Effect of Starting Dialysis Versus Continuing Medical Management on Survival and Home Time in Older Adults With Kidney Failure: A Target Trial Emulation Study: Annals of Internal Medicine: Vol 177, No 9

Background: For older adults with kidney failure who are not referred for transplant, medical management is an alternative to dialysis. Objective: To compare survival and home time between older adults who started dialysis at an estimated glomerular filtration rate (eGFR) less than 12 mL/min/1.73 m2 and those who continued medical management. Design: Observational cohort study using target trial emulation. Setting: U.S. Department of Veterans Affairs, 2010 to 2018. Participants: Adults aged 65 years or older with chronic kidney failure and eGFR below 12 mL/min/1.73 m2 who were not referred for transplant. Intervention: Starting dialysis within 30 days versus continuing medical management. Measurements: Mean survival and number of days at home. Results: Among 20 440 adults (mean age, 77.9 years [SD, 8.8]), the median time to dialysis start was 8.0 days in the group starting dialysis and 3.0 years in the group continuing medical management. Over a 3-year horizon, the group starting dialysis survived 770 days and the group continuing medical management survived 761 days (difference, 9.3 days [95% CI, −17.4 to 30.1 days]). Compared with the group continuing medical management, the group starting dialysis had 13.6 fewer days at home (CI, 7.7 to 20.5 fewer days at home). Compared with the group continuing medical management and forgoing dialysis completely, the group starting dialysis had longer survival by 77.6 days (CI, 62.8 to 91.1 days) and 14.7 fewer days at home (CI, 11.2 to 16.5 fewer days at home). Limitation: Potential for unmeasured confounding due to lack of symptom assessments at eligibility; limited generalizability to women and nonveterans. Conclusion: Older adults starting dialysis when their eGFR fell below 12 mL/min/1.73 m2 who were not referred for transplant had modest gains in life expectancy and less time at home. Primary Funding Source: U.S. Department of Veterans Affairs and National Institutes of Health.

Where Are All the Specialists? Current Challenges of Integrating Specialty Care Into Population-Based Total Cost of Care Payment Models

The Centers for Medicare & Medicaid Services Innovation Center (CMMI) has set the goal for 100% of traditional Medicare beneficiaries to be part of an accountable care relationship by 2030. Lack of meaningful financial incentives, intolerable or unpredictable risk, infrastructure costs, patient engagement, voluntary participation, and operational complexity have been noted by the provider and health care delivery community as barriers to participation or reasons for exiting programs. In addition, most piloted and implemented population-based total cost of care (PB-TCOC) payment models have focused on the role of the primary care physician being the accountability (that is, attributable) leader of a patient’s multifaceted care team as well as acting as the mayor of the “medical neighborhood,” leaving the role of specialty care physicians undefined. Successful provider specialist integration into PB-TCOC models includes meaningful participation of specialists in achieving whole-person, high-value care where all providers are financially motivated to participate; there is unambiguous prospective attribution and clearly defined accountability for each participating party throughout the care journey or episode; there is a known care attribution transition accountability plan; there is actionable, transparent, and timely data available with appropriate data development and basic analytic costs covered; and there is advanced payment to the accountable person or entity for management of the care episode that is part of a longitudinal care plan. Payment models should be created to address the 7 challenges raised here if specialists are to be incented to join TCOC models that achieve CMMI’s goal.

Disparities in Tuberculosis Incidence by Race and Ethnicity Among the U.S.-Born Population in the United States, 2011 to 2021: An Analysis of National Disease Registry Data: Annals of Internal Medicine: Vol 177, No 4

Background: Elevated tuberculosis (TB) incidence rates have recently been reported for racial/ethnic minority populations in the United States. Tracking such disparities is important for assessing progress toward national health equity goals and implementing change. Objective: To quantify trends in racial/ethnic disparities in TB incidence among U.S.-born persons. Design: Time-series analysis of national TB registry data for 2011 to 2021. Setting: United States. Participants: U.S.-born persons stratified by race/ethnicity. Measurements: TB incidence rates, incidence rate differences, and incidence rate ratios compared with non-Hispanic White persons; excess TB cases (calculated from incidence rate differences); and the index of disparity. Analyses were stratified by sex and by attribution of TB disease to recent transmission and were adjusted for age, year, and state of residence. Results: In analyses of TB incidence rates for each racial/ethnic population compared with non-Hispanic White persons, incidence rate ratios were as high as 14.2 (95% CI, 13.0 to 15.5) among American Indian or Alaska Native (AI/AN) females. Relative disparities were greater for females, younger persons, and TB attributed to recent transmission. Absolute disparities were greater for males. Excess TB cases in 2011 to 2021 represented 69% (CI, 66% to 71%) and 62% (CI, 60% to 64%) of total cases for females and males, respectively. No evidence was found to indicate that incidence rate ratios decreased over time, and most relative disparity measures showed small, statistically nonsignificant increases. Limitation: Analyses assumed complete TB case diagnosis and self-report of race/ethnicity and were not adjusted for medical comorbidities or social determinants of health. Conclusion: There are persistent disparities in TB incidence by race/ethnicity. Relative disparities were greater for AI/AN persons, females, and younger persons, and absolute disparities were greater for males. Eliminating these disparities could reduce overall TB incidence by more than 60% among the U.S.-born population. Primary Funding Source: Centers for Disease Control and Prevention.

