Acute Pain Management in People With Opioid Use Disorder: A Systematic Review: Annals of Internal Medicine: Vol 178, No 4

Background: Guidance on acute pain management among people with opioid use disorder (OUD) is limited. Purpose: To synthesize evidence on the benefits and harms of acute pain interventions among people with OUD. Data Sources: APA PsycArticles, APA PsycInfo, APA PsycExtra, Allied and Complementary Medicine Database, CINAHL, Cochrane Library, Google Scholar, Ovid Embase, Ovid MEDLINE, PubMed, Scopus, and the Web of Science Core Collection through 7 July 2024. Study Selection: Studies of any design that evaluated acute pain interventions among adults with OUD and included pain or OUD outcomes. Data Extraction: Independent dual screening, single-investigator data extraction with verification, and dual quality and strength of evidence assessment. Data Synthesis: Seventeen trials, 20 controlled observational studies, and 78 uncontrolled observational studies met eligibility criteria. Continuing use of buprenorphine during acute pain episodes may be associated with similar or improved pain-related outcomes versus discontinuing, based on cohort studies conducted primarily in perioperative settings. Single well-conducted randomized controlled trials in emergency department (ED) or perioperative settings in adults not prescribed medications for OUD suggest oral clonidine, intramuscular haloperidol and midazolam with intravenous (IV) morphine, and intraoperative IV lidocaine may improve pain outcomes and warrant study in diverse patient populations. Few studies evaluated methadone or the effect of interventions on OUD outcomes. Limitations: Most evidence is observational and at risk of bias due to confounding. All studies were conducted in ED or hospital settings, most before widespread use of high-potency synthetic opioids or among non-U.S. populations using opium. Conclusion: The overall evidence for pain outcomes in people with OUD is low. The effect of pain interventions on OUD outcomes is an important evidence gap. Primary Funding Source: None. (Protocol registered a priori on Open Science Framework [https://osf.io/25hbs])

How Would You Manage This Patient With Obesity? Grand Rounds Discussion From Beth Israel Deaconess Medical Center

In 2022, 1 in 8 people in the world were living with obesity, and lifestyle interventions that include diet, exercise, and behavioral modification have been the foundation for management of obesity. Recently, pharmacologic therapies have been developed for management of obesity, the newest of these being glucagon-like peptide 1 receptor agonists. With the development of new pharmacologic options, the American Gastroenterological Association developed a guideline in 2022 to provide evidence-based recommendations for the pharmacologic management of obesity in adults and recommended, for adults with obesity or overweight with weight-related complications who have had an inadequate response to lifestyle interventions, adding pharmacologic agents to lifestyle interventions over continuing lifestyle interventions alone. In this article, 2 experts review the available evidence to answer the following questions: How effective are lifestyle interventions for the treatment of obesity? How effective are pharmacologic interventions for the treatment of obesity? Given these options, how do you engage in a shared decision-making discussion to develop a mutually agreed-on treatment plan?

The Effect of 4:3 Intermittent Fasting on Weight Loss at 12 Months: A Randomized Clinical Trial: Annals of Internal Medicine: Vol 178, No 5

Background: Long-term (≥12 months) randomized trials evaluating the efficacy of intermittent fasting (IMF) as a dietary weight loss strategy are limited. Furthermore, no studies have compared IMF versus daily caloric restriction (DCR) when both interventions are provided in the context of a guidelines-based behavioral weight loss program. Objective: To compare the effects of 4:3 IMF versus DCR on changes in weight at 12 months, with comprehensive behavioral support provided to both groups. Design: Randomized clinical trial. (ClinicalTrials.gov: NCT03411356) Setting: Denver, Colorado, and surrounding metropolitan area. Participants: Adults aged 18 to 60 years with body mass index (BMI) of 27 to 46 kg/m2. Intervention: The IMF group was instructed to restrict energy intake by 80% on 3 nonconsecutive days per week, with ad libitum intake (no restriction) the other 4 days (4:3 IMF). The DCR group was instructed to reduce daily energy intake by 34% to match the weekly energy deficit of 4:3 IMF. Both groups received a high-intensity comprehensive behavioral weight loss program that included group-based behavioral support and a recommendation to increase moderate-intensity physical activity to 300 minutes per week. Measurements: The primary outcome was change in body weight (in kilograms) at 12 months. Results: Of the 165 (4:3 IMF, n = 84; DCR, n = 81) randomly assigned participants (mean age, 42 years [SD, 9]; mean BMI, 34.1 kg/m2 [SD, 4.4]; 73.9% female), 125 completed the trial. In an intention-to-treat analysis, 4:3 IMF showed greater reductions in weight than DCR at 12 months (mean difference, 2.89 kg [95% CI, 5.65 to 0.14 kg]; P = 0.040). Limitation: Limited generalizability. Conclusion: Compared with DCR, 4:3 IMF resulted in modestly greater weight loss among adults with overweight or obesity enrolled in a 12-month, high-intensity, comprehensive behavioral weight loss program. Primary Funding Source: National Institute of Diabetes and Digestive and Kidney Diseases.

