Risks and Benefits of Dolutegravir- and Efavirenz-Based Strategies for South African Women With HIV of Child-Bearing Potential: A Modeling Study: Annals of Internal Medicine: Vol 170, No 9

Background: Dolutegravir is superior to efavirenz for HIV antiretroviral therapy (ART) but may be associated with an increased risk for neural tube defects (NTDs) in newborns if used by women at conception. Objective: To project clinical outcomes of ART policies for women of child-bearing potential in South Africa. Design: Model of 3 strategies: efavirenz for all women of child-bearing potential (EFV), dolutegravir for all women of child-bearing potential (DTG), or World Health Organization (WHO)-recommended efavirenz without contraception or dolutegravir with contraception (WHO approach). Data Sources: Published data on NTD risks (efavirenz, 0.05%; dolutegravir, 0.67% [Tsepamo study]), 48-week ART efficacy with initiation (efavirenz, 60% to 91%; dolutegravir, 96%), and age-stratified fertility rates (2 to 139 per 1000 women). Target Population: 3.1 million South African women with HIV (aged 15 to 49 years) starting or continuing first-line ART, and their children. Time Horizon: 5 years. Perspective: Societal. Intervention: EFV, DTG, and WHO approach. Outcome Measures: Deaths among women and children, sexual and pediatric HIV transmissions, and NTDs. Results of Base-Case Analysis: Compared with EFV, DTG averted 13 700 women's deaths (0.44% decrease) and 57 700 sexual HIV transmissions, but increased total pediatric deaths by 4400 because of more NTDs. The WHO approach offered some benefits compared with EFV, averting 4900 women's deaths and 20 500 sexual transmissions while adding 300 pediatric deaths. Overall, combined deaths among women and children were lowest with DTG (358 000 deaths) compared with the WHO approach (362 800 deaths) or EFV (367 300 deaths). Results of Sensitivity Analysis: Women's deaths averted with DTG exceeded pediatric deaths added with EFV unless dolutegravir-associated NTD risk was 1.5% or greater. Limitation: Uncertainty in NTD risks and dolutegravir efficacy in resource-limited settings, each examined in sensitivity analyses. Conclusion: Although NTD risks may be higher with dolutegravir than efavirenz, dolutegravir will lead to many fewer deaths among women, as well as fewer overall HIV transmissions. These results argue against a uniform policy of avoiding dolutegravir in women of child-bearing potential. Primary Funding Source: National Institutes of Health, National Institute of Allergy and Infectious Diseases and Eunice Kennedy Shriver National Institute of Child Health and Human Development; Massachusetts General Hospital; and Harvard University Center for AIDS Research.

Local Area Variation in Morbidity Among Low-Income, Older Adults in the United States: A Cross-sectional Study: Annals of Internal Medicine: Vol 171, No 7

Background: Recent studies have reported that low-income adults living in more affluent areas of the United States have longer life expectancies. Less is known about the relationship between the affluence of a geographic area and morbidity of the low-income population. Objective: To evaluate the association between the prevalence of chronic conditions among low-income, older adults and the economic affluence of a local area. Design: Cross-sectional association study. Setting: Medicare in 2015. Participants: 6 363 097 Medicare beneficiaries aged 66 to 100 years with a history of low-income support under Medicare Part D. Measurements: Adjusted prevalence of 48 chronic conditions was computed for 736 commuting zones (CZs). Factor analysis was used to assess spatial covariation of condition prevalence and to construct a composite condition prevalence index for each CZ. The association between morbidity and area affluence was measured by comparing the average of condition prevalence index across deciles of median CZ house values. Results: The mean age of study participants was 77.7 years (SD, 8.2); 67% were women, and 61% were white. The crude prevalence of 48 chronic conditions ranged from 72.5 per 100 for hypertension to 0.6 per 100 for posttraumatic stress disorder. The prevalence of these 48 chronic conditions was highly spatially correlated. Composite condition prevalence was on average substantially lower in more affluent CZs. Limitation: Low-income status measured on the basis of receipt of Medicare Part D low-income subsidies and not capturing persons not enrolled in Medicare Part D. Conclusion: Low-income, older adults living in more affluent areas of the country are healthier, and areas with poor health in the low-income, older adult population tend to have a high prevalence of most chronic conditions. Primary Funding Source: National Institute on Aging.

