Journal: Ann Intern Med

Sorted by: date / impact
Abstract

Postdiagnosis Smoking Cessation and Reduced Risk for Lung Cancer Progression and Mortality : A Prospective Cohort Study.

Sheikh M, Mukeriya A, Shangina O, Brennan P, Zaridze D
Background
Lung cancer is the leading cause of cancer death worldwide, and about one half of patients with lung cancer are active smokers at diagnosis.
Objective
To determine whether quitting smoking after diagnosis of lung cancer affects the risk for disease progression and mortality.
Design
Prospective study of patients with non-small cell lung cancer (NSCLC) who were recruited between 2007 and 2016 and followed annually through 2020.
Setting
N.N. Blokhin National Medical Research Center of Oncology and City Clinical Oncological Hospital No. 1, Moscow, Russia.
Patients
517 current smokers who were diagnosed with early-stage (IA-IIIA) NSCLC.
Measurements
Probabilities of overall survival, progression-free survival, and lung cancer-specific mortality and hazard ratios (HRs) for all-cause and cancer-specific mortality.
Results
During an average of 7 years of follow-up, 327 (63.2%) deaths, 273 (52.8%) cancer-specific deaths, and 172 (33.7%) cases of tumor progression (local recurrence or metastasis) were recorded. The adjusted median overall survival time was 21.6 months higher among patients who had quit smoking than those who continued smoking (6.6 vs. 4.8 years, respectively; P = 0.001). Higher 5-year overall survival (60.6% vs. 48.6%; P = 0.001) and progression-free survival (54.4% vs. 43.8%; P = 0.004) were observed among patients who quit than those who continued smoking. After adjustments, smoking cessation remained associated with decreased risk for all-cause mortality (HR, 0.67 [95% CI, 0.53 to 0.85]), cancer-specific mortality (HR, 0.75 [CI, 0.58 to 0.98]), and disease progression (HR, 0.70 [CI, 0.56 to 0.89]). Similar effects were observed among mild to moderate and heavy smokers and patients with earlier and later cancer stages.
Limitation
Exposure measurements were based on self-reported questionnaires.
Conclusion
Smoking cessation after diagnosis materially improved overall and progression-free survival among current smokers with early-stage lung cancer.



Ann Intern Med: 26 Jul 2021; epub ahead of print
Sheikh M, Mukeriya A, Shangina O, Brennan P, Zaridze D
Ann Intern Med: 26 Jul 2021; epub ahead of print | PMID: 34310171
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Abstract

Clinical Validation of a Multitarget Fecal Immunochemical Test for Colorectal Cancer Screening : A Diagnostic Test Accuracy Study.

de Klaver W, Wisse PHA, van Wifferen F, Bosch LJW, ... de Wit M, Meijer GA
Background
The fecal immunochemical test (FIT) is used in colorectal cancer (CRC) screening, yet it leaves room for improvement.
Objective
To develop a multitarget FIT (mtFIT) with better diagnostic performance than FIT.
Design
Diagnostic test accuracy study.
Setting
Colonoscopy-controlled series.
Participants
Persons (n = 1284) from a screening (n = 1038) and referral (n = 246) population were classified by their most advanced lesion (CRC [n = 47], advanced adenoma [n = 135], advanced serrated polyp [n = 30], nonadvanced adenoma [n = 250], and nonadvanced serrated polyp [n = 53]), along with control participants (n = 769).
Measurements
Antibody-based assays were developed and applied to leftover FIT material. Classification and regression tree (CART) analysis was applied to biomarker concentrations to identify the optimal combination for detecting advanced neoplasia. Performance of this combination, the mtFIT, was cross-validated using a leave-one-out approach and compared with FIT at equal specificity.
Results
The CART analysis showed a combination of hemoglobin, calprotectin, and serpin family F member 2-the mtFIT-to have a cross-validated sensitivity for advanced neoplasia of 42.9% (95% CI, 36.2% to 49.9%) versus 37.3% (CI, 30.7% to 44.2%) for FIT (P = 0.025), with equal specificity of 96.6%. In particular, cross-validated sensitivity for advanced adenomas increased from 28.1% (CI, 20.8% to 36.5%) to 37.8% (CI, 29.6% to 46.5%) (P = 0.006). On the basis of these results, early health technology assessment indicated that mtFIT-based screening could be cost-effective compared with FIT.
Limitation
Study population is enriched with persons from a referral population.
Conclusion
Compared with FIT, the mtFIT showed better diagnostic accuracy in detecting advanced neoplasia because of an increased detection of advanced adenomas. Moreover, early health technology assessment indicated that these results provide a sound basis to pursue further development of mtFIT as a future test for population-based CRC screening. A prospective screening trial is in preparation.
Primary funding source
Stand Up to Cancer/Dutch Cancer Society, Dutch Digestive Foundation, and HealthHolland.



Ann Intern Med: 19 Jul 2021; epub ahead of print
de Klaver W, Wisse PHA, van Wifferen F, Bosch LJW, ... de Wit M, Meijer GA
Ann Intern Med: 19 Jul 2021; epub ahead of print | PMID: 34280333
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Abstract

SARS-CoV-2 Vaccine Effectiveness in a High-Risk National Population in a Real-World Setting.

Butt AA, Omer SB, Yan P, Shaikh OS, Mayr FB
Background
With the emergency use authorization of multiple vaccines against SARS-CoV-2 infection, data are urgently needed to determine their effectiveness in a real-world setting.
Objective
To evaluate the short-term effectiveness of vaccines in preventing SARS-CoV-2 infection.
Design
Test-negative case-control study using conditional logistic regression.
Setting
U.S. Department of Veterans Affairs health care system.
Participants
All veterans who had testing for SARS-CoV-2 infection between 15 December 2020 and 4 March 2021 and no confirmed infection before 15 December 2020.
Intervention
SARS-CoV-2 vaccination with either the BNT-162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) vaccine as part of routine clinical care.
Measurements
Effectiveness of vaccination against confirmed SARS-CoV-2 infection.
Results
Among 54 360 persons who tested positive and 54 360 propensity score-matched control participants, the median age was 61 years, 83.6% were male, and 62% were White. Median body mass index was 31 kg/m2 among those who tested positive and 30 kg/m2 among those who tested negative. Among those who tested positive, 9800 (18.0%) had been vaccinated; among those who tested negative, 17 825 (32.8%) had been vaccinated. Overall vaccine effectiveness 7 or more days after the second dose was 97.1% (95% CI, 96.6% to 97.5%). Effectiveness was 96.2% (CI, 95.5% to 96.9%) for the Pfizer-BioNTech BNT-162b2 vaccine and 98.2% (CI, 97.5% to 98.6%) for the Moderna mRNA-1273 vaccine. Effectiveness remained above 95% regardless of age group, sex, race, or presence of comorbidities.
Limitations
Predominantly male population; lack of data on disease severity, mortality, and effectiveness by SARS-CoV-2 variants of concern; and short-term follow-up.
Conclusion
Currently used vaccines against SARS-CoV-2 infection are highly effective in preventing confirmed infection in a high-risk population in a real-world setting.
Primary funding source
None.



Ann Intern Med: 19 Jul 2021; epub ahead of print
Butt AA, Omer SB, Yan P, Shaikh OS, Mayr FB
Ann Intern Med: 19 Jul 2021; epub ahead of print | PMID: 34280332
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Abstract

Frailty and Clinical Outcomes of Direct Oral Anticoagulants Versus Warfarin in Older Adults With Atrial Fibrillation : A Cohort Study.

Kim DH, Pawar A, Gagne JJ, Bessette LG, ... Glynn RJ, Schneeweiss S
Background
The role of differing levels of frailty in the choice of oral anticoagulants for older adults with atrial fibrillation (AF) is unclear.
Objective
To examine the outcomes of direct oral anticoagulants (DOACs) versus warfarin by frailty levels.
Design
1:1 propensity score-matched analysis of Medicare data, 2010 to 2017.
Setting
Community.
Patients
Medicare beneficiaries with AF who initiated use of dabigatran, rivaroxaban, apixaban, or warfarin.
Measurements
Composite end point of death, ischemic stroke, or major bleeding by frailty levels, defined by a claims-based frailty index.
Results
In the dabigatran-warfarin cohort (n = 158 730; median follow-up, 72 days), the event rate per 1000 person-years was 63.5 for dabigatran initiators and 65.6 for warfarin initiators (hazard ratio [HR], 0.98 [95% CI, 0.92 to 1.05]; rate difference [RD], -2.2 [CI, -6.5 to 2.1]). For nonfrail, prefrail, and frail persons, HRs were 0.81 (CI, 0.68 to 0.97), 0.98 (CI, 0.90 to 1.08), and 1.09 (CI, 0.96 to 1.23), respectively. In the rivaroxaban-warfarin cohort (n = 275 944; median follow-up, 82 days), the event rate per 1000 person-years was 77.8 for rivaroxaban initiators and 83.7 for warfarin initiators (HR, 0.98 [CI, 0.94 to 1.02]; RD, -5.9 [CI, -9.4 to -2.4]). For nonfrail, prefrail, and frail persons, HRs were 0.88 (CI, 0.77 to 0.99), 1.04 (CI, 0.98 to 1.10), and 0.96 (CI, 0.89 to 1.04), respectively. In the apixaban-warfarin cohort (n = 218 738; median follow-up, 84 days), the event rate per 1000 person-years was 60.1 for apixaban initiators and 92.3 for warfarin initiators (HR, 0.68 [CI, 0.65 to 0.72]; RD, -32.2 [CI, -36.1 to -28.3]). For nonfrail, prefrail, and frail persons, HRs were 0.61 (CI, 0.52 to 0.71), 0.66 (CI, 0.61 to 0.70), and 0.73 (CI, 0.67 to 0.80), respectively.
Limitations
Residual confounding and lack of clinical frailty assessment.
Conclusion
For older adults with AF, apixaban was associated with lower rates of adverse events across all frailty levels. Dabigatran and rivaroxaban were associated with lower event rates only among nonfrail patients.
Primary funding source
National Institute on Aging.



Ann Intern Med: 19 Jul 2021; epub ahead of print
Kim DH, Pawar A, Gagne JJ, Bessette LG, ... Glynn RJ, Schneeweiss S
Ann Intern Med: 19 Jul 2021; epub ahead of print | PMID: 34280330
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Abstract

Evaluation of the Effects of Remdesivir and Hydroxychloroquine on Viral Clearance in COVID-19 : A Randomized Trial.

Barratt-Due A, Olsen IC, Nezvalova-Henriksen K, Kåsine T, ... Trøseid M, Aukrust P
Background
New treatment modalities are urgently needed for patients with COVID-19. The World Health Organization (WHO) Solidarity trial showed no effect of remdesivir or hydroxychloroquine (HCQ) on mortality, but the antiviral effects of these drugs are not known.
Objective
To evaluate the effects of remdesivir and HCQ on all-cause, in-hospital mortality; the degree of respiratory failure and inflammation; and viral clearance in the oropharynx.
Design
NOR-Solidarity is an independent, add-on, randomized controlled trial to the WHO Solidarity trial that included biobanking and 3 months of clinical follow-up (ClinicalTrials.gov: NCT04321616).
Setting
23 hospitals in Norway.
Patients
Eligible patients were adults hospitalized with confirmed SARS-CoV-2 infection.
Intervention
Between 28 March and 4 October 2020, a total of 185 patients were randomly assigned and 181 were included in the full analysis set. Patients received remdesivir (n = 42), HCQ (n = 52), or standard of care (SoC) (n = 87).
Measurements
In addition to the primary end point of WHO Solidarity, study-specific outcomes were viral clearance in oropharyngeal specimens, the degree of respiratory failure, and inflammatory variables.
Results
No significant differences were seen between treatment groups in mortality during hospitalization. There was a marked decrease in SARS-CoV-2 load in the oropharynx during the first week overall, with similar decreases and 10-day viral loads among the remdesivir, HCQ, and SoC groups. Remdesivir and HCQ did not affect the degree of respiratory failure or inflammatory variables in plasma or serum. The lack of antiviral effect was not associated with symptom duration, level of viral load, degree of inflammation, or presence of antibodies against SARS-CoV-2 at hospital admittance.
Limitation
The trial had no placebo group.
Conclusion
Neither remdesivir nor HCQ affected viral clearance in hospitalized patients with COVID-19.
Primary funding source
National Clinical Therapy Research in the Specialist Health Services, Norway.



Ann Intern Med: 12 Jul 2021; epub ahead of print
Barratt-Due A, Olsen IC, Nezvalova-Henriksen K, Kåsine T, ... Trøseid M, Aukrust P
Ann Intern Med: 12 Jul 2021; epub ahead of print | PMID: 34251903
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Abstract

Mortality Among Persons Entering HIV Care Compared With the General U.S. Population : An Observational Study.

Edwards JK, Cole SR, Breger TL, Rudolph JE, ... Saag M, Eron JJ
Background
Understanding advances in the care and treatment of adults with HIV as well as remaining gaps requires comparing differences in mortality between persons entering care for HIV and the general population.
Objective
To assess the extent to which mortality among persons entering HIV care in the United States is elevated over mortality among matched persons in the general U.S. population and trends in this difference over time.
Design
Observational cohort study.
Setting
Thirteen sites from the U.S. North American AIDS Cohort Collaboration on Research and Design.
Participants
82 766 adults entering HIV clinical care between 1999 and 2017 and a subset of the U.S. population matched on calendar time, age, sex, race/ethnicity, and county using U.S. mortality and population data compiled by the National Center for Health Statistics.
Measurements
Five-year all-cause mortality, estimated using the Kaplan-Meier estimator of the survival function.
Results
Overall 5-year mortality among persons entering HIV care was 10.6%, and mortality among the matched U.S. population was 2.9%, for a difference of 7.7 (95% CI, 7.4 to 7.9) percentage points. This difference decreased over time, from 11.1 percentage points among those entering care between 1999 and 2004 to 2.7 percentage points among those entering care between 2011 and 2017.
Limitation
Matching on available covariates may have failed to account for differences in mortality that were due to sociodemographic factors rather than consequences of HIV infection and other modifiable factors.
Conclusion
Mortality among persons entering HIV care decreased dramatically between 1999 and 2017, although those entering care remained at modestly higher risk for death in the years after starting care than comparable persons in the general U.S. population.
Primary funding source
National Institutes of Health.