Association Between Autoimmune Diseases and Monoclonal Gammopathy of Undetermined Significance: An Analysis From a Population-Based Screening Study: Annals of Internal Medicine: Vol 177, No 6

Background: Monoclonal gammopathy of undetermined significance (MGUS) is a precursor of multiple myeloma (MM) and related conditions. In previous registry-based, retrospective studies, autoimmune diseases have been associated with MGUS. However, these studies were not based on a screened population and are therefore prone to ascertainment bias. Objective: To examine whether MGUS is associated with autoimmune diseases. Design: A cross-sectional study within iStopMM (Iceland Screens, Treats, or Prevents MM), a prospective, population-based screening study of MGUS. Setting: Icelandic population of adults aged 40 years or older. Patients: 75 422 persons screened for MGUS. Measurements: Poisson regression for prevalence ratios (PRs) of MGUS among persons with or without an autoimmune disease, adjusted for age and sex. Results: A total of 10 818 participants had an autoimmune disorder, of whom 599 had MGUS (61 with a prior clinical diagnosis and 538 diagnosed at study screening or evaluation). A diagnosis of an autoimmune disease was not associated with MGUS (PR, 1.05 [95% CI, 0.97 to 1.15]). However, autoimmune disease diagnoses were associated with a prior clinical diagnosis of MGUS (PR, 2.11 [CI, 1.64 to 2.70]). Limitation: Registry data were used to gather information on autoimmune diseases, and the homogeneity of the Icelandic population may limit the generalizability of these results. Conclusion: The study did not find an association between autoimmune disease and MGUS in a systematically screened population. Previous studies not done in systematically screened populations have likely been subject to ascertainment bias. The findings indicate that recommendations to routinely screen patients with autoimmune disease for MGUS may not be warranted. Primary Funding Source: The International Myeloma Foundation and the European Research Council.

Association of Albuminuria With Chronic Kidney Disease Progression in Persons With Chronic Kidney Disease and Normoalbuminuria: A Cohort Study: Annals of Internal Medicine: Vol 177, No 4

Background: Albuminuria is a major risk factor for chronic kidney disease (CKD) progression, especially when categorized as moderate (30 to 300 mg/g) or severe (>300 mg/g). However, there are limited data on the prognostic value of albuminuria within the normoalbuminuric range (<30 mg/g) in persons with CKD. Objective: To estimate the increase in the cumulative incidence of CKD progression with greater baseline levels of albuminuria among persons with CKD who had normoalbuminuria (<30 mg/g). Design: Multicenter prospective cohort study. Setting: 7 U.S. clinical centers. Participants: 1629 participants meeting criteria from the CRIC (Chronic Renal Insufficiency Cohort) study with CKD (estimated glomerular filtration rate [eGFR], 20 to 70 mL/min/1.73 m2) and urine albumin–creatinine ratio (UACR) less than 30 mg/g. Measurements: Baseline spot urine albumin divided by spot urine creatinine to calculate UACR as the exposure variable. The 10-year adjusted cumulative incidences of CKD progression (composite of 50% eGFR decline or kidney failure [dialysis or kidney transplantation]) from confounder adjusted survival curves using the G-formula. Results: Over a median follow-up of 9.8 years, 182 of 1629 participants experienced CKD progression. The 10-year adjusted cumulative incidences of CKD progression were 8.7% (95% CI, 5.9% to 11.6%), 11.5% (CI, 8.8% to 14.3%), and 19.5% (CI, 15.4% to 23.5%) for UACR levels of 0 to less than 5 mg/g, 5 to less than 15 mg/g, and 15 mg/g or more, respectively. Comparing persons with UACR 15 mg/g or more to those with UACR 5 to less than 15 mg/g and 0 to less than 5 mg/g, the absolute risk differences were 7.9% (CI, 3.0% to 12.7%) and 10.7% (CI, 5.8% to 15.6%), respectively. The 10-year adjusted cumulative incidence increased linearly based on baseline UACR levels. Limitation: UACR was measured once. Conclusion: Persons with CKD and normoalbuminuria (<30 mg/g) had excess risk for CKD progression, which increased in a linear fashion with higher levels of albuminuria. Primary Funding Source: None.

