of other vascular events at younger ages.
Objective
To determine temporal changes in incidence of stroke and other major vascular events at younger vs older ages.
Design, setting, and participants
Prospective population-based incidence study conducted from April 2002 to March 2018 with a mean catchment population of 94 567 in Oxfordshire, England.
Exposures
Calendar time, premorbid vascular risk factors, and occupation.
Main outcomes and measures
Changes in incidence of stroke, transient ischemic attack (TIA), and other major vascular events (myocardial infarction, sudden cardiac death, and peripheral vascular events) stratified by age, sex, diagnostic workup, etiology, and severity.
Results
A total of 2429 incident strokes were ascertained (mean age, 73.6 [SD, 14.4] years; 51.3% female). From 2002-2010 to 2010-2018, stroke incidence increased significantly among participants younger than 55 years (incidence rate ratio [IRR], 1.67; 95% CI, 1.31-2.14) but fell significantly among participants aged 55 years or older (IRR, 0.85; 95% CI, 0.78-0.92; P < .001 for difference). The significant increase in incidence at younger than 55 years was independent of sex, stroke severity, pathological subtype, and changes in investigation and was also seen for TIA (IRR, 1.87; 95% CI, 1.36-2.57) but not for myocardial infarction and other major vascular events (IRR, 0.73; 95% CI, 0.58-0.93). Although TIA and stroke at younger than 55 years were significantly associated with diabetes (risk ratio [RR], 3.47; 95% CI, 2.54-4.74), hypertension (RR, 2.52; 95% CI, 2.04-3.12), current smoking (RR, 2.38; 95% CI, 1.92-2.94), and obesity (RR, 1.36; 95% CI, 1.07-1.72), the significant increase in incidence from 2002-2010 to 2010-2018 was still seen in individuals without these risk factors. The increase was greatest in professional/managerial occupations (IRR, 2.52; 95% CI, 1.75-3.62) and least in partially skilled/unskilled occupations (IRR, 1.17; 95% CI, 0.79-1.74). The proportion of TIAs and strokes among those younger than 55 years without known vascular risk factors increased significantly over time (45 [30.4%] vs 115 [42.4%]; absolute difference, 12.0%; 95% CI, 2.6-21.5), especially in patients with cryptogenic events (10 [18.5%] vs 63 [49.2%]; absolute difference, 30.7%; 95% CI, 17.2-44.2; P < .001; P = .002 for heterogeneity).

Conclusions:
and relevance
Comparing persons living in Oxfordshire, England, in 2002-2010 vs 2010-2018, there was a significant increase in stroke incidence in those younger than 55 years, but a decrease in those aged 55 years or older. Given the absence of this divergence for other vascular events, further research is needed to understand the causes of this difference.



JAMA: 09 Aug 2022; 328:563-574
Li L, Scott CA, Rothwell PM
JAMA: 09 Aug 2022; 328:563-574 | PMID: 35943470
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Impact:
Abstract

Effect of Intravenous Tirofiban vs Placebo Before Endovascular Thrombectomy on Functional Outcomes in Large Vessel Occlusion Stroke: The RESCUE BT Randomized Clinical Trial.

RESCUE BT Trial Investigators, Qiu Z, Li F, Sang H, ... Zi W, Yang Q
Importance
Tirofiban is a highly selective nonpeptide antagonist of glycoprotein IIb/IIIa receptor, which reversibly inhibits platelet aggregation. It remains uncertain whether intravenous tirofiban is effective to improve functional outcomes for patients with large vessel occlusion ischemic stroke undergoing endovascular thrombectomy.
Objective
To assess the efficacy and adverse events of intravenous tirofiban before endovascular thrombectomy for acute ischemic stroke secondary to large vessel occlusion.
Design, setting, and participants
This investigator-initiated, randomized, double-blind, placebo-controlled trial was implemented at 55 hospitals in China, enrolling 948 patients with stroke and proximal intracranial large vessel occlusion presenting within 24 hours of time last known well. Recruitment took place between October 10, 2018, and October 31, 2021, with final follow-up on January 15, 2022.
Interventions
Participants received intravenous tirofiban (n = 463) or placebo (n = 485) prior to endovascular thrombectomy.
Main outcomes and measures
The primary outcome was disability level at 90 days as measured by overall distribution of the modified Rankin Scale scores from 0 (no symptoms) to 6 (death). The primary safety outcome was the incidence of symptomatic intracranial hemorrhage within 48 hours.
Results
Among 948 patients randomized (mean age, 67 years; 391 [41.2%] women), 948 (100%) completed the trial. The median (IQR) 90-day modified Rankin Scale score in the tirofiban group vs placebo group was 3 (1-4) vs 3 (1-4). The adjusted common odds ratio for a lower level of disability with tirofiban vs placebo was 1.08 (95% CI, 0.86-1.36). Incidence of symptomatic intracranial hemorrhage was 9.7% in the tirofiban group vs 6.4% in the placebo group (difference, 3.3% [95% CI, -0.2% to 6.8%]).

Conclusions:
and relevance
Among patients with large vessel occlusion acute ischemic stroke undergoing endovascular thrombectomy, treatment with intravenous tirofiban, compared with placebo, before endovascular therapy resulted in no significant difference in disability severity at 90 days. The findings do not support use of intravenous tirofiban before endovascular thrombectomy for acute ischemic stroke.
Trial registration
Chinese Clinical Trial Registry Identifier: ChiCTR-IOR-17014167.



JAMA: 09 Aug 2022; 328:543-553
RESCUE BT Trial Investigators, Qiu Z, Li F, Sang H, ... Zi W, Yang Q
JAMA: 09 Aug 2022; 328:543-553 | PMID: 35943471
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Impact:
Abstract

Effect of Stenting Plus Medical Therapy vs Medical Therapy Alone on Risk of Stroke and Death in Patients With Symptomatic Intracranial Stenosis: The CASSISS Randomized Clinical Trial.

Gao P, Wang T, Wang D, Liebeskind DS, ... Jiao L, CASSISS Trial Investigators
Importance
Prior randomized trials have generally shown harm or no benefit of stenting added to medical therapy for patients with symptomatic severe intracranial atherosclerotic stenosis, but it remains uncertain as to whether refined patient selection and more experienced surgeons might result in improved outcomes.
Objective
To compare stenting plus medical therapy vs medical therapy alone in patients with symptomatic severe intracranial atherosclerotic stenosis.
Design, setting, and participants
Multicenter, open-label, randomized, outcome assessor-blinded trial conducted at 8 centers in China. A total of 380 patients with transient ischemic attack or nondisabling, nonperforator (defined as nonbrainstem or non-basal ganglia end artery) territory ischemic stroke attributed to severe intracranial stenosis (70%-99%) and beyond a duration of 3 weeks from the latest ischemic symptom onset were recruited between March 5, 2014, and November 10, 2016, and followed up for 3 years (final follow-up: November 10, 2019).
Interventions
Medical therapy plus stenting (n = 176) or medical therapy alone (n = 182). Medical therapy included dual-antiplatelet therapy for 90 days (single antiplatelet therapy thereafter) and stroke risk factor control.
Main outcomes and measures
The primary outcome was a composite of stroke or death within 30 days or stroke in the qualifying artery territory beyond 30 days through 1 year. There were 5 secondary outcomes, including stroke in the qualifying artery territory at 2 years and 3 years as well as mortality at 3 years.
Results
Among 380 patients who were randomized, 358 were confirmed eligible (mean age, 56.3 years; 263 male [73.5%]) and 343 (95.8%) completed the trial. For the stenting plus medical therapy group vs medical therapy alone, no significant difference was found for the primary outcome of risk of stroke or death (8.0% [14/176] vs 7.2% [13/181]; difference, 0.4% [95% CI, -5.0% to 5.9%]; hazard ratio, 1.10 [95% CI, 0.52-2.35]; P = .82). Of the 5 prespecified secondary end points, none showed a significant difference including stroke in the qualifying artery territory at 2 years (9.9% [17/171] vs 9.0% [16/178]; difference, 0.7% [95% CI, -5.4% to 6.7%]; hazard ratio, 1.10 [95% CI, 0.56-2.16]; P = .80) and 3 years (11.3% [19/168] vs 11.2% [19/170]; difference, -0.2% [95% CI, -7.0% to 6.5%]; hazard ratio, 1.00 [95% CI, 0.53-1.90]; P > .99). Mortality at 3 years was 4.4% (7/160) in the stenting plus medical therapy group vs 1.3% (2/159) in the medical therapy alone group (difference, 3.2% [95% CI, -0.5% to 6.9%]; hazard ratio, 3.75 [95% CI, 0.77-18.13]; P = .08).