Ann Intern Med: 05 Jul 2021; epub ahead of print
Edwards JK, Cole SR, Breger TL, Rudolph JE, ... Saag M, Eron JJ
Ann Intern Med: 05 Jul 2021; epub ahead of print | PMID: 34224262
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Impact:
Abstract

Treatment of Acute Pain in Adults With Sickle Cell Disease in an Infusion Center Versus the Emergency Department : A Multicenter Prospective Cohort Study.

Lanzkron S, Little J, Wang H, Field JJ, ... Segal JB, Varadhan R
Background
Patients with sickle cell disease (SCD) have vaso-occlusive crises (VOCs). Infusion centers (ICs) are alternatives to emergency department (ED) care and may improve patient outcomes.
Objective
To assess whether care in ICs or EDs leads to better outcomes for the treatment of uncomplicated VOCs.
Design
Prospective cohort. (ClinicalTrials.gov: NCT02411396).
Setting
4 U.S. sites, with recruitment between April 2015 and December 2016.
Participants
Adults with SCD living within 60 miles of a study site.
Measurements
Participants were followed for 18 months after enrollment. Outcomes of interest were time to first dose of parenteral pain medication, whether pain reassessment was completed within 30 minutes after the first dose, and patient disposition on discharge from the acute care visit. Treatment effects for ICs versus EDs were estimated using a time-varying propensity score adjustment.
Results
Researchers enrolled 483 participants; the 269 who had acute care visits on weekdays are included in this report. With inverse probability of treatment-weighted adjustment, the mean time to first dose was 62 minutes in ICs and 132 minutes in EDs; the difference was 70 minutes (95% CI, 54 to 98 minutes; E-value, 2.8). The probability of pain reassessment within 30 minutes of the first dose of parenteral pain medication was 3.8 times greater (CI, 2.63 to 5.64 times greater; E-value, 4.7) in the IC than the ED. The probability that a participant\'s visit would end in discharge home was 4.0 times greater (CI, 3.0 to 5.42 times greater; E-value, 5.4) with treatment in an IC than with treatment in an ED.
Limitation
The study was restricted to participants with uncomplicated VOCs.
Conclusion
In adults with SCD having a VOC, treatment in an IC is associated with substantially better outcomes than treatment in an ED.
Primary funding source
Patient-Centered Outcomes Research Institute.



Ann Intern Med: 05 Jul 2021; epub ahead of print
Lanzkron S, Little J, Wang H, Field JJ, ... Segal JB, Varadhan R
Ann Intern Med: 05 Jul 2021; epub ahead of print | PMID: 34224261
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Impact:
Abstract

Association Between Caseload Surge and COVID-19 Survival in 558 U.S. Hospitals, March to August 2020.

Kadri SS, Sun J, Lawandi A, Strich JR, ... Demirkale CY, Warner S
Background
Several U.S. hospitals had surges in COVID-19 caseload, but their effect on COVID-19 survival rates remains unclear, especially independent of temporal changes in survival.
Objective
To determine the association between hospitals\' severity-weighted COVID-19 caseload and COVID-19 mortality risk and identify effect modifiers of this relationship.
Design
Retrospective cohort study. (ClinicalTrials.gov: NCT04688372).
Setting
558 U.S. hospitals in the Premier Healthcare Database.
Participants
Adult COVID-19-coded inpatients admitted from March to August 2020 with discharge dispositions by October 2020.
Measurements
Each hospital-month was stratified by percentile rank on a surge index (a severity-weighted measure of COVID-19 caseload relative to pre-COVID-19 bed capacity). The effect of surge index on risk-adjusted odds ratio (aOR) of in-hospital mortality or discharge to hospice was calculated using hierarchical modeling; interaction by surge attributes was assessed.
Results
Of 144 116 inpatients with COVID-19 at 558 U.S. hospitals, 78 144 (54.2%) were admitted to hospitals in the top surge index decile. Overall, 25 344 (17.6%) died; crude COVID-19 mortality decreased over time across all surge index strata. However, compared with nonsurging (<50th surge index percentile) hospital-months, aORs in the 50th to 75th, 75th to 90th, 90th to 95th, 95th to 99th, and greater than 99th percentiles were 1.11 (95% CI, 1.01 to 1.23), 1.24 (CI, 1.12 to 1.38), 1.42 (CI, 1.27 to 1.60), 1.59 (CI, 1.41 to 1.80), and 2.00 (CI, 1.69 to 2.38), respectively. The surge index was associated with mortality across ward, intensive care unit, and intubated patients. The surge-mortality relationship was stronger in June to August than in March to May (slope difference, 0.10 [CI, 0.033 to 0.16]) despite greater corticosteroid use and more judicious intubation during later and higher-surging months. Nearly 1 in 4 COVID-19 deaths (5868 [CI, 3584 to 8171]; 23.2%) was potentially attributable to hospitals strained by surging caseload.
Limitation
Residual confounding.
Conclusion
Despite improvements in COVID-19 survival between March and August 2020, surges in hospital COVID-19 caseload remained detrimental to survival and potentially eroded benefits gained from emerging treatments. Bolstering preventive measures and supporting surging hospitals will save many lives.
Primary funding source
Intramural Research Program of the National Institutes of Health Clinical Center, the National Institute of Allergy and Infectious Diseases, and the National Cancer Institute.



Ann Intern Med: 05 Jul 2021; epub ahead of print
Kadri SS, Sun J, Lawandi A, Strich JR, ... Demirkale CY, Warner S
Ann Intern Med: 05 Jul 2021; epub ahead of print | PMID: 34224257
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Impact:
Abstract

Prevalence of Symptoms More Than Seven Months After Diagnosis of Symptomatic COVID-19 in an Outpatient Setting.

Nehme M, Braillard O, Chappuis F, Courvoisier DS, Guessous I
Background
With millions of SARS-CoV-2 infections worldwide, increasing numbers of patients are coming forward with long-term clinical effects of the disease lasting several weeks to months.
Objective
To characterize symptoms 7 to 9 months after diagnosis of COVID-19.
Design
Self-reported surveys and semistructured telephone interviews at enrollment and 30 to 45 days and 7 to 9 months from diagnosis.
Setting
From 18 March to 15 May 2020, symptomatic persons who tested positive for SARS-CoV-2 at the Geneva University Hospitals were followed by CoviCare, a virtual, clinical, outpatient follow-up program. Persons were contacted again at 30 to 45 days and 7 to 9 months from diagnosis.
Participants
Persons who were a part of the CoviCare program from 18 March to 15 May 2020.
Measurements
A standardized interview of symptoms consistent with COVID-19, with grading of intensity.
Results
Of the 629 participants in the study who completed the baseline interviews, 410 completed follow-up at 7 to 9 months after COVID-19 diagnosis; 39.0% reported residual symptoms. Fatigue (20.7%) was the most common symptom reported, followed by loss of taste or smell (16.8%), dyspnea (11.7%), and headache (10.0%).
Limitation
Limitations include generalizability and missing data for 34.8% of participants.
Conclusion
Residual symptoms after SARS-CoV-2 infection are common among otherwise young and healthy persons followed in an outpatient setting. These findings contribute to the recognition of long-term effects in a disease mostly counted by its death toll to date by promoting communication on postacute sequelae of SARS-CoV-2 and encouraging physicians to continue long-term monitoring of their patients.
Primary funding source
None.



Ann Intern Med: 05 Jul 2021; epub ahead of print
Nehme M, Braillard O, Chappuis F, Courvoisier DS, Guessous I
Ann Intern Med: 05 Jul 2021; epub ahead of print | PMID: 34224254
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Impact:
Abstract

Estimated Effect on Life Expectancy of Alleviating Primary Care Shortages in the United States.

Basu S, Phillips RS, Berkowitz SA, Landon BE, Bitton A, Phillips RL
Background
Prior studies have reported that greater numbers of primary care physicians (PCPs) per population are associated with reduced population mortality, but the effect of increasing PCP density in areas of low density is poorly understood.
Objective
To estimate how alleviating PCP shortages might change life expectancy and mortality.
Design
Generalized additive models, mixed-effects models, and generalized estimating equations.
Setting
3104 U.S. counties from 2010 to 2017.
Participants
Children and adults.
Measurements
Age-adjusted life expectancy; all-cause mortality; and mortality due to cardiovascular disease, cancer, infectious disease, respiratory disease, and substance use or injury.
Results
Persons living in counties with less than 1 physician per 3500 persons in 2017 had a mean life expectancy that was 310.9 days shorter than for persons living in counties above that threshold. In the low-density counties (n = 1218), increasing the density of PCPs above the 1:3500 threshold would be expected to increase mean life expectancy by 22.4 days (median, 19.4 days [95% CI, 0.9 to 45.6 days]), and all such counties would require 17 651 more physicians, or about 14.5 more physicians per shortage county. If counties with less than 1 physician per 1500 persons (n = 2636) were to reach the 1:1500 threshold, life expectancy would be expected to increase by 56.3 days (median, 55.6 days [CI, 4.2 to 105.6 days]), and all such counties would require 95 754 more physicians, or about 36.3 more physicians per shortage county.
Limitation
Some projections are based on extrapolations of the actual data.
Conclusion
In counties with fewer PCPs per population, increases in PCP density would be expected to substantially improve life expectancy.
Primary funding source
None.



Ann Intern Med: 29 Jun 2021; 174:920-926
Basu S, Phillips RS, Berkowitz SA, Landon BE, Bitton A, Phillips RL
Ann Intern Med: 29 Jun 2021; 174:920-926 | PMID: 33750188
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Impact:
Abstract

Effectiveness and Safety of Direct Oral Anticoagulants Versus Warfarin in Patients With Valvular Atrial Fibrillation : A Population-Based Cohort Study.

Dawwas GK, Dietrich E, Cuker A, Barnes GD, Leonard CE, Lewis JD
Background
Direct oral anticoagulants (DOACs) are increasingly used in place of warfarin, but evidence about their effectiveness and safety in patients with valvular atrial fibrillation (AF) remains limited.
Objective
To assess the effectiveness and safety of DOACs compared with warfarin in patients with valvular AF.
Design
New-user retrospective propensity score-matched cohort study.
Setting
U.S.-based commercial health care database from 1 January 2010 to 30 June 2019.
Participants
Adults with valvular AF who were newly prescribed DOACs or warfarin.
Measurements
The primary effectiveness outcome was a composite of ischemic stroke or systemic embolism. The primary safety outcome was a composite of intracranial or gastrointestinal bleeding.
Results
Among a total of 56 336 patients with valvular AF matched on propensity score, use of DOACs (vs. warfarin) was associated with lower risk for ischemic stroke or systemic embolism (hazard ratio [HR], 0.64 [95% CI, 0.59 to 0.70]) and major bleeding events (HR, 0.67 [CI, 0.63 to 0.72]). The results for the effectiveness and safety outcomes remained consistent for apixaban (HRs, 0.54 [CI, 0.47 to 0.61] and 0.52 [CI, 0.47 to 0.57], respectively) and rivaroxaban (HRs, 0.74 [CI, 0.64 to 0.86] and 0.87 [CI, 0.79 to 0.96], respectively); with dabigatran, results were consistent for the major bleeding outcome (HR, 0.81 [CI, 0.68 to 0.97]) but not for effectiveness (HR, 1.03 [CI, 0.81 to 1.31]).
Limitation
Relatively short follow-up; inability to ascertain disease severity.
Conclusion
In this comparative effectiveness study using practice-based claims data, patients with valvular AF who were new users of DOACs had lower risks for ischemic stroke or systemic embolism and major bleeding than new users of warfarin. These data may be used to guide risk-benefit discussions regarding anticoagulant choices for patients with valvular AF.
Primary funding source
None.



Ann Intern Med: 29 Jun 2021; 174:910-919
Dawwas GK, Dietrich E, Cuker A, Barnes GD, Leonard CE, Lewis JD
Ann Intern Med: 29 Jun 2021; 174:910-919 | PMID: 33780291
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Impact:
Abstract

Preventing Hospital Readmission for Patients With Comorbid Substance Use Disorder : A Randomized Trial.

Gryczynski J, Nordeck CD, Welsh C, Mitchell SG, O\'Grady KE, Schwartz RP
Background
Hospitalized patients with comorbid substance use disorders (SUDs) are at high risk for poor outcomes, including readmission and emergency department (ED) use.
Objective
To determine whether patient navigation services reduce hospital readmissions.
Design
Randomized controlled trial comparing Navigation Services to Avoid Rehospitalization (NavSTAR) versus treatment as usual (TAU). (ClinicalTrials.gov: NCT02599818).
Setting
Urban academic hospital in Baltimore, Maryland, with an SUD consultation service.
Participants
400 hospitalized adults with comorbid SUD (opioid, cocaine, or alcohol).
Intervention
NavSTAR used proactive case management, advocacy, service linkage, and motivational support to resolve internal and external barriers to care and address SUD, medical, and basic needs for 3 months after discharge.
Measurements
Data on inpatient readmissions (primary outcome) and ED visits for 12 months were obtained for all participants via the regional health information exchange. Entry into SUD treatment, substance use, and related outcomes were assessed at 3-, 6-, and 12-month follow-up.
Results
Participants had high levels of acute care use: 69% had an inpatient readmission and 79% visited the ED over the 12-month observation period. Event rates per 1000 person-days were 6.05 (NavSTAR) versus 8.13 (TAU) for inpatient admissions (hazard ratio, 0.74 [95% CI, 0.58 to 0.96]; P = 0.020) and 17.66 (NavSTAR) versus 27.85 (TAU) for ED visits (hazard ratio, 0.66 [CI, 0.49 to 0.89]; P = 0.006). Participants in the NavSTAR group were less likely to have an inpatient readmission within 30 days than those receiving TAU (15.5% vs. 30.0%; P < 0.001) and were more likely to enter community SUD treatment after discharge (P = 0.014; treatment entry within 3 months, 50.3% NavSTAR vs. 35.3% TAU).
Limitation
Single-site trial, which limits generalizability.
Conclusion
Patient navigation reduced inpatient readmissions and ED visits in this clinically challenging sample of hospitalized patients with comorbid SUDs.
Primary funding source
National Institute on Drug Abuse.