The Management of Posttraumatic Stress Disorder and Acute Stress Disorder: Synopsis of the 2023 U.S. Department of Veterans Affairs and U.S. Department of Defense Clinical Practice Guideline

Description: The U.S. Department of Veterans Affairs (VA) and Department of Defense (DoD) worked together to revise the 2017 VA/DoD Clinical Practice Guideline for the Management of Posttraumatic Stress Disorder and Acute Stress Disorder. This article summarizes the 2023 clinical practice guideline (CPG) and its development process, focusing on assessments and treatments for which evidence was sufficient to support a recommendation for or against. Methods: Subject experts from both departments developed 12 key questions and reviewed the published literature after a systematic search using the PICOTS (population, intervention, comparator, outcomes, timing of outcomes measurement, and setting) method. The evidence was then evaluated using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) method. Recommendations were made after consensus was reached; they were based on quality and strength of evidence and informed by other factors, including feasibility and patient perspectives. Once the draft was peer reviewed by an external group of experts and their inputs were incorporated, the final document was completed. Recommendations: The revised CPG includes 34 recommendations in the following 5 topic areas: assessment and diagnosis, prevention, treatment, treatment of nightmares, and treatment of posttraumatic stress disorder (PTSD) with co-occurring conditions. Six recommendations on PTSD treatment were rated as strong. The CPG recommends use of specific manualized psychotherapies over pharmacotherapy; prolonged exposure, cognitive processing therapy, or eye movement desensitization and reprocessing psychotherapy; paroxetine, sertraline, or venlafaxine; and secure video teleconferencing to deliver recommended psychotherapy when that therapy has been validated for use with video teleconferencing or when other options are unavailable. The CPG also recommends against use of benzodiazepines, cannabis, or cannabis-derived products. Providers are encouraged to use this guideline to support evidence-based, patient-centered care and shared decision making to optimize individuals’ health outcomes and quality of life.

Medication-Induced Weight Change Across Common Antidepressant Treatments: A Target Trial Emulation Study: Annals of Internal Medicine: Vol 177, No 8

Background: Antidepressants are among the most commonly prescribed medications, but evidence on comparative weight change for specific first-line treatments is limited. Objective: To compare weight change across common first-line antidepressant treatments by emulating a target trial. Design: Observational cohort study over 24 months. Setting: Electronic health record (EHR) data from 2010 to 2019 across 8 U.S. health systems. Participants: 183 118 patients. Measurements: Prescription data determined initiation of treatment with sertraline, citalopram, escitalopram, fluoxetine, paroxetine, bupropion, duloxetine, or venlafaxine. The investigators estimated the population-level effects of initiating each treatment, relative to sertraline, on mean weight change (primary) and the probability of gaining at least 5% of baseline weight (secondary) 6 months after initiation. Inverse probability weighting of repeated outcome marginal structural models was used to account for baseline confounding and informative outcome measurement. In secondary analyses, the effects of initiating and adhering to each treatment protocol were estimated. Results: Compared with that for sertraline, estimated 6-month weight gain was higher for escitalopram (difference, 0.41 kg [95% CI, 0.31 to 0.52 kg]), paroxetine (difference, 0.37 kg [CI, 0.20 to 0.54 kg]), duloxetine (difference, 0.34 kg [CI, 0.22 to 0.44 kg]), venlafaxine (difference, 0.17 kg [CI, 0.03 to 0.31 kg]), and citalopram (difference, 0.12 kg [CI, 0.02 to 0.23 kg]); similar for fluoxetine (difference, −0.07 kg [CI, −0.19 to 0.04 kg]); and lower for bupropion (difference, −0.22 kg [CI, −0.33 to −0.12 kg]). Escitalopram, paroxetine, and duloxetine were associated with 10% to 15% higher risk for gaining at least 5% of baseline weight, whereas bupropion was associated with 15% reduced risk. When the effects of initiation and adherence were estimated, associations were stronger but had wider CIs. Six-month adherence ranged from 28% (duloxetine) to 41% (bupropion). Limitation: No data on medication dispensing, low medication adherence, incomplete data on adherence, and incomplete data on weight measures across time points. Conclusion: Small differences in mean weight change were found between 8 first-line antidepressants, with bupropion consistently showing the least weight gain, although adherence to medications over follow-up was low. Clinicians could consider potential weight gain when initiating antidepressant treatment. Primary Funding Source: National Institutes of Health.