Conclusions:
and relevance
Among patients with transient ischemic attack or ischemic stroke due to symptomatic severe intracranial atherosclerotic stenosis, the addition of percutaneous transluminal angioplasty and stenting to medical therapy, compared with medical therapy alone, resulted in no significant difference in the risk of stroke or death within 30 days or stroke in the qualifying artery territory beyond 30 days through 1 year. The findings do not support the addition of percutaneous transluminal angioplasty and stenting to medical therapy for the treatment of patients with symptomatic severe intracranial atherosclerotic stenosis.
Trial registration
ClinicalTrials.gov Identifier: NCT01763320.



JAMA: 09 Aug 2022; 328:534-542
Gao P, Wang T, Wang D, Liebeskind DS, ... Jiao L, CASSISS Trial Investigators
JAMA: 09 Aug 2022; 328:534-542 | PMID: 35943472
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Impact:
Abstract

Association of Dual Antiplatelet Therapy With Ticagrelor With Vein Graft Failure After Coronary Artery Bypass Graft Surgery: A Systematic Review and Meta-analysis.

Sandner S, Redfors B, Angiolillo DJ, Audisio K, ... Zhu Y, Gaudino M
Importance
The role of ticagrelor with or without aspirin after coronary artery bypass graft surgery remains unclear.
Objective
To compare the risks of vein graft failure and bleeding associated with ticagrelor dual antiplatelet therapy (DAPT) or ticagrelor monotherapy vs aspirin among patients undergoing coronary artery bypass graft surgery.
Data sources
MEDLINE, Embase, and Cochrane Library databases from inception to June 1, 2022, without language restriction.
Study selection
Randomized clinical trials (RCTs) comparing the effects of ticagrelor DAPT or ticagrelor monotherapy vs aspirin on saphenous vein graft failure.
Data extraction and synthesis
Individual patient data provided by each trial were synthesized into a combined data set for independent analysis. Multilevel logistic regression models were used.
Main outcomes and measures
The primary analysis assessed the incidence of saphenous vein graft failure per graft (primary outcome) in RCTs comparing ticagrelor DAPT with aspirin. Secondary outcomes were saphenous vein graft failure per patient and Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding events. A supplementary analysis included RCTs comparing ticagrelor monotherapy with aspirin.
Results
A total of 4 RCTs were included in the meta-analysis, involving 1316 patients and 1668 saphenous vein grafts. Of the 871 patients in the primary analysis, 435 received ticagrelor DAPT (median age, 67 years [IQR, 60-72 years]; 65 women [14.9%]; 370 men [85.1%]) and 436 received aspirin (median age, 66 years [IQR, 61-73 years]; 63 women [14.5%]; 373 men [85.5%]). Ticagrelor DAPT was associated with a significantly lower incidence of saphenous vein graft failure (11.2%) per graft than was aspirin (20%; difference, -8.7% [95% CI, -13.5% to -3.9%]; OR, 0.51 [95% CI, 0.35 to 0.74]; P < .001) and was associated with a significantly lower incidence of saphenous vein graft failure per patient (13.2% vs 23.0%, difference, -9.7% [95% CI, -14.9% to -4.4%]; OR, 0.51 [95% CI, 0.35 to 0.74]; P < .001). Ticagrelor DAPT (22.1%) was associated with a significantly higher incidence of BARC type 2, 3, or 5 bleeding events than was aspirin (8.7%; difference, 13.3% [95% CI, 8.6% to 18.0%]; OR, 2.98 [95% CI, 1.99 to 4.47]; P < .001), but not BARC type 3 or 5 bleeding events (1.8% vs 1.8%, difference, 0% [95% CI, -1.8% to 1.8%]; OR, 1.00 [95% CI, 0.37 to 2.69]; P = .99). Compared with aspirin, ticagrelor monotherapy was not significantly associated with saphenous vein graft failure (19.3% vs 21.7%, difference, -2.6% [95% CI, -9.1% to 3.9%]; OR, 0.86 [95% CI, 0.58 to 1.27]; P = .44) or BARC type 2, 3, or 5 bleeding events (8.9% vs 7.3%, difference, 1.7% [95% CI, -2.8% to 6.1%]; OR, 1.25 [95% CI, 0.69 to 2.29]; P = .46).

Conclusions:
and relevance
Among patients undergoing coronary artery bypass graft surgery, adding ticagrelor to aspirin was associated with a significantly decreased risk of vein graft failure. However, this was accompanied by a significantly increased risk of clinically important bleeding.



JAMA: 09 Aug 2022; 328:554-562
Sandner S, Redfors B, Angiolillo DJ, Audisio K, ... Zhu Y, Gaudino M
JAMA: 09 Aug 2022; 328:554-562 | PMID: 35943473
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Impact:
Abstract

Diagnosis, Treatment, and Prevention of Malaria in the US: A Review.

Daily JP, Minuti A, Khan N
Importance
Malaria is caused by protozoa parasites of the genus Plasmodium and is diagnosed in approximately 2000 people in the US each year who have returned from visiting regions with endemic malaria. The mortality rate from malaria is approximately 0.3% in the US and 0.26% worldwide.
Observations
In the US, most malaria is diagnosed in people who traveled to an endemic region. More than 80% of people diagnosed with malaria in the US acquired the infection in Africa. Of the approximately 2000 people diagnosed with malaria in the US in 2017, an estimated 82.4% were adults and about 78.6% were Black or African American. Among US residents diagnosed with malaria, 71.7% had not taken malaria chemoprophylaxis during travel. In 2017 in the US, P falciparum was the species diagnosed in approximately 79% of patients, whereas P vivax was diagnosed in an estimated 11.2% of patients. In 2017 in the US, severe malaria, defined as vital organ involvement including shock, pulmonary edema, significant bleeding, seizures, impaired consciousness, and laboratory abnormalities such as kidney impairment, acidosis, anemia, or high parasitemia, occurred in approximately 14% of patients, and an estimated 0.3% of those receiving a diagnosis of malaria in the US died. P falciparum has developed resistance to chloroquine in most regions of the world, including Africa. First-line therapy for P falciparum malaria in the US is combination therapy that includes artemisinin. If P falciparum was acquired in a known chloroquine-sensitive region such as Haiti, chloroquine remains an alternative option. When artemisinin-based combination therapies are not available, atovaquone-proguanil or quinine plus clindamycin is used for chloroquine-resistant malaria. P vivax, P ovale, P malariae, and P knowlesi are typically chloroquine sensitive, and treatment with either artemisinin-based combination therapy or chloroquine for regions with chloroquine-susceptible infections for uncomplicated malaria is recommended. For severe malaria, intravenous artesunate is first-line therapy. Treatment of mild malaria due to a chloroquine-resistant parasite consists of a combination therapy that includes artemisinin or chloroquine for chloroquine-sensitive malaria. P vivax and P ovale require additional therapy with an 8-aminoquinoline to eradicate the liver stage. Several options exist for chemoprophylaxis and selection should be based on patient characteristics and preferences.