Ann Intern Med: 29 Jun 2021; 174:899-909
Gryczynski J, Nordeck CD, Welsh C, Mitchell SG, O'Grady KE, Schwartz RP
Ann Intern Med: 29 Jun 2021; 174:899-909 | PMID: 33819055
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Impact:
Abstract

Is Comprehensive Geriatric Assessment Admission Avoidance Hospital at Home an Alternative to Hospital Admission for Older Persons? : A Randomized Trial.

Shepperd S, Butler C, Cradduck-Bamford A, Ellis G, ... Yu LM, Young J
Background
Delivering hospital-level care with comprehensive geriatric assessment (CGA) in the home is one approach to deal with the increased demand for bed-based hospital care, but clinical effectiveness is uncertain.
Objective
To assess the clinical effectiveness of admission avoidance hospital at home (HAH) with CGA for older persons.
Design
Multisite randomized trial. (ISRCTN registry number: ISRCTN60477865).
Setting
9 hospital and community sites in the United Kingdom.
Patients
1055 older persons who were medically unwell, were physiologically stable, and were referred for a hospital admission.
Intervention
Admission avoidance HAH with CGA versus hospital admission with CGA when available using 2:1 randomization.
Measurements
The primary outcome of living at home was measured at 6 months. Secondary outcomes were new admission to long-term residential care, death, health status, delirium, and patient satisfaction.
Results
Participants had a mean age of 83.3 years (SD, 7.0). At 6-month follow-up, 528 of 672 (78.6%) participants in the CGA HAH group versus 247 of 328 (75.3%) participants in the hospital group were living at home (relative risk [RR], 1.05 [95% CI, 0.95 to 1.15]; P = 0.36); 114 of 673 (16.9%) versus 58 of 328 (17.7%) had died (RR, 0.98 [CI, 0.65 to 1.47]; P = 0.92); and 37 of 646 (5.7%) versus 27 of 311 (8.7%) were in long-term residential care (RR, 0.58 [CI, 0.45 to 0.76]; P < 0.001).
Limitation
The findings are most applicable to older persons referred from a hospital short-stay acute medical assessment unit; episodes of delirium may have been undetected.
Conclusion
Admission avoidance HAH with CGA led to similar outcomes as hospital admission in the proportion of older persons living at home as well as a decrease in admissions to long-term residential care at 6 months. This type of service can provide an alternative to hospitalization for selected older persons.
Primary funding source
The National Institute for Health Research Health Services and Delivery Research Programme (12/209/66).



Ann Intern Med: 29 Jun 2021; 174:889-898
Shepperd S, Butler C, Cradduck-Bamford A, Ellis G, ... Yu LM, Young J
Ann Intern Med: 29 Jun 2021; 174:889-898 | PMID: 33872045
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Treatment Patterns and Clinical Outcomes After the Introduction of the Medicare Sepsis Performance Measure (SEP-1).

Barbash IJ, Davis BS, Yabes JG, Seymour CW, Angus DC, Kahn JM
Background
Medicare requires that hospitals report on their adherence to the Severe Sepsis and Septic Shock Early Management Bundle (SEP-1).
Objective
To evaluate the effect of SEP-1 on treatment patterns and patient outcomes.
Design
Longitudinal study of hospitals using repeated cross-sectional cohorts of patients.
Setting
11 hospitals within an integrated health system.
Patients
54 225 encounters between January 2013 and December 2017 for adults with sepsis who were hospitalized through the emergency department.
Intervention
Onset of the SEP-1 reporting requirement in October 2015.
Measurements
Changes in SEP-1-targeted processes, including antibiotic administration, lactate measurement, and fluid administration at 3 hours from sepsis onset; repeated lactate and vasopressor administration for hypotension within 6 hours of sepsis onset; and sepsis outcomes, including risk-adjusted intensive care unit (ICU) admission, in-hospital mortality, and home discharge among survivors.
Results
Two years after its implementation, SEP-1 was associated with variable changes in process measures, with the greatest effect being an increase in lactate measurement within 3 hours of sepsis onset (absolute increase, 23.7 percentage points [95% CI, 20.7 to 26.7 percentage points]; P < 0.001). There were small increases in antibiotic administration (absolute increase, 4.7 percentage points [CI, 1.9 to 7.6 percentage points]; P = 0.001) and fluid administration of 30 mL/kg of body weight within 3 hours of sepsis onset (absolute increase, 3.4 percentage points [CI, 1.5 to 5.2 percentage points]; P < 0.001). There was no change in vasopressor administration. There was a small increase in ICU admissions (absolute increase, 2.0 percentage points [CI, 0 to 4.0 percentage points]; P = 0.055) and no changes in mortality (absolute change, 0.1 percentage points [CI, -0.9 to 1.1 percentage points]; P = 0.87) or discharge to home.
Limitation
Data are from a single health system.
Conclusion
Implementation of the SEP-1 mandatory reporting program was associated with variable changes in process measures, without improvements in clinical outcomes. Revising the measure may optimize its future effect.
Primary funding source
Agency for Healthcare Research and Quality.



Ann Intern Med: 29 Jun 2021; 174:927-935
Barbash IJ, Davis BS, Yabes JG, Seymour CW, Angus DC, Kahn JM
Ann Intern Med: 29 Jun 2021; 174:927-935 | PMID: 33872042
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Impact:
Abstract

Point-of-Care Ultrasonography in Patients With Acute Dyspnea: An Evidence Report for a Clinical Practice Guideline by the American College of Physicians.

Gartlehner G, Wagner G, Affengruber L, Chapman A, ... Kaminski-Hartenthaler A, Spiel AO
Background
Dyspnea is a common and often debilitating symptom with a complex diagnostic work-up.
Purpose
To evaluate the benefits, harms, and diagnostic test accuracy of point-of-care ultrasonography (POCUS) in patients with acute dyspnea. (PROSPERO: CRD42019126419).
Data sources
Searches of multiple electronic databases without language limitations (January 2004 to August 2020) and reference lists of pertinent articles and reviews.
Study selection
Five randomized controlled trials (RCTs) and 44 prospective cohort-type studies in patients with acute dyspnea evaluated POCUS as a diagnostic tool to determine the underlying cause of dyspnea. Two investigators independently screened the literature for inclusion.
Data extraction
Data abstraction by a single investigator was confirmed by a second investigator; 2 investigators independently rated risk of bias and determined certainty of evidence.
Data synthesis
Point-of-care ultrasonography, when added to a standard diagnostic pathway, led to statistically significantly more correct diagnoses in patients with dyspnea than the standard diagnostic pathway alone. In-hospital mortality and length of hospital stay did not differ significantly between patients who did or did not receive POCUS in addition to standard diagnostic tests. Finally, POCUS consistently improved the sensitivities of standard diagnostic pathways to detect congestive heart failure, pneumonia, pulmonary embolism, pleural effusion, or pneumothorax; specificities increased in most but not all studies.
Limitations
Most studies assessed diagnostic test accuracy, which has limited utility for clinical decision making. Studies rarely reported on the proportion of indeterminate sonography results, and no evidence is available on adverse health outcomes of false-positive or false-negative POCUS results.
Conclusion
Point-of-care ultrasonography can improve the correctness of diagnosis in patients with acute dyspnea.
Primary funding source
American College of Physicians.



Ann Intern Med: 29 Jun 2021; 174:967-976
Gartlehner G, Wagner G, Affengruber L, Chapman A, ... Kaminski-Hartenthaler A, Spiel AO
Ann Intern Med: 29 Jun 2021; 174:967-976 | PMID: 33900798
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Impact:
Abstract

Health Information Privacy, Protection, and Use in the Expanding Digital Health Ecosystem: A Position Paper of the American College of Physicians.

Rockwern B, Johnson D, Snyder Sulmasy L, Medical Informatics Committee and Ethics, Professionalism and Human Rights Committee of the American College of Physicians
Technologic advancements and the evolving digital health landscape have offered innovative solutions to several of our health care system\'s issues as well as increased the number of digital interactions and type of personal health information that is generated and collected, both within and outside of traditional health care. This American College of Physicians\' position paper discusses the state of privacy legislation and regulations, highlights existing gaps in health information privacy protections, and outlines policy principles and recommendations for the development of health information privacy and security protections that are comprehensive, transparent, understandable, adaptable, and enforceable. The principles and recommendations aim to improve on the privacy framework in which physicians have practiced for decades and expand similar privacy guardrails to entities not currently governed by privacy laws and regulations. The expanded privacy framework should protect personal health information from unauthorized, discriminatory, deceptive, or harmful uses and align with the principles of medical ethics, respect individual rights, and support the culture of trust necessary to maintain and improve care delivery.



Ann Intern Med: 29 Jun 2021; 174:994-998
Rockwern B, Johnson D, Snyder Sulmasy L, Medical Informatics Committee and Ethics, Professionalism and Human Rights Committee of the American College of Physicians
Ann Intern Med: 29 Jun 2021; 174:994-998 | PMID: 33900797
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Impact:
Abstract

Appropriate Use of High-Flow Nasal Oxygen in Hospitalized Patients for Initial or Postextubation Management of Acute Respiratory Failure: A Clinical Guideline From the American College of Physicians.

Qaseem A, Etxeandia-Ikobaltzeta I, Fitterman N, Williams JW, Kansagara D, Clinical Guidelines Committee of the American College of Physicians
Description
The American College of Physicians (ACP) developed this guideline to provide clinical recommendations on the appropriate use of high-flow nasal oxygen (HFNO) in hospitalized patients for initial or postextubation management of acute respiratory failure. It is based on the best available evidence on the benefits and harms of HFNO, taken in the context of costs and patient values and preferences.
Methods
The ACP Clinical Guidelines Committee based these recommendations on a systematic review on the efficacy and safety of HFNO. The patient-centered health outcomes evaluated included all-cause mortality, hospital length of stay, 30-day hospital readmissions, hospital-acquired pneumonia, days of intubation or reintubation, intensive care unit (ICU) admission and ICU transfers, patient comfort, dyspnea, delirium, barotrauma, compromised nutrition, gastric dysfunction, functional independence at discharge, discharge disposition, and skin breakdown. This guideline was developed using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) method.
Target audience and patient population
The target audience is all clinicians, and the target patient population is adult patients with acute respiratory failure treated in a hospital setting (including emergency departments, hospital wards, intermediate or step-down units, and ICUs).
Recommendation 1a
ACP suggests that clinicians use high-flow nasal oxygen rather than noninvasive ventilation in hospitalized adults for the management of acute hypoxemic respiratory failure (conditional recommendation; low-certainty evidence).
Recommendation 1b
ACP suggests that clinicians use high-flow nasal oxygen rather than conventional oxygen therapy for hospitalized adults with postextubation acute hypoxemic respiratory failure (conditional recommendation; low-certainty evidence).



Ann Intern Med: 29 Jun 2021; 174:977-984
Qaseem A, Etxeandia-Ikobaltzeta I, Fitterman N, Williams JW, Kansagara D, Clinical Guidelines Committee of the American College of Physicians
Ann Intern Med: 29 Jun 2021; 174:977-984 | PMID: 33900796
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Impact:
Abstract

Effectiveness and Harms of High-Flow Nasal Oxygen for Acute Respiratory Failure: An Evidence Report for a Clinical Guideline From the American College of Physicians.

Baldomero AK, Melzer AC, Greer N, Majeski BN, ... Linskens EJ, Wilt TJ
Background
Use of high-flow nasal oxygen (HFNO) for treatment of adults with acute respiratory failure (ARF) has increased.
Purpose
To assess HFNO versus noninvasive ventilation (NIV) or conventional oxygen therapy (COT) for ARF in hospitalized adults.
Data sources
English-language searches of MEDLINE, Embase, CINAHL, and Cochrane Library from January 2000 to July 2020; systematic review reference lists.
Study selection
29 randomized controlled trials evaluated HFNO versus NIV (k = 11) or COT (k = 21).
Data extraction
Data extraction by a single investigator was verified by a second, 2 investigators assessed risk of bias, and evidence certainty was determined by consensus.
Data synthesis
Results are reported separately for HFNO versus NIV, for HFNO versus COT, and by initial or postextubation management. Compared with NIV, HFNO may reduce all-cause mortality, intubation, and hospital-acquired pneumonia and improve patient comfort in initial ARF management (low-certainty evidence) but not in postextubation management. Compared with COT, HFNO may reduce reintubation and improve patient comfort in postextubation ARF management (low-certainty evidence).
Limitations
Trials varied in populations enrolled, ARF causes, and treatment protocols. Trial design, sample size, duration of treatment and follow-up, and results reporting were often insufficient to adequately assess many outcomes. Protocols, clinician and health system training, cost, and resource use were poorly characterized.
Conclusion
Compared with NIV, HFNO as initial ARF management may improve several clinical outcomes. Compared with COT, HFNO as postextubation management may reduce reintubations and improve patient comfort; HFNO resulted in fewer harms than NIV or COT. Broad applicability, including required clinician and health system experience and resource use, is not well known.
Primary funding source
American College of Physicians. (PROSPERO: CRD42019146691).



Ann Intern Med: 29 Jun 2021; 174:952-966
Baldomero AK, Melzer AC, Greer N, Majeski BN, ... Linskens EJ, Wilt TJ
Ann Intern Med: 29 Jun 2021; 174:952-966 | PMID: 33900793
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Appropriate Use of Point-of-Care Ultrasonography in Patients With Acute Dyspnea in Emergency Department or Inpatient Settings: A Clinical Guideline From the American College of Physicians.

