Journal: Ann Intern Med

Sorted by: date / impact
Abstract

Medicare Spending on Drugs With Accelerated Approval.

Ballreich J, Socal M, Bennett CL, Schoen MW, ... Xuan A, Anderson G
Background
The U.S. Food and Drug Administration provides accelerated approval to drugs on the basis of surrogate end points deemed to be \"reasonably likely\" to predict clinical benefit. To receive full approval, drugs must complete a confirmatory trial. Although most accelerated approved drugs ultimately receive full approval, others remain on the market without full approval for many years, and some are withdrawn before full approval is granted. Until confirmatory trials are completed and full approval is granted, there is uncertainty surrounding each drug\'s clinical benefits.
Objective
To estimate fee-for-service Medicare payments on accelerated approved drugs without full approvals.
Design
Cross-sectional analysis.
Setting
Fee-for-service Medicare Part B and Part D drug claims in 2019.
Participants
Beneficiaries enrolled in Medicare Part B and Part D plans.
Measurements
Medicare spending for drugs treating accelerated approved indications without full approval, beneficiary spending, and drug characteristics.
Results
In 2019, 45 drugs associated with 69 accelerated approved indications lacked full approval. Of those, the fee-for-service Medicare program spent $1.2 billion on 36 drugs across 55 indications. Medicare beneficiaries had $209 million in out-of-pocket spending on these drugs. Oncology drugs represented 82% of these indications and 72% of the Medicare spending. Extrapolating to Medicare Advantage, total Medicare spending on these drugs in 2019 was $1.8 billion.
Limitations
The study drugs may have clinical benefit and may come to receive full approval after this analysis. The algorithm used to identify accelerated approved indications is novel. Generalizability to other years is unclear.
Conclusion
In 2019, fee-for-service Medicare spent $1.2 billion on accelerated approved drugs without full approval. Medicare should adjust incentives to encourage sponsors to complete confirmatory trials as soon as possible.
Primary funding source
Laura and John Arnold Foundation.



Ann Intern Med: 24 May 2022; epub ahead of print
Ballreich J, Socal M, Bennett CL, Schoen MW, ... Xuan A, Anderson G
Ann Intern Med: 24 May 2022; epub ahead of print | PMID: 35605235
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Abstract

Cardiovascular Outcomes in Patients Initiating First-Line Treatment of Type 2 Diabetes With Sodium-Glucose Cotransporter-2 Inhibitors Versus Metformin : A Cohort Study.

Shin H, Schneeweiss S, Glynn RJ, Patorno E
Background
Evidence on the risk for cardiovascular events associated with use of first-line sodium-glucose cotransporter-2 inhibitors (SGLT-2i) compared with metformin is limited.
Objective
To assess cardiovascular outcomes among adults with type 2 diabetes (T2D) who initiated first-line treatment with SGLT-2i versus metformin.
Design
Population-based cohort study.
Setting
Claims data from 2 large U.S. commercial and Medicare databases (April 2013 to March 2020).
Participants
Patients with T2D aged 18 years and older (>65 years in Medicare) initiating treatment with SGLT-2i or metformin during April 2013 to March 2020, without any use of antidiabetic medications before cohort entry, were identified. After 1:2 propensity score matching in each database, pooled hazard ratios (HRs) and 95% CIs were reported.
Intervention
First-line SGLT-2i (canagliflozin, empagliflozin, or dapagliflozin) or metformin.
Measurements
Primary outcomes were a composite of hospitalization for myocardial infarction (MI), hospitalization for ischemic or hemorrhagic stroke or all-cause mortality (MI/stroke/mortality), and a composite of hospitalization for heart failure (HHF) or all-cause mortality (HHF/mortality). Safety outcomes including genital infections were assessed.
Results
Among 8613 first-line SGLT-2i initiators matched to 17 226 metformin initiators, SGLT-2i initiators had a similar risk for MI/stroke/mortality (HR, 0.96; 95% CI, 0.77 to 1.19) and a lower risk for HHF/mortality (HR, 0.80; CI, 0.66 to 0.97) during a mean follow-up of 12 months. Initiators receiving SGLT-2i showed a lower risk for HHF (HR, 0.78; CI, 0.63 to 0.97), a numerically lower risk for MI (HR, 0.70; CI, 0.48 to 1.00), and similar risk for stroke, mortality, and MI/stroke/HHF/mortality compared with metformin. Initiators receiving SGLT-2i had a higher risk for genital infections (HR, 2.19; CI, 1.91 to 2.51) and otherwise similar safety as those receiving metformin.
Limitation
Treatment selection was not randomized.
Conclusion
As first-line T2D treatment, initiators receiving SGLT-2i showed a similar risk for MI/stroke/mortality, lower risk for HHF/mortality and HHF, and a similar safety profile except for an increased risk for genital infections compared with those receiving metformin.
Primary funding source
Brigham and Women\'s Hospital and Harvard Medical School.



Ann Intern Med: 24 May 2022; epub ahead of print
Shin H, Schneeweiss S, Glynn RJ, Patorno E
Ann Intern Med: 24 May 2022; epub ahead of print | PMID: 35605236
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Abstract

A Longitudinal Study of COVID-19 Sequelae and Immunity: Baseline Findings.

Sneller MC, Liang CJ, Marques AR, Chung JY, ... Chun TW, Lane HC
Background
A substantial proportion of persons who develop COVID-19 report persistent symptoms after acute illness. Various pathophysiologic mechanisms have been implicated in the pathogenesis of postacute sequelae of SARS-CoV-2 infection (PASC).
Objective
To characterize medical sequelae and persistent symptoms after recovery from COVID-19 in a cohort of disease survivors and controls.
Design
Cohort study. (ClinicalTrials.gov: NCT04411147).
Setting
National Institutes of Health Clinical Center, Bethesda, Maryland.
Participants
Self-referred adults with laboratory-documented SARS-CoV-2 infection who were at least 6 weeks from symptom onset were enrolled regardless of presence of PASC. A control group comprised persons with no history of COVID-19 or serologic evidence of SARS-CoV-2 infection, recruited regardless of their current health status. Both groups were enrolled over the same period and from the same geographic area.
Measurements
All participants had the same evaluations regardless of presence of symptoms, including physical examination, laboratory tests and questionnaires, cognitive function testing, and cardiopulmonary evaluation. A subset also underwent exploratory immunologic and virologic evaluations.
Results
189 persons with laboratory-documented COVID-19 (12% of whom were hospitalized during acute illness) and 120 antibody-negative control participants were enrolled. At enrollment, symptoms consistent with PASC were reported by 55% of the COVID-19 cohort and 13% of control participants. Increased risk for PASC was noted in women and those with a history of anxiety disorder. Participants with findings meeting the definition of PASC reported lower quality of life on standardized testing. Abnormal findings on physical examination and diagnostic testing were uncommon. Neutralizing antibody levels to spike protein were negative in 27% of the unvaccinated COVID-19 cohort and none of the vaccinated COVID-19 cohort. Exploratory studies found no evidence of persistent viral infection, autoimmunity, or abnormal immune activation in participants with PASC.
Limitations
Most participants with COVID-19 had mild to moderate acute illness that did not require hospitalization. The prevalence of reported PASC was likely overestimated in this cohort because persons with PASC may have been more motivated to enroll. The study did not capture PASC that resolved before enrollment.
Conclusion
A high burden of persistent symptoms was observed in persons after COVID-19. Extensive diagnostic evaluation revealed no specific cause of reported symptoms in most cases. Antibody levels were highly variable after COVID-19.
Primary funding source
Division of Intramural Research, National Institute of Allergy and Infectious Diseases.



Ann Intern Med: 24 May 2022; epub ahead of print
Sneller MC, Liang CJ, Marques AR, Chung JY, ... Chun TW, Lane HC
Ann Intern Med: 24 May 2022; epub ahead of print | PMID: 35605238
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Abstract

Effectiveness and Harms of Contraceptive Counseling and Provision Interventions for Women : A Systematic Review and Meta-analysis.

Nelson HD, Cantor A, Jungbauer RM, Eden KB, ... Goueth R, Fu R
Background
The effectiveness and harms of contraceptive counseling and provision interventions are unclear.
Purpose
To evaluate evidence of the effectiveness of contraceptive counseling and provision interventions for women to increase use of contraceptives and reduce unintended pregnancy, as well as evidence of their potential harms.
Data sources
English-language searches of Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, PsycINFO, SocINDEX, and MEDLINE (1 January 2000 to 3 February 2022) and reference lists of key studies and systematic reviews.
Study selection
Randomized controlled trials of interventions providing enhanced contraceptive counseling, contraceptives, or both versus usual care or an active control.
Data extraction
Dual extraction and quality assessment of studies; results combined using a profile likelihood random-effects model.
Data synthesis
A total of 38 trials (43 articles [25 472 participants]) met inclusion criteria. Contraceptive use was higher with various counseling interventions (risk ratio [RR], 1.39 [95% CI, 1.16 to 1.72]; I 2 = 85.3%; 10 trials), provision of emergency contraception in advance of use (RR, 2.12 [CI, 1.79 to 2.36]; I 2 = 0.0%; 8 trials), and counseling or provision postpartum (RR, 1.15 [CI, 1.01 to 1.52]; I 2 = 6.6%; 5 trials) or at the time of abortion (RR, 1.19 [CI, 1.09 to 1.32]; I 2 = 0.0%; 5 trials) than with usual care or active controls in multiple clinical settings. Pregnancy rates were generally lower with interventions, although most trials were underpowered and did not distinguish pregnancy intention. Interventions did not increase risk for sexually transmitted infections (STIs) (RR, 1.05 [CI, 0.87 to 1.25]; I 2 = 0.0%; 5 trials) or reduce condom use (RR, 1.03 [CI, 0.94 to 1.13]; I 2 = 0.0%; 6 trials).
Limitation
Interventions varied; few trials were adequately designed to determine unintended pregnancy outcomes.
Conclusion
Contraceptive counseling and provision interventions that provide services beyond usual care increase contraceptive use without increasing STIs or reducing condom use. Contraceptive care in clinical practice could be improved by implementing enhanced contraceptive counseling, provision, and follow-up; providing emergency contraception in advance; and delivering contraceptive services immediately postpartum or at the time of abortion.
Primary funding source
Resources Legacy Fund. (PROSPERO: CRD42020192981).



Ann Intern Med: 24 May 2022; epub ahead of print
Nelson HD, Cantor A, Jungbauer RM, Eden KB, ... Goueth R, Fu R
Ann Intern Med: 24 May 2022; epub ahead of print | PMID: 35605239
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Abstract

Addressing Inequities in SARS-CoV-2 Vaccine Uptake: The Boston Medical Center Health System Experience.