Conclusions:
and relevance
Approximately 2000 cases of malaria are diagnosed each year in the US, most commonly in travelers returning from visiting endemic areas. Prevention and treatment of malaria depend on the species and the drug sensitivity of parasites from the region of acquisition. Intravenous artesunate is first-line therapy for severe malaria.



JAMA: 02 Aug 2022; 328:460-471
Daily JP, Minuti A, Khan N
JAMA: 02 Aug 2022; 328:460-471 | PMID: 35916842
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Impact:
Abstract

Association Between Gout Flare and Subsequent Cardiovascular Events Among Patients With Gout.

Cipolletta E, Tata LJ, Nakafero G, Avery AJ, Mamas MA, Abhishek A
Importance
Gout is associated with cardiovascular diseases. The temporal association between gout flares and cardiovascular events has not been investigated.
Objective
To investigate whether there is a transient increase in risk of cardiovascular events after a recent gout flare.
Design, setting, and participants
A retrospective observational study was conducted using electronic health records from the Clinical Practice Research Datalink in England between January 1, 1997, and December 31, 2020. A multivariable nested case-control study was performed among 62 574 patients with gout, and a self-controlled case series, adjusted for season and age, was performed among 1421 patients with gout flare and cardiovascular event.
Exposures
Gout flares were ascertained using hospitalization, primary care outpatient, and prescription records.
Main outcomes and measures
The primary outcome was a cardiovascular event, defined as an acute myocardial infarction or stroke. Association with recent prior gout flares was measured using adjusted odds ratios (ORs) with 95% CIs in a nested case-control study and adjusted incidence rate ratios (IRRs) with 95% CIs in a self-controlled case series.
Results
Among patients with a new diagnosis of gout (mean age, 76.5 years; 69.3% men, 30.7% women), 10 475 patients with subsequent cardiovascular events were matched with 52 099 patients without cardiovascular events. Patients with cardiovascular events, compared with those who did not have cardiovascular events, had significantly higher odds of gout flare within the prior 0 to 60 days (204/10 475 [2.0%] vs 743/52 099 [1.4%]; adjusted OR, 1.93 [95% CI, 1.57-2.38]) and within the prior 61 to 120 days (170/10 475 [1.6%] vs 628/52 099 [1.2%]; adjusted OR, 1.57 [95% CI, 1.26-1.96]). There was no significant difference in the odds of gout flare within the prior 121 to 180 days (148/10 475 [1.4%] vs 662/52 099 [1.3%]; adjusted OR, 1.06 [95% CI, 0.84-1.34]). In the self-controlled case series (N = 1421), cardiovascular event rates per 1000 person-days were 2.49 (95% CI, 2.16-2.82) within days 0 to 60; 2.16 (95% CI, 1.85-2.47) within days 61 to 120; and 1.70 (95% CI, 1.42-1.98) within days 121 to 180 after a gout flare, compared with cardiovascular event rates of 1.32 (95% CI, 1.23-1.41) per 1000 person-days within the 150 days before or the 181 to 540 days after the gout flare. Compared with 150 days before or the 181 to 540 days after a gout flare, incidence rate differences for cardiovascular events were 1.17 (95% CI, 0.83-1.52) per 1000 person-days, and adjusted IRRs were 1.89 (95% CI, 1.54-2.30) within days 0 to 60; 0.84 (95% CI, 0.52-1.17) per 1000 person-days and 1.64 (95% CI, 1.45-1.86) within days 61 to 120; and 0.38 (95% CI, 0.09-0.67) per 1000 person-days and 1.29 (95% CI, 1.02-1.64) within days 121 to 180 after a gout flare.

Conclusions:
and relevance
Among individuals with gout, those who experienced a cardiovascular event, compared with those who did not experience such an event, had significantly higher odds of a recent gout flare in the preceding days. These findings suggest gout flares are associated with a transient increase in cardiovascular events following the flare.



JAMA: 02 Aug 2022; 328:440-450
Cipolletta E, Tata LJ, Nakafero G, Avery AJ, Mamas MA, Abhishek A
JAMA: 02 Aug 2022; 328:440-450 | PMID: 35916846
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Impact:
Abstract

Association Between Dialysis Facility Ownership and Access to the Waiting List and Transplant in Pediatric Patients With End-stage Kidney Disease in the US.

Amaral S, McCulloch CE, Lin F, Grimes BA, ... Siyahian S, Ku E
Importance
Care of adults at profit vs nonprofit dialysis facilities has been associated with lower access to transplant. Whether profit status is associated with transplant access for pediatric patients with end-stage kidney disease is unknown.
Objective
To determine whether profit status of dialysis facilities is associated with placement on the kidney transplant waiting list or receipt of kidney transplant among pediatric patients receiving maintenance dialysis.
Design, setting, and participants
This retrospective cohort study reviewed the US Renal Data System records of 13 333 patients younger than 18 years who started dialysis from 2000 through 2018 in US dialysis facilities (followed up through June 30, 2019).
Exposures
Time-updated profit status of dialysis facilities.
Main outcomes and measures
Cox models, adjusted for clinical and demographic factors, were used to examine time to wait-listing and receipt of kidney transplant by profit status of dialysis facilities.
Results
A total of 13 333 pediatric patients who started receiving maintenance dialysis were included in the analysis (median age, 12 years [IQR, 3-15 years]; 6054 females [45%]; 3321 non-Hispanic Black patients [25%]; 3695 Hispanic patients [28%]). During a median follow-up of 0.87 years (IQR, 0.39-1.85 years), the incidence of wait-listing was lower at profit facilities than at nonprofit facilities, 36.2 vs 49.8 per 100 person-years, respectively (absolute risk difference, -13.6 (95% CI, -15.4 to -11.8 per 100 person-years; adjusted hazard ratio [HR] for wait-listing at profit vs nonprofit facilities, 0.79; 95% CI, 0.75-0.83). During a median follow-up of 1.52 years (IQR, 0.75-2.87 years), the incidence of kidney transplant (living or deceased donor) was also lower at profit facilities than at nonprofit facilities, 21.5 vs 31.3 per 100 person-years, respectively; absolute risk difference, -9.8 (95% CI, -10.9 to -8.6 per 100 person-years) adjusted HR for kidney transplant at profit vs nonprofit facilities, 0.71 (95% CI, 0.67-0.74).

Conclusions:
and relevance
Among a cohort of pediatric patients receiving dialysis in the US from 2000 through 2018, profit facility status was associated with longer time to wait-listing and longer time to kidney transplant.



JAMA: 02 Aug 2022; 328:451-459
Amaral S, McCulloch CE, Lin F, Grimes BA, ... Siyahian S, Ku E
JAMA: 02 Aug 2022; 328:451-459 | PMID: 35916847
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Impact:
Abstract

Effect of Graded Sensorimotor Retraining on Pain Intensity in Patients With Chronic Low Back Pain: A Randomized Clinical Trial.