Thyroid Function Reference Intervals by Age, Sex, and Race: A Cross-Sectional Study: Annals of Internal Medicine: Vol 178, No 7

Background: Current clinical practice uses a one-size-fits-all approach to define reference intervals for the results of diagnostic tests about thyroid function. This approach does not recognize subgroup differences according to age, sex, or race. Objective: To identify age-, sex-, and race-specific reference intervals for the common diagnostic tests that measure thyroid function and to examine how these new reference intervals reclassify persons into disease categories when compared with current reference intervals. Design: Cross-sectional analysis. Setting: Data from the U.S. NHANES (National Health and Nutrition Examination Survey) supplemented with data from a multicenter Chinese study. Participants: A nationally representative sample from NHANES aged 20 years or older (n = 8308) supplemented with a Chinese database of routine health checkups from 49 hospitals in 10 provinces aged 18 years or older (n = 314 302). Measurements: The thyroid function reference interval was defined as the interval of diagnostic indicator levels from the 2.5th (lower limit) to the 97.5th (upper limit) percentile by age, sex, and race subgroups. Results: In 8308 NHANES participants, the 97.5th percentile levels of thyroid-stimulating hormone (TSH) increased with age, whereas total triiodothyronine (TT3) levels declined with age and total thyroxine (TT4) levels were stable across different ages. Women had higher TT4 levels, and White participants had higher TSH levels. Using current reference intervals, the prevalence of subclinical hypothyroidism increased from 2.4% for ages 20 to 29 years to 5.9% for ages 70 years and older. In contrast, using age-, sex-, and race-specific reference intervals reclassified 48.5% of persons with subclinical hypothyroidism as normal, especially women and White participants, and reclassified 31.2% of persons with subclinical hyperthyroidism as normal, especially women, Black participants, and Hispanic participants. When compared with the findings from U.S. participants, many of the findings from 314 302 Chinese participants were similar. Limitation: Cross-sectional data; sample size limitations for subgroup. Conclusion: These findings should help establish more accurate reference intervals for thyroid diseases and facilitate development of a consensus about how to define and manage those diseases. Primary Funding Source: National Key Research and Development Program of China and National Natural Science Foundation.

Prevalence of Chronic Medical Conditions Among Medicare Advantage and Traditional Medicare Beneficiaries