Assoumou SA, Peterson A, Ginman E, James T, ... Linas BP, Martin Cherry P
Academic medical centers could play an important role in increasing access to and uptake of SARS-CoV-2 vaccines, especially in Black and Latino communities that have been disproportionately affected by the pandemic. This article describes the vaccination program developed by the Boston Medical Center (BMC) health system (New England\'s largest safety-net health system), its affiliated community health centers (CHCs), and community partners. The program was based on a conceptual framework for community interventions and aimed to increase equitable access to vaccination in the hardest-hit communities through community-based sites in churches and community centers, mobile vaccination events, and vaccination on the BMC campus. Key strategies included a communication campaign featuring trusted messengers, a focus on health equity, established partnerships with community leaders and CHCs, and strong collaboration with local health departments and the Commonwealth of Massachusetts to ensure equitable allocation of the vaccine supply. Process factors involved the use of robust analytics relying on the Centers for Disease Control and Prevention\'s Social Vulnerability Index (SVI). The vaccination program administered 109 938 first doses, with 94 703 (86%) given at community sites and 2466 (2%) given at mobile sites. Mobile vaccination events were key in reaching younger people living in locations with the highest SVIs. Challenges included the need for a robust operational infrastructure and mistrust of the health system given the long history of economic disinvestment in the surrounding community. The BMC model could serve as a blueprint for other medical centers interested in implementing programs aimed at increasing vaccine uptake during a pandemic and in developing an infrastructure to address other health-related disparities.



Ann Intern Med: 17 May 2022; epub ahead of print
Assoumou SA, Peterson A, Ginman E, James T, ... Linas BP, Martin Cherry P
Ann Intern Med: 17 May 2022; epub ahead of print | PMID: 35576586
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Abstract

Evolving Practice Choices by Newly Certified and More Senior General Internists : A Cross-Sectional and Panel Comparison.

Gray BM, Vandergrift JL, Stevens JP, Landon BE
Background
Hospital medicine has grown as a field. However, no study has examined trends in career choices by internists over the past decade.
Objective
To measure changes in practice setting for general internists.
Design
Using Medicare fee-for-service claims (2008 to 2018) and data from the American Board of Internal Medicine, practice setting types were measured annually for general internists initially certifying between 1990 and 2017.
Setting
General internists (non-subspecializing) treating Medicare fee-for-service beneficiaries.
Patients
Medicare fee-for-service beneficiaries aged 65 years and older with at least 20 evaluation and management (E&M) visits annually.
Measurements
Practice setting types were defined as hospitalist (>95% inpatient E&M), outpatient only (100% outpatient E&M), or mixed.
Results
67 902 general internists, comprising 80% of all general internists initially certified from 1990 to 2017 (n = 84 581), were studied. From 2008 to 2018, both hospitalists and outpatient-only physicians increased as percentages of general internists (25% to 40% and 23% to 38%, respectively). This was accompanied by a 56% decline in the percentage of mixed-practice physicians (52% to 23%) as these physicians largely migrated to outpatient-only practice. By 2018, 71% of newly certified general internists practiced as hospitalists compared with only 8% practicing as outpatient-only physicians. Most (86% of hospitalists in 2013) had the same practice type 5 years later. This retention rate was similar across early career and more senior physicians (86% and 85% for the 1999 and 2012 initial certification cohorts, respectively) and for the outpatient-only practice type (95%) but was only 57% for the mixed practice type.
Limitation
Practice setting measurement relied only on Medicare fee-for-service claims.
Conclusion
Newly certified general internists are largely choosing hospital medicine as their career choice whereas more senior physicians increasingly see patients only in the outpatient setting.
Primary funding source
This study did not receive direct funding.



Ann Intern Med: 17 May 2022; epub ahead of print
Gray BM, Vandergrift JL, Stevens JP, Landon BE
Ann Intern Med: 17 May 2022; epub ahead of print | PMID: 35576587
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Impact:
Abstract

Human Papillomavirus Vaccine Impact and Effectiveness Through 12 Years After Vaccine Introduction in the United States, 2003 to 2018.

Rosenblum HG, Lewis RM, Gargano JW, Querec TD, Unger ER, Markowitz LE
Background
Human papillomavirus (HPV) vaccination was introduced in 2006 for females and in 2011 for males.
Objective
To estimate vaccine impact and effectiveness against quadrivalent HPV vaccine (4vHPV)-type prevalent infection among sexually experienced U.S. females and vaccine effectiveness for sexually experienced U.S. males.
Design
NHANES (National Health and Nutrition Examination Survey) conducted in 2003 to 2006 (prevaccine era) and in 2007 to 2010, 2011 to 2014, and 2015 to 2018 (vaccine eras).
Setting
Nationally representative U.S. surveys.
Participants
Sexually experienced participants aged 14 to 24 years.
Intervention
U.S. HPV vaccination program.
Measurements
Participant-collected cervicovaginal and penile specimens were tested for HPV DNA. The prevalences of 4vHPV and non-4vHPV types were estimated in each era for females and in 2013 to 2016 for males. Prevalences among the female population overall, vaccinated females, and unvaccinated females were compared in vaccine eras versus the prevaccine era (vaccine impact). Within each vaccine era, prevalence among vaccinated females was compared with that among unvaccinated females (vaccine effectiveness). Vaccine impact and effectiveness were estimated as (1 - prevalence ratio) · 100.
Results
Among sexually experienced females aged 14 to 24 years, the impact on 4vHPV-type prevalence in 2015 to 2018 was 85% overall, 90% among vaccinated females, and 74% among unvaccinated females. No significant declines were found in non-4vHPV-type prevalence. Vaccine effectiveness ranged from 60% to 84% during vaccine eras for females and was 51% during 2013 to 2016 for males.
Limitation
Self- or parent-reported vaccination history and small numbers in certain subgroups limited precision.
Conclusion
Nationally representative data show increasing impact of the vaccination program and herd protection. Vaccine effectiveness estimates will be increasingly affected by herd effects.
Primary funding source
Centers for Disease Control and Prevention.



Ann Intern Med: 17 May 2022; epub ahead of print
Rosenblum HG, Lewis RM, Gargano JW, Querec TD, Unger ER, Markowitz LE
Ann Intern Med: 17 May 2022; epub ahead of print | PMID: 35576590
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Impact:
Abstract

Diabetes Screening by Race and Ethnicity in the United States: Equivalent Body Mass Index and Age Thresholds.

Aggarwal R, Bibbins-Domingo K, Yeh RW, Song Y, ... Shen C, Kazi DS
Background
Racial/ethnic minority populations in the United States have increased rates of diabetes compared with White populations. The 2021 guidelines from the U.S. Preventive Services Task Force recommend diabetes screening for adults aged 35 to 70 years with a body mass index (BMI) of 25 kg/m2 or greater.
Objective
To determine the BMI threshold for diabetes screening in major racial/ethnic minority populations with benefits and harms equivalent to those of the current diabetes screening threshold in White adults.
Design
Cross-sectional study.
Setting
NHANES (National Health and Nutrition Examination Survey), 2011 to 2018.
Participants
Nonpregnant U.S. adults aged 18 to 70 years (n = 19 335).
Measurements
A logistic regression model was used to estimate diabetes prevalence at various BMIs for White, Asian, Black, and Hispanic Americans. For each racial/ethnic minority group, the equivalent BMI threshold was defined as the BMI at which the prevalence of diabetes in 35-year-old persons in that group is equal to that in 35-year-old White adults at a BMI of 25 kg/m2. Ranges were estimated to account for the uncertainty in prevalence estimates for White and racial/ethnic minority populations.
Results
Among adults aged 35 years with a BMI of 25 kg/m2, the prevalence of diabetes in Asian Americans (3.8% [95% CI, 2.8% to 5.1%]), Black Americans (3.5% [CI, 2.7% to 4.7%]), and Hispanic Americans (3.0% [CI, 2.1% to 4.2%]) was significantly higher than that in White Americans (1.4% [CI, 1.0% to 2.0%]). Compared with a BMI threshold of 25 kg/m2 in White Americans, the equivalent BMI thresholds for diabetes prevalence were 20 kg/m2 (range, <18.5 to 23 kg/m2) for Asian Americans, less than 18.5 kg/m2 (range, <18.5 to 23 kg/m2) for Black Americans, and 18.5 kg/m2 (range, <18.5 to 24 kg/m2) for Hispanic Americans.
Limitation
Sample size limitations precluded assessment of heterogeneity within racial/ethnic groups.
Conclusion
Among U.S. adults aged 35 years or older, offering diabetes screening to Black Americans and Hispanic Americans with a BMI of 18.5 kg/m2 or greater and Asian Americans with a BMI of 20 kg/m2 or greater would be equivalent to screening White adults with a BMI of 25 kg/m2 or greater. Using screening thresholds specific to race/ethnicity has the potential to reduce disparities in diabetes diagnosis.
Primary funding source
Richard A. and Susan F. Smith Center for Outcomes Research in Cardiology.



Ann Intern Med: 10 May 2022; epub ahead of print
Aggarwal R, Bibbins-Domingo K, Yeh RW, Song Y, ... Shen C, Kazi DS
Ann Intern Med: 10 May 2022; epub ahead of print | PMID: 35533384
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Impact:
Abstract

Care of the Patient After Metabolic and Bariatric Surgery.

Bramante C, Wise E, Chaudhry Z
Weight loss surgery, also known as metabolic and bariatric surgery (MBS), is an effective weight loss treatment and is associated with reduced mortality and improvements in obesity-related health conditions and quality of life. Postsurgical anatomical and physiologic changes include decreased absorption of micronutrients and alterations in gut-brain hormonal regulation that affect many aspects of health. Patients require ongoing monitoring of their physical and mental health for lasting success. Internists, particularly primary care clinicians, are in an ideal position to monitor for nonserious complications in the short and long term, adjust management of chronic diseases accordingly, and monitor for mental health changes. This article reviews key issues that internists should be aware of for supporting patients\' health in the short and long term after MBS.



Ann Intern Med: 10 May 2022; epub ahead of print
Bramante C, Wise E, Chaudhry Z
Ann Intern Med: 10 May 2022; epub ahead of print | PMID: 35533387
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Impact:
Abstract

Association Between SARS-CoV-2 Messenger RNA Vaccines and Lower Infection Rates in Kidney Transplant Recipients : A Registry-Based Report.

Zahradka I, Petr V, Modos I, Magicova M, Dusek L, Viklicky O
Background
The real-world protection provided by SARS-CoV-2 messenger RNA (mRNA) vaccines to kidney transplant recipients (KTRs) remains uncertain.
Objective
To study the association between mRNA vaccination and SARS-CoV-2 infection rate in KTRs.
Design
Retrospective observational cohort study.
Setting
The Czech Republic (17 February to 16 May 2021).
Patients
2101 KTRs followed in the Department of Nephrology at the Institute for Clinical and Experimental Medicine.
Measurements
Positive result for SARS-CoV-2 on polymerase chain reaction test and vaccination status of KTRs.
Results
The incidence rate in the vaccinated group was 0.474 per 1000 person-days (33 cases in 69 672 days at risk). The incidence rate in the unvaccinated group was 1.370 per 1000 person-days (79 cases in 57 658 days at risk). The unadjusted incidence rate ratio (IRR; incidence rate of vaccinated/incidence rate of unvaccinated) for KTRs was 0.346 (95% CI, 0.227 to 0.514). The multivariable adjusted IRR for KTRs was 0.544 (CI, 0.324 to 0.876).
Limitation
Retrospective observational design, uneven follow-up of patient groups, and different exposition to SARS-CoV-2 stemming from strong temporal trends and differences in clinical and probably behavioral characteristics.
Conclusion
Vaccination of KTRs is associated with lower risk for SARS-CoV-2 infection.
Primary funding source
The Ministry of Health of the Czech Republic.