Bagg MK, Wand BM, Cashin AG, Lee H, ... Moseley GL, McAuley JH
Importance
The effects of altered neural processing, defined as altering neural networks responsible for perceptions of pain and function, on chronic pain remains unclear.
Objective
To estimate the effect of a graded sensorimotor retraining intervention (RESOLVE) on pain intensity in people with chronic low back pain.
Design, setting, and participants
This parallel, 2-group, randomized clinical trial recruited participants with chronic (>3 months) nonspecific low back pain from primary care and community settings. A total of 276 adults were randomized (in a 1:1 ratio) to the intervention or sham procedure and attention control groups delivered by clinicians at a medical research institute in Sydney, Australia. The first participant was randomized on December 10, 2015, and the last was randomized on July 25, 2019. Follow-up was completed on February 3, 2020.
Interventions
Participants randomized to the intervention group (n = 138) were asked to participate in 12 weekly clinical sessions and home training designed to educate them about and assist them with movement and physical activity while experiencing lower back pain. Participants randomized to the control group (n = 138) were asked to participate in 12 weekly clinical sessions and home training that required similar time as the intervention but did not focus on education, movement, and physical activity. The control group included sham laser and shortwave diathermy applied to the back and sham noninvasive brain stimulation.
Main outcomes and measures
The primary outcome was pain intensity at 18 weeks, measured on an 11-point numerical rating scale (range, 0 [no pain] to 10 [worst pain imaginable]) for which the between-group minimum clinically important difference is 1.0 point.
Results
Among 276 randomized patients (mean [SD] age, 46 [14.3] years; 138 [50%] women), 261 (95%) completed follow-up at 18 weeks. The mean pain intensity was 5.6 at baseline and 3.1 at 18 weeks in the intervention group and 5.8 at baseline and 4.0 at 18 weeks in the control group, with an estimated between-group mean difference at 18 weeks of -1.0 point ([95% CI, -1.5 to -0.4]; P = .001), favoring the intervention group.

Conclusions:
and relevance
In this randomized clinical trial conducted at a single center among patients with chronic low back pain, graded sensorimotor retraining, compared with a sham procedure and attention control, significantly improved pain intensity at 18 weeks. The improvements in pain intensity were small, and further research is needed to understand the generalizability of the findings.
Trial registration
ANZCTR Identifier: ACTRN12615000610538.



JAMA: 02 Aug 2022; 328:430-439
Bagg MK, Wand BM, Cashin AG, Lee H, ... Moseley GL, McAuley JH
JAMA: 02 Aug 2022; 328:430-439 | PMID: 35916848
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Impact:
Abstract

Behavioral Counseling Interventions to Promote a Healthy Diet and Physical Activity for Cardiovascular Disease Prevention in Adults Without Cardiovascular Disease Risk Factors: US Preventive Services Task Force Recommendation Statement.

US Preventive Services Task Force, Mangione CM, Barry MJ, Nicholson WK, ... Stevermer J, Wong JB
Importance
Cardiovascular disease (CVD), which includes heart disease, myocardial infarction, and stroke, is the leading cause of death in the US. A large proportion of CVD cases can be prevented by addressing modifiable risk factors, including smoking, obesity, diabetes, elevated blood pressure or hypertension, dyslipidemia, lack of physical activity, and unhealthy diet. Adults who adhere to national guidelines for a healthy diet and physical activity have lower rates of cardiovascular morbidity and mortality than those who do not; however, most US adults do not consume healthy diets or engage in physical activity at recommended levels.
Objective
To update its 2017 recommendation, the US Preventive Services Task Force (USPSTF) commissioned a review of the evidence on the benefits and harms of behavioral counseling interventions to promote healthy behaviors in adults without CVD risk factors.
Population
Adults 18 years or older without known CVD risk factors, which include hypertension or elevated blood pressure, dyslipidemia, impaired fasting glucose or glucose tolerance, or mixed or multiple risk factors such as metabolic syndrome or an estimated 10-year CVD risk of 7.5% or greater.
Evidence assessment
The USPSTF concludes with moderate certainty that behavioral counseling interventions have a small net benefit on CVD risk in adults without CVD risk factors.
Recommendation
The USPSTF recommends that clinicians individualize the decision to offer or refer adults without CVD risk factors to behavioral counseling interventions to promote a healthy diet and physical activity. (C recommendation).



JAMA: 26 Jul 2022; 328:367-374
US Preventive Services Task Force, Mangione CM, Barry MJ, Nicholson WK, ... Stevermer J, Wong JB
JAMA: 26 Jul 2022; 328:367-374 | PMID: 35881115
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Impact:
Abstract

Behavioral Counseling Interventions to Promote a Healthy Diet and Physical Activity for Cardiovascular Disease Prevention in Adults Without Known Cardiovascular Disease Risk Factors: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Patnode CD, Redmond N, Iacocca MO, Henninger M
Importance
Unhealthful dietary patterns, low levels of physical activity, and high sedentary time increase the risk of cardiovascular disease.
Objective
To synthesize the evidence on benefits and harms of behavioral counseling interventions to promote a healthy diet and physical activity in adults without known cardiovascular disease (CVD) risk factors to inform a US Preventive Services Task Force recommendation.
Data sources
MEDLINE, PsycINFO, and the Cochrane Central Register of Controlled Trials through February 2021, with ongoing surveillance through February 2022.
Study selection
Randomized clinical trials (RCTs) of behavioral counseling interventions targeting improved diet, increased physical activity, or decreased sedentary time among adults without known elevated blood pressure, elevated lipid levels, or impaired fasting glucose.
Data extraction and synthesis
Independent data abstraction and study quality rating and random effects meta-analysis.
Main outcomes and measures
CVD events, CVD risk factors, diet and physical activity measures, and harms.
Results
One-hundred thirteen RCTs were included (N = 129 993). Three RCTs reported CVD-related outcomes: 1 study (n = 47 179) found no significant differences between groups on any CVD outcome at up to 13.4 years of follow-up; a combined analysis of the other 2 RCTs (n = 1203) found a statistically significant association of the intervention with nonfatal CVD events (hazard ratio, 0.27 [95% CI, 0.08 to 0.88]) and fatal CVD events (hazard ratio, 0.31 [95% CI, 0.11 to 0.93]) at 4 years. Diet and physical activity behavioral counseling interventions were associated with small, statistically significant reductions in continuous measures of blood pressure (systolic mean difference, -0.8 [95% CI, -1.3 to -0.3]; 23 RCTs [n = 57 079]; diastolic mean difference, -0.4 [95% CI, -0.8 to -0.0]; 24 RCTs [n = 57 148]), low-density lipoprotein cholesterol level (mean difference, 2.2 mg/dL [95% CI, -3.8 to -0.6]; 15 RCTs [n = 6350]), adiposity-related outcomes (body mass index mean difference, -0.3 [95% CI, -0.5 to -0.1]; 27 RCTs [n = 59 239]), dietary outcomes, and physical activity at 6 months to 1.5 years of follow-up vs control conditions. There was no evidence of greater harm among intervention vs control groups.

Conclusions:
and relevance
Healthy diet and physical activity behavioral counseling interventions for persons without a known risk of CVD were associated with small but statistically significant benefits across a variety of important intermediate health outcomes and small to moderate effects on dietary and physical activity behaviors. There was limited evidence regarding the long-term health outcomes or harmful effects of these interventions.