Qaseem A, Etxeandia-Ikobaltzeta I, Mustafa RA, Kansagara D, ... Wilt TJ, Clinical Guidelines Committee of the American College of Physicians
Description
The American College of Physicians (ACP) developed this guideline to provide clinical recommendations on the appropriate use of point-of-care ultrasonography (POCUS) in patients with acute dyspnea in emergency department (ED) or inpatient settings to improve the diagnostic, treatment, and health outcomes of those with suspected congestive heart failure, pneumonia, pulmonary embolism, pleural effusion, or pneumothorax.
Methods
The ACP Clinical Guidelines Committee based this guideline on a systematic review on the benefits, harms, and diagnostic test accuracy of POCUS; patient values and preferences; and costs of POCUS. The systematic review evaluated health outcomes, diagnostic timeliness, treatment decisions, and test accuracy. The critical health, diagnostic, and treatment outcomes evaluated were in-hospital mortality, time to diagnosis, and time to treatment. The important outcomes evaluated were intensive care unit admissions, correctness of diagnosis, disease-specific outcomes, hospital readmissions, length of hospital stay, and quality of life. The critical test accuracy outcomes included false-positive results for suspected pneumonia, pneumothorax, and pulmonary embolism and false-negative results for suspected congestive heart failure, pneumonia, pneumothorax, and pulmonary embolism. Important test accuracy outcomes included false-positive results for suspected congestive heart failure and false-negative and false-positive results for suspected pleural effusion. This guideline was developed using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) method.
Target audience and patient population
The target audience is all clinicians, and the target patient population is adult patients with acute dyspnea in ED or inpatient settings.
Recommendation
ACP suggests that clinicians may use point-of-care ultrasonography in addition to the standard diagnostic pathway when there is diagnostic uncertainty in patients with acute dyspnea in emergency department or inpatient settings (conditional recommendation; low-certainty evidence).



Ann Intern Med: 29 Jun 2021; 174:985-993
Qaseem A, Etxeandia-Ikobaltzeta I, Mustafa RA, Kansagara D, ... Wilt TJ, Clinical Guidelines Committee of the American College of Physicians
Ann Intern Med: 29 Jun 2021; 174:985-993 | PMID: 33900792
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Impact:
Abstract

Performance Evaluation of Serial SARS-CoV-2 Rapid Antigen Testing During a Nursing Home Outbreak.

McKay SL, Tobolowsky FA, Moritz ED, Hatfield KM, ... Kutty PK, CDC Infection Prevention and Control Team and the CDC COVID-19 Surge Laboratory Group
Background
To address high COVID-19 burden in U.S. nursing homes, rapid SARS-CoV-2 antigen tests have been widely distributed in those facilities. However, performance data are lacking, especially in asymptomatic people.
Objective
To evaluate the performance of SARS-CoV-2 antigen testing when used for facility-wide testing during a nursing home outbreak.
Design
A prospective evaluation involving 3 facility-wide rounds of testing where paired respiratory specimens were collected to evaluate the performance of the BinaxNOW antigen test compared with virus culture and real-time reverse transcription polymerase chain reaction (RT-PCR). Early and late infection were defined using changes in RT-PCR cycle threshold values and prior test results.
Setting
A nursing home with an ongoing SARS-CoV-2 outbreak.
Participants
532 paired specimens collected from 234 available residents and staff.
Measurements
Percentage of positive agreement (PPA) and percentage of negative agreement (PNA) for BinaxNOW compared with RT-PCR and virus culture.
Results
BinaxNOW PPA with virus culture, used for detection of replication-competent virus, was 95%. However, the overall PPA of antigen testing with RT-PCR was 69%, and PNA was 98%. When only the first positive test result was analyzed for each participant, PPA of antigen testing with RT-PCR was 82% among 45 symptomatic people and 52% among 343 asymptomatic people. Compared with RT-PCR and virus culture, the BinaxNOW test performed well in early infection (86% and 95%, respectively) and poorly in late infection (51% and no recovered virus, respectively).
Limitation
Accurate symptom ascertainment was challenging in nursing home residents; test performance may not be representative of testing done by nonlaboratory staff.
Conclusion
Despite lower positive agreement compared with RT-PCR, antigen test positivity had higher agreement with shedding of replication-competent virus. These results suggest that antigen testing could be a useful tool to rapidly identify contagious people at risk for transmitting SARS-CoV-2 during nascent outbreaks and help reduce COVID-19 burden in nursing homes.
Primary funding source
None.



Ann Intern Med: 29 Jun 2021; 174:945-951
McKay SL, Tobolowsky FA, Moritz ED, Hatfield KM, ... Kutty PK, CDC Infection Prevention and Control Team and the CDC COVID-19 Surge Laboratory Group
Ann Intern Med: 29 Jun 2021; 174:945-951 | PMID: 33900791
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Impact:
Abstract

Menopause.

McNeil MA, Merriam SB
This review focuses on the diagnosis and management of menopause, highlighting both hormonal and nonhormonal treatment options. In particular, the article focuses on recent data on the risks and benefits of hormone therapy to help clinicians better counsel their patients about decision making with regard to understanding and treating menopause symptoms.



Ann Intern Med: 29 Jun 2021; 174:ITC97-ITC112
McNeil MA, Merriam SB
Ann Intern Med: 29 Jun 2021; 174:ITC97-ITC112 | PMID: 34251902
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Impact:
Abstract

Colorectal cancer screening offering colonoscopy and FIT vs. colonoscopy alone improved participation.

Imperiale TF
Source citation
Pilonis ND, Bugajski M, Wieszczy P, et al. Participation in competing strategies for colorectal cancer screening: a randomized health services study (PICCOLINO study). Gastroenterology. 2021;160:1097-105. 33307024.



Ann Intern Med: 29 Jun 2021; 174:JC76
Imperiale TF
Ann Intern Med: 29 Jun 2021; 174:JC76 | PMID: 34224268
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Impact:
Abstract

In patients with AMI and anemia, a restrictive vs. liberal blood transfusion strategy was noninferior for 30-d MACE.

Jiang D, Garcia D
Source citation
Ducrocq G, Gonzalez-Juanatey JR, Puymirat E, et al. Effect of a restrictive vs liberal blood transfusion strategy on major cardiovascular events among patients with acute myocardial infarction and anemia: the REALITY randomized clinical trial. JAMA. 2021;325:552-60. 33560322.



Ann Intern Med: 29 Jun 2021; 174:JC77
Jiang D, Garcia D
Ann Intern Med: 29 Jun 2021; 174:JC77 | PMID: 34224267
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Impact:
Abstract

In patients having transjugular intrahepatic portosystemic shunt, rifaximin prevented overt hepatic encephalopathy.

Koretz RL
Source citation
Bureau C, Thabut D, Jezequel C, et al. The use of rifaximin in the prevention of overt hepatic encephalopathy after transjugular intrahepatic portosystemic shunt: a randomized controlled trial. Ann Intern Med. 2021;174:633-40. 33524293.



Ann Intern Med: 29 Jun 2021; 174:JC78
Koretz RL
Ann Intern Med: 29 Jun 2021; 174:JC78 | PMID: 34224266
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Impact:
Abstract

In older adults with subclinical hypothyroidism, levothyroxine therapy did not reduce depressive symptoms at 12 mo.

Watt J
Source citation
Wildisen L, Feller M, Del Giovane C, et al. Effect of levothyroxine therapy on the development of depressive symptoms in older adults with subclinical hypothyroidism: an ancillary study of a randomized clinical trial. JAMA Netw Open. 2021;4:e2036645. 33566107.



Ann Intern Med: 29 Jun 2021; 174:JC81
Watt J
Ann Intern Med: 29 Jun 2021; 174:JC81 | PMID: 34224256
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Impact:
Abstract

In adults and children, a rapid POC antigen test for COVID-19 (LumiraDx) had ≥97% sensitivity and specificity vs. RT-PCR.

Fekete T
Source citation
Drain PK, Ampajwala M, Chappel C, et al. A rapid, high-sensitivity SARS-CoV-2 nucleocapsid immunoassay to aid diagnosis of acute COVID-19 at the point of care: a clinical performance study. Infect Dis Ther. 2021;10:753-61 33629225.



Ann Intern Med: 29 Jun 2021; 174:JC82
Fekete T
Ann Intern Med: 29 Jun 2021; 174:JC82 | PMID: 34224255
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Impact:
Abstract

Effect of Bedside Compared With Outside the Room Patient Case Presentation on Patients\' Knowledge About Their Medical Care : A Randomized, Controlled, Multicenter Trial.

Becker C, Gamp M, Schuetz P, Beck K, ... Bassetti S, Hunziker S
Background
Although bedside case presentation contributes to patient-centered care through active patient participation in medical discussions, the complexity of medical information and jargon-induced confusion may cause misunderstandings and patient discomfort.
Objective
To compare bedside versus outside the room patient case presentation regarding patients\' knowledge about their medical care.
Design
Randomized, controlled, parallel-group trial. (ClinicalTrials.gov: NCT03210987).
Setting
3 Swiss teaching hospitals.
Patients
Adult medical patients who were hospitalized.
Intervention
Patients were randomly assigned to bedside or outside the room case presentation.
Measurements
The primary endpoint was patients\' average knowledge of 3 dimensions of their medical care (each rated on a visual analogue scale from 0 to 100): understanding their disease, the therapeutic approach being used, and further plans for care.
Results
Compared with patients in the outside the room group (n = 443), those in the bedside presentation group (n = 476) reported similar knowledge about their medical care (mean, 79.5 points [SD, 21.6] vs. 79.4 points [SD, 19.8]; adjusted difference, 0.09 points [95% CI, -2.58 to 2.76 points]; P = 0.95). Also, an objective rating of patient knowledge by the study team was similar for the 2 groups, but the bedside presentation group had higher ratings of confusion about medical jargon and uncertainty caused by team discussions. Bedside ward rounds were more efficient (mean, 11.89 minutes per patient [SD, 4.92] vs. 14.14 minutes per patient [SD, 5.65]; adjusted difference, -2.31 minutes [CI, -2.98 to -1.63 minutes]; P < 0.001).
Limitation
Only Swiss hospitals and medical patients were included.
Conclusion
Compared with outside the room case presentation, bedside case presentation was shorter and resulted in similar patient knowledge, but sensitive topics were more often avoided and patient confusion was higher. Physicians presenting at the bedside need to be skilled in the use of medical language to avoid confusion and misunderstandings.
Primary funding source
Swiss National Foundation (10531C_ 182422).



Ann Intern Med: 28 Jun 2021; epub ahead of print
Becker C, Gamp M, Schuetz P, Beck K, ... Bassetti S, Hunziker S
Ann Intern Med: 28 Jun 2021; epub ahead of print | PMID: 34181449
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Impact:
Abstract

The Evidence Behind Robot-Assisted Abdominopelvic Surgery : A Systematic Review.

Dhanani NH, Olavarria OA, Bernardi K, Lyons NB, ... Haynes AB, Liang MK
Background
Use of robot-assisted surgery has increased dramatically since its advent in the 1980s, and nearly all surgical subspecialties have adopted it. However, whether it has advantages compared with laparoscopy or open surgery is unknown.
Purpose
To assess the quality of evidence and outcomes of robot-assisted surgery compared with laparoscopy and open surgery in adults.
Data sources
PubMed, EMBASE, Scopus, and the Cochrane Central Register of Controlled Trials were searched from inception to April 2021.
Study selection
Randomized controlled trials that compared robot-assisted abdominopelvic surgery with laparoscopy, open surgery, or both.
Data extraction
Two reviewers independently extracted study data and risk of bias.
Data synthesis
A total of 50 studies with 4898 patients were included. Of the 39 studies that reported incidence of Clavien-Dindo complications, 4 (10%) showed fewer complications with robot-assisted surgery. The majority of studies showed no difference in intraoperative complications, conversion rates, and long-term outcomes. Overall, robot-assisted surgery had longer operative duration than laparoscopy, but no obvious difference was seen versus open surgery.
Limitations
Heterogeneity was present among and within the included surgical subspecialties, which precluded meta-analysis. Several trials may not have been powered to assess relevant differences in outcomes.
Conclusion
There is currently no clear advantage with existing robotic platforms, which are costly and increase operative duration. With refinement, competition, and cost reduction, future versions have the potential to improve clinical outcomes without the existing disadvantages.
Primary funding source
None. (PROSPERO: CRD42020182027).



Ann Intern Med: 28 Jun 2021; epub ahead of print
Dhanani NH, Olavarria OA, Bernardi K, Lyons NB, ... Haynes AB, Liang MK
Ann Intern Med: 28 Jun 2021; epub ahead of print | PMID: 34181448
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Impact:
Abstract

Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV): Designing Master Protocols for Evaluation of Candidate COVID-19 Therapeutics.

LaVange L, Adam SJ, Currier JS, Higgs ES, ... Read SW, ACTIV Therapeutics-Clinical Working Group
Working in an unprecedented time frame, the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) public-private partnership developed and launched 9 master protocols between 14 April 2020 and 31 May 2021 to allow for the coordinated and efficient evaluation of multiple investigational therapeutic agents for COVID-19. The ACTIV master protocols were designed with a portfolio approach to serve the following patient populations with COVID-19: mild to moderately ill outpatients, moderately ill inpatients, and critically ill inpatients. To facilitate the execution of these studies and minimize start-up time, ACTIV selected several existing networks to launch the master protocols. The master protocols were also designed to test several agent classes prioritized by ACTIV that covered the spectrum of the disease pathophysiology. Each protocol, either adaptive or pragmatic, was designed to efficiently select those treatments that provide benefit to patients while rapidly eliminating those that were either ineffective or unsafe. The ACTIV Therapeutics-Clinical Working Group members describe the process by which these master protocols were designed, developed, and launched. Lessons learned that may be useful in meeting the challenges of a future pandemic are also described.