Ann Intern Med: 03 May 2022; epub ahead of print
Zahradka I, Petr V, Modos I, Magicova M, Dusek L, Viklicky O
Ann Intern Med: 03 May 2022; epub ahead of print | PMID: 35500256
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Impact:
Abstract

Affirmative Action Bans and Enrollment of Students From Underrepresented Racial and Ethnic Groups in U.S. Public Medical Schools.

Ly DP, Essien UR, Olenski AR, Jena AB
Background
The percentage of U.S. physicians who identify as being from an underrepresented racial or ethnic group remains low relative to their proportion in the U.S. population. How this percentage may have been affected by state bans on affirmative action in public postsecondary institutions has received relatively little attention.
Objective
To examine the association between state affirmative action bans and percentage of enrollment in U.S. public medical schools from underrepresented racial and ethnic groups.
Design
Event study comparing public medical schools in states that implemented affirmative action bans with those in states without bans.
Setting
U.S. public medical schools.
Participants
21 public medical schools in 8 states with affirmative action bans matched to 32 public medical schools in 24 states without bans from 1985 to 2019.
Measurements
Percentage of total enrollment from racial and ethnic groups underrepresented in medicine (Black, Hispanic, American Indian or Alaska Native, and Native Hawaiian or other Pacific Islander).
Results
The percentage of enrollment from underrepresented racial and ethnic groups was 14.8% in U.S. public medical schools in the year before ban implementation in states with bans. The adjusted percentage of underrepresented students in ban schools decreased by 4.8 percentage points (95% CI, -6.3 to -3.2 percentage points) 5 years after ban implementation relative to the year before implementation, whereas the adjusted percentage in control schools increased by 0.7 percentage point (CI, -0.1 to 1.6 percentage points), for a relative difference, or difference-in-differences estimate, of -5.5 percentage points (CI, -7.1 to -3.9 percentage points).
Limitation
Inability to account for the effect of these bans on undergraduate enrollment.
Conclusion
State affirmative action bans were associated with significant reductions in the percentage of students in U.S. public medical schools from underrepresented racial and ethnic groups.
Primary funding source
None.



Ann Intern Med: 03 May 2022; epub ahead of print
Ly DP, Essien UR, Olenski AR, Jena AB
Ann Intern Med: 03 May 2022; epub ahead of print | PMID: 35500257
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Impact:
Abstract

In patients with type 2 diabetes and CKD, finerenone improved CV and kidney outcomes.

Mayne KJ, Herrington WG
Source citation
Agarwal R, Filippatos G, Pitt B, et al. Cardiovascular and kidney outcomes with finerenone in patients with type 2 diabetes and chronic kidney disease: the FIDELITY pooled analysis. Eur Heart J. 2022;43:474-84. 35023547.



Ann Intern Med: 03 May 2022; epub ahead of print
Mayne KJ, Herrington WG
Ann Intern Med: 03 May 2022; epub ahead of print | PMID: 35500259
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Impact:
Abstract

In older adults having hip fracture surgery, regional vs. general anesthesia did not reduce postoperative delirium.

Gill SS
Source citation
Li T, Li J, Yuan L, et al. Effect of regional vs general anesthesia on incidence of postoperative delirium in older patients undergoing hip fracture surgery: the RAGA randomized trial. JAMA. 2022;327:50-8. 34928310.



Ann Intern Med: 03 May 2022; epub ahead of print
Gill SS
Ann Intern Med: 03 May 2022; epub ahead of print | PMID: 35500260
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Impact:
Abstract

In overweight or obesity without diabetes, weekly semaglutide vs. daily liraglutide increased weight loss at 68 wk.

Kauffman RP
Source citation
Rubino DM, Greenway FL, Khalid U, et al. Effect of weekly subcutaneous semaglutide vs daily liraglutide on body weight in adults with overweight or obesity without diabetes: the STEP 8 randomized clinical trial. JAMA. 2022;327:138-50. 35015037.



Ann Intern Med: 03 May 2022; epub ahead of print
Kauffman RP
Ann Intern Med: 03 May 2022; epub ahead of print | PMID: 35500264
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Impact:
Abstract

In CKD, the Kidney Failure Risk Equation predicted 2-y risk for ESKD better than eGFR alone.

Aguilar-Ramirez D, Herrington WG
Source citation
Bundy JD, Mills KT, Anderson AH, et al. Prediction of end-stage kidney disease using estimated glomerular filtration rate with and without race: a prospective cohort study. Ann Intern Med. 2022;175:305-13. 35007146.



Ann Intern Med: 03 May 2022; epub ahead of print
Aguilar-Ramirez D, Herrington WG
Ann Intern Med: 03 May 2022; epub ahead of print | PMID: 35500267
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Impact:
Abstract

International Validation of the Canadian Syncope Risk Score : A Cohort Study.

Zimmermann T, de Lavallaz JDF, Nestelberger T, Gualandro DM, ... Mueller C, BASEL IX Investigators†
Background
The Canadian Syncope Risk Score (CSRS) was developed to predict 30-day serious outcomes not evident during emergency department (ED) evaluation.
Objective
To externally validate the CSRS and compare it with another validated score, the Osservatorio Epidemiologico della Sincope nel Lazio (OESIL) score.
Design
Prospective cohort study.
Setting
Large, international, multicenter study recruiting patients in EDs in 8 countries on 3 continents.
Participants
Patients with syncope aged 40 years or older presenting to the ED within 12 hours of syncope.
Measurements
Composite outcome of serious clinical plus procedural events (primary outcome) and the primary composite outcome excluding procedural interventions (secondary outcome).
Results
Among 2283 patients with a mean age of 68 years, the primary composite outcome occurred in 7.2%, and the composite outcome excluding procedural interventions occurred in 3.1% at 30 days. Prognostic performance of the CSRS was good for both 30-day composite outcomes and better compared with the OESIL score (area under the receiver-operating characteristic curve [AUC], 0.85 [95% CI, 0.83 to 0.88] vs. 0.74 [CI, 0.71 to 0.78] and 0.80 [CI, 0.75 to 0.84] vs. 0.69 [CI, 0.64 to 0.75], respectively). Safety of triage, as measured by the frequency of the primary composite outcome in the low-risk group, was higher using the CSRS (19 of 1388 [0.6%]) versus the OESIL score (17 of 1104 [1.5%]). A simplified model including only the clinician classification of syncope (cardiac syncope, vasovagal syncope, or other) variable at ED discharge-a component of the CSRS-achieved similar discrimination as the CSRS (AUC, 0.83 [CI, 0.80 to 0.87] for the primary composite outcome).
Limitation
Unable to disentangle the influence of other CSRS components on clinician classification of syncope at ED discharge.
Conclusion
This international external validation of the CSRS showed good performance in identifying patients at low risk for serious outcomes outside of Canada and superior performance compared with the OESIL score. However, clinician classification of syncope at ED discharge seems to explain much of the performance of the CSRS in this study. The clinical utility of the CSRS remains uncertain.
Primary funding source
Swiss National Science Foundation & Swiss Heart Foundation.



Ann Intern Med: 26 Apr 2022; epub ahead of print
Zimmermann T, de Lavallaz JDF, Nestelberger T, Gualandro DM, ... Mueller C, BASEL IX Investigators†
Ann Intern Med: 26 Apr 2022; epub ahead of print | PMID: 35467933
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Impact:
Abstract

Efficacy and Safety of Dapagliflozin According to Frailty in Heart Failure With Reduced Ejection Fraction : A Post Hoc Analysis of the DAPA-HF Trial.

Butt JH, Dewan P, Merkely B, Belohlávek J, ... Køber L, McMurray JJV
Background
Frailty may modify the risk-benefit profile of certain treatments, and frail patients may have reduced tolerance to treatments.
Objective
To investigate the efficacy of dapagliflozin according to frailty status, using the Rockwood cumulative deficit approach, in DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure).
Design
Post hoc analysis of a phase 3 randomized clinical trial. (ClinicalTrials.gov: NCT03036124).
Setting
410 sites in 20 countries.
Patients
Patients with symptomatic heart failure (HF) with a left ventricular ejection fraction of 40% or less and elevated natriuretic peptide.
Intervention
Addition of once-daily 10 mg of dapagliflozin or placebo to guideline-recommended therapy.
Measurements
The primary outcome was worsening HF or cardiovascular death.
Results
Of the 4744 patients randomly assigned in DAPA-HF, a frailty index (FI) was calculable in 4742. In total, 2392 patients (50.4%) were in FI class 1 (FI ≤0.210; not frail), 1606 (33.9%) in FI class 2 (FI 0.211 to 0.310; more frail), and 744 (15.7%) in FI class 3 (FI ≥0.311; most frail). The median follow-up time was 18.2 months. Dapagliflozin reduced the risk for worsening HF or cardiovascular death, regardless of FI class. The differences in event rate per 100 person-years for dapagliflozin versus placebo from lowest to highest FI class were -3.5 (95% CI, -5.7 to -1.2), -3.6 (CI, -6.6 to -0.5), and -7.9 (CI, -13.9 to -1.9). Consistent benefits were observed for other clinical events and health status, but the absolute reductions were generally larger in the most frail patients. Study drug discontinuation and serious adverse events were not more frequent with dapagliflozin than placebo, regardless of FI class.
Limitation
Enrollment criteria precluded the inclusion of very high-risk patients.
Conclusion
Dapagliflozin improved all outcomes examined, regardless of frailty status. However, the absolute reductions were larger in more frail patients.
Primary funding source
AstraZeneca.



Ann Intern Med: 26 Apr 2022; epub ahead of print
Butt JH, Dewan P, Merkely B, Belohlávek J, ... Køber L, McMurray JJV
Ann Intern Med: 26 Apr 2022; epub ahead of print | PMID: 35467935
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Impact:
Abstract

The Challenge of Genetic Variants of Uncertain Clinical Significance : A Narrative Review.

Burke W, Parens E, Chung WK, Berger SM, Appelbaum PS
Genomic tests expand diagnostic and screening opportunities but also identify genetic variants of uncertain clinical significance (VUSs). Only a minority of VUSs are likely to prove pathogenic when later reassessed, but resolution of the uncertainty is rarely timely. That uncertainty adds complexity to clinical decision making and can result in harms and costs to patients and the health care system, including the time-consuming analysis required to interpret a VUS and the potential for unnecessary treatment and adverse psychological effects. Current efforts to improve variant interpretation will help reduce the scope of the problem, but the high prevalence of rare and novel variants in the human genome points to VUSs as an ongoing challenge. Additional strategies can help mitigate the potential harms of VUSs, including testing protocols that limit identification or reporting of VUSs, subclassification of VUSs according to the likelihood of pathogenicity, routine family-based evaluation of variants, and enhanced counseling efforts. All involve tradeoffs, and the appropriate balance of measures is likely to vary for different test uses and clinical settings. Cross-specialty deliberation and public input could contribute to systematic and broadly supported policies for managing VUSs.