Medicare Spending and the Adequacy of Support With Daily Activities in Community-Living Older Adults With Disability: An Observational Study: Annals of Internal Medicine: Vol 170, No 12

Background: Identifying factors that affect variation in health care spending among older adults with disability may reveal opportunities to better address their care needs while offsetting excess spending. Objective: To quantify differences in total Medicare spending among older adults with disability by whether they experience negative consequences due to inadequate support with household activities, mobility, or self-care. Design: Observational study of in-person interviews and linked Medicare claims. Setting: United States, 2015. Participants: 3716 community-living older adults who participated in the 2015 NHATS (National Health and Aging Trends Study) and survived for 12 months. Measurements: Total Medicare spending by spending quartile in multivariable regression models that adjusted for individual characteristics. Results: Negative consequences were experienced by 18.3% of participants with disability in household activities, 25.6% with mobility disability, and 20.0% with self-care disability. Median Medicare spending was higher for those who experienced negative consequences due to household ($4866 vs. $4095), mobility ($7266 vs. $4115), and self-care ($10 935 vs. $4436) disability versus those who did not. In regression-adjusted analyses, median spending did not differ appreciably for participants who experienced negative consequences in household activities ($338 [95% CI, −$768 to $1444]), but was higher for those with mobility ($2309 [CI, $208 to $4409]) and self-care ($3187 [CI, $432 to $5942]) disability. In the bottom-spending quartile, differences were observed for self-care only ($1460 [CI, $358 to $2561]). No differences were observed in the top quartile. Limitation: This observational study could not establish causality. Conclusion: Inadequate support for mobility and self-care is associated with higher Medicare spending, especially in the middle and lower ends of the spending distribution. Better support for the care needs of older adults with disability could offset some Medicare spending. Primary Funding Source: The Commonwealth Fund.

Should This Woman With Dense Breasts Receive Supplemental Breast Cancer Screening?: Grand Rounds Discussion From Beth Israel Deaconess Medical Center: Annals of Internal Medicine: Vol 169, No 7

Breast cancer will develop in 12% of women during their lifetime and is the second leading cause of cancer death among U.S. women. Mammography is the most commonly used tool to screen for breast cancer. Considerable uncertainty exists regarding the age at which to begin screening and the optimal screening interval. Breast density is a risk factor for breast cancer. In addition, for women with dense breasts, small tumors may be missed on mammography and the sensitivity of screening is diminished. At the time of publication, 35 states had passed laws mandating that breast density be reported in the letters that radiologists send to women with their mammogram results. The mandated language may be challenging for patients to understand, and such reporting may increase worry for women who are told that their risk for breast cancer is higher than average on the basis of breast density alone. The U.S. Preventive Services Task Force and the American College of Radiology (ACR) have each issued guidelines that address breast cancer screening for women with dense breasts. Both organizations found insufficient evidence to recommend for or against magnetic resonance screening, whereas the ACR advises consideration of ultrasonography for supplemental screening. In this Beyond the Guidelines, 2 experts—a radiologist and a general internist—discuss these controversies. In particular, the discussants review the role of supplemental breast cancer screening, including breast ultrasonography or magnetic resonance imaging for women with dense breasts. Finally, the experts offer specific advice for a patient who finds her mammography reports confusing.

Self-reported Physical Health of Women Who Did and Did Not Terminate Pregnancy After Seeking Abortion Services: A Cohort Study: Annals of Internal Medicine: Vol 171, No 4

Background: Research demonstrates worse short-term morbidity and mortality associated with childbirth than with abortion, but little research has examined long-term physical health in women with unwanted pregnancies after abortion versus childbirth. Objective: To examine the physical health of women who seek and receive or are denied abortion. Design: Prospective cohort study. Setting: 30 U.S. abortion facilities from 2008 to 2010. Participants: Of 1132 women seeking abortion who consented to participate, 874 were included in this analysis (328 who had first-trimester abortion, 383 who had second-trimester abortion, and 163 who gave birth). Measurements: Self-reported overall health; chronic abdominal, pelvic, back, and joint pain; chronic headaches or migraines; obesity; asthma; gestational and nongestational hypertension and diabetes; and hyperlipidemia were assessed semiannually for 5 years. Mortality was assessed by using verbal autopsy and public records. Results: No significant differences were observed in self-rated health or chronic pain after first-trimester versus second-trimester abortion. At 5 years, 27% (95% CI, 21% to 34%) of women who gave birth reported fair or poor health compared with 20% (CI, 16% to 24%) of women who had first-trimester abortion and 21% (CI, 18% to 25%) who had second-trimester abortion. Women who gave birth also reported more chronic headaches or migraines and joint pain, but experienced similar levels of other types of chronic pain and obesity. Gestational hypertension was reported by 9.4% of participants who gave birth. Eight of 1132 participants died during follow-up, 2 in the postpartum period. Maternal mortality did not differ statistically by group. Limitation: Self-reported outcome measures, uncertain generalizability, and 41% loss to follow-up at 5 years. Conclusion: Although some argue that abortion is detrimental to women's health, these study data indicate that physical health is no worse in women who sought and underwent abortion than in women who were denied abortion. Indeed, differences emerged suggesting worse health among those who gave birth. Primary Funding Source: An anonymous foundation.