Background: The federal government spends billions of dollars per year on payments to Medicare Advantage (MA) plans based, in part, on beneficiaries’ risk scores. Despite this, little is known about the true burden of chronic medical conditions among MA beneficiaries compared with those in fee-for-service (FFS) Medicare. Objective: To determine whether the prevalence of chronic medical conditions is higher among MA compared with FFS beneficiaries. Design: Cross-sectional. Setting: Population based. Participants: Adults aged 65 years or older enrolled in MA or FFS Medicare. Measurements: Using direct physical examination and laboratory data from the National Health and Nutrition Examination Survey (2015 to 2018), we compared the age- and sex-standardized prevalence of obesity, hypertension, hyperlipidemia, diabetes, and chronic kidney disease between MA and FFS beneficiaries. Results: The unweighted study population included 2446 respondents corresponding to a weighted total of 45 426 711 adults (34.4% MA, 65.6% FFS Medicare). The prevalence of obesity (41.1% vs. 40.6%; standardized difference [SDiff], 0.48 percentage points [pp] [95% CI, −5.2 to 6.2 pp]), hypertension (70.9% vs. 71.0%; SDiff, −0.05 pp [CI, −5.8 to 5.7 pp]), hyperlipidemia (79.4% vs. 82.3%; SDiff, −2.86 pp [CI, −7.0 to 1.3 pp]), and chronic kidney disease (19.2% vs. 22.8%; SDiff, −3.48 pp [CI, −9.2 to 2.3 pp]) was not higher among MA beneficiaries compared with FFS beneficiaries. However, the prevalence of diabetes was higher in MA (33.3% vs. 26.3%; SDiff, 7.00 pp [CI, 3.3 to 10.7 pp]). Limitation: Differences in the severity of specific medical conditions between groups could not be assessed. Conclusion: In this nationally representative study from 2015 to 2018, the prevalence of obesity, hypertension, hyperlipidemia, and chronic kidney disease was not higher among MA compared with FFS beneficiaries; however, the prevalence of diabetes was higher among MA beneficiaries. Primary Funding Source: National Heart, Lung, and Blood Institute (NHLBI) and American Heart Association (AHA).

Addressing Missingness in Predictive Models That Use Electronic Health Record Data

Electronic health record (EHR) data are increasingly used to develop prediction models that guide clinical decision making at the point of care. These include algorithms that use high-frequency data, like in sepsis prediction, as well as simpler equations, such as the Pooled Cohort Equations for cardiovascular outcome prediction. Although EHR data used in prediction models are often highly granular and more current than other data, there is systematic and nonsystematic missingness in EHR data as there is with most data. Despite growing use for clinical decisions, algorithms implemented in EHRs are mostly unregulated and are often opaque to the user. Guidelines about the development, validation, implementation, and reporting on clinical prediction models are sparse in their recommendations regarding missing data. This article characterizes missingness in EHR data, summarizes methods for attending to missing data when developing prediction models, makes recommendations about validation and implementation of models in practice when data are missing, and identifies research needs in this field.

Screening for Anal Cancer Among Men Who Have Sex With Men With HIV: Benefits, Harms, and Cost-Effectiveness Analyses

Background: Following the success of the ANCHOR (Anal Cancer–HSIL Outcomes Research) trial, the U.S. Department of Health and Human Services recommends anal cancer screening for high-risk persons, particularly men who have sex with men (MSM) with HIV. Objective: To quantify the cost-effectiveness and benefits versus harms of different anal cancer screening strategies. Design: Microsimulation model. Data Sources: The ANCHOR trial and published literature. Target Population: MSM with HIV. Time Horizon: Lifetime. Perspective: Health care sector. Intervention: Cytology alone and human papillomavirus (HPV) testing (high-risk HPV [hrHPV], HPV16/18, and HPV16), co-testing, and triage options; ages at which to begin screening (≥35, ≥40, or ≥45 years); screening interval (annual, biennial, triennial, or quadrennial). Outcome Measures: Incremental cost-effectiveness ratios (ICERs) of dollars per quality-adjusted life-year (QALY) and the tradeoff of harms (high-resolution anoscopies [HRAs]) versus benefits (cancer cases averted and life-years gained). Results of Base-Case Analysis: Screening initiation at age 35 years or older using cytology dominated initiation at ages 40 and 45 years or older, with ICERs ranging from $87 731 for a quadrennial interval to $350 100 for an annual interval. In the comparative analysis, the following unique strategies were on the cost-effectiveness frontier: quadrennial HPV16, quadrennial HPV16/18, triennial HPV16/18, triennial hrHPV, biennial HPV16/18, biennial hrHPV, annual cytology with hrHPV triage, and annual hrHPV; ICERs ranged from $81 341 to $2 510 847. In the harm-to-benefit analysis, triage options offered the most efficient HRA use. Results of Sensitivity Analysis: ICERs decreased for newly eligible persons. For 35-year-old newly eligible MSM with HIV, ICERs for cytology ranged from $70 750 (quadrennial) to $223 895 (annual). Limitation: Findings are not generalizable to other high-risk populations. Conclusion: Anal cancer screening among MSM with HIV aged 35 years or older is cost-effective, but value-based prioritization of strategies is needed to optimize screening use. Primary Funding Source: National Cancer Institute.