Ann Intern Med: 19 Apr 2022; epub ahead of print
Burke W, Parens E, Chung WK, Berger SM, Appelbaum PS
Ann Intern Med: 19 Apr 2022; epub ahead of print | PMID: 35436152
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Impact:
Abstract

Mortality and Morbidity in Mild Primary Hyperparathyroidism: Results From a 10-Year Prospective Randomized Controlled Trial of Parathyroidectomy Versus Observation.

Pretorius M, Lundstam K, Heck A, Fagerland MW, ... Hellström M, Bollerslev J
Background
Primary hyperparathyroidism (PHPT) is a common endocrine disorder associated with increased risk for fractures, cardiovascular disease, kidney disease, and cancer and increased mortality. In mild PHPT with modest hypercalcemia and without known morbidities, parathyroidectomy (PTX) is debated because no long-term randomized trials have been performed.
Objective
To examine the effect of PTX on mild PHPT with regard to mortality (primary end point) and key morbidities (secondary end point).
Design
Prospective randomized controlled trial. (ClinicalTrials.gov: NCT00522028).
Setting
Eight Scandinavian referral centers.
Patients
From 1998 to 2005, 191 patients with mild PHPT were included.
Intervention
Ninety-five patients were randomly assigned to PTX, and 96 were assigned to observation without intervention (OBS).
Measurements
Date and causes of death were obtained from the Swedish and Norwegian Cause of Death Registries 10 years after randomization and after an extended observation period lasting until 2018. Morbidity events were prospectively registered annually.
Results
After 10 years, 15 patients had died (8 in the PTX group and 7 in the OBS group). Within the extended observation period, 44 deaths occurred, which were evenly distributed between groups (24 in the PTX group and 20 in the OBS group). A total of 101 morbidity events (cardiovascular events, cerebrovascular events, cancer, peripheral fractures, and renal stones) were also similarly distributed between groups (52 in the PTX group and 49 in the OBS group). During the study, a total of 16 vertebral fractures occurred in 14 patients (7 in each group).
Limitation
During the study period, 23 patients in the PTX group and 27 in the OBS group withdrew.
Conclusion
Parathyroidectomy does not appear to reduce morbidity or mortality in mild PHPT. Thus, no evidence of adverse effects of observation was seen for at least a decade with respect to mortality, fractures, cancer, cardiovascular and cerebrovascular events, or renal morbidities.
Primary funding source
Swedish government, Norwegian Research Council, and South-Eastern Norway Regional Health Authority.



Ann Intern Med: 19 Apr 2022; epub ahead of print
Pretorius M, Lundstam K, Heck A, Fagerland MW, ... Hellström M, Bollerslev J
Ann Intern Med: 19 Apr 2022; epub ahead of print | PMID: 35436153
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Impact:
Abstract

Adverse Events Associated With Coprescription of Phosphodiesterase Type 5 Inhibitors and Oral Organic Nitrates in Male Patients With Ischemic Heart Disease : A Case-Crossover Study.

Holt A, Blanche P, Jensen AKG, Nouhravesh N, ... McGettigan P, Lamberts M
Background
Concomitant use of oral organic nitrates (nitrates) and phosphodiesterase type 5 (PDE5) inhibitors is contraindicated.
Objective
To measure temporal trends in the coprescription of nitrates and PDE5 inhibitors and to measure the association between cardiovascular outcomes and the coprescription of nitrates with PDE5 inhibitors.
Design
Case-crossover design.
Setting
Nationwide study of Danish patients from 2000 to 2018.
Patients
Male patients with International Classification of Diseases, 10th Revision (ICD-10) codes for ischemic heart disease (IHD), including those who had a continuing prescription for nitrates and a new, filled prescription for PDE5 inhibitors.
Measurements
Two composite outcomes were measured: 1) cardiac arrest, shock, myocardial infarction, ischemic stroke, or acute coronary arteriography and 2) syncope, angina pectoris, or drug-related adverse event.
Results
From 2000 to 2018, 249 541 male patients with IHD were identified. Of these, 42 073 patients had continuing prescriptions for nitrates. During this period, the prescription rate for PDE5 inhibitors in patients with IHD who were taking nitrates increased from an average of 0.9 prescriptions (95% CI, 0.5 to 1.2 prescriptions) per 100 persons per year in 2000 to 19.5 prescriptions (CI, 18.0 to 21.1 prescriptions) in 2018. No statistically significant association was found between the coprescription of nitrates with PDE5 inhibitors and the risk for either composite outcome (odds ratio [OR], 0.58 [CI, 0.28 to 1.13] for the first outcome and OR, 0.73 [CI, 0.40 to 1.32] for the second outcome).
Limitation
An assumption was made that concurrently filled prescriptions for nitrates and PDE5 inhibitors equaled concomitant use.
Conclusion
From 2000 to 2018, the use of PDE5 inhibitors increased 20-fold among Danish patients with IHD who were taking nitrates. A statistically significant association between concomitant use of these medications and cardiovascular adverse events could not be identified.
Primary funding source
Ib Mogens Kristiansens Almene Fond and Helsefonden.



Ann Intern Med: 19 Apr 2022; epub ahead of print
Holt A, Blanche P, Jensen AKG, Nouhravesh N, ... McGettigan P, Lamberts M
Ann Intern Med: 19 Apr 2022; epub ahead of print | PMID: 35436155
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Impact:
Abstract

Sodium-Glucose Cotransporter-2 Inhibitors in Patients With Heart Failure : A Systematic Review and Meta-analysis.

Zou X, Shi Q, Vandvik PO, Guyatt G, ... Zhu Z, Li S
Background
Randomized controlled trials established the cardiac protection of sodium-glucose cotransporter-2 (SGLT2) inhibitors among adults with type 2 diabetes. New evidence suggests that these results could extend to people without diabetes.
Purpose
To evaluate the effect of SGLT2 inhibitors in patients with heart failure, regardless of the presence of type 2 diabetes.
Data sources
PubMed, Web of Science, Cochrane Library, and Embase (OVID interface).
Study selection
Eligible trials randomly assigned adults with heart failure to SGLT2 inhibitors or control.
Data extraction
Time-to-event individual patient data were reconstructed from published Kaplan-Meier plots; time-varying risk ratios (RRs) were calculated in half-, 1-, and 2-year time frames; and anticipated absolute benefits were calculated using simple models applying relative effects to baseline risks.
Data synthesis
Sodium-glucose cotransporter-2 inhibitors reduce hospitalization for heart failure by 37% (95% CI, 25% to 47%) at 6 months, 32% (CI, 20% to 42%) at 1 year, and 26% (CI, 10% to 40%) at 2 years (all high certainty) and reduce cardiovascular death by 14% (CI, 1% to 25%) at 1 year (high certainty). Nevertheless, low-certainty evidence did not indicate protection against all-cause death, kidney disease progression, or kidney failure. Anticipated absolute benefits are greater for patients treated in the first year and for those with poorer prognoses, such as those newly diagnosed with heart failure in the hospital. In addition, SGLT2 inhibitors doubled the risk for genital infections (RR, 2.69 [CI, 1.61 to 4.52]; high certainty).
Limitation
Covariates were unavailable in meta-analyses with reconstructed individual patient data.
Conclusion
Among people with heart failure, SGLT2 inhibitors reduce hospitalizations for heart failure regardless of the presence of diabetes; absolute benefits are most pronounced in first-year treatment and vary with prognostic factors. Clinicians should note the increased risk for genital infection in patients receiving SGLT2 inhibitors.
Primary funding source
1.3.5 Project for Disciplines of Excellence, West China Hospital of Sichuan University. (PROSPERO: CRD42021255544).



Ann Intern Med: 12 Apr 2022; epub ahead of print
Zou X, Shi Q, Vandvik PO, Guyatt G, ... Zhu Z, Li S
Ann Intern Med: 12 Apr 2022; epub ahead of print | PMID: 35404670
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Impact:
Abstract

Changes in Health Care Spending, Use, and Clinical Outcomes After Nonfatal Firearm Injuries Among Survivors and Family Members : A Cohort Study.

Song Z, Zubizarreta JR, Giuriato M, Paulos E, Koh KA
Background
Despite increasing awareness of firearm-related deaths, evidence on the clinical and economic implications of nonfatal firearm injuries is limited.
Objective
To measure changes in clinical and economic outcomes after nonfatal firearm injuries among survivors and their family members.
Design
Cohort study.
Setting
MarketScan Medicare and commercial claims data, 2008 to 2018.
Participants
6498 survivors of firearm injuries matched to 32 490 control participants and 12 489 family members of survivors matched to 62 445 control participants.
Intervention
Exposure to nonfatal firearm injury as a survivor or family member of a survivor.
Measurements
Changes in health care spending, use, and morbidity from preinjury through 1 year postinjury relative to control participants, on average and by type and severity of firearm injury.
Results
After nonfatal firearm injury, medical spending increased $2495 per person per month (402%) and cost sharing increased $102 per person per month (176%) among survivors relative to control participants (P < 0.001) in the first year after injury, driven by an increase in the first month of $25 554 (4122%) in spending and $1112 (1917%) in cost sharing per survivor (P < 0.001). All categories of health care use increased relative to the control group. Survivors had a 40% increase in pain diagnoses, a 51% increase in psychiatric disorders, and an 85% increase in substance use disorders after firearm injury relative to control participants (P < 0.001), accompanied by increased pain and psychiatric medications. Family members had a 12% increase in psychiatric disorders relative to their control participants (P = 0.003). These overall clinical and economic changes were driven by intentional firearm injuries and more severe firearm injuries.
Limitation
Precision of diagnostic codes and generalizability to other patient populations, including Medicaid and uninsured patients.
Conclusion
In survivors, nonfatal firearm injuries led to increases in psychiatric disorders, substance use disorders, and pain diagnoses, alongside substantial increases in health care spending and use. In addition, mental health worsened among family members.
Primary funding source
National Institutes of Health.



Ann Intern Med: 05 Apr 2022; epub ahead of print
Song Z, Zubizarreta JR, Giuriato M, Paulos E, Koh KA
Ann Intern Med: 05 Apr 2022; epub ahead of print | PMID: 35377713
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Impact:
Abstract

Homicide Deaths Among Adult Cohabitants of Handgun Owners in California, 2004 to 2016 : A Cohort Study.

