Impact of Social Needs Case Management on Use of Medical and Behavioral Health Services: Secondary Analysis of a Randomized Controlled Trial

Risk for Congenital Anomalies in Children Conceived With Medically Assisted Fertility Treatment: A Population-Based Cohort Study: Annals of Internal Medicine: Vol 176, No 10

Background: More than 2 million children are conceived annually using assisted reproductive technologies (ARTs), with a similar number conceived using ovulation induction and intrauterine insemination (OI/IUI). Previous studies suggest that ART-conceived children are at increased risk for congenital anomalies (CAs). However, the role of underlying infertility in this risk remains unclear, and ART clinical and laboratory practices have changed drastically over time, particularly there has been an increase in intracytoplasmic sperm injection (ICSI) and cryopreservation. Objective: To investigate the role of underlying infertility and fertility treatment on CA risks in the first 2 years of life. Design: Propensity score–weighted population-based cohort study. Setting: New South Wales, Australia. Participants: 851 984 infants (828 099 singletons and 23 885 plural children) delivered between 2009 and 2017. Measurements: Adjusted risk difference (aRD) in CAs of infants conceived through fertility treatment compared with 2 naturally conceived (NC) control groups—those with and without a parental history of infertility (NC-infertile and NC-fertile). Results: The overall incidence of CAs was 459 per 10 000 singleton births and 757 per 10 000 plural births. Compared with NC-fertile singleton control infants (n = 747 018), ART-conceived singleton infants (n = 31 256) had an elevated risk for major genitourinary abnormalities (aRD, 19.0 cases per 10 000 births [95% CI, 2.3 to 35.6]); the risk remained unchanged (aRD, 22 cases per 10 000 births [CI, 4.6 to 39.4]) when compared with NC-infertile singleton control infants (n = 36 251) (that is, after accounting for parental infertility), indicating that ART remained an independent risk. After accounting for parental infertility, ICSI in couples without male infertility was associated with an increased risk for major genitourinary abnormalities (aRD, 47.8 cases per 10 000 singleton births [CI, 12.6 to 83.1]). There was some suggestion of increased risk for CAs after fresh embryo transfer, although estimates were imprecise and inconsistent. There were no increased risks for CAs among OI/IUI-conceived infants (n = 13 574). Limitations: This study measured the risk for CAs only in those children who were born at or after 20 weeks' gestation. Observational study design precludes causal inference. Many estimates were imprecise. Conclusion: Patients should be counseled on the small increased risk for genitourinary abnormalities after ART, particularly after ICSI, which should be avoided in couples without problems of male infertility. Primary Funding Source: Australian National Health and Medical Research Council.

Gabapentinoids and Risk for Severe Exacerbation in Chronic Obstructive Pulmonary Disease: A Population-Based Cohort Study: Annals of Internal Medicine: Vol 177, No 2

Background: North American and European health agencies recently warned of severe breathing problems associated with gabapentinoids, including in patients with chronic obstructive pulmonary disease (COPD), although supporting evidence is limited. Objective: To assess whether gabapentinoid use is associated with severe exacerbation in patients with COPD. Design: Time-conditional propensity score–matched, new-user cohort study. Setting: Health insurance databases from the Régie de l’assurance maladie du Québec in Canada. Patients: Within a base cohort of patients with COPD between 1994 and 2015, patients initiating gabapentinoid therapy with an indication (epilepsy, neuropathic pain, or other chronic pain) were matched 1:1 with nonusers on COPD duration, indication for gabapentinoids, age, sex, calendar year, and time-conditional propensity score. Measurements: The primary outcome was severe COPD exacerbation requiring hospitalization. Hazard ratios (HRs) associated with gabapentinoid use were estimated in subcohorts according to gabapentinoid indication and in the overall cohort. Results: The cohort included 356 gabapentinoid users with epilepsy, 9411 with neuropathic pain, and 3737 with other chronic pain, matched 1:1 to nonusers. Compared with nonuse, gabapentinoid use was associated with increased risk for severe COPD exacerbation across the indications of epilepsy (HR, 1.58 [95% CI, 1.08 to 2.30]), neuropathic pain (HR, 1.35 [CI, 1.24 to 1.48]), and other chronic pain (HR, 1.49 [CI, 1.27 to 1.73]) and overall (HR, 1.39 [CI, 1.29 to 1.50]). Limitation: Residual confounding, including from lack of smoking information. Conclusion: In patients with COPD, gabapentinoid use was associated with increased risk for severe exacerbation. This study supports the warnings from regulatory agencies and highlights the importance of considering this potential risk when prescribing gabapentin and pregabalin to patients with COPD. Primary Funding Source: Canadian Institutes of Health Research and Canadian Lung Association.