JAMA: 26 Jul 2022; 328:375-388
Patnode CD, Redmond N, Iacocca MO, Henninger M
JAMA: 26 Jul 2022; 328:375-388 | PMID: 35881116
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Impact:
Abstract

Effect of High- vs Low-Dose Tranexamic Acid Infusion on Need for Red Blood Cell Transfusion and Adverse Events in Patients Undergoing Cardiac Surgery: The OPTIMAL Randomized Clinical Trial.

Shi J, Zhou C, Pan W, Sun H, ... Zheng Z, OPTIMAL Study Group
Importance
Tranexamic acid is recommended for reducing blood loss and transfusion in cardiac surgery. However, it remains unknown whether a high dose of tranexamic acid provides better blood-sparing effect than a low dose without increasing the risk of thrombotic complications or seizures in cardiac surgery.
Objective
To compare the efficacy and adverse events of high-dose vs low-dose tranexamic acid in patients undergoing cardiac surgery with cardiopulmonary bypass.
Design, setting, and participants
Multicenter, double-blind, randomized clinical trial among adult patients undergoing cardiac surgery with cardiopulmonary bypass. The study enrolled 3079 patients at 4 hospitals in China from December 26, 2018, to April 21, 2021; final follow-up was on May 21, 2021.
Interventions
Participants received either a high-dose tranexamic acid regimen comprising a 30-mg/kg bolus, a 16-mg/kg/h maintenance dose, and a 2-mg/kg prime (n = 1525) or a low-dose regimen comprising a 10-mg/kg bolus, a 2-mg/kg/h maintenance dose, and a 1-mg/kg prime (n = 1506).
Main outcomes and measures
The primary efficacy end point was the rate of allogeneic red blood cell transfusion after start of operation (superiority hypothesis), and the primary safety end point was a composite of the 30-day postoperative rate of mortality, seizure, kidney dysfunction (stage 2 or 3 Kidney Disease: Improving Global Outcomes [KDIGO] criteria), and thrombotic events (myocardial infarction, ischemic stroke, deep vein thrombosis, and pulmonary embolism) (noninferiority hypothesis with a margin of 5%). There were 15 secondary end points, including the individual components of the primary safety end point.
Results
Among 3079 patients who were randomized to treatment groups (mean age, 52.8 years; 38.1% women), 3031 (98.4%) completed the trial. Allogeneic red blood cell transfusion occurred in 333 of 1525 patients (21.8%) in the high-dose group and 391 of 1506 patients (26.0%) in the low-dose group (risk difference [RD], -4.1% [1-sided 97.55% CI, -∞ to -1.1%]; relative risk, 0.84 [1-sided 97.55% CI, -∞ to 0.96; P = .004]). The composite of postoperative seizure, thrombotic events, kidney dysfunction, and death occurred in 265 patients in the high-dose group (17.6%) and 249 patients in the low-dose group (16.8%) (RD, 0.8%; 1-sided 97.55% CI, -∞ to 3.9%; P = .003 for noninferiority). Fourteen of the 15 prespecified secondary end points were not significantly different between groups, including seizure, which occurred in 15 patients (1.0%) in the high-dose group and 6 patients (0.4%) in the low-dose group (RD, 0.6%; 95% CI, -0.0% to 1.2%; P = .05).

Conclusions:
and relevance
Among patients who underwent cardiac surgery with cardiopulmonary bypass, high-dose compared with low-dose tranexamic acid infusion resulted in a modest statistically significant reduction in the proportion of patients who received allogeneic red blood cell transfusion and met criteria for noninferiority with respect to a composite primary safety end point consisting of 30-day mortality, seizure, kidney dysfunction, and thrombotic events.
Trial registration
ClinicalTrials.gov Identifier: NCT03782350.



JAMA: 26 Jul 2022; 328:336-347
Shi J, Zhou C, Pan W, Sun H, ... Zheng Z, OPTIMAL Study Group
JAMA: 26 Jul 2022; 328:336-347 | PMID: 35881121
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Impact:
Abstract

Effect of Intravitreal Aflibercept vs Laser Photocoagulation on Treatment Success of Retinopathy of Prematurity: The FIREFLEYE Randomized Clinical Trial.

Stahl A, Sukgen EA, Wu WC, Lepore D, ... Azuma N, FIREFLEYE Study Group
Importance
Laser photocoagulation, which is the standard treatment for retinopathy of prematurity (ROP), can have adverse events. Studies of anti-vascular endothelial growth factor injections have suggested efficacy in the treatment of ROP, but few studies have directly compared them with laser treatments.
Objective
To compare intravitreal aflibercept vs laser photocoagulation in infants with ROP requiring treatment.
Design, setting, and participants
This noninferiority, phase 3, 24-week, randomized clinical trial was conducted in 27 countries (64 hospital sites) throughout Asia, Europe, and South America. Overall, 118 infants (gestational age ≤32 weeks at birth or birth weight ≤1500 g) with ROP severity (zone I stage 1+ [stage 1 plus increased disease activity], zone I stage 2+, zone I stage 3, zone I stage 3+, zone II stage 2+, or zone II stage 3+) requiring treatment or with aggressive posterior ROP in at least 1 eye were enrolled between September 25, 2019, and August 28, 2020 (the last visit occurred on February 12, 2021).
Interventions
Infants were randomized 2:1 to receive a 0.4-mg dose of intravitreal aflibercept (n = 75) or laser photocoagulation (n = 43) at baseline. Additional treatment was allowed as prespecified.
Main outcomes and measures
The primary outcome was the proportion of infants without active ROP and unfavorable structural outcomes 24 weeks after starting treatment (assessed by investigators). The requirement for rescue treatment was considered treatment failure. Intravitreal aflibercept was deemed noninferior if the lower limit of the 1-sided 95% bayesian credible interval for the treatment difference was greater than -5%.
Results
Among 118 infants randomized, 113 were treated (mean gestational age, 26.3 [SD, 1.9] weeks; 53 [46.9%] were female; 16.8% had aggressive posterior ROP, 19.5% had zone I ROP, and 63.7% had zone II ROP) and 104 completed the study. Treatment (intravitreal aflibercept: n = 75; laser photocoagulation: n = 38) was mostly bilateral (92.9%), and 82.2% of eyes in the intravitreal aflibercept group received 1 injection per eye. Treatment success was 85.5% with intravitreal aflibercept vs 82.1% with laser photocoagulation (between-group difference, 3.4% [1-sided 95% credible interval, -8.0% to ∞]). Rescue treatment was required in 4.8% (95% CI, 1.9% to 9.6%) of eyes in the intravitreal aflibercept group vs 11.1% (95% CI, 4.9% to 20.7%) of eyes in the laser photocoagulation group. The serious adverse event rates were 13.3% (ocular) and 24.0% (systemic) in the intravitreal aflibercept group compared with 7.9% and 36.8%, respectively, in the laser photocoagulation group. Three deaths, which occurred 4 to 9 weeks after intravitreal aflibercept treatment, were considered unrelated to aflibercept by the investigators.

Conclusions:
and relevance
Among infants with ROP, intravitreal aflibercept compared with laser photocoagulation did not meet criteria for noninferiority with respect to the primary outcome of the proportion of infants achieving treatment success at week 24. Further data would be required for more definitive conclusions regarding the comparative effects of intravitreal aflibercept and laser photocoagulation in this population.
Trial registration
ClinicalTrials.gov Identifier: NCT04004208.



JAMA: 26 Jul 2022; 328:348-359
Stahl A, Sukgen EA, Wu WC, Lepore D, ... Azuma N, FIREFLEYE Study Group
JAMA: 26 Jul 2022; 328:348-359 | PMID: 35881122
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Impact:
Abstract

Spirituality in Serious Illness and Health.