Studdert DM, Zhang Y, Holsinger EE, Prince L, ... Wintemute GJ, Miller M
Background
Although personal protection is a major motivation for purchasing firearms, existing studies suggest that people living in homes with firearms have higher risks for dying by homicide. Distribution of those risks among household members is poorly understood.
Objective
To estimate the association between living with a lawful handgun owner and risk for homicide victimization.
Design
This retrospective cohort study followed 17.6 million adult residents of California for up to 12 years 2 months (18 October 2004 through 31 December 2016). Cohort members did not own handguns, but some started residing with lawful handgun owners during follow-up.
Setting
California.
Participants
17 569 096 voter registrants aged 21 years or older.
Measurements
Homicide (overall, by firearm, and by other methods) and homicide occurring in the victim\'s home.
Results
Of 595 448 cohort members who commenced residing with handgun owners, two thirds were women. A total of 737 012 cohort members died; 2293 died by homicide. Overall rates of homicide were more than twice as high among cohabitants of handgun owners than among cohabitants of nonowners (adjusted hazard ratio, 2.33 [95% CI, 1.78 to 3.05]). These elevated rates were driven largely by higher rates of homicide by firearm (adjusted hazard ratio, 2.83 [CI, 2.05 to 3.91]). Among homicides occurring at home, cohabitants of owners had sevenfold higher rates of being fatally shot by a spouse or intimate partner (adjusted hazard ratio, 7.16 [CI, 4.04 to 12.69]); 84% of these victims were female.
Limitations
Some cohort members classified as unexposed may have lived in homes with handguns. Residents of homes with and without handguns may have differed on unobserved traits associated with homicide risk.
Conclusion
Living with a handgun owner is associated with substantially elevated risk for dying by homicide. Women are disproportionately affected.
Primary funding source
The National Collaborative on Gun Violence Research, the Fund for a Safer Future, the Joyce Foundation, Stanford Law School, and the Stanford University School of Medicine.



Ann Intern Med: 05 Apr 2022; epub ahead of print
Studdert DM, Zhang Y, Holsinger EE, Prince L, ... Wintemute GJ, Miller M
Ann Intern Med: 05 Apr 2022; epub ahead of print | PMID: 35377715
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Impact:
Abstract

In inpatients with COVID-19 who need supplemental oxygen, lenzilumab increased ventilation-free survival.

Mariano VJ, Mylonakis E
Source citation
Temesgen Z, Burger CD, Baker J, et al. Lenzilumab in hospitalised patients with COVID-19 pneumonia (LIVE-AIR): a phase 3, randomised, placebo-controlled trial. Lancet Respir Med. 2022;10:237-46. 34863332.



Ann Intern Med: 31 Mar 2022; 175:JC39
Mariano VJ, Mylonakis E
Ann Intern Med: 31 Mar 2022; 175:JC39 | PMID: 35377717
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Impact:
Abstract

In osteoporosis or osteopenia, exercise interventions improve BMD; effects vary by exercise type and BMD site.

Ott SM
Source citation
Zhang S, Huang X, Zhao X, et al. Effect of exercise on bone mineral density among patients with osteoporosis and osteopenia: a systematic review and network meta-analysis. J Clin Nurs. 2021. [Epub ahead of print]. 34725872.



Ann Intern Med: 31 Mar 2022; 175:JC46
Ott SM
Ann Intern Med: 31 Mar 2022; 175:JC46 | PMID: 35377720
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Impact:
Abstract

PICC vs. midline catheter use for short-term indications was linked to major complications at ≤30 d.

Auron M
Source citation
Swaminathan L, Flanders S, Horowitz J, et al. Safety and outcomes of midline catheters vs peripherally inserted central catheters for patients with short-term indications: a multicenter study. JAMA Intern Med. 2022;182:50-8. 34842905.



Ann Intern Med: 31 Mar 2022; 175:JC47
Auron M
Ann Intern Med: 31 Mar 2022; 175:JC47 | PMID: 35377721
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Impact:
Abstract

In suspected PE, YEARS rule + D-dimer was noninferior to D-dimer alone to rule out PE.

Goumeniouk N, Lang E
Source citation
Freund Y, Chauvin A, Jimenez S, et al. Effect of a diagnostic strategy using an elevated and age-adjusted D-dimer threshold on thromboembolic events in emergency department patients with suspected pulmonary embolism: a randomized clinical trial. JAMA. 2021;326:2141-9. 34874418.



Ann Intern Med: 31 Mar 2022; 175:JC43
Goumeniouk N, Lang E
Ann Intern Med: 31 Mar 2022; 175:JC43 | PMID: 35377723
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Impact:
Abstract

In severe COVID-19, high-flow vs. conventional oxygen therapy reduced intubation and time to clinical recovery at 28 d.

Carpenter CR, Steel PAD
Source citation
Ospina-Tascón GA, Calderón-Tapia LE, García AF, et al. Effect of high-flow oxygen therapy vs conventional oxygen therapy on invasive mechanical ventilation and clinical recovery in patients with severe COVID-19: a randomized clinical trial. JAMA. 2021;326:2161-71. 34874419.



Ann Intern Med: 31 Mar 2022; 175:JC38
Carpenter CR, Steel PAD
Ann Intern Med: 31 Mar 2022; 175:JC38 | PMID: 35377724
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Impact:
Abstract

How Would You Treat This Patient With Acute and Chronic Pain From Sickle Cell Disease? : Grand Rounds Discussion From Beth Israel Deaconess Medical Center.

Kanjee Z, Achebe MO, Smith WR, Burns RB
Sickle cell disease is prevalent in large numbers of patients in the United States and has a significant global impact. Its complications span numerous organs and lead to reduced life expectancy. Acute and chronic sickle cell pain is a common cause of patient suffering. The American Society of Hematology published updated guidelines on management of acute and chronic pain from sickle cell disease in 2019. Several of the recommendations are conditional and leave specific decisions to the treating physician. These include conditional recommendations about the use of ketamine for acute pain and the initiation and discontinuation of long-term opioid therapy for chronic pain. Here, 2 hematologists discuss these guidelines and make contrasting recommendations for the management of acute and chronic pain for a patient with sickle cell disease.



Ann Intern Med: 31 Mar 2022; 175:566-573
Kanjee Z, Achebe MO, Smith WR, Burns RB
Ann Intern Med: 31 Mar 2022; 175:566-573 | PMID: 35404671
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Impact:
Abstract

Community-Acquired Pneumonia.

Rothberg MB
Community-acquired pneumonia is an important cause of morbidity and mortality. It can be caused by bacteria, viruses, or fungi and can be prevented through vaccination with pneumococcal, influenza, and COVID-19 vaccines. Diagnosis requires suggestive history and physical findings in conjunction with radiographic evidence of infiltrates. Laboratory testing can help guide therapy. Important issues in treatment include choosing the proper venue, timely initiation of the appropriate antibiotic or antiviral, appropriate respiratory support, deescalation after negative culture results, switching to oral therapy, and short treatment duration.



Ann Intern Med: 31 Mar 2022; 175:ITC49-ITC64
Rothberg MB
Ann Intern Med: 31 Mar 2022; 175:ITC49-ITC64 | PMID: 35404672
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Impact:
Abstract

Risks for Anaphylaxis With Intravenous Iron Formulations : A Retrospective Cohort Study.

Dave CV, Brittenham GM, Carson JL, Setoguchi S
Background
The risks for anaphylaxis among intravenous (IV) iron products currently in use have not been assessed.
Objective
To compare risks for anaphylaxis among 5 IV iron products that are used frequently.
Design
Retrospective cohort study using a target trial emulation framework.
Setting
Medicare fee-for-service data with Part D coverage between July 2013 and December 2018.
Participants
Older adults receiving their first administration of IV iron.
Measurements
The primary outcome was the occurrence of anaphylaxis within 1 day of IV iron administration, ascertained using a validated case definition. Analysis was adjusted for 40 baseline covariates using inverse probability of treatment weighting. The adjusted incidence rates (IRs) for anaphylaxis per 10 000 first administrations and odds ratios (ORs) were computed.
Results
The adjusted IRs for anaphylaxis per 10 000 first administrations were 9.8 cases (95% CI, 6.2 to 15.3 cases) for iron dextran, 4.0 cases (CI, 2.5 to 6.6 cases) for ferumoxytol, 1.5 cases (CI, 0.3 to 6.6 cases) for ferric gluconate, 1.2 cases (CI, 0.6 to 2.5 cases) for iron sucrose, and 0.8 cases (CI, 0.3 to 2.6 cases) for ferric carboxymaltose. Using iron sucrose as the referent category, the adjusted ORs for anaphylaxis were 8.3 (CI, 3.5 to 19.8) for iron dextran and 3.4 (CI, 1.4 to 8.3) for ferumoxytol. When cohort entry was restricted to the period after withdrawal of high-molecular-weight iron dextran from the U.S. market in 2014, the risk for anaphylaxis associated with low-molecular-weight iron dextran (OR, 8.4 [CI, 2.8 to 24.7]) did not change appreciably. Anaphylactic reactions requiring hospitalizations were observed only among patients using iron dextran or ferumoxytol.
Limitation
Generalizability to non-Medicare populations.
Conclusion
The rates of anaphylaxis were very low with all IV iron products but were 3- to 8-fold greater for iron dextran and ferumoxytol than for iron sucrose.
Primary funding source
None.



Ann Intern Med: 29 Mar 2022; epub ahead of print
Dave CV, Brittenham GM, Carson JL, Setoguchi S
Ann Intern Med: 29 Mar 2022; epub ahead of print | PMID: 35344378
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Impact:
Abstract

Effectiveness of Motivational Interviewing in Managing Overweight and Obesity : A Systematic Review and Meta-analysis.

Michalopoulou M, Ferrey AE, Harmer G, Goddard L, ... Jebb SA, Aveyard P
Background
Motivational interviewing (MI) is potentially useful in management of overweight and obesity, but staff training and increased delivery time are barriers, and its effectiveness independent of other behavioral components is unclear.
Purpose
To assess the independent contribution of MI as part of a behavioral weight management program (BWMP) in controlling weight and improving psychological well-being.
Data sources
6 electronic databases and 2 trial registries, searched from database inception through 24 September 2021.
Study selection
Randomized controlled trials in adults or adolescents aimed at weight loss or maintenance and comparing programs incorporating MI versus interventions without MI.
Data extraction
Two reviewers independently screened studies, extracted data, and assessed risk of bias. Outcomes included weight, anxiety, depression, quality of life, and other aspects of psychological well-being. Pooled mean differences or standardized mean differences were obtained using random- and fixed-effects meta-analyses.
Data synthesis
Forty-six studies involving 11 077 participants, predominantly with obesity, were included. At 6 months, BWMPs using MI were more effective than no/minimal intervention (-0.88 [95% CI, -1.27 to -0.48] kg; I 2 = 0%) but were not statistically significantly more effective than lower-intensity (-0.88 [CI, -2.39 to 0.62] kg; I 2 = 55.8%) or similar-intensity (-1.36 [CI, -2.80 to 0.07] kg; I 2 = 18.8%) BWMPs. At 1 year, data were too sparse to pool comparisons with no/minimal intervention, but MI did not produce statistically significantly greater weight change compared with lower-intensity (-1.16 [CI, -2.49 to 0.17] kg; I 2 = 88.7%) or similar-intensity (-0.18 [CI, -2.40 to 2.04] kg; I 2 = 72.7%) BWMPs without MI. Studies with 18-month follow-up were also sparse; MI did not produce statistically significant benefit in any of the comparator categories. There was no evidence of subgroup differences based on study, participant, or intervention characteristics. Too few studies assessed effects on psychological well-being to pool, but data did not suggest that MI was independently effective.
Limitations
High statistical heterogeneity among studies, largely unexplained by sensitivity and subgroup analyses; stratification by comparator intensity and follow-up duration resulted in pooling of few studies.
Conclusion
There is no evidence that MI increases effectiveness of BWMPs in controlling weight. Given the intensive training required for its delivery, MI may not be a worthwhile addition to BWMPs.
Primary funding source
National Institute for Health Research Biomedical Research Centre. (PROSPERO: CRD42020177259).