Response of Human Epidermal Growth Factor Receptor 2–Expressing Prostate Cancer to Trastuzumab Deruxtecan

Strategies to Address Racial and Ethnic Disparities in Health and Health Care for Chronic Conditions: An Evidence Map of Research From 2017 to 2024: Annals of Internal Medicine: Vol 178, No 1

Background: Racial and ethnic disparities in health and health care persist in the United States, adversely affecting outcomes in prevention and treatment of chronic conditions among adults. Purpose: To map interventions aimed at reducing racial and ethnic disparities and improving health outcomes in the prevention and treatment of chronic conditions in adults. Data Sources: Searches of MEDLINE, CINAHL, and Scopus from January 2017 to April 2024, supplemented with gray literature. Study Selection: U.S.-based studies of interventions targeting racial and ethnic disparities in adults with chronic conditions. Data Extraction: Information on intervention types, targets, outcomes, study designs, study settings, chronic conditions, and delivery personnel was extracted and categorized. Data Synthesis: Among 174 unique studies, 12 intervention types were identified, with self-management support and patient navigation the most common. Most interventions targeted patient behaviors; few studies addressed disparities directly or focused on underrepresented racial and ethnic marginalized groups. Limitations: The lack of standardized terminology and the underrepresentation of certain racial and ethnic groups limit the evidence base. Although the literature search accurately reflects the current state of the literature, it also limits the body of evidence by excluding health disparities research conducted before January 2017, so significant findings from earlier studies may have been overlooked. Conclusion: The literature highlights diverse interventions targeting health disparities, but few studies evaluated their effectiveness in reducing the health disparities gaps. There is an urgent need for research focused on underrepresented racial and ethnic groups, particularly in promising areas such as patient navigation for cancer and diabetes self-management. Future research should prioritize robust study designs to assess the long-term effect and broader applicability of interventions, thus helping organizations and stakeholders to tailor strategies to community-specific needs. Primary Funding Source: Agency for Healthcare Research and Quality.

Sexual Trauma, Suicide, and Overdose in a National Cohort of Older Veterans

Background: Little is known about the association between military sexual trauma (MST) and risk for suicide-related outcomes later in life. Objective: To determine the association between MST and risk for suicide, overdose, and related mortality among older men and women at specific age landmarks and to investigate whether posttraumatic stress disorder (PTSD) modifies risk. Design: Longitudinal cohort study; baseline in 2012 to 2013, with follow-up through 31 December 2020. Setting: All U.S. Department of Veterans Affairs (VA) medical centers in the United States. Participants: 5 059 526 veterans aged 50 years or older. Measurements: Positive MST screening result, nonfatal suicide attempt, death by suicide, or overdose death. Results: MST was documented for 15.7% of older women and 1.3% of older men. The adjusted cumulative incidence of any suicide attempt was higher for those with MST (men, 18.67%; women, 8.66%) than for those without MST (men, 6.25%; women, 2.92%) at age 90 years. The adjusted risk differences among men and women were 12.41% (95% CI, 11.72% to 13.10%) and 5.74% (CI, 5.22% to 6.26%) for any late-life suicide attempt, 11.92% (CI, 11.27% to 12.57%) and 5.58% (CI, 5.08% to 6.08%) for nonfatal suicide attempt, 0.27% (CI, 0.00% to 0.54%) and 0.15% (CI, 0.00% to 0.30%) for fatal suicide attempt, and 1.05% (CI, 0.79% to 1.31%) and 0.48% (CI, 0.28% to 0.68%) for any drug overdose at age 90 years. MST remained a significant risk factor for any suicide attempt among people with and without PTSD. Limitations: Selection bias, generalizability to non-VA veterans, possible unmeasured confounding, and missingness. Conclusion: Late-life suicide attempt and death by suicide or overdose are associated with prior MST. These findings advance our understanding of the lasting effect of sexual trauma on suicide risk and mortality and suggest that monitoring and treatment of MST-related conditions are vital over the long term. Primary Funding Source: VA Office of Research and Development.