Balboni TA, VanderWeele TJ, Doan-Soares SD, Long KNG, ... Sulmasy DP, Koh HK
Importance
Despite growing evidence, the role of spirituality in serious illness and health has not been systematically assessed.
Objective
To review evidence concerning spirituality in serious illness and health and to identify implications for patient care and health outcomes.
Evidence review
Searches of PubMed, PsycINFO, and Web of Science identified articles with evidence addressing spirituality in serious illness or health, published January 2000 to April 2022. Independent reviewers screened, summarized, and graded articles that met eligibility criteria. Eligible serious illness studies included 100 or more participants; were prospective cohort studies, cross-sectional descriptive studies, meta-analyses, or randomized clinical trials; and included validated spirituality measures. Eligible health outcome studies prospectively examined associations with spirituality as cohort studies, case-control studies, or meta-analyses with samples of at least 1000 or were randomized trials with samples of at least 100 and used validated spirituality measures. Applying Cochrane criteria, studies were graded as having low, moderate, serious, or critical risk of bias, and studies with serious and critical risk of bias were excluded. Multidisciplinary Delphi panels consisting of clinicians, public health personnel, researchers, health systems leaders, and medical ethicists qualitatively synthesized and assessed the evidence and offered implications for health care. Evidence-synthesis statements and implications were derived from panelists\' qualitative input; panelists rated the former on a 9-point scale (from \"inconclusive\" to \"strongest evidence\") and ranked the latter by order of priority.
Findings
Of 8946 articles identified, 371 articles met inclusion criteria for serious illness; of these, 76.9% had low to moderate risk of bias. The Delphi panel review yielded 8 evidence statements supported by evidence categorized as strong and proposed 3 top-ranked implications of this evidence for serious illness: (1) incorporate spiritual care into care for patients with serious illness; (2) incorporate spiritual care education into training of interdisciplinary teams caring for persons with serious illness; and (3) include specialty practitioners of spiritual care in care of patients with serious illness. Of 6485 health outcomes articles, 215 met inclusion criteria; of these, 66.0% had low to moderate risk of bias. The Delphi panel review yielded 8 evidence statements supported by evidence categorized as strong and proposed 3 top-ranked implications of this evidence for health outcomes: (1) incorporate patient-centered and evidence-based approaches regarding associations of spiritual community with improved patient and population health outcomes; (2) increase awareness among health professionals of evidence for protective health associations of spiritual community; and (3) recognize spirituality as a social factor associated with health in research, community assessments, and program implementation.

Conclusions:
and relevance
This systematic review, analysis, and process, based on highest-quality evidence available and expert consensus, provided suggested implications for addressing spirituality in serious illness and health outcomes as part of person-centered, value-sensitive care.



JAMA: 12 Jul 2022; 328:184-197
Balboni TA, VanderWeele TJ, Doan-Soares SD, Long KNG, ... Sulmasy DP, Koh HK
JAMA: 12 Jul 2022; 328:184-197 | PMID: 35819420
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Impact:
Abstract

Effect of Pharmacogenomic Testing for Drug-Gene Interactions on Medication Selection and Remission of Symptoms in Major Depressive Disorder: The PRIME Care Randomized Clinical Trial.

Oslin DW, Lynch KG, Shih MC, Ingram EP, ... Wiechers IR, Wood AE
Importance
Selecting effective antidepressants for the treatment of major depressive disorder (MDD) is an imprecise practice, with remission rates of about 30% at the initial treatment.
Objective
To determine whether pharmacogenomic testing affects antidepressant medication selection and whether such testing leads to better clinical outcomes.
Design, setting, and participants
A pragmatic, randomized clinical trial that compared treatment guided by pharmacogenomic testing vs usual care. Participants included 676 clinicians and 1944 patients. Participants were enrolled from 22 Department of Veterans Affairs medical centers from July 2017 through February 2021, with follow-up ending November 2021. Eligible patients were those with MDD who were initiating or switching treatment with a single antidepressant. Exclusion criteria included an active substance use disorder, mania, psychosis, or concurrent treatment with a specified list of medications.
Interventions
Results from a commercial pharmacogenomic test were given to clinicians in the pharmacogenomic-guided group (n = 966). The comparison group received usual care and access to pharmacogenomic results after 24 weeks (n = 978).
Main outcomes and measures
The co-primary outcomes were the proportion of prescriptions with a predicted drug-gene interaction written in the 30 days after randomization and remission of depressive symptoms as measured by the Patient Health Questionnaire-9 (PHQ-9) (remission was defined as PHQ-9 ≤ 5). Remission was analyzed as a repeated measure across 24 weeks by blinded raters.
Results
Among 1944 patients who were randomized (mean age, 48 years; 491 women [25%]), 1541 (79%) completed the 24-week assessment. The estimated risks for receiving an antidepressant with none, moderate, and substantial drug-gene interactions for the pharmacogenomic-guided group were 59.3%, 30.0%, and 10.7% compared with 25.7%, 54.6%, and 19.7% in the usual care group. The pharmacogenomic-guided group was more likely to receive a medication with a lower potential drug-gene interaction for no drug-gene vs moderate/substantial interaction (odds ratio [OR], 4.32 [95% CI, 3.47 to 5.39]; P < .001) and no/moderate vs substantial interaction (OR, 2.08 [95% CI, 1.52 to 2.84]; P = .005) (P < .001 for overall comparison). Remission rates over 24 weeks were higher among patients whose care was guided by pharmacogenomic testing than those in usual care (OR, 1.28 [95% CI, 1.05 to 1.57]; P = .02; risk difference, 2.8% [95% CI, 0.6% to 5.1%]) but were not significantly higher at week 24 when 130 patients in the pharmacogenomic-guided group and 126 patients in the usual care group were in remission (estimated risk difference, 1.5% [95% CI, -2.4% to 5.3%]; P = .45).

Conclusions:
and relevance
Among patients with MDD, provision of pharmacogenomic testing for drug-gene interactions reduced prescription of medications with predicted drug-gene interactions compared with usual care. Provision of test results had small nonpersistent effects on symptom remission.
Trial registration
ClinicalTrials.gov Identifier: NCT03170362.



JAMA: 12 Jul 2022; 328:151-161
Oslin DW, Lynch KG, Shih MC, Ingram EP, ... Wiechers IR, Wood AE
JAMA: 12 Jul 2022; 328:151-161 | PMID: 35819423
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Impact:
Abstract

Trends in Adverse Event Rates in Hospitalized Patients, 2010-2019.