Ann Intern Med: 29 Mar 2022; epub ahead of print
Michalopoulou M, Ferrey AE, Harmer G, Goddard L, ... Jebb SA, Aveyard P
Ann Intern Med: 29 Mar 2022; epub ahead of print | PMID: 35344379
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Impact:
Abstract

Preconception Antidiabetic Drugs in Men and Birth Defects in Offspring : A Nationwide Cohort Study.

Wensink MJ, Lu Y, Tian L, Shaw GM, ... Lindahl-Jacobsen R, Eisenberg ML
Background
Diabetes reduces semen quality and increasingly occurs during reproductive years. Diabetes medications, such as metformin, have glucose-independent effects on the male reproductive system. Associations with birth defects in offspring are unknown.
Objective
To evaluate whether the risk for birth defects in offspring varies with preconceptional pharmacologic treatment of fathers with diabetes.
Design
Nationwide prospective registry-based cohort study.
Setting
Denmark from 1997 to 2016.
Participants
All liveborn singletons from mothers without histories of diabetes or essential hypertension.
Measurements
Offspring were considered exposed if their father filled 1 or more prescriptions for a diabetes drug during the development of fertilizing sperm. Sex and frequencies of major birth defects were compared across drugs, times of exposure, and siblings.
Results
Of 1 116 779 offspring included, 3.3% had 1 or more major birth defects (reference). Insulin-exposed offspring (n = 5298) had the reference birth defect frequency (adjusted odds ratio [aOR], 0.98 [95% CI, 0.85 to 1.14]). Metformin-exposed offspring (n = 1451) had an elevated birth defect frequency (aOR, 1.40 [CI, 1.08 to 1.82]). For sulfonylurea-exposed offspring (n = 647), the aOR was 1.34 (CI, 0.94 to 1.92). Offspring whose fathers filled a metformin prescription in the year before (n = 1751) or after (n = 2484) sperm development had reference birth defect frequencies (aORs, 0.88 [CI, 0.59 to 1.31] and 0.92 [CI, 0.68 to 1.26], respectively), as did unexposed siblings of exposed offspring (3.2%; exposed vs. unexposed OR, 1.54 [CI, 0.94 to 2.53]). Among metformin-exposed offspring, genital birth defects, all in boys, were more common (aOR, 3.39 [CI, 1.82 to 6.30]), while the proportion of male offspring was lower (49.4% vs. 51.4%, P = 0.073).
Limitation
Information on underlying disease status was limited.
Conclusion
Preconception paternal metformin treatment is associated with major birth defects, particularly genital birth defects in boys. Further research should replicate these findings and clarify the causation.
Primary funding source
National Institutes of Health.



Ann Intern Med: 29 Mar 2022; epub ahead of print
Wensink MJ, Lu Y, Tian L, Shaw GM, ... Lindahl-Jacobsen R, Eisenberg ML
Ann Intern Med: 29 Mar 2022; epub ahead of print | PMID: 35344380
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Impact:
Abstract

Risk for Shoulder Conditions After Vaccination: A Population-Based Study Using Real-World Data.

Zheng C, Duffy J, Liu IA, Sy LS, ... Mercado C, Jacobsen SJ
Background
Although shoulder conditions have been reported as an adverse event after intramuscular vaccination in the deltoid muscle, epidemiologic data on shoulder conditions after vaccination are limited.
Objective
To estimate the risk for shoulder conditions after vaccination and assess possible risk factors.
Design
Retrospective cohort study.
Setting
Kaiser Permanente Southern California, a large integrated health care organization.
Participants
Kaiser Permanente Southern California members aged 3 years or older who had an intramuscular vaccination administered in the deltoid muscle between 1 April 2016 and 31 December 2017.
Measurements
A natural language processing (NLP) algorithm was used to identify potential shoulder conditions among vaccinated persons with shoulder disorder diagnosis codes. All NLP-identified cases were manually chart confirmed on the basis of our case definition. The characteristics of vaccinated persons with and without shoulder conditions were compared.
Results
Among 3 758 764 administered vaccinations, 371 cases of shoulder condition were identified, with an estimated incidence of 0.99 (95% CI, 0.89 to 1.09) per 10 000 vaccinations. The incidence was 1.22 (CI, 1.10 to 1.35) for the adult (aged ≥18 years) and 0.05 (CI, 0.02 to 0.14) for the pediatric (aged 3 to 17 years) vaccinated populations. In the adult vaccinated population, advanced age, female sex, an increased number of outpatient visits in the 6 months before vaccination, lower Charlson Comorbidity Index, and pneumococcal conjugate vaccine were associated with a higher risk for shoulder conditions. Among influenza vaccines, quadrivalent vaccines were associated with an increased risk for shoulder conditions. Simultaneous administration of vaccines was associated with a higher risk for shoulder conditions among elderly persons.
Limitation
Generalizability to other health care settings, use of administrative data, and residual confounding.
Conclusion
These population-based data suggest a small absolute risk for shoulder conditions after vaccination. Given the high burden of shoulder conditions, clinicians should pay attention to any factors that may further increase risks.
Primary funding source
Centers for Disease Control and Prevention.



Ann Intern Med: 22 Mar 2022; epub ahead of print
Zheng C, Duffy J, Liu IA, Sy LS, ... Mercado C, Jacobsen SJ
Ann Intern Med: 22 Mar 2022; epub ahead of print | PMID: 35313110
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Impact:
Abstract

Risk for Acute Myocardial Infarction After Ophthalmologic Procedures.

Sen A, Gémes K, Stålhammar G, Svensen C, ... Janszky I, Möller J
Background
Preoperative cardiovascular evaluations are frequently done before ambulatory ophthalmologic procedures. However, whether these procedures can trigger an acute myocardial infarction (AMI) is unknown.
Objective
To assess the short-term risk for AMI associated with ophthalmologic procedures.
Design
Case-crossover design.
Setting
Population-based nationwide study from Norway and Sweden.
Participants
First-time patients with AMI, aged 40 years and older, identified via inpatient registries and linked to outpatient surgical procedures in Norway (2008 to 2014) and Sweden (2001 to 2014), respectively.
Measurements
Using self-matching, for each participant, exposure to ophthalmologic procedures in the 0 to 7 days before AMI diagnosis (hazard period) was compared with an 8-day period 30 days earlier, that is, days 29 to 36 before AMI (control period) to estimate the relative risk for an AMI the week after an ophthalmologic procedure. The odds ratios (ORs) with 95% CIs were calculated, using conditional logistic regression. Only patients who had a procedure of interest during either the hazard or control period were included.
Results
For the 806 patients with AMI included in this study, there was a lower likelihood of AMI in the week after an ophthalmologic procedure than during the control week (OR, 0.83; 95% CI, 0.75 to 0.91). Furthermore, there was no evidence of increased risk for AMI when analyses were stratified by surgery subtype, anesthesia (local or general), duration, invasiveness (low, intermediate, or high), patient\'s age (<65 years or ≥65 years), or comorbidity (none vs. any).
Limitation
Potential bias from time-varying confounders between the hazard and the control periods.
Conclusion
Ophthalmologic procedures done in an outpatient setting did not seem to be associated with an increased risk for AMI.
Primary funding source
Central Norway Regional Health Authority and the Swedish Research Council.



Ann Intern Med: 22 Mar 2022; epub ahead of print
Sen A, Gémes K, Stålhammar G, Svensen C, ... Janszky I, Möller J
Ann Intern Med: 22 Mar 2022; epub ahead of print | PMID: 35313112
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Impact:
Abstract

The Management of Substance Use Disorders: Synopsis of the 2021 U.S. Department of Veterans Affairs and U.S. Department of Defense Clinical Practice Guideline.

Perry C, Liberto J, Milliken C, Burden J, ... Gordon AJ, VA/DoD Guideline Development Group*
Description
In August 2021, leadership within the U.S. Department of Veterans Affairs (VA) and U.S. Department of Defense (DoD) approved a joint clinical practice guideline (CPG) for the management of substance use disorders (SUDs). This synopsis summarizes key recommendations.
Methods
In March 2020, the VA/DoD Evidence-Based Practice Work Group assembled a team to update the 2015 VA/DoD Clinical Practice Guideline for the Management of Substance Use Disorders that included clinical stakeholders and conformed to the National Academy of Medicine\'s tenets for trustworthy CPGs. The guideline panel developed key questions, systematically searched and evaluated the literature, created two 1-page algorithms, and distilled 35 recommendations for care using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. This synopsis presents the recommendations that were believed to be the most clinically impactful.
Recommendations
The scope of the CPG is broad; however, this synopsis focuses on key recommendations for the management of alcohol use disorder, use of buprenorphine in opioid use disorder, contingency management, and use of technology and telehealth to manage patients remotely.



Ann Intern Med: 22 Mar 2022; epub ahead of print
Perry C, Liberto J, Milliken C, Burden J, ... Gordon AJ, VA/DoD Guideline Development Group*
Ann Intern Med: 22 Mar 2022; epub ahead of print | PMID: 35313113
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Impact:
Abstract

Telehealth for Substance Use Disorders: A Rapid Review for the 2021 U.S. Department of Veterans Affairs and U.S. Department of Defense Guidelines for Management of Substance Use Disorders.

Uhl S, Bloschichak A, Moran A, McShea K, ... McKay JR, D\'Anci KE
Background
Approximately 20.4 million Americans met criteria for a substance use disorder (SUD) in 2019; however, only about 12.2% of persons with an SUD receive specialty care. Telehealth offers alternatives to traditional forms of substance use treatment.
Purpose
To synthesize recent findings on the efficacy of telehealth for SUDs.
Data sources
MEDLINE, Embase, PubMed, and the Cochrane Library from January 2015 through August 2021 (English language only).
Study selection
Randomized controlled trials (RCTs) of adults with a diagnosis of SUD based on the Diagnostic and Statistical Manual of Mental Disorders or International Classification of Diseases.
Data extraction
One investigator abstracted data and assessed study quality, and a second checked for accuracy.
Data synthesis
This rapid review synthesized evidence from 17 RCTs. Evidence is very uncertain that telehealth provided as videoconference therapy (1 RCT) or web-based cognitive behavioral therapy (CBT) (3 RCTs) has similar effects to in-person therapy for improving abstinence from alcohol or cannabis. Low-strength evidence suggests that web-based CBT has similar effects for improving abstinence in multiple SUDs (2 RCTs). Low-strength evidence suggests that adding supportive text messaging to follow-up care improves abstinence and amount of alcohol per day (2 RCTs) but does not improve emergency department visits or frequency of consumption (2 RCTs). Enhanced telephone monitoring likely reduces readmissions for SUD detoxification compared with usual follow-up alone (1 RCT) but does not reduce days of substance use (low-strength evidence).
Limitation
Narrative synthesis, heterogeneity of telehealth interventions, no assessment of publication bias, and study methodology.
Conclusion
Evidence is very uncertain that telehealth is similar to in-person care for SUD outcomes. Limited evidence suggests some benefit of adding telehealth to usual SUD care.
Primary funding source
U.S. Department of Veterans Affairs Veterans Health Administration.