Ann Intern Med: 28 Jun 2021; epub ahead of print
LaVange L, Adam SJ, Currier JS, Higgs ES, ... Read SW, ACTIV Therapeutics-Clinical Working Group
Ann Intern Med: 28 Jun 2021; epub ahead of print | PMID: 34181444
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Impact:
Abstract

Management of Blood Pressure in Patients With Chronic Kidney Disease Not Receiving Dialysis: Synopsis of the 2021 KDIGO Clinical Practice Guideline.

Tomson CRV, Cheung AK, Mann JFE, Chang TI, ... Ix JH, Sarnak MJ
Description
The Kidney Disease: Improving Global Outcomes (KDIGO) 2021 clinical practice guideline for the management of blood pressure (BP) in patients with chronic kidney disease (CKD) not receiving dialysis is an update of the KDIGO 2012 guideline on the same topic and reflects new evidence on the risks and benefits of BP-lowering therapy among patients with CKD. It is intended to support shared decision making by health care professionals working with patients with CKD worldwide. This article is a synopsis of the full guideline.
Methods
The KDIGO leadership commissioned 2 co-chairs to convene an international Work Group of researchers and clinicians. After a Controversies Conference in September 2017, the Work Group defined the scope of the evidence review, which was undertaken by an evidence review team between October 2017 and April 2020. Evidence reviews were done according to the Cochrane Handbook. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach was used to guide the development of the recommendations and rate the strength and quality of the evidence. Practice points were included to provide guidance when evidence was insufficient to make a graded recommendation. The guideline was revised after public consultation between January and March 2020.
Recommendations
The updated guideline comprises 11 recommendations and 20 practice points. This synopsis summarizes key recommendations pertinent to the diagnosis and management of high BP in adults with CKD, excluding those receiving kidney replacement therapy. In particular, the synopsis focuses on recommendations for standardized BP measurement and a target systolic BP of less than 120 mm Hg, because these recommendations differ from some other guidelines.



Ann Intern Med: 21 Jun 2021; epub ahead of print
Tomson CRV, Cheung AK, Mann JFE, Chang TI, ... Ix JH, Sarnak MJ
Ann Intern Med: 21 Jun 2021; epub ahead of print | PMID: 34152826
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Impact:
Abstract

Developing Treatment Guidelines During a Pandemic Health Crisis: Lessons Learned From COVID-19.

Kuriakose S, Singh K, Pau AK, Daar E, ... Lane HC, Masur H
The development of the National Institutes of Health (NIH) COVID-19 Treatment Guidelines began in March 2020 in response to a request from the White House Coronavirus Task Force. Within 4 days of the request, the NIH COVID-19 Treatment Guidelines Panel was established and the first meeting took place (virtually-as did subsequent meetings). The Panel comprises 57 individuals representing 6 governmental agencies, 11 professional societies, and 33 medical centers, plus 2 community members, who have worked together to create and frequently update the guidelines on the basis of evidence from the most recent clinical studies available. The initial version of the guidelines was completed within 2 weeks and posted online on 21 April 2020. Initially, sparse evidence was available to guide COVID-19 treatment recommendations. However, treatment data rapidly accrued based on results from clinical studies that used various study designs and evaluated different therapeutic agents and approaches. Data have continued to evolve at a rapid pace, leading to 24 revisions and updates of the guidelines in the first year. This process has provided important lessons for responding to an unprecedented public health emergency: Providers and stakeholders are eager to access credible, current treatment guidelines; governmental agencies, professional societies, and health care leaders can work together effectively and expeditiously; panelists from various disciplines, including biostatistics, are important for quickly developing well-informed recommendations; well-powered randomized clinical trials continue to provide the most compelling evidence to guide treatment recommendations; treatment recommendations need to be developed in a confidential setting free from external pressures; development of a user-friendly, web-based format for communicating with health care providers requires substantial administrative support; and frequent updates are necessary as clinical evidence rapidly emerges.



Ann Intern Med: 14 Jun 2021; epub ahead of print
Kuriakose S, Singh K, Pau AK, Daar E, ... Lane HC, Masur H
Ann Intern Med: 14 Jun 2021; epub ahead of print | PMID: 34125574
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Impact:
Abstract

Optimizing SARS-CoV-2 Surveillance in the United States: Insights From the National Football League Occupational Health Program.

Mack CD, Osterholm M, Wasserman EB, Petruski-Ivleva N, ... Mancell J, Sills A
Background
Evidence to understand effective strategies for surveillance and early detection of SARS-CoV-2 is limited.
Objective
To describe the results of a rigorous, large-scale COVID-19 testing and monitoring program.
Design
The U.S. National Football League (NFL) and the NFL Players Association (NFLPA) instituted a large-scale COVID-19 monitoring program involving daily testing using 2 reverse transcription polymerase chain reaction (RT-PCR) platforms (Roche cobas and Thermo Fisher QuantStudio), a transcription-mediated amplification platform (Hologic Panther), and an antigen point-of-care (aPOC) test (Quidel Sofia).
Setting
32 NFL clubs in 24 states during the 2020 NFL season.
Participants
NFL players and staff.
Measurements
SARS-CoV-2 test results were described in the context of medically adjudicated status. Cycle threshold (Ct) values are reported when available.
Results
A total of 632 370 tests administered across 11 668 persons identified 270 (2.4%) COVID-19 cases from 1 August to 14 November 2020. Positive predictive values ranged from 73.0% to 82.0% across the RT-PCR platforms. High Ct values (33 to 37) often indicated early infection. For the first positive result, the median Ct value was 32.77 (interquartile range, 30.02 to 34.72) and 22% of Ct values were above 35. Among adjudicated COVID-19 cases tested with aPOC, 42.3% had a negative result. Positive concordance between aPOC test result and adjudicated case status increased as viral load increased.
Limitations
Platforms varied by laboratory, and test variability may reflect procedural differences.
Conclusion
Routine RT-PCR testing allowed early detection of infection. Cycle threshold values provided a useful guidepost for understanding results, with high values often indicating early infection. Antigen POC testing was unable to reliably rule out COVID-19 early in infection.
Primary funding source
The NFL and the NFLPA.



Ann Intern Med: 14 Jun 2021; epub ahead of print
Mack CD, Osterholm M, Wasserman EB, Petruski-Ivleva N, ... Mancell J, Sills A
Ann Intern Med: 14 Jun 2021; epub ahead of print | PMID: 34125571
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Impact:
Abstract

Passing the Test: A Model-Based Analysis of Safe School-Reopening Strategies.

Bilinski A, Salomon JA, Giardina J, Ciaranello A, Fitzpatrick MC
Background
The COVID-19 pandemic has induced historic educational disruptions. In April 2021, about 40% of U.S. public school students were not offered full-time in-person education.
Objective
To assess the risk for SARS-CoV-2 transmission in schools.
Design
An agent-based network model was developed to simulate transmission in elementary and high school communities, including home, school, and interhousehold interactions.
Setting
School structure was parametrized to reflect average U.S. classrooms, with elementary schools of 638 students and high schools of 1451 students. Daily local incidence was varied from 1 to 100 cases per 100 000 persons.
Participants
Students, faculty, staff, and adult household members.
Intervention
Isolation of symptomatic individuals, quarantine of an infected individual\'s contacts, reduced class sizes, alternative schedules, staff vaccination, and weekly asymptomatic screening.
Measurements
Transmission was projected among students, staff, and families after a single infection in school and over an 8-week quarter, contingent on local incidence.
Results
School transmission varies according to student age and local incidence and is substantially reduced with mitigation measures. Nevertheless, when transmission occurs, it may be difficult to detect without regular testing because of the subclinical nature of most children\'s infections. Teacher vaccination can reduce transmission to staff, and asymptomatic screening improves understanding of local circumstances and reduces transmission.
Limitation
Uncertainty exists about the susceptibility and infectiousness of children, and precision is low regarding the effectiveness of specific countermeasures, particularly with new variants.
Conclusion
With controlled community transmission and moderate mitigation, elementary schools can open safety, but high schools require more intensive mitigation. Asymptomatic screening can facilitate reopening at higher local incidence while minimizing transmission risk.
Primary funding source
Centers for Disease Control and Prevention through the Council of State and Territorial Epidemiologists, National Institute of Allergy and Infectious Diseases, National Institute on Drug Abuse, and Facebook.



Ann Intern Med: 07 Jun 2021; epub ahead of print
Bilinski A, Salomon JA, Giardina J, Ciaranello A, Fitzpatrick MC
Ann Intern Med: 07 Jun 2021; epub ahead of print | PMID: 34097433
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Impact:
Abstract

Patient Characteristics and Costs Associated With COVID-19-Related Medical Care Among Medicare Fee-for-Service Beneficiaries.

Tsai Y, Vogt TM, Zhou F
Background
New cases of COVID-19 continue to occur daily in the United States, and the need for medical treatments continues to grow. Knowledge of the direct medical costs of COVID-19 treatments is limited.
Objective
To examine the characteristics of older adults with COVID-19 and their costs for COVID-19-related medical care.
Design
Retrospective observational study.
Setting
Medical claims for Medicare fee-for-service (FFS) beneficiaries.
Patients
Medicare FFS beneficiaries aged 65 years or older who had a COVID-19-related medical encounter during April through December 2020.
Measurements
Patient characteristics and direct medical costs of COVID-19-related hospitalizations and outpatient visits.
Results
Among 28.1 million Medicare FFS beneficiaries, 1 181 127 (4.2%) sought COVID-19-related medical care. Among these patients, 23.0% had an inpatient stay and 4.2% died during hospitalization. The majority of the patients were female (57.0%), non-Hispanic White (79.6%), and residents of an urban county (77.2%). Medicare FFS costs for COVID-19-related medical care were $6.3 billion; 92.6% of costs were for hospitalizations. The mean hospitalization cost was $21 752, and the mean length of stay was 9.2 days; hospitalization cost and length of stay were higher if the patient needed a ventilator ($49 441 and 17.1 days) or died ($32 015 and 11.3 days). The mean cost per outpatient visit was $164. Patients aged 75 years or older were more likely to be hospitalized, but their hospitalizations were associated with lower costs than for younger patients. Male sex and non-White race/ethnicity were associated with higher probability of being hospitalized and higher medical costs.
Limitation
Results are based on Medicare FFS patients.
Conclusion
The COVID-19 pandemic has resulted in substantial disease and economic burden among older Americans, particularly those of non-White race/ethnicity.
Primary funding source
None.



Ann Intern Med: 31 May 2021; epub ahead of print
Tsai Y, Vogt TM, Zhou F
Ann Intern Med: 31 May 2021; epub ahead of print | PMID: 34058109
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Impact:
Abstract

Medical Schools as Racialized Organizations: A Primer.

Nguemeni Tiako MJ, South EC, Ray V
The year 2020 saw the largest social movement in response to the police killings of Black people and anti-Black racism in U.S. history. As a result, medical schools and professional societies such as the American Medical Association and the Association of American Medical Colleges are reckoning with their role in perpetuating racial inequality and the impact of structural racism on medical training. Whether these efforts will translate into meaningful change has yet to be determined. Success depends on a deep understanding of the fundamental role racism plays in how medical schools function and an acknowledgment that current organizational structures and processes often serve to entrench, not dismantle, racial inequities. Drawing on racialized organizations theory from the field of sociology, this article gives an overview of scholarship on race and racism in medical training to demonstrate how seemingly race-neutral processes and structures within medical education, in conjunction with individuals\' biases and interpersonal discrimination, serve to reproduce and sustain racial inequality. From entrance into medical school through the residency application process, organizational factors such as reliance on standardized tests to predict future success, a hostile learning climate, and racially biased performance metrics ultimately stunt the careers of trainees of color, particularly those from backgrounds underrepresented in medicine (URM). These compounding disadvantages contribute to URM trainees\' lower matching odds, steering into less competitive and lucrative specialties, and burnout and attrition from academic careers. In their commitment against structural racism in medical training and academic medicine, medical schools and larger organizations like the Association of American Medical Colleges should prioritize interventions targeted at these structural barriers to achieve equity.



Ann Intern Med: 31 May 2021; epub ahead of print
Nguemeni Tiako MJ, South EC, Ray V
Ann Intern Med: 31 May 2021; epub ahead of print | PMID: 34058105
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Impact:
Abstract

Changes in Dialysis Center Quality Associated With the End-Stage Renal Disease Quality Incentive Program : An Observational Study With a Regression Discontinuity Design.

Sheetz KH, Gerhardinger L, Ryan AM, Waits SA
Background
In 2012, the Centers for Medicare & Medicaid Services started levying performance-based financial penalties against outpatient dialysis centers under the mandatory End-Stage Renal Disease Quality Incentive Program.
Objective
To determine whether penalization was associated with improvement in dialysis center quality.
Design
Leveraging the threshold for penalization (total performance score < 60), a regression discontinuity design was used to examine the effect of penalization on quality over 2 years. Publicly available Medicare data from 2015-2018 were used. The effect of penalization at dialysis centers with different characteristics (for example, size or chain affiliation) was also examined.
Setting
United States.
Participants
Outpatient dialysis centers (n = 5830).
Measurements
Dialysis center total performance scores (a composite metric ranging from 0 to 100 based on clinical quality and adherence to reporting requirements) and individual measures that contribute to the total performance score.
Results
There were 1109 (19.0%) outpatient dialysis centers that received penalties in 2017 on the basis of performance in 2015. Penalized centers were located in ZIP codes with a higher average proportion of non-White residents (36.4% vs. 31.2%; P < 0.001) and residents with lower median income ($49 290 vs. $51 686; P < 0.001). Penalization was not associated with improvement in total performance scores in 2017 (0.4 point [95% CI, -2.5 to 3.2 points]) or 2018 (0.3 point [CI, -2.8 to 3.4 points]). This was consistent across dialysis centers with different characteristics. There was also no association between penalization and improvement in specific measures.
Limitation
The study could not account for how centers respond to penalization.
Conclusion
Penalization under the End-Stage Renal Disease Quality Incentive Program was not associated with improvement in the quality of outpatient dialysis centers.
Primary funding source
None.