Eldridge N, Wang Y, Metersky M, Eckenrode S, ... Drye E, Krumholz HM
Importance
Patient safety is a US national priority, yet lacks a comprehensive assessment of progress over the past decade.
Objective
To determine the change in the rate of adverse events in hospitalized patients.
Design, setting, and participants
This serial cross-sectional study used data from the Medicare Patient Safety Monitoring System from 2010 to 2019 to assess in-hospital adverse events in patients. The study included 244 542 adult patients hospitalized in 3156 US acute care hospitals across 4 condition groups from 2010 through 2019: acute myocardial infarction (17%), heart failure (17%), pneumonia (21%), and major surgical procedures (22%); and patients hospitalized from 2012 through 2019 for all other conditions (22%).
Exposures
Adults aged 18 years or older hospitalized during each included calendar year.
Main outcomes and measures
Information on adverse events (abstracted from medical records) included 21 measures across 4 adverse event domains: adverse drug events, hospital-acquired infections, adverse events after a procedure, and general adverse events (hospital-acquired pressure ulcers and falls). The outcomes were the total change over time for the observed and risk-adjusted adverse event rates in the subpopulations.
Results
The study sample included 190 286 hospital discharges combined in the 4 condition-based groups of acute myocardial infarction, heart failure, pneumonia, and major surgical procedures (mean age, 68.0 [SD, 15.9] years; 52.6% were female) and 54 256 hospital discharges for the group including all other conditions (mean age, 57.7 [SD, 20.7] years; 59.8% were female) from 3156 acute care hospitals across the US. From 2010 to 2019, the total change was from 218 to 139 adverse events per 1000 discharges for acute myocardial infarction, from 168 to 116 adverse events per 1000 discharges for heart failure, from 195 to 119 adverse events per 1000 discharges for pneumonia, and from 204 to 130 adverse events per 1000 discharges for major surgical procedures. From 2012 to 2019, the rate of adverse events for all other conditions remained unchanged at 70 adverse events per 1000 discharges. After adjustment for patient and hospital characteristics, the annual change represented by relative risk in all adverse events per 1000 discharges was 0.94 (95% CI, 0.93-0.94) for acute myocardial infarction, 0.95 (95% CI, 0.94-0.96) for heart failure, 0.94 (95% CI, 0.93-0.95) for pneumonia, 0.93 (95% CI, 0.92-0.94) for major surgical procedures, and 0.97 (95% CI, 0.96-0.99) for all other conditions. The risk-adjusted adverse event rates declined significantly in all patient groups for adverse drug events, hospital-acquired infections, and general adverse events. For patients in the major surgical procedures group, the risk-adjusted rates of events after a procedure declined significantly.

Conclusions:
and relevance
In the US between 2010 and 2019, there was a significant decrease in the rates of adverse events abstracted from medical records for patients admitted for acute myocardial infarction, heart failure, pneumonia, and major surgical procedures and there was a significant decrease in the adjusted rates of adverse events between 2012 and 2019 for all other conditions. Further research is needed to understand the extent to which these trends represent a change in patient safety.



JAMA: 12 Jul 2022; 328:173-183
Eldridge N, Wang Y, Metersky M, Eckenrode S, ... Drye E, Krumholz HM
JAMA: 12 Jul 2022; 328:173-183 | PMID: 35819424
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Impact:
Abstract

Changes in the Relationship Between Income and Life Expectancy Before and During the COVID-19 Pandemic, California, 2015-2021.

Schwandt H, Currie J, von Wachter T, Kowarski J, Chapman D, Woolf SH
Importance
The COVID-19 pandemic caused a large decrease in US life expectancy in 2020, but whether a similar decrease occurred in 2021 and whether the relationship between income and life expectancy intensified during the pandemic are unclear.
Objective
To measure changes in life expectancy in 2020 and 2021 and the relationship between income and life expectancy by race and ethnicity.
Design, setting, and participants
Retrospective ecological analysis of deaths in California in 2015 to 2021 to calculate state- and census tract-level life expectancy. Tracts were grouped by median household income (MHI), obtained from the American Community Survey, and the slope of the life expectancy-income gradient was compared by year and by racial and ethnic composition.
Exposures
California in 2015 to 2019 (before the COVID-19 pandemic) and 2020 to 2021 (during the COVID-19 pandemic).
Main outcomes and measures
Life expectancy at birth.
Results
California experienced 1 988 606 deaths during 2015 to 2021, including 654 887 in 2020 to 2021. State life expectancy declined from 81.40 years in 2019 to 79.20 years in 2020 and 78.37 years in 2021. MHI data were available for 7962 of 8057 census tracts (98.8%; n = 1 899 065 deaths). Mean MHI ranged from $21 279 to $232 261 between the lowest and highest percentiles. The slope of the relationship between life expectancy and MHI increased significantly, from 0.075 (95% CI, 0.07-0.08) years per percentile in 2019 to 0.103 (95% CI, 0.098-0.108; P < .001) years per percentile in 2020 and 0.107 (95% CI, 0.102-0.112; P < .001) years per percentile in 2021. The gap in life expectancy between the richest and poorest percentiles increased from 11.52 years in 2019 to 14.67 years in 2020 and 15.51 years in 2021. Among Hispanic and non-Hispanic Asian, Black, and White populations, life expectancy declined 5.74 years among the Hispanic population, 3.04 years among the non-Hispanic Asian population, 3.84 years among the non-Hispanic Black population, and 1.90 years among the non-Hispanic White population between 2019 and 2021. The income-life expectancy gradient in these groups increased significantly between 2019 and 2020 (0.038 [95% CI, 0.030-0.045; P < .001] years per percentile among Hispanic individuals; 0.024 [95% CI: 0.005-0.044; P = .02] years per percentile among Asian individuals; 0.015 [95% CI, 0.010-0.020; P < .001] years per percentile among Black individuals; and 0.011 [95% CI, 0.007-0.015; P < .001] years per percentile among White individuals) and between 2019 and 2021 (0.033 [95% CI, 0.026-0.040; P < .001] years per percentile among Hispanic individuals; 0.024 [95% CI, 0.010-0.038; P = .002] years among Asian individuals; 0.024 [95% CI, 0.011-0.037; P = .003] years per percentile among Black individuals; and 0.013 [95% CI, 0.008-0.018; P < .001] years per percentile among White individuals). The increase in the gradient was significantly greater among Hispanic vs White populations in 2020 and 2021 (P < .001 in both years) and among Black vs White populations in 2021 (P = .04).

Conclusions:
and relevance
This retrospective analysis of census tract-level income and mortality data in California from 2015 to 2021 demonstrated a decrease in life expectancy in both 2020 and 2021 and an increase in the life expectancy gap by income level relative to the prepandemic period that disproportionately affected some racial and ethnic minority populations. Inferences at the individual level are limited by the ecological nature of the study, and the generalizability of the findings outside of California are unknown.



JAMA: 07 Jul 2022; epub ahead of print
Schwandt H, Currie J, von Wachter T, Kowarski J, Chapman D, Woolf SH
JAMA: 07 Jul 2022; epub ahead of print | PMID: 35797033
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Impact:
Abstract

Sickle Cell Disease: A Review.

Kavanagh PL, Fasipe TA, Wun T
Importance
Sickle cell disease (SCD) is an inherited disorder of hemoglobin, characterized by formation of long chains of hemoglobin when deoxygenated within capillary beds, resulting in sickle-shaped red blood cells, progressive multiorgan damage, and increased mortality. An estimated 300 000 infants are born annually worldwide with SCD. Most individuals with SCD live in sub-Saharan Africa, India, the Mediterranean, and Middle East; approximately 100 000 individuals with SCD live in the US.
Observations
SCD is diagnosed through newborn screening programs, where available, or when patients present with unexplained severe atraumatic pain or normocytic anemia. In SCD, sickling and hemolysis of red blood cells result in vaso-occlusion with associated ischemia. SCD is characterized by repeated episodes of severe acute pain and acute chest syndrome, and by other complications including stroke, chronic pain, nephropathy, retinopathy, avascular necrosis, priapism, and leg ulcers. In the US, nearly all children with SCD survive to adulthood, but average life expectancy remains 20 years less than the general population, with higher mortality as individuals transition from pediatric to adult-focused health care systems. Until 2017, hydroxyurea, which increases fetal hemoglobin and reduces red blood cell sickling, was the only disease-modifying therapy available for SCD and remains first-line therapy for most individuals with SCD. Three additional therapies, L-glutamine, crizanlizumab, and voxelotor, have been approved as adjunctive or second-line agents. In clinical trials, L-glutamine reduced hospitalization rates by 33% and mean length of stay from 11 to 7 days compared with placebo. Crizanlizumab reduced pain crises from 2.98 to 1.63 per year compared with placebo. Voxelotor increased hemoglobin by at least 1 g/dL, significantly more than placebo (51% vs 7%). Hematopoietic stem cell transplant is the only curative therapy, but it is limited by donor availability, with best results seen in children with a matched sibling donor. While SCD is characterized by acute and chronic pain, patients are not more likely to develop addiction to pain medications than the general population.