Percutaneous Closure Versus Medical Treatment in Stroke Patients With Patent Foramen Ovale: A Systematic Review and Meta-analysis: Annals of Internal Medicine: Vol 168, No 5

Background: New evidence emerged recently regarding the percutaneous closure of patent foramen ovale (PFO) to prevent recurrent stroke in patients with cryptogenic stroke. Purpose: To compare risks for recurrent cerebrovascular events in adults with PFO and cryptogenic stroke who underwent PFO closure versus those who received medical therapy alone. Data Sources: PubMed, Scopus, and Google Scholar from 1 December 2004 through 14 September 2017; references of eligible studies; relevant scientific session abstracts; and cardiology Web sites. Study Selection: Randomized controlled trials, published in English, that compared PFO closure using a currently available device with medical treatment alone and that reported, at minimum, the rates of stroke or transient ischemic attack (TIA) or of new-onset atrial fibrillation (AF) or atrial flutter (AFL). Data Extraction: 2 investigators independently extracted study data and assessed study quality. Data Synthesis: 4 of 5 trials comparing PFO closure with medical therapy used commercially available devices. These 4 trials, involving 2531 patients, found that PFO closure reduced the risk for the main outcome of stroke or TIA (risk difference [RD], −0.029 [95% CI, −0.050 to −0.007]) and increased the risk for new-onset AF or AFL (RD, 0.033 [CI, 0.012 to 0.054]). The beneficial effect of PFO closure was associated with larger interatrial shunts (P = 0.034). Limitation: Trials were not double-blind, and inclusion criteria were heterogeneous. Conclusion: Compared with medical treatment, PFO closure prevents recurrent stroke and TIA but increases the incidence of AF or AFL in PFO carriers with cryptogenic stroke. Primary Funding Source: Italian Ministry of Education, University and Research (MIUR). (PROSPERO: CRD42017074686)

Accuracy of Cardiovascular Risk Prediction Varies by Neighborhood Socioeconomic Position: A Retrospective Cohort Study: Annals of Internal Medicine: Vol 167, No 7

Background: Inequality in health outcomes in relation to Americans' socioeconomic position is rising. Objective: First, to evaluate the spatial relationship between neighborhood disadvantage and major atherosclerotic cardiovascular disease (ASCVD)–related events; second, to evaluate the relative extent to which neighborhood disadvantage and physiologic risk account for neighborhood-level variation in ASCVD event rates. Design: Observational cohort analysis of geocoded longitudinal electronic health records. Setting: A single academic health center and surrounding neighborhoods in northeastern Ohio. Patients: 109 793 patients from the Cleveland Clinic Health System (CCHS) who had an outpatient lipid panel drawn between 2007 and 2010. The date of the first qualifying lipid panel served as the study baseline. Measurements: Time from baseline to the first occurrence of a major ASCVD event (myocardial infarction, stroke, or cardiovascular death) within 5 years, modeled as a function of a locally derived neighborhood disadvantage index (NDI) and the predicted 5-year ASCVD event rate from the Pooled Cohort Equations Risk Model (PCERM) of the American College of Cardiology and American Heart Association. Outcome data were censored if no CCHS encounters occurred for 2 consecutive years or when state death data were no longer available (that is, from 2014 onward). Results: The PCERM systematically underpredicted ASCVD event risk among patients from disadvantaged communities. Model discrimination was poorer among these patients (concordance index [C], 0.70 [95% CI, 0.67 to 0.74]) than those from the most affluent communities (C, 0.80 [CI, 0.78 to 0.81]). The NDI alone accounted for 32.0% of census tract–level variation in ASCVD event rates, compared with 10.0% accounted for by the PCERM. Limitations: Patients from affluent communities were overrepresented. Outcomes of patients who received treatment for cardiovascular disease at Cleveland Clinic were assumed to be independent of whether the patients came from a disadvantaged or an affluent neighborhood. Conclusion: Neighborhood disadvantage may be a powerful regulator of ASCVD event risk. In addition to supplemental risk models and clinical screening criteria, population-based solutions are needed to ameliorate the deleterious effects of neighborhood disadvantage on health outcomes. Primary Funding Source: The Clinical and Translational Science Collaborative of Cleveland and National Institutes of Health.