Ann Intern Med: 31 May 2021; epub ahead of print
Sheetz KH, Gerhardinger L, Ryan AM, Waits SA
Ann Intern Med: 31 May 2021; epub ahead of print | PMID: 34058101
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Impact:
Abstract

Effects of Tai Chi or Conventional Exercise on Central Obesity in Middle-Aged and Older Adults : A Three-Group Randomized Controlled Trial.

Siu PM, Yu AP, Chin EC, Yu DS, ... Wei GX, Irwin MR
Background
Central obesity is a major manifestation of metabolic syndrome, which is a common health problem in middle-aged and older adults.
Objective
To examine the therapeutic efficacy of tai chi for management of central obesity.
Design
Randomized, controlled, assessor-blinded trial. (ClinicalTrials.gov: NCT03107741).
Setting
A single research site in Hong Kong between 27 February 2016 and 28 February 2019.
Participants
Adults aged 50 years or older with central obesity.
Intervention
543 participants were randomly assigned in a 1:1:1 ratio to a control group with no exercise intervention (n = 181), conventional exercise consisting of aerobic exercise and strength training (EX group) (n = 181), and a tai chi group (TC group) (n = 181). Interventions lasted 12 weeks.
Measurements
Outcomes were assessed at baseline, week 12, and week 38. The primary outcome was waist circumference (WC). Secondary outcomes were body weight; body mass index; high-density lipoprotein cholesterol (HDL-C), triglyceride, and fasting plasma glucose levels; blood pressure; and incidence of remission of central obesity.
Results
The adjusted mean difference in WC from baseline to week 12 in the control group was 0.8 cm (95% CI, -4.1 to 5.7 cm). Both intervention groups showed reductions in WC relative to control (adjusted mean differences: TC group vs. control, -1.8 cm [CI, -2.3 to -1.4 cm]; P < 0.001; EX group vs. control: -1.3 cm [CI, -1.8 to -0.9 cm]; P < 0.001); both intervention groups also showed reductions in body weight (P < 0.05) and attenuation of the decrease in HDL-C level relative to the control group. The favorable changes in WC and body weight were maintained in both the TC and EX groups, whereas the beneficial effect on HDL-C was only maintained in the TC group at week 38.
Limitations
High attrition and no dietary intervention.
Conclusion
Tai chi is an effective approach to reduce WC in adults with central obesity aged 50 years or older.
Primary funding source
Health and Medical Research Fund.



Ann Intern Med: 31 May 2021; epub ahead of print
Siu PM, Yu AP, Chin EC, Yu DS, ... Wei GX, Irwin MR
Ann Intern Med: 31 May 2021; epub ahead of print | PMID: 34058100
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Impact:
Abstract

In COPD, prophylactic macrolides, but not tetracyclines or quinolones, reduce exacerbations, with fewer serious adverse events.

Adams SG, Peters JI
Source citation
Janjua S, Mathioudakis AG, Fortescue R, et al. Prophylactic antibiotics for adults with chronic obstructive pulmonary disease: a network meta-analysis. Cochrane Database Syst Rev. 2021;1:CD013198. 33448349.



Ann Intern Med: 30 May 2021; 174:JC66
Adams SG, Peters JI
Ann Intern Med: 30 May 2021; 174:JC66 | PMID: 34058115
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Impact:
Abstract

In type 2 diabetes, SGLT2 inhibitors reduce all-cause, but not cardiovascular, mortality vs. GLP-1 RAs.

Tanner M
Source citation
Palmer SC, Tendal B, Mustafa RA, et al. Sodium-glucose cotransporter protein-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists for type 2 diabetes: systematic review and network meta-analysis of randomised controlled trials. BMJ. 2021;372:m4573. 33441402.



Ann Intern Med: 30 May 2021; 174:JC67
Tanner M
Ann Intern Med: 30 May 2021; 174:JC67 | PMID: 34058114
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Impact:
Abstract

Comparative Effectiveness and Harms of Antibiotics for Outpatient Diverticulitis : Two Nationwide Cohort Studies.

Gaber CE, Kinlaw AC, Edwards JK, Lund JL, ... Sandler RS, Peery AF
Background
Outpatient diverticulitis is commonly treated with either a combination of metronidazole and a fluoroquinolone (metronidazole-with-fluoroquinolone) or amoxicillin-clavulanate alone. The U.S. Food and Drug Administration advised that fluoroquinolones be reserved for conditions with no alternative treatment options. The comparative effectiveness of metronidazole-with-fluoroquinolone versus amoxicillin-clavulanate for diverticulitis is uncertain.
Objective
To determine the effectiveness and harms of metronidazole-with-fluoroquinolone versus amoxicillin-clavulanate for outpatient diverticulitis.
Design
Active-comparator, new-user, retrospective cohort studies.
Setting
Nationwide population-based claims data on U.S. residents aged 18 to 64 years with private employer-sponsored insurance (2000 to 2018) or those aged 65 years or older with Medicare (2006 to 2015).
Participants
Immunocompetent adults with diverticulitis in the outpatient setting.
Intervention
Metronidazole-with-fluoroquinolone or amoxicillin-clavulanate.
Measurements
1-year risks for inpatient admission, urgent surgery, and Clostridioides difficile infection (CDI) and 3-year risk for elective surgery.
Results
In MarketScan (IBM Watson Health), new users of metronidazole-with-fluoroquinolone (n = 106 361) and amoxicillin-clavulanate (n = 13 160) were identified. There were no differences in 1-year admission risk (risk difference, 0.1 percentage points [95% CI, -0.3 to 0.6]), 1-year urgent surgery risk (risk difference, 0.0 percentage points [CI, -0.1 to 0.1]), 3-year elective surgery risk (risk difference, 0.2 percentage points [CI, -0.3 to 0.7]), or 1-year CDI risk (risk difference, 0.0 percentage points [CI, -0.1 to 0.1]) between groups. In Medicare, new users of metronidazole-with-fluoroquinolone (n = 17 639) and amoxicillin-clavulanate (n = 2709) were identified. There were no differences in 1-year admission risk (risk difference, 0.1 percentage points [CI, -0.7 to 0.9]), 1-year urgent surgery risk (risk difference, -0.2 percentage points [CI, -0.6 to 0.1]), or 3-year elective surgery risk (risk difference, -0.3 percentage points [CI, -1.1 to 0.4]) between groups. The 1-year CDI risk was higher for metronidazole-with-fluoroquinolone than for amoxicillin-clavulanate (risk difference, 0.6 percentage points [CI, 0.2 to 1.0]).
Limitation
Residual confounding is possible, and not all harms associated with these antibiotics, most notably drug-induced liver injury, could be assessed.
Conclusion
Treating diverticulitis in the outpatient setting with amoxicillin-clavulanate may reduce the risk for fluoroquinolone-related harms without adversely affecting diverticulitis-specific outcomes.
Primary funding source
National Institutes of Health.



Ann Intern Med: 30 May 2021; 174:737-746
Gaber CE, Kinlaw AC, Edwards JK, Lund JL, ... Sandler RS, Peery AF
Ann Intern Med: 30 May 2021; 174:737-746 | PMID: 33617725
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Impact:
Abstract

The Value of Total Knee Replacement in Patients With Knee Osteoarthritis and a Body Mass Index of 40 kg/m or Greater : A Cost-Effectiveness Analysis.

Chen AT, Bronsther CI, Stanley EE, Paltiel AD, ... Katz JN, Losina E
Background
Total knee replacement (TKR) is an effective and cost-effective strategy for treating end-stage knee osteoarthritis. Greater risk for complications among TKR recipients with a body mass index (BMI) of 40 kg/m2 or greater has raised concerns about the value of TKR in this population.
Objective
To assess the value of TKR in recipients with a BMI of 40 kg/m2 or greater using a cost-effectiveness analysis.
Design
Osteoarthritis Policy Model to assess long-term clinical benefits, costs, and cost-effectiveness of TKR in patients with a BMI of 40 kg/m2 or greater.
Data sources
Total knee replacement parameters from longitudinal studies and published literature, and costs from Medicare Physician Fee Schedules, the Healthcare Cost and Utilization Project, and published data.
Target population
Recipients of TKR with a BMI of 40 kg/m2 or greater in the United States.
Time horizon
Lifetime.
Perspective
Health care sector.
Intervention
Total knee replacement.
Outcome measures
Cost, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs), discounted at 3% annually.
Results of base-case analysis
Total knee replacement increased QALYs by 0.71 year and lifetime medical costs by $25 200 among patients aged 50 to 65 years with a BMI of 40 kg/m2 or greater, resulting in an ICER of $35 200. Total knee replacement in patients older than 65 years with a BMI of 40 kg/m2 or greater increased QALYs by 0.39 year and costs by $21 100, resulting in an ICER of $54 100.
Results of sensitivity analysis
In TKR recipients with a BMI of 40 kg/m2 or greater and diabetes and cardiovascular disease, ICERs were below $75 000 per QALY. Results were most sensitive to complication rates and preoperative pain levels. In the probabilistic sensitivity analysis, at a $55 000-per-QALY willingness-to-pay threshold, TKR had a 100% and 90% likelihood of being a cost-effective strategy for patients aged 50 to 65 years and patients older than 65 years, respectively.
Limitation
Data are derived from several sources.
Conclusion
From a cost-effectiveness perspective, TKR offers good value in patients with a BMI of 40 kg/m2 or greater, including those with multiple comorbidities.
Primary funding source
National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health.



Ann Intern Med: 30 May 2021; 174:747-757
Chen AT, Bronsther CI, Stanley EE, Paltiel AD, ... Katz JN, Losina E
Ann Intern Med: 30 May 2021; 174:747-757 | PMID: 33750190
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Impact:
Abstract

Weight and Metabolic Changes After Switching From Tenofovir Disoproxil Fumarate to Tenofovir Alafenamide in People Living With HIV : A Cohort Study.

Surial B, Mugglin C, Calmy A, Cavassini M, ... Rauch A, Swiss HIV Cohort Study
Background
Tenofovir-based antiretroviral therapy (ART) has become first-line in all major HIV treatment guidelines. Compared with tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF) has a favorable renal and bone safety profile, but concerns about metabolic complications remain.
Objective
To assess weight changes, the development of overweight/obesity, and changes in lipid levels 18 months after replacing TDF with TAF.
Design
Cohort study.
Setting
5 university hospitals, affiliated hospitals, and private physicians in Switzerland.
Participants
4375 adults living with HIV who received TDF-containing ART for 6 months or longer.
Measurements
Changes in weight and lipid levels were assessed using mixed-effect models. Differences in proportions of newly overweight/obese participants were calculated using 2-proportions Z tests.
Results
4375 individuals were included, with follow-up between 1 January 2016 and 31 July 2019. Median age was 50 years (interquartile range, 43 to 56 years), 25.9% were female, and 51.7% had a normal body mass index (BMI); 3484 (79.6%) switched to TAF and 891 (20.4%) continued TDF. After 18 months, switching to TAF was associated with an adjusted mean weight increase of 1.7 kg (95% CI, 1.5 to 2.0 kg), compared with 0.7 kg (CI, 0.4 to 1.0 kg) with the continued use of TDF (between-group difference, 1.1 kg [CI, 0.7 to 1.4 kg]). Among individuals with a normal BMI, 13.8% who switched to TAF became overweight/obese, compared with 8.4% of those continuing TDF (difference, 5.4 percentage points [CI, 2.1 to 8.8 percentage points]). Switching to TAF led to increases in adjusted mean total cholesterol (0.25 mmol/L [9.5 mg/dL]), high-density lipoprotein cholesterol (0.05 mmol/L [1.9 mg/dL]), low-density lipoprotein cholesterol (0.12 mmol/L [4.7 mg/dL]), and triglyceride (0.18 mmol/L [16.1 mg/dL]) levels after 18 months.
Limitation
Short follow-up, small subgroup analyses, and potential residual confounding.
Conclusion
Replacing TDF with TAF is associated with adverse metabolic changes, including weight increase, development of obesity, and worsening serum lipid levels.
Primary funding source
Swiss National Science Foundation.



Ann Intern Med: 30 May 2021; 174:758-767
Surial B, Mugglin C, Calmy A, Cavassini M, ... Rauch A, Swiss HIV Cohort Study
Ann Intern Med: 30 May 2021; 174:758-767 | PMID: 33721521
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Impact:
Abstract

In HFrEF, adding empagliflozin to medical therapy reduced a composite outcome, regardless of CKD status.

Santos-Gallego CG, Van Spall HGC
Source citation
Zannad F, Ferreira JP, Pocock SJ, et al. Cardiac and kidney benefits of empagliflozin in heart failure across the spectrum of kidney function: insights from EMPEROR-Reduced. Circulation. 2021;143:310-21. 33095032.



Ann Intern Med: 30 May 2021; 174:JC68
Santos-Gallego CG, Van Spall HGC
Ann Intern Med: 30 May 2021; 174:JC68 | PMID: 34058113
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Impact:
Abstract

In older patients with permanent AF and HF, digoxin and bisoprolol did not differ for QoL at 6 mo.

Karimzad K, Deswal A
Source citation
Kotecha D, Bunting KV, Gill SK, et al. Effect of digoxin vs bisoprolol for heart rate control in atrial fibrillation on patient-reported quality of life: the RATE-AF randomized clinical trial. JAMA. 2020;324:2497-508. 33351042.



Ann Intern Med: 30 May 2021; 174:JC69
Karimzad K, Deswal A
Ann Intern Med: 30 May 2021; 174:JC69 | PMID: 34058112
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Impact:
Abstract

In obesity with T2DM, biliopancreatic diversion increased T2DM remission vs. medical and lifestyle therapy at 10 y.

Sarma S, Lipscombe LL
Source citation
Mingrone G, Panunzi S, De Gaetano A, et al. Metabolic surgery versus conventional medical therapy in patients with type 2 diabetes: 10-year follow-up of an open-label, single-centre, randomised controlled trial. Lancet. 2021;397:293-304. 33485454.