Clinical Outcomes With Electronic Nudges to Increase Influenza Vaccination: A Prespecified Analysis of a Nationwide, Pragmatic, Registry-Based, Randomized Implementation Trial: Annals of Internal Medicine: Vol 177, No 4

Background: In the NUDGE-FLU (Nationwide Utilization of Danish Government Electronic letter system for increasing inFLUenza vaccine uptake) trial, electronic letters incorporating cardiovascular (CV) gain-framing and repeated messaging increased influenza vaccination by approximately 1 percentage point. Objective: To evaluate the effects of the successful nudging interventions on downstream clinical outcomes. Design: Prespecified exploratory analysis of a nationwide randomized implementation trial. (ClinicalTrials.gov: NCT05542004) Setting: The 2022 to 2023 influenza season. Participants: 964 870 Danish citizens aged 65 years or older. Intervention: Usual care or 9 different electronically delivered behavioral nudging letters. Measurements: Cardiovascular, respiratory, and other clinical end points during follow-up from intervention delivery (16 September 2022) through 31 May 2023. Results: The analysis set included 691 820 participants. Hospitalization for pneumonia or influenza occurred in 3354 of 346 327 (1.0%) participants in the usual care group, 396 of 38 586 (1.0%) in the CV gain-framing group (hazard ratio [HR], 1.06 [95% CI, 0.95 to 1.18]; versus usual care), and 403 of 38 231 (1.1%) in the repeated letter group (HR, 1.09 [CI, 0.98 to 1.21]; versus usual care). In the usual care group, 44 682 (12.9%) participants were hospitalized for any cause, compared with 5002 (13.0%) in the CV gain-framing group (HR, 1.00 [CI, 0.97 to 1.03]; versus usual care) and 4965 (13.0%) in the repeated letter group (HR, 1.01 [CI, 0.98 to 1.04]; versus usual care). A total of 6341 (1.8%) participants died in the usual care group, compared with 721 (1.9%) in the CV gain-framing group (HR, 1.02 [CI, 0.94 to 1.10]; versus usual care) and 646 (1.7%) in the repeated letter group (HR, 0.92 [CI, 0.85 to 1.00]; versus usual care). Limitation: Prespecified but exploratory analysis, potential misclassification of events in routinely collected registry data, and results may not be generalizable to other health systems or countries with other racial compositions and/or cultural or societal norms. Conclusion: In a prespecified exploratory analysis, modest increases in influenza vaccination rates seen with electronic nudges did not translate into observable improvements in clinical outcomes. Seasonal influenza vaccination should remain strongly recommended. Primary Funding Source: Sanofi.

Long-Term Effect of Salt Substitution for Cardiovascular Outcomes: A Systematic Review and Meta-analysis: Annals of Internal Medicine: Vol 177, No 5

Background: Salt substitution is a simple yet increasingly promising strategy to improve cardiovascular outcomes. Purpose: To evaluate the long-term effects of salt substitution on cardiovascular outcomes. Data Sources: PubMed, EMBASE, Cochrane CENTRAL, and CINAHL searched from inception to 23 August 2023. Trial registries, citation analysis, and hand-search were also done. Study Selection: Randomized controlled trials (RCTs) comparing provision of or advice to use a salt substitute with no intervention or use of regular salt among adults for 6 months or longer in total study duration. Data Extraction: Two authors independently screened articles, extracted data, and assessed risk of bias. Primary outcomes include mortality, major cardiovascular events (MACE), and adverse events at 6 months or greater. Secondary and post hoc outcomes include blood pressure, cause-specific mortality, and urinary excretion at 6 months or greater. Random-effects meta-analyses were done and certainty of effect estimates were assessed using GRADE (Grading of Recommendations Assessment, Development and Evaluation). Data Synthesis: Of the 16 included RCTs, 8 reported on primary outcomes. Most (n = 7 of 8) were done in China or Taiwan, 3 were done in residential facilities, and 7 included populations of older age (average 62 years) and/or with higher-than-average cardiovascular risk. In this population, salt substitute may reduce risk for all-cause mortality (6 RCTs; 27 710 participants; rate ratio [RR], 0.88 [95% CI, 0.82 to 0.93]; low certainty) and cardiovascular mortality (4 RCTs; 25 050 participants; RR, 0.83 [CI, 0.73 to 0.95]; low certainty). Salt substitute may result in a slight reduction in MACE (3 RCTs; 23 215 participants; RR, 0.85 [CI, 0.71 to 1.00]; very low certainty), with very low-certainty evidence of serious adverse events (6 RCTs; 27 995 participants; risk ratio, 1.04 [CI, 0.87 to 1.25]) Limitations: The evidence base is dominated by a single, large RCT. Most RCTs were from China or Taiwan and involved participants with higher-than-average cardiovascular risk; therefore, generalizability to other populations is very limited. Conclusion: Salt substitution may reduce all-cause or cardiovascular mortality, but the evidence for reducing cardiovascular events and for not increasing serious adverse events is uncertain, particularly for a Western population. The certainty of evidence is higher among populations at higher cardiovascular risk and/or following a Chinese diet. Primary Funding Source: National Health and Medical Research Council. (PROSPERO: CRD42022327566)

Submitting Your Work to Annals: Author-Friendly Features