The Importance of the Childhood Immunization Schedule for Internal Medicine

Vaporized Nicotine Products for Smoking Cessation Among People Experiencing Social Disadvantage: A Randomized Clinical Trial: Annals of Internal Medicine: Vol 178, No 8

Background: Vaporized nicotine products (VNPs) are more effective than nicotine replacement therapy (NRT) for smoking cessation in general populations, but their effectiveness among low socioeconomic groups is largely unknown. Objective: To examine whether VNPs are more effective than NRT for smoking cessation among people experiencing social disadvantage. Design: Two-group, open-label, randomized trial with blinded outcome ascertainment. (Australian New Zealand Clinical Trials Registry ACTRN12621000076875) Setting: Australia, between March 2021 and December 2022. Participants: 1045 adults who smoked daily, were willing to quit smoking, and were receiving a government pension/allowance (proxy for social disadvantage). Intervention: Participants were randomly assigned (1:1) to either a free 8-week supply of NRT or VNPs, and all participants received text-message support. Measurements: The primary outcome was 6-month continuous smoking abstinence verified using a carbon monoxide breath test at 7-month follow-up. Analysis included randomly assigned participants in accordance with Russell Standard criteria and the intention-to-treat principle. Results: Among 1045 randomly assigned participants, 866 (82.9%) completed final follow-up. The verified 6-month continuous abstinence rate was 9.6% (50 of 523) in the NRT group and 28.4% (148 of 522) in the VNP group (posterior risk difference estimate, 18.7% [95% credible interval, 14.1% to 23.3%]; >99% posterior probability that VNP is superior). Self-reported adverse events occurred less frequently in the VNP group (355 events among 237 participants) compared with the NRT group (442 events among 278 participants; incident rate ratio, 0.75 [95% CI, 0.65 to 0.88]; P < 0.001). Limitations: Biochemical verification method tested short-term exposure to cigarette smoke. Conclusion: Findings indicate that VNPs were more effective than NRT for smoking cessation in this population. Given the challenges for cessation among these socially disadvantaged populations, VNPs present a promising treatment option for this priority group. Primary Funding Source: Australian National Health and Medical Research Council.

Effectiveness of Psychological Therapies for Depression During the Perinatal Period: A Systematic Review and Meta-analysis: Annals of Internal Medicine: Vol 178, No 12

Background: Perinatal depression can have a deleterious impact on mothers and infants. Purpose: To evaluate psychological therapies for perinatal depression. Data Sources: 6 databases from January 2000 to March 2025. Study Selection: Randomized controlled trials (RCTs) of psychological therapies for people with depression during pregnancy and up to 1 year postpartum. Data Extraction: 6 researchers extracted study data and assessed the risk of bias and strength of evidence (SoE). Data Synthesis: Forty-four RCTs were included. Cognitive behavioral therapy (CBT; k = 25, n = 2962) was probably more effective than treatment as usual (TAU) in reducing depressive symptoms by an equivalent −1.7 points (95% CI, −2.0 to −1.3 points) on the Edinburgh Postnatal Depression Scale (EPDS; range, 0 to 30 points) (moderate SoE) and may have greater recovery rates from depressive symptoms (relative risk [RR], 1.7 [CI, 1.3 to 2.3]) (low SoE). Behavioral activation (k = 3, n = 508) may be more effective than TAU in reducing depressive symptoms by an equivalent −1.5 EPDS points (CI, −2.6 to −0.5 points) (low SoE). There may be no differences in depressive symptoms between CBT and counseling (k = 3, n = 226; EPDS, −0.5 [CI, −1.5 to 0.5]) or counseling and TAU (k = 3, n = 247; EPDS, −0.8 [CI, −2.6 to 1.0) (low SoE). Interpersonal therapy (IPT; k = 9, n = 1003) was probably more effective than TAU in reducing depressive symptoms by an equivalent −1.7 EPDS points (CI, −2.9 to −0.5 points) (moderate SoE) and may have greater recovery rates from depressive symptoms (RR, 1.2 [CI, 0.97 to 1.5]) (low SoE). Limitations: Participants were not blinded to treatment, study variation in country, interventions, populations, or reducing SoE. Differences may not be clinically important. Conclusion: For treatment of perinatal depression, CBT, behavioral activation, and IPT may be effective. Primary Funding Source: Agency for Healthcare Research and Quality (AHRQ).