Ann Intern Med: 30 May 2021; 174:JC70
Sarma S, Lipscombe LL
Ann Intern Med: 30 May 2021; 174:JC70 | PMID: 34058110
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Impact:
Abstract

USPSTF recommends against screening adults in the general population for asymptomatic carotid artery stenosis.

Tanner M
Source citation
U.S. Preventive Services Task Force, Krist AH, Davidson KW, et al. Screening for asymptomatic carotid artery stenosis: US Preventive Services Task Force recommendation statement. JAMA. 2021;325:476-81. 33528542.



Ann Intern Med: 30 May 2021; 174:JC62
Tanner M
Ann Intern Med: 30 May 2021; 174:JC62 | PMID: 34058106
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Impact:
Abstract

In recurrent infection, oral FMT capsules have a pooled cure rate of 82% (low-quality evidence).

Horton LC, Feuerstein JD
Source citation
Du C, Luo Y, Walsh S, Grinspan A. Oral fecal microbiota transplant capsules are safe and effective for recurrent Clostridioides difficile infection: a systematic review and meta-analysis. J Clin Gastroenterol. 2021;55:300-8. 33471490.



Ann Intern Med: 30 May 2021; 174:JC65
Horton LC, Feuerstein JD
Ann Intern Med: 30 May 2021; 174:JC65 | PMID: 34058102
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Impact:
Abstract

Multiple Sclerosis.

Olek MJ
Many groundbreaking advances have occurred in the field of multiple sclerosis since this series last reviewed the disorder in 2014. The U.S. Food and Drug Administration has approved 7 new medications for relapsing-remitting multiple sclerosis and approved the first medication for primary progressive multiple sclerosis. The McDonald criteria for diagnosing multiple sclerosis were updated in 2017. New blood tests can now differentiate patients with multiple sclerosis from those with neuromyelitis optica spectrum disorder, and 3 new medications have been approved specifically for the latter disorder. Also, new medications for treating the symptoms of multiple sclerosis have been introduced.



Ann Intern Med: 30 May 2021; 174:ITC81-ITC96
Olek MJ
Ann Intern Med: 30 May 2021; 174:ITC81-ITC96 | PMID: 34097429
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Impact:
Abstract

\"We Do Not Want Him Because He Is a Jew\": The Montreal Interns\' Strike of 1934.

Halperin EC
Speeches by modern-day White supremacists often include such statements as \"Jews will not replace us.\" In 1934, the French-speaking medical interns of Montreal\'s Roman Catholic hospitals went on strike because, they alleged, a Jew \"replaced\" a Roman Catholic French Canadian. Anti-Semitic social and economic boycotts and educational quotas were in existence in Canada from the 19th through the mid-20th century. There were particularly strong anti-immigrant and anti-Semitic feelings in the first half of the 20th century in Quebec, along with anti-Semitic pro-fascist political parties. In 1934, Montreal\'s Hôpital Notre-Dame (HND), a teaching hospital of the Université de Montréal (UM) medical school, was unable to hire a full complement of medical interns from among the newly graduated French-speaking Roman Catholic medical students. The hospital hired a French-speaking Jewish graduate of UM, Samuel Rabinovitch. The prospective interns at HND submitted a petition demanding that Rabinovitch be fired, stating, \"We do not want him because he is a Jew.\" On 14 and 15 June 1934, HND\'s interns went on strike to prevent Rabinovitch from taking up his duties. The strike spread to multiple hospitals in Montreal. A Jewish urology trainee at the Hôtel Dieu hospital, Abram Stilman, was also targeted. Rabinovitch resigned in order to bring the strike to an end. The strike buttressed the case in the first half of the 20th century for American and Canadian Jewish hospitals and medical schools to ensure the education of Jewish physicians, reminds us of the origins of the slogans of modern White supremacists, and reinforces the historical basis of efforts to promote diversity and inclusion in medical education.



Ann Intern Med: 30 May 2021; 174:852-857
Halperin EC
Ann Intern Med: 30 May 2021; 174:852-857 | PMID: 34126016
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Impact:
Abstract

Association Between Mortality and Levels of Autonomous Cortisol Secretion by Adrenal Incidentalomas : A Cohort Study.

Kjellbom A, Lindgren O, Puvaneswaralingam S, Löndahl M, Olsen H
Background
Autonomous cortisol secretion in patients with adrenal incidentalomas is associated with increased mortality, but detailed information about the risk associated with specific levels of autonomous cortisol secretion is not available.
Objective
To measure the association between mortality and levels of autonomous cortisol secretion in patients with adrenal incidentalomas.
Design
Retrospective cohort study. (ClinicalTrials.gov: NCT03919734).
Setting
Two hospitals in southern Sweden.
Patients
Consecutive patients who had adrenal incidentalomas identified between 2005 and 2015 and were followed for up to 14 years. Outcome data were collected from national registers.
Measurements
Patients were grouped according to plasma cortisol level after a 1-mg dexamethasone suppression test (cortisolDST; <50, 50 to 82, 83 to 137, or ≥138 nmol/L).
Results
During a median follow-up of 6.4 years, 170 of 1048 patients died. Compared with a cortisolDST less than 50 nmol/L, a cortisolDST of 50 to 82 nmol/L was not associated with increased mortality (hazard ratio [HR], 1.15 [95% CI, 0.78 to 1.70]). However, a cortisolDST of 83 to 137 nmol/L (n = 119) had an HR of 2.30 (CI, 1.52 to 3.49), and a cortisolDST of 138 nmol/L or higher (n = 82) had an HR of 3.04 (CI, 1.86 to 4.98). Analyses using restricted cubic splines indicated that the association between cortisolDST and mortality was linear up to a cortisolDST of 200 nmol/L.
Limitation
The results are not based on verified autonomous cortisol secretion; thus, the association may be underestimated.
Conclusion
The association between mortality and cortisolDST increased linearly until cortisolDST reached 200 nmol/L. A cortisolDST of 83 to 137 nmol/L was associated with a 2-fold increase in mortality, and a cortisolDST of 138 nmol/L or higher was associated with a 3-fold increase in mortality. Additional studies should be done, and until those studies are completed some clinicians may consider these findings when deciding which patients to recommend for surgery.
Primary funding source
Lisa and Johan Grönberg Foundation and Gyllenstiernska Krapperup Foundation.



Ann Intern Med: 24 May 2021; epub ahead of print
Kjellbom A, Lindgren O, Puvaneswaralingam S, Löndahl M, Olsen H
Ann Intern Med: 24 May 2021; epub ahead of print | PMID: 34029490
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Impact:
Abstract

The Development of Living, Rapid Practice Points: Summary of Methods From the Scientific Medical Policy Committee of the American College of Physicians.

Qaseem A, Yost J, Forciea MA, Jokela JA, ... Obley A, Humphrey LL
In response to the COVID-19 pandemic, the Scientific Medical Policy Committee (SMPC) of the American College of Physicians (ACP) began developing \"practice points\" to provide clinical advice based on the best available evidence for the public, patients, clinicians, and public health professionals. As one of the first organizations in the United States to develop evidence-based clinical guidelines, ACP continues to lead and advance the science of evidence-based medicine by implementing new methods to rapidly publish practice points and maintain them as living advice that regularly assesses and incorporates new evidence. The overarching aim of practice points is to answer targeted key questions for which there is a timely need to synthesize evidence for decision making. The SMPC believes these methods can potentially be adapted to address various clinical and public health topics beyond the COVID-19 pandemic. This article presents an overview of the SMPC\'s living, rapid practice points development process, which includes a rapid systematic review, use of the GRADE (Grading of Recommendations Assessment, Development and Evaluation) method, use of stringent policies on the disclosure of interests and management of conflicts of interest, incorporating a public (nonclinician) perspective, and maintenance of the documents as living through ongoing surveillance and synthesis of new evidence as it emerges.



Ann Intern Med: 24 May 2021; epub ahead of print
Qaseem A, Yost J, Forciea MA, Jokela JA, ... Obley A, Humphrey LL
Ann Intern Med: 24 May 2021; epub ahead of print | PMID: 34029483
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Abstract

Serial SARS-CoV-2 Receptor-Binding Domain Antibody Responses in Patients Receiving Dialysis.

Anand S, Montez-Rath ME, Han J, Garcia P, ... Chertow GM, Parsonnet J
Background
Assessing the evolution of SARS-CoV-2 immune response among patients receiving dialysis can define its durability in a highly clinically relevant context because patients receiving dialysis share the characteristics of persons most susceptible to SARS-CoV-2 infection.
Objective
To evaluate the persistence of SARS-CoV-2 receptor-binding domain (RBD) IgG in seroprevalent patients receiving dialysis.
Design
Prospective.
Setting
Nationwide sample from dialysis facilities.
Patients
2215 patients receiving dialysis who had evidence of SARS-CoV-2 infection as of July 2020.
Measurements
Remainder plasma from routine monthly laboratories was used to measure semiquantitative RBD IgG index value over 6 months.
Results
A total of 2063 (93%) seroprevalent patients reached an assay detectable response (IgG index value ≥1). Most (n = 1323, 60%) had responses in July with index values classified as high (IgG ≥10); 1003 (76%) remained within this stratum. Adjusted median index values declined slowly but continuously (July vs. December values were 21 vs. 13; P < 0.001). The trajectory of the response did not vary by age group, sex, race/ethnicity, or diabetes status. Patients without an assay detectable response (n = 137) were more likely to be White and in the younger (18 to 44 years) or older (≥80 years) age groups and less likely to have diabetes and hypoalbuminemia.
Limitation
Lack of data on symptoms or reverse transcriptase polymerase chain reaction diagnosis, cohort of persons who survived infection, and use of a semiquantitative assay.
Conclusion
Despite impaired immunity, most seropositive patients receiving dialysis maintained RBD antibody levels over 6 months. A slow and continual decline in median antibody levels over time was seen, but no indication that subgroups with impaired immunity had a shorter-lived humoral response was found.
Primary funding source
Ascend Clinical Laboratories.



Ann Intern Med: 17 May 2021; epub ahead of print
Anand S, Montez-Rath ME, Han J, Garcia P, ... Chertow GM, Parsonnet J
Ann Intern Med: 17 May 2021; epub ahead of print | PMID: 34000201
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Abstract

The Reign of the Ventilator: Acute Respiratory Distress Syndrome, COVID-19, and Technological Imperatives in Intensive Care.

Prkachin Y
In the early phase of the COVID-19 pandemic, a dispute arose as to whether the disease caused a typical or atypical version of acute respiratory distress syndrome (ARDS). This essay recounts the emergence of ARDS and places it in the context of the technological transformation of modern hospital care-particularly the emergence of intensive care after the 1952 Copenhagen polio epidemic. The polio epidemic seemed to show the value of manual positive-pressure ventilation, leading to the proliferation of mechanical ventilators and the expansion of intensive care units in the 1960s. This created the conditions of possibility for ARDS to be described and institutionalized within modern intensive care. Yet the centrality of the ventilator to descriptions and definitions of ARDS quickly made it difficult to conceive of the disorder outside the framework of mechanical ventilation and blood gas levels, or to acknowledge the degree to which the ventilator was a source of iatrogenic injury and complications. Moreover, the imperative to understand and treat ARDS with mechanical ventilation set the stage for the early confusion about whether patients with COVID-19 should receive mechanical ventilation. This history offers many crucial lessons about how new technologies can lead to new and valuable therapies but can also subtly shape and constrain medical thinking. Moreover, ventilators not only changed how respiratory disorders were conceived; they also brought new forms of respiratory illness into existence.



Ann Intern Med: 03 May 2021; epub ahead of print
Prkachin Y
Ann Intern Med: 03 May 2021; epub ahead of print | PMID: 33939486
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Abstract

The Effect of Preconception-Initiated Low-Dose Aspirin on Human Chorionic Gonadotropin-Detected Pregnancy, Pregnancy Loss, and Live Birth : Per Protocol Analysis of a Randomized Trial.

Naimi AI, Perkins NJ, Sjaarda LA, Mumford SL, ... Silver RM, Schisterman EF
Background
A previous large randomized trial indicated that preconception-initiated low-dose aspirin (LDA) therapy did not have a positive effect on pregnancy outcomes. However, this trial was subject to nonadherence, which was not taken into account by the intention-to-treat approach.
Objective
To estimate per protocol effects of preconception-initiated LDA on pregnancy loss and live birth.
Design
The EAGeR (Effects of Aspirin on Gestation and Reproduction) trial was used to construct a prospective cohort for a post hoc analysis. (ClinicalTrials.gov: NCT00467363).
Setting
4 university medical centers in the United States.
Participants
1227 women between the ages of 18 and 40 years who had 1 or 2 previous pregnancy losses and were attempting pregnancy.
Measurements
Adherence to LDA or placebo, assessed by measuring pill bottle weights at regular intervals during follow-up. Primary outcomes were human chorionic gonadotropin (hCG)-detected pregnancies, pregnancy losses, and live births, determined by pregnancy tests and medical records.
Results
Relative to placebo, adhering to LDA for 5 of 7 days per week led to 8 more hCG-detected pregnancies (95% CI, 4.64 to 10.96 pregnancies), 15 more live births (CI, 7.65 to 21.15 births), and 6 fewer pregnancy losses (CI, -12.00 to -0.20 losses) for every 100 women in the trial. In addition, compared with placebo, postconception initiation of LDA therapy led to a reduction in the estimated effects. Furthermore, effects were obtained in a minimum of 4 of 7 days per week.
Limitation
The EAGeR trial data for this study were analyzed as observational data, thus are subject to the limitations of prospective observational studies.
Conclusion
Per protocol results suggest that preconception use of LDA at least 4 days per week may improve reproductive outcomes for women who have had 1 or 2 pregnancy losses. Increasing adherence to daily LDA seems to be key to improving effectiveness.
Primary funding source
National Institutes of Health.