Ann Intern Med: 22 Mar 2022; epub ahead of print
Uhl S, Bloschichak A, Moran A, McShea K, ... McKay JR, D'Anci KE
Ann Intern Med: 22 Mar 2022; epub ahead of print | PMID: 35313116
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Impact:
Abstract

Effects of State Opioid Prescribing Laws on Use of Opioid and Other Pain Treatments Among Commercially Insured U.S. Adults.

McGinty EE, Bicket MC, Seewald NJ, Stuart EA, ... McCourt AD, Rutkow L
Background
There is concern that state laws to curb opioid prescribing may adversely affect patients with chronic noncancer pain, but the laws\' effects are unclear because of challenges in disentangling multiple laws implemented around the same time.
Objective
To study the association between state opioid prescribing cap laws, pill mill laws, and mandatory prescription drug monitoring program query or enrollment laws and trends in opioid and guideline-concordant nonopioid pain treatment among commercially insured adults, including a subgroup with chronic noncancer pain conditions.
Design
Thirteen treatment states that implemented a single law of interest in a 4-year period and unique groups of control states for each treatment state were identified. Augmented synthetic control analyses were used to estimate the association between each state law and outcomes.
Setting
United States, 2008 to 2019.
Patients
7 694 514 commercially insured adults aged 18 years or older, including 1 976 355 diagnosed with arthritis, low back pain, headache, fibromyalgia, and/or neuropathic pain.
Measurements
Proportion of patients receiving any opioid prescription or guideline-concordant nonopioid pain treatment per month, and mean days\' supply and morphine milligram equivalents (MME) of prescribed opioids per day, per patient, per month.
Results
Laws were associated with small-in-magnitude and non-statistically significant changes in outcomes, although CIs around some estimates were wide. For adults overall and those with chronic noncancer pain, the 13 state laws were each associated with a change of less than 1 percentage point in the proportion of patients receiving any opioid prescription and a change of less than 2 percentage points in the proportion receiving any guideline-concordant nonopioid treatment, per month. The laws were associated with a change of less than 1 in days\' supply of opioid prescriptions and a change of less than 4 in average monthly MME per day per patient prescribed opioids.
Limitations
Results may not be generalizable to non-commercially insured populations and were imprecise for some estimates. Use of claims data precluded assessment of the clinical appropriateness of pain treatments.
Conclusion
This study did not identify changes in opioid prescribing or nonopioid pain treatment attributable to state laws.
Primary funding source
National Institute on Drug Abuse.



Ann Intern Med: 14 Mar 2022; epub ahead of print
McGinty EE, Bicket MC, Seewald NJ, Stuart EA, ... McCourt AD, Rutkow L
Ann Intern Med: 14 Mar 2022; epub ahead of print | PMID: 35286141
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Impact:
Abstract

A Reporting Tool for Adapted Guidelines in Health Care: The RIGHT-Ad@pt Checklist.

Song Y, Alonso-Coello P, Ballesteros M, Cluzeau F, ... García LM, RIGHT-Ad@pt Working Group*
Background
Adaptation of existing guidelines can be an efficient way to develop contextualized recommendations. Transparent reporting of the adaptation approach can support the transparency and usability of the adapted guidelines.
Objective
To develop an extension of the RIGHT (Reporting Items for practice Guidelines in HealThcare) statement for the reporting of adapted guidelines (including recommendations that have been adopted, adapted, or developed de novo), the RIGHT-Ad@pt checklist.
Design
A multistep process was followed to develop the checklist: establishing a working group, generating an initial checklist, optimizing the checklist (through an initial assessment of adapted guidelines, semistructured interviews, a Delphi consensus survey, an external review, and a final assessment of adapted guidelines), and approval of the final checklist by the working group.
Setting
International collaboration.
Participants
A total of 119 professionals participated in the development process.
Measurements
Participants\' consensus on items in the checklist.
Results
The RIGHT-Ad@pt checklist contains 34 items grouped in 7 sections: basic information (7 items); scope (6 items); rigor of development (10 items); recommendations (4 items); external review and quality assurance (2 items); funding, declaration, and management of interest (2 items); and other information (3 items). A user guide with explanations and real-world examples for each item was developed to provide a better user experience.
Limitation
The RIGHT-Ad@pt checklist requires further validation in real-life use.
Conclusion
The RIGHT-Ad@pt checklist has been developed to improve the reporting of adapted guidelines, focusing on the standardization, rigor, and transparency of the process and the clarity and explicitness of adapted recommendations.
Primary funding source
None.



Ann Intern Med: 14 Mar 2022; epub ahead of print
Song Y, Alonso-Coello P, Ballesteros M, Cluzeau F, ... García LM, RIGHT-Ad@pt Working Group*
Ann Intern Med: 14 Mar 2022; epub ahead of print | PMID: 35286143
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Impact:
Abstract

Comparison of SARS-CoV-2 Reverse Transcriptase Polymerase Chain Reaction and BinaxNOW Rapid Antigen Tests at a Community Site During an Omicron Surge : A Cross-Sectional Study.

Schrom J, Marquez C, Pilarowski G, Wang CY, ... DeRisi J, Havlir D
Background
SARS-CoV-2 rapid antigen tests are an important public health tool.
Objective
To evaluate field performance of the BinaxNOW rapid antigen test (Abbott) compared with reverse transcriptase polymerase chain reaction (RT-PCR) for detecting infection with the Omicron variant of SARS-CoV-2.
Design
Cross-sectional surveillance study.
Setting
Free, walk-up, outdoor, urban community testing and vaccine site led by Unidos en Salud, serving a predominantly Latinx community highly impacted by COVID-19.
Participants
Persons seeking COVID-19 testing in January 2022.
Measurements
Simultaneous BinaxNOW and RT-PCR from nasal, cheek, and throat swabs, including cycle threshold (Ct) measures; a lower Ct value is a surrogate for higher amounts of virus.
Results
Among 731 persons tested with nasal swabs, there were 296 (40.5%) positive results on RT-PCR; 98.9% were the Omicron variant. BinaxNOW detected 95.2% (95% CI, 91% to 98%) of persons who tested positive on RT-PCR with a Ct value below 30, 82.1% (CI, 77% to 87%) of those who tested positive on RT-PCR with a Ct value below 35, and 65.2% (CI, 60% to 71%) of all who were positive on RT-PCR. Among 75 persons with simultaneous nasal and cheek swabs, BinaxNOW using a cheek swab failed to detect 91% (20 of 22) of specimens that were positive on BinaxNOW with a nasal swab. Among persons with simultaneous nasal and throat swabs who were positive on RT-PCR with a Ct value below 30, 42 of 49 (85.7%) were detected by nasal BinaxNOW, 23 of 49 (46.9%) by throat BinaxNOW, and 44 of 49 (89.8%) by either.
Limitation
Participants were a cross-sectional sample from a community-based sentinel surveillance site, precluding study of viral or symptom dynamics.
Conclusion
BinaxNOW detected persons with high SARS-CoV-2 levels during the Omicron surge, enabling rapid responses to positive test results. Cheek or throat swabs should not replace nasal swabs. As currently recommended, high-risk persons with an initial negative BinaxNOW result should have repeated testing.
Primary funding source
University of California, San Francisco.



Ann Intern Med: 14 Mar 2022; epub ahead of print
Schrom J, Marquez C, Pilarowski G, Wang CY, ... DeRisi J, Havlir D
Ann Intern Med: 14 Mar 2022; epub ahead of print | PMID: 35286144
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Impact:
Abstract

Comparison of Patients Infected With Delta Versus Omicron COVID-19 Variants Presenting to Paris Emergency Departments : A Retrospective Cohort Study.

Bouzid D, Visseaux B, Kassasseya C, Daoud A, ... Freund Y, IMProving Emergency Care (IMPEC) FHU Collaborators Group*
Background
At the end of 2021, the B.1.1.529 SARS-CoV-2 variant (Omicron) wave superseded the B.1.617.2 variant (Delta) wave.
Objective
To compare baseline characteristics and in-hospital outcomes of patients with SARS-CoV-2 infection with the Delta variant versus the Omicron variant in the emergency department (ED).
Design
Retrospective chart reviews.
Setting
13 adult EDs in academic hospitals in the Paris area from 29 November 2021 to 10 January 2022.
Patients
Patients with a positive reverse transcriptase polymerase chain reaction (RT-PCR) test result for SARS-CoV-2 and variant identification.
Measurements
Main outcome measures were baseline clinical and biological characteristics at ED presentation, intensive care unit (ICU) admission, mechanical ventilation, and in-hospital mortality.
Results
A total of 3728 patients had a positive RT-PCR test result for SARS-CoV-2 during the study period; 1716 patients who had a variant determination (818 Delta and 898 Omicron) were included. Median age was 58 years, and 49% were women. Patients infected with the Omicron variant were younger (54 vs. 62 years; difference, 8.0 years [95% CI, 4.6 to 11.4 years]), had a lower rate of obesity (8.0% vs. 12.5%; difference, 4.5 percentage points [CI, 1.5 to 7.5 percentage points]), were more vaccinated (65% vs. 39% for 1 dose and 22% vs. 11% for 3 doses), had a lower rate of dyspnea (26% vs. 50%; difference, 23.6 percentage points [CI, 19.0 to 28.2 percentage points]), and had a higher rate of discharge home from the ED (59% vs. 37%; difference, 21.9 percentage points [-26.5 to -17.1 percentage points]). Compared with Delta, Omicron infection was independently associated with a lower risk for ICU admission (adjusted difference, 11.4 percentage points [CI, 8.4 to 14.4 percentage points]), mechanical ventilation (adjusted difference, 3.6 percentage points [CI, 1.7 to 5.6 percentage points]), and in-hospital mortality (adjusted difference, 4.2 percentage points [CI, 2.0 to 6.5 percentage points]).
Limitation
Patients with COVID-19 illness and no SARS-CoV-2 variant determination in the ED were excluded.
Conclusion
Compared with the Delta variant, infection with the Omicron variant in patients in the ED had different clinical and biological patterns and was associated with better in-hospital outcomes, including higher survival.
Primary funding source
None.