Conclusions:
and relevance
In the US, approximately 100 000 people have SCD, which is characterized by hemolytic anemia, acute and chronic pain, acute chest syndrome; increased incidence of stroke, nephropathy, and retinopathy; and a life span that is 20 years shorter than the general population. While hydroxyurea is first-line therapy for SCD, L-glutamine, crizanlizumab, and voxelotor have been approved in the US since 2017 as adjunctive or second-line treatments, and hematopoietic stem cell transplant with a matched sibling donor is now standard care for severe disease.



JAMA: 05 Jul 2022; 328:57-68
Kavanagh PL, Fasipe TA, Wun T
JAMA: 05 Jul 2022; 328:57-68 | PMID: 35788790
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Impact:
Abstract

Effect of an Intensive Nurse Home Visiting Program on Adverse Birth Outcomes in a Medicaid-Eligible Population: A Randomized Clinical Trial.

McConnell MA, Rokicki S, Ayers S, Allouch F, ... Bates MA, Baicker K
Importance
Improving birth outcomes for low-income mothers is a public health priority. Intensive nurse home visiting has been proposed as an intervention to improve these outcomes.
Objective
To determine the effect of an intensive nurse home visiting program on a composite outcome of preterm birth, low birth weight, small for gestational age, or perinatal mortality.
Design, setting, and participants
This was a randomized clinical trial that included 5670 Medicaid-eligible, nulliparous pregnant individuals at less than 28 weeks\' gestation, enrolled between April 1, 2016, and March 17, 2020, with follow-up through February 2021.
Interventions
Participants were randomized 2:1 to Nurse Family Partnership program (n = 3806) or control (n = 1864). The program is an established model of nurse home visiting; regular visits begin prenatally and continue through 2 postnatal years. Nurses provide education, assessments, and goal-setting related to prenatal health, child health and development, and maternal life course. The control group received usual care services and a list of community resources. Neither staff nor participants were blinded to intervention group.
Main outcomes and measures
There were 3 primary outcomes. This article reports on a composite of adverse birth outcomes: preterm birth, low birth weight, small for gestational age, or perinatal mortality based on vital records, Medicaid claims, and hospital discharge records through February 2021. The other primary outcomes of interbirth intervals of less than 21 months and major injury or concern for abuse or neglect in the child\'s first 24 months have not yet completed measurement. There were 54 secondary outcomes; those related to maternal and newborn health that have completed measurement included all elements of the composite plus birth weight, gestational length, large for gestational age, extremely preterm, very low birth weight, overnight neonatal intensive care unit admission, severe maternal morbidity, and cesarean delivery.
Results
Among 5670 participants enrolled, 4966 (3319 intervention; 1647 control) were analyzed for the primary maternal and neonatal health outcome (median age, 21 years [1.2% non-Hispanic Asian, Indigenous, or Native Hawaiian and Pacific Islander; 5.7% Hispanic; 55.2% non-Hispanic Black; 34.8% non-Hispanic White; and 3.0% more than 1 race reported [non-Hispanic]). The incidence of the composite adverse birth outcome was 26.9% in the intervention group and 26.1% in the control group (adjusted between-group difference, 0.5% [95% CI, -2.1% to 3.1%]). Outcomes for the intervention group were not significantly better for any of the maternal and newborn health primary or secondary outcomes in the overall sample or in either of the prespecified subgroups.

Conclusions:
and relevance
In this South Carolina-based trial of Medicaid-eligible pregnant individuals, assignment to participate in an intensive nurse home visiting program did not significantly reduce the incidence of a composite of adverse birth outcomes. Evaluation of the overall effectiveness of this program is incomplete, pending assessment of early childhood and birth spacing outcomes.
Trial registration
ClinicalTrials.gov Identifier: NCT03360539.



JAMA: 05 Jul 2022; 328:27-37
McConnell MA, Rokicki S, Ayers S, Allouch F, ... Bates MA, Baicker K
JAMA: 05 Jul 2022; 328:27-37 | PMID: 35788794
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Impact:
Abstract

Association Between Earlier Introduction of Peanut and Prevalence of Peanut Allergy in Infants in Australia.

Soriano VX, Peters RL, Moreno-Betancur M, Ponsonby AL, ... Dharmage SC, Koplin JJ
Importance
Randomized clinical trials showed that earlier peanut introduction can prevent peanut allergy in select high-risk populations. This led to changes in infant feeding guidelines in 2016 to recommend early peanut introduction for all infants to reduce the risk of peanut allergy.
Objective
To measure the change in population prevalence of peanut allergy in infants after the introduction of these new guidelines and evaluate the association between early peanut introduction and peanut allergy.
Design
Two population-based cross-sectional samples of infants aged 12 months were recruited 10 years apart using the same sampling frame and methods to allow comparison of changes over time. Infants were recruited from immunization centers around Melbourne, Australia. Infants attending their 12-month immunization visit were eligible to participate (eligible age range, 11-15 months), regardless of history of peanut exposure or allergy history.
Exposures
Questionnaires collected data on demographics, food allergy risk factors, peanut introduction, and reactions.
Main outcome and measures
All infants underwent skin prick tests to peanut and those with positive results underwent oral food challenges. Prevalence estimates were standardized to account for changes in population demographics over time.
Results
This study included 7209 infants (1933 in 2018-2019 and 5276 in 2007-2011). Of the participants in the older vs more recent cohort, 51.8% vs 50.8% were male; median (IQR) ages were 12.5 (12.2-13.0) months vs 12.4 (12.2-12.9) months. There was an increase in infants of East Asian ancestry over time (16.5% in 2018-2019 vs 10.5% in 2007-2011), which is a food allergy risk factor. After standardizing for infant ancestry and other demographics changes, peanut allergy prevalence was 2.6% (95% CI, 1.8%-3.4%) in 2018-2019, compared with 3.1% in 2007-2011 (difference, -0.5% [95% CI, -1.4% to 0.4%]; P = .26). Earlier age of peanut introduction was significantly associated with a lower risk of peanut allergy among infants of Australian ancestry in 2018-2019 (age 12 months compared with age 6 months or younger: adjusted odds ratio, 0.08 [05% CI, 0.02-0.36]; age 12 months compared with 7 to less than 10 months: adjusted odds ratio, 0.09 [95% CI, 0.02-0.53]), but not significant among infants of East Asian ancestry (P for interaction = .002).

Conclusions:
and relevance
In cross-sectional analyses, introduction of a guideline recommending early peanut introduction in Australia was not associated with a statistically significant lower or higher prevalence of peanut allergy across the population.



JAMA: 05 Jul 2022; 328:48-56
Soriano VX, Peters RL, Moreno-Betancur M, Ponsonby AL, ... Dharmage SC, Koplin JJ
JAMA: 05 Jul 2022; 328:48-56 | PMID: 35788795
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Impact:

This program is still in alpha version.