Ann Intern Med: 29 Apr 2021; 174:595-601
Naimi AI, Perkins NJ, Sjaarda LA, Mumford SL, ... Silver RM, Schisterman EF
Ann Intern Med: 29 Apr 2021; 174:595-601 | PMID: 33493011
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Abstract

The Use of Rifaximin in the Prevention of Overt Hepatic Encephalopathy After Transjugular Intrahepatic Portosystemic Shunt : A Randomized Controlled Trial.

Bureau C, Thabut D, Jezequel C, Archambeaud I, ... Péron JM, Vinel JP
Background
The efficacy of rifaximin in the secondary prevention of overt hepatic encephalopathy (HE) is well documented, but its effectiveness in preventing a first episode in patients after transjugular intrahepatic portosystemic shunt (TIPS) has not been established.
Objective
To determine whether rifaximin prevents overt HE after TIPS compared with placebo.
Design
Randomized, double-blind, multicenter, placebo-controlled trial. (ClinicalTrials.gov: NCT02016196).
Participants
197 patients with cirrhosis undergoing TIPS for intractable ascites or prevention of variceal rebleeding.
Intervention
Patients were randomly assigned to receive rifaximin (600 mg twice daily) or placebo, beginning 14 days before TIPS and continuing for 168 days after the procedure.
Measurements
The primary efficacy end point was incidence of overt HE within 168 days after the TIPS procedure.
Results
An episode of overt HE occurred in 34% (95% CI, 25% to 44%) of patients in the rifaximin group (n = 93) and 53% (CI, 43% to 63%) in the placebo group (n = 93) during the postprocedure period (odds ratio, 0.48 [CI, 0.27 to 0.87]). Neither the incidence of adverse events nor transplant-free survival was significantly different between the 2 groups.
Limitations
The study\'s conclusion applies mainly to patients with alcoholic cirrhosis, who made up the study population. The potential benefit of rifaximin 6 months after TIPS and beyond remains to be investigated.
Conclusion
In patients with cirrhosis treated with TIPS, rifaximin was well tolerated and reduced the risk for overt HE. Rifaximin should therefore be considered for prophylaxis of post-TIPS HE.
Primary funding source
French Public Health Ministry.



Ann Intern Med: 29 Apr 2021; 174:633-640
Bureau C, Thabut D, Jezequel C, Archambeaud I, ... Péron JM, Vinel JP
Ann Intern Med: 29 Apr 2021; 174:633-640 | PMID: 33524293
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Abstract

Incorporating Baseline Breast Density When Screening Women at Average Risk for Breast Cancer : A Cost-Effectiveness Analysis.

Shih YT, Dong W, Xu Y, Etzioni R, Shen Y
Background
Breast density classification is largely determined by mammography, making the timing of the first screening mammogram clinically important.
Objective
To evaluate the cost-effectiveness of breast cancer screening strategies that are stratified by breast density.
Design
Microsimulation model to generate the natural history of breast cancer for women with and those without dense breasts and assessment of the cost-effectiveness of strategies tailored to breast density and nontailored strategies.
Data sources
Model parameters from the literature; statistical modeling; and analysis of Surveillance, Epidemiology, and End Results-Medicare data.
Target population
Women aged 40 years or older.
Time horizon
Lifetime.
Perspective
Societal.
Intervention
No screening; biennial or triennial mammography from age 50 to 75 years; annual mammography from age 50 to 75 years for women with dense breasts at age 50 years and biennial or triennial mammography from age 50 to 75 years for those without dense breasts at age 50 years; and annual mammography at age 40 to 75 years for women with dense breasts at age 40 years and biennial or triennial mammography at age 50 to 75 years for those without dense breasts at age 40 years.
Outcome measures
Lifetime costs and quality-adjusted life-years (QALYs), discounted at 3% annually.
Results of base-case analysis
Baseline screening at age 40 years followed by annual screening at age 40 to 75 years for women with dense breasts and biennial screening at age 50 to 75 years for women without dense breasts was effective and cost-effective, yielding an incremental cost-effectiveness ratio of $36 200 per QALY versus the biennial strategy at age 50 to 75 years.
Results of sensitivity analysis
At a societal willingness-to-pay threshold of $100 000 per QALY, the probability that the density-stratified strategy at age 40 years was optimal was 56% compared with 6 other strategies.
Limitation
Findings may not be generalizable outside the United States.
Conclusion
The study findings advocate for breast density-stratified screening with baseline mammography at age 40 years.
Primary funding source
National Cancer Institute.



Ann Intern Med: 29 Apr 2021; 174:602-612
Shih YT, Dong W, Xu Y, Etzioni R, Shen Y
Ann Intern Med: 29 Apr 2021; 174:602-612 | PMID: 33556275
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Abstract

A Double-Blind, Randomized, Placebo-Controlled Phase 1 Study of Ad26.ZIKV.001, an Ad26-Vectored Anti-Zika Virus Vaccine.

Salisch NC, Stephenson KE, Williams K, Cox F, ... Schuitemaker H, Barouch DH
Background
Zika virus (ZIKV) may cause severe congenital disease after maternal-fetal transmission. No vaccine is currently available.
Objective
To assess the safety and immunogenicity of Ad26.ZIKV.001, a prophylactic ZIKV vaccine candidate.
Design
Phase 1 randomized, double-blind, placebo-controlled clinical study. (ClinicalTrials.gov: NCT03356561).
Setting
United States.
Participants
100 healthy adult volunteers.
Intervention
Ad26.ZIKV.001, an adenovirus serotype 26 vector encoding ZIKV M-Env, administered in 1- or 2-dose regimens of 5 × 1010 or 1 × 1011 viral particles (vp), or placebo.
Measurements
Local and systemic adverse events; neutralization titers by microneutralization assay (MN50) and T-cell responses by interferon-γ enzyme-linked immunospot and intracellular cytokine staining; and protectivity of vaccine-induced antibodies in a subset of participants through transfer in an exploratory mouse ZIKV challenge model.
Results
All regimens were well tolerated, with no safety concerns identified. In both 2-dose regimens, ZIKV neutralizing titers peaked 14 days after the second vaccination, with geometric mean MN50 titers (GMTs) of 1065.6 (95% CI, 494.9 to 2294.5) for 5 × 1010 vp and 956.6 (595.8 to 1535.8) for 1 × 1011 vp. Titers persisted for at least 1 year at a GMT of 68.7 (CI, 26.4-178.9) for 5 × 1010 vp and 87.0 (CI, 29.3 to 258.6) for 1 × 1011 vp. A 1-dose regimen of 1 × 1011 vp Ad26.ZIKV.001 induced seroconversion in all participants 56 days after the first vaccination (GMT, 103.4 [CI, 52.7 to 202.9]), with titers persisting for at least 1 year (GMT, 90.2 [CI, 38.4 to 212.2]). Env-specific cellular responses were induced. Protection against ZIKV challenge was observed after antibody transfer from participants into mice, and MN50 titers correlated with protection in this model.
Limitation
The study was conducted in a nonendemic area, so it did not assess safety and immunogenicity in a flavivirus-exposed population.
Conclusion
The safety and immunogenicity profile makes Ad26.ZIKV.001 a promising candidate for further development if the need reemerges.
Primary funding source
Janssen Vaccines and Infectious Diseases.



Ann Intern Med: 29 Apr 2021; 174:585-594
Salisch NC, Stephenson KE, Williams K, Cox F, ... Schuitemaker H, Barouch DH
Ann Intern Med: 29 Apr 2021; 174:585-594 | PMID: 33587687
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Abstract

Safety and Efficacy of Checkpoint Inhibition in Patients With Melanoma and Preexisting Autoimmune Disease : A Cohort Study.

van der Kooij MK, Suijkerbuijk KPM, Aarts MJB, van den Berkmortel FWPJ, ... Dekkers OM, Kapiteijn E
Background
Because immune checkpoint inhibition (ICI) can cause immune-related adverse events (irAEs) mimicking immunologic diseases, patients with preexisting autoimmune disease (AID) have been excluded from clinical trials.
Objective
To evaluate the safety and efficacy of ICI in patients with advanced melanoma with and without AID.
Design
Nationwide cohort study.
Setting
The Netherlands.
Patients
4367 patients with advanced melanoma enrolled in the Dutch Melanoma Treatment Registry (DMTR) between July 2013 and July 2018 and followed through February 2019.
Measurements
Patient, clinical, and treatment characteristics; irAEs of grade 3 or higher; treatment response; and survival.
Results
A total of 415 patients (9.5%) had AID, categorized as rheumatologic AID (n = 227), endocrine AID (n = 143), inflammatory bowel disease (IBD) (n = 55), or \"other\" (n = 8). Of these, 228 patients (55%) were treated with ICI (vs. 2546 [58%] without AID); 87 were treated with anti-cytotoxic T lymphocyte-associated protein 4 (CTLA-4), 187 with anti-programmed cell death 1 (PD-1), and 34 with the combination. The incidences of irAEs of grade 3 or higher in patients with AID were 30% (95% CI, 21% to 41%) with anti-CTLA-4, 17% (CI, 12% to 23%) with anti-PD-1, and 44% (CI, 27% to 62%) with combination therapy; for patients without AID, the incidences were 30% (CI, 27% to 33%) (n = 916), 13% (CI, 12% to 15%) (n = 1540), and 48% (CI, 43% to 53%) (n = 388), respectively. Patients with AID more often discontinued anti-PD-1 treatment because of toxicity than patients without AID (17% [CI, 12% to 23%] vs. 9% [CI, 8% to 11%]). Patients with IBD were more prone to anti-PD-1-induced colitis (6/31 = 19% [CI, 7% to 37%]) than patients with other AIDs (3% [CI, 0% to 6%]) and patients without AID (2% [CI, 2% to 3%]).The objective response rate was similar in patients with versus without AID who were treated with anti-CTLA-4 (10% [CI, 5% to 19%] vs. 16% [CI, 14% to 19%]), anti-PD-1 (40% [CI, 33% to 47%] vs. 44% [CI, 41% to 46%]), or the combination (39% [CI, 20% to 59%] vs. 43% [CI, 38% to 49%]). Survival did not differ between patients with and those without AID (median, 13 months [CI, 10 to 16 months] vs. 14 months [CI, 13 to 15 months]).
Limitation
Information was limited on AID severity and immunosuppressive treatment.
Conclusion
Response to ICI with anti-CTLA-4, anti-PD-1, or their combination for advanced melanoma and overall incidence of any irAEs of grade 3 or higher were similar in patients with and without preexisting AID. However, severe colitis and toxicity requiring early discontinuation of treatment occurred more frequently among patients with preexisting IBD, warranting close follow-up.
Primary funding source
The Netherlands Organization for Health Research and Development.



Ann Intern Med: 29 Apr 2021; 174:641-648
van der Kooij MK, Suijkerbuijk KPM, Aarts MJB, van den Berkmortel FWPJ, ... Dekkers OM, Kapiteijn E
Ann Intern Med: 29 Apr 2021; 174:641-648 | PMID: 33587686
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Abstract

In CKD, the effect of dapagliflozin on kidney outcomes did not vary by T2DM status or CKD cause.

Kohn OF
Source citation
Wheeler DC, Stefánsson BV, Jongs N, et al. Effects of dapagliflozin on major adverse kidney and cardiovascular events in patients with diabetic and non-diabetic chronic kidney disease: a prespecified analysis from the DAPA-CKD trial. Lancet Diabetes Endocrinol. 2021;9:22-31. 33338413.



Ann Intern Med: 29 Apr 2021; 174:JC53
Kohn OF
Ann Intern Med: 29 Apr 2021; 174:JC53 | PMID: 33939480
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Impact:
Abstract

In men who are overweight or obese, adding testosterone therapy reduced glucose intolerance/T2DM.

Griffin TP, Dinneen SF
Source citation
Wittert G, Bracken K, Robledo KP, et al. Testosterone treatment to prevent or revert type 2 diabetes in men enrolled in a lifestyle programme (T4DM): a randomised, double-blind, placebo-controlled, 2-year, phase 3b trial. Lancet Diabetes Endocrinol. 2021;9:32-45. 33338415.



Ann Intern Med: 29 Apr 2021; 174:JC54
Griffin TP, Dinneen SF
Ann Intern Med: 29 Apr 2021; 174:JC54 | PMID: 33939479
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Abstract

Depression.

McCarron RM, Shapiro B, Rawles J, Luo J
Most psychiatric care is delivered in primary care settings, where depression is the most common presenting psychiatric symptom. Given the high prevalence of depression worldwide and the well-established consequences of untreated depression, the ability of primary care clinicians to effectively diagnose and treat it is critically important. This article offers up-to-date guidance for the diagnosis and treatment of major depressive disorder, including practical considerations for delivering optimal and efficient care for these patients.



Ann Intern Med: 29 Apr 2021; 174:ITC65-ITC80
McCarron RM, Shapiro B, Rawles J, Luo J
Ann Intern Med: 29 Apr 2021; 174:ITC65-ITC80 | PMID: 33971098
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Abstract

Fighting Prejudice and Absorbing Refugees From Nazism: The National Committee for the Resettlement of Foreign Physicians, 1939-1945.

Leff L, Schoen RE
In the 1930s and 1940s, the medical profession reacted with hostility and erected formidable barriers to refugee physicians from Nazi-dominated Europe who sought to practice medicine in the United States. Yet, refugee physicians ultimately succeeded, with 77% of them working as doctors by 1945 and 98.6% by 1947. Although physician skills are readily transferable, and the United States had a genuine need for doctors after World War II drew 55 000 physicians into the military, refugee physicians\' success can be attributed to the courageous physician leaders who lobbied on their behalf and the creation of the National Committee for the Resettlement of Foreign Physicians-an organization that helped immigrant physicians pass licensing examinations, identify locations for employment, and overcome barriers to integration into American society.



Ann Intern Med: 29 Apr 2021; 174:680-686
Leff L, Schoen RE
Ann Intern Med: 29 Apr 2021; 174:680-686 | PMID: 33999678
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Impact:

This program is still in alpha version.