Ann Intern Med: 14 Mar 2022; epub ahead of print
Bouzid D, Visseaux B, Kassasseya C, Daoud A, ... Freund Y, IMProving Emergency Care (IMPEC) FHU Collaborators Group*
Ann Intern Med: 14 Mar 2022; epub ahead of print | PMID: 35286147
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Impact:
Abstract

Type 1 Diabetes Mellitus.

Syed FZ
Type 1 diabetes mellitus (T1DM) is an endocrine disorder in which pancreatic β cells stop producing insulin, typically due to autoimmune destruction. This results in hyperglycemia and ketosis; thus, insulin replacement is vital to management. Incidence peaks in puberty and early adulthood, but onset can occur at any age. However, prevalence is highest among adults because persons with T1DM live for many years. Symptoms include polyuria, polydipsia, and weight loss. Acute complications include diabetic ketoacidosis, which requires urgent management. Long-term complications include microvascular and macrovascular disease. Patients with T1DM are at higher risk for other autoimmune diseases and psychosocial issues. Management should focus on optimizing glucose control to reduce acute and long-term complications.



Ann Intern Med: 07 Mar 2022; epub ahead of print
Syed FZ
Ann Intern Med: 07 Mar 2022; epub ahead of print | PMID: 35254878
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Impact:
Abstract

Association Between Socioeconomic Disadvantage and Decline in Function, Cognition, and Mental Health After Critical Illness Among Older Adults : A Cohort Study.

Jain S, Murphy TE, O\'Leary JR, Leo-Summers L, Ferrante LE
Background
Older adults admitted to an intensive care unit (ICU) are at risk for developing impairments in function, cognition, and mental health. It is not known whether socioeconomically disadvantaged older persons are at greater risk for these impairments than their less vulnerable counterparts.
Objective
To evaluate the association between socioeconomic disadvantage and decline in function, cognition, and mental health among older survivors of an ICU hospitalization.
Design
Retrospective analysis of a longitudinal cohort study.
Setting
Community-dwelling older adults in the National Health and Aging Trends Study (NHATS).
Participants
Participants with ICU hospitalizations between 2011 and 2017.
Measurements
Socioeconomic disadvantage was assessed as dual-eligible Medicare-Medicaid status. The outcome of function was defined as the count of disabilities in 7 activities of daily living and mobility tasks, the cognitive outcome as the transition from no or possible to probable dementia, and the mental health outcome as the Patient Health Questionnaire-4 score in the NHATS interview after ICU hospitalization. The analytic sample included 641 ICU hospitalizations for function, 458 for cognition, and 519 for mental health.
Results
After accounting for sociodemographic and clinical characteristics, dual eligibility was associated with a 28% increase in disability after ICU hospitalization (incidence rate ratio, 1.28; 95% CI, 1.00 to 1.64); and nearly 10-fold greater odds of transitioning to probable dementia (odds ratio, 9.79; 95% CI, 3.46 to 27.65). Dual eligibility was not associated with symptoms of depression and anxiety after ICU hospitalization (incidence rate ratio, 1.33; 95% CI, 0.99 to 1.79).
Limitation
Administrative data, variability in timing of baseline and outcome assessments, proxy selection.
Conclusion
Dual-eligible older persons are at greater risk for decline in function and cognition after an ICU hospitalization than their more advantaged counterparts. This finding highlights the need to prioritize low-income seniors in rehabilitation and recovery efforts after critical illness and warrants investigation into factors leading to this disparity.
Primary funding source
National Institute on Aging.



Ann Intern Med: 07 Mar 2022; epub ahead of print
Jain S, Murphy TE, O'Leary JR, Leo-Summers L, Ferrante LE
Ann Intern Med: 07 Mar 2022; epub ahead of print | PMID: 35254879
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Impact:
Abstract

Estimation of Breast Cancer Overdiagnosis in a U.S. Breast Screening Cohort.

Ryser MD, Lange J, Inoue LYT, O\'Meara ES, ... Hwang ES, Etzioni RB
Background
Mammography screening can lead to overdiagnosis-that is, screen-detected breast cancer that would not have caused symptoms or signs in the remaining lifetime. There is no consensus about the frequency of breast cancer overdiagnosis.
Objective
To estimate the rate of breast cancer overdiagnosis in contemporary mammography practice accounting for the detection of nonprogressive cancer.
Design
Bayesian inference of the natural history of breast cancer using individual screening and diagnosis records, allowing for nonprogressive preclinical cancer. Combination of fitted natural history model with life-table data to predict the rate of overdiagnosis among screen-detected cancer under biennial screening.
Setting
Breast Cancer Surveillance Consortium (BCSC) facilities.
Participants
Women aged 50 to 74 years at first mammography screen between 2000 and 2018.
Measurements
Screening mammograms and screen-detected or interval breast cancer.
Results
The cohort included 35 986 women, 82 677 mammograms, and 718 breast cancer diagnoses. Among all preclinical cancer cases, 4.5% (95% uncertainty interval [UI], 0.1% to 14.8%) were estimated to be nonprogressive. In a program of biennial screening from age 50 to 74 years, 15.4% (UI, 9.4% to 26.5%) of screen-detected cancer cases were estimated to be overdiagnosed, with 6.1% (UI, 0.2% to 20.1%) due to detecting indolent preclinical cancer and 9.3% (UI, 5.5% to 13.5%) due to detecting progressive preclinical cancer in women who would have died of an unrelated cause before clinical diagnosis.
Limitations
Exclusion of women with first mammography screen outside BCSC.
Conclusion
On the basis of an authoritative U.S. population data set, the analysis projected that among biennially screened women aged 50 to 74 years, about 1 in 7 cases of screen-detected cancer is overdiagnosed. This information clarifies the risk for breast cancer overdiagnosis in contemporary screening practice and should facilitate shared and informed decision making about mammography screening.
Primary funding source
National Cancer Institute.



Ann Intern Med: 28 Feb 2022; epub ahead of print
Ryser MD, Lange J, Inoue LYT, O'Meara ES, ... Hwang ES, Etzioni RB
Ann Intern Med: 28 Feb 2022; epub ahead of print | PMID: 35226520
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Impact:
Abstract

Major Update 2: Remdesivir for Adults With COVID-19: A Living Systematic Review and Meta-analysis for the American College of Physicians Practice Points.

Kaka AS, MacDonald R, Linskens EJ, Langsetmo L, ... Duan-Porter W, Wilt TJ
Background
Remdesivir is approved for the treatment of adults hospitalized with COVID-19.
Purpose
To update a living review of remdesivir for adults with COVID-19.
Data sources
Several electronic U.S. Food and Drug Administration, company, and journal websites from 1 January 2020 through 19 October 2021.
Study selection
English-language, randomized controlled trials (RCTs) of remdesivir for COVID-19.
Data extraction
One reviewer abstracted, and a second reviewer verified data. The Cochrane Risk of Bias Tool and GRADE (Grading of Recommendations Assessment, Development and Evaluation) method were used.
Data synthesis
Since the last update (search date 9 August 2021), 1 new RCT and 1 new subtrial comparing a 10-day course of remdesivir with control (placebo or standard care) were identified. This review summarizes and updates the evidence on the cumulative 5 RCTs and 2 subtrials for this comparison. Our updated results confirm a 10-day course of remdesivir, compared with control, probably results in little to no mortality reduction (5 RCTs). Updated results also confirm that remdesivir probably results in a moderate increase in the proportion of patients recovered by day 29 (4 RCTs) and may reduce time to clinical improvement (2 RCTs) and hospital length of stay (4 RCTs). New RCTs, by increasing the strength of evidence, lead to an updated conclusion that remdesivir probably results in a small reduction in the proportion of patients receiving ventilation or extracorporeal membrane oxygenation at specific follow-up times (4 RCTs). New RCTs also alter the conclusions for harms-remdesivir, compared with control, may lead to a small reduction in serious adverse events but may lead to a small increase in any adverse event.
Limitation
The RCTs differed in definitions of COVID-19 severity and outcomes reported.
Conclusion
In hospitalized adults with COVID-19, the findings confirm that remdesivir probably results in little to no difference in mortality and increases the proportion of patients recovered. Remdesivir may reduce time to clinical improvement and may lead to small reductions in serious adverse events but may result in a small increase in any adverse event.
Primary funding source
U.S. Department of Veterans Affairs.



Ann Intern Med: 28 Feb 2022; epub ahead of print
Kaka AS, MacDonald R, Linskens EJ, Langsetmo L, ... Duan-Porter W, Wilt TJ
Ann Intern Med: 28 Feb 2022; epub ahead of print | PMID: 35226522
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Impact:
Abstract

SARS-CoV-2 Vaccine Antibody Response and Breakthrough Infection in Patients Receiving Dialysis.

Anand S, Montez-Rath ME, Han J, Garcia P, ... Chertow GM, Parsonnet J
Background
Whether breakthrough SARS-CoV-2 infections after vaccination are related to the level of postvaccine circulating antibody is unclear.
Objective
To determine longitudinal antibody-based response and risk for breakthrough infection after SARS-CoV-2 vaccination.
Design
Prospective study.
Setting
Nationwide sample from dialysis facilities.
Patients
4791 patients receiving dialysis.
Measurements
Remainder plasma from a laboratory processing routine monthly tests was used to measure qualitative and semiquantitative antibodies to the receptor-binding domain (RBD) of SARS-CoV-2. To evaluate whether peak or prebreakthrough RBD values were associated with breakthrough infection, a nested case-control analysis matched each breakthrough case patient to 5 control patients by age, sex, and vaccination month and adjusted for diabetes status and region of residence.
Results
Of the 4791 patients followed with monthly RBD assays, 2563 were vaccinated as of 14 September 2021. Among the vaccinated patients, the estimated proportion with an undetectable RBD response increased from 6.6% (95% CI, 5.5% to 7.8%) 14 to 30 days after vaccination to 20.2% (CI, 17.0% to 23.3%) 5 to 6 months after vaccination. Estimated median index values decreased from 91.9 (CI, 78.6 to 105.2) 14 to 30 days after vaccination to 8.4 (CI, 7.6 to 9.3) 5 to 6 months after vaccination. Breakthrough infections occurred in 56 patients, with samples collected a median of 21 days before breakthrough infection. Compared with prebreakthrough index RBD values of 23 or higher (equivalent to ≥506 binding antibody units per milliliter), prebreakthrough RBD values less than 10 and values from 10 to less than 23 were associated with higher odds for breakthrough infection (rate ratios, 11.6 [CI, 3.4 to 39.5] and 6.0 [CI, 1.5 to 23.6], respectively).
Limitations
Single measure of vaccine response; ascertainment of COVID-19 diagnosis from electronic health records.
Conclusion
The antibody response to SARS-CoV-2 vaccination wanes rapidly in persons receiving dialysis. In this population, the circulating antibody response is associated with risk for breakthrough infection.
Primary funding source
Ascend Clinical Laboratory.



Ann Intern Med: 28 Feb 2022; 175:371-378
Anand S, Montez-Rath ME, Han J, Garcia P, ... Chertow GM, Parsonnet J
Ann Intern Med: 28 Feb 2022; 175:371-378 | PMID: 34904856
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Impact:

This program is still in alpha version.