A Call for a National Policy of Scheduled Dialysis and Transplantation for All People With Kidney Failure Living in the United States

Inappropriate Prescribing to Older Patients by Nurse Practitioners and Primary Care Physicians

Background: Many U.S. states have legislated to allow nurse practitioners (NPs) to independently prescribe drugs. Critics contend that these moves will adversely affect quality of care. Objective: To compare rates of inappropriate prescribing among NPs and primary care physicians. Design: Rates of inappropriate prescribing were calculated and compared for 23 669 NPs and 50 060 primary care physicians who wrote prescriptions for 100 or more patients per year, with adjustment for practice experience, patient volume and risk, clinical setting, year, and state. Setting: 29 states that had granted NPs prescriptive authority by 2019. Patients: Medicare Part D beneficiaries aged 65 years or older in 2013 to 2019. Measurements: Inappropriate prescriptions, defined as drugs that typically should not be prescribed for adults aged 65 years or older, according to the American Geriatrics Society’s Beers Criteria. Results: Mean rates of inappropriate prescribing by NPs and primary care physicians were virtually identical (adjusted odds ratio, 0.99 [95% CI, 0.97 to 1.01]; crude rates, 1.63 vs. 1.69 per 100 prescriptions; adjusted rates, 1.66 vs. 1.68). However, NPs were overrepresented among clinicians with the highest and lowest rates of inappropriate prescribing. For both types of practitioners, discrepancies in inappropriate prescribing rates across states tended to be larger than discrepancies between these practitioners within states. Limitation: The Beers Criteria addresses the appropriateness of a selected subset of drugs and may not be valid in some clinical settings. Conclusion: Nurse practitioners were no more likely than physicians to prescribe inappropriately to older patients. Broad efforts to improve the performance of all clinicians who prescribe may be more effective than limiting independent prescriptive authority to physicians. Primary Funding Source: The Robert Wood Johnson Foundation and National Science Foundation.

Hunger and the Obesity Epidemic: Old Insights Reaffirmed by New Medicines?

Comparative Effectiveness of Sodium–Glucose Cotransporter-2 Inhibitors for Recurrent Gout Flares and Gout-Primary Emergency Department Visits and Hospitalizations: A General Population Cohort Study: Annals of Internal Medicine: Vol 176, No 8

Background: Sodium–glucose cotransporter-2 inhibitors (SGLT2is) decrease serum urate levels, but whether this translates into prevention of recurrent flares among patients with gout and gout-primary emergency department (ED) visits or hospitalizations is unknown. Objective: To compare gout flares and cardiovascular events among patients with gout initiating SGLT2is versus dipeptidyl peptidase 4 inhibitors (DPP-4is), another second-line glucose-lowering agent not associated with serum urate levels or cardiovascular risk. Design: Propensity score–matched, new-user cohort study. Setting: General population database from 1 January 2014 to 30 June 2022. Participants: Patients with gout and type 2 diabetes. Measurements: The primary outcome was recurrent gout flare counts ascertained by ED, hospitalization, outpatient, and medication dispensing records. Secondary outcomes included myocardial infarction and stroke; genital infection (positive control) and osteoarthritis encounter (negative control) were also assessed. Poisson and Cox proportional hazards regressions were used with 1:1 propensity score matching (primary analysis) and overlap weighting (sensitivity analysis). Results: After propensity score matching, the flare rate was lower among SGLT2i initiators than DPP-4i initiators (52.4 and 79.7 events per 1000 person-years, respectively), with a rate ratio (RR) of 0.66 (95% CI, 0.57 to 0.75) and a rate difference (RD) of −27.4 (CI, −36.0 to −18.7) per 1000 person-years. The corresponding RR and RD for gout-primary ED visits and hospitalizations were 0.52 (CI, 0.32 to 0.84) and −3.4 (CI, −5.8 to −0.9) per 1000 person-years, respectively. The corresponding hazard ratio (HR) and RD for myocardial infarction were 0.69 (CI, 0.54 to 0.88) and −7.6 (CI, −12.4 to −2.8) per 1000 person-years; the HR for stroke was 0.81 (CI, 0.62 to 1.05). Those who initiated SGLT2is showed higher risk for genital infection (HR, 2.15 [CI, 1.39 to 3.30]) and no altered risk for osteoarthritis encounter (HR, 1.07 [CI, 0.95 to 1.20]). Results were similar when propensity score overlap weighting was applied. Limitation: Participants had concurrent type 2 diabetes. Conclusion: Among patients with gout, SGLT2is may reduce recurrent flares and gout-primary ED visits and hospitalizations and may provide cardiovascular benefits. Primary Funding Source: National Institute of Arthritis and Musculoskeletal and Skin Diseases.

Clinical Characteristics and Outcomes Among Travelers With Severe Dengue: A GeoSentinel Analysis: Annals of Internal Medicine: Vol 176, No 7

Background: Dengue virus is a flavivirus transmitted by Aedes mosquitoes and is an important cause of illness worldwide. Data on the severity of travel-associated dengue illness are limited. Objective: To describe the epidemiology, clinical characteristics, and outcomes among international travelers with severe dengue or dengue with warning signs as defined by the 2009 World Health Organization classification (that is, complicated dengue). Design: Retrospective chart review and analysis of travelers with complicated dengue reported to GeoSentinel from January 2007 through July 2022. Setting: 20 of 71 international GeoSentinel sites. Patients: Returning travelers with complicated dengue. Measurements: Routinely collected surveillance data plus chart review with abstraction of clinical information using predefined grading criteria to characterize the manifestations of complicated dengue. Results: Of 5958 patients with dengue, 95 (2%) had complicated dengue. Eighty-six (91%) patients had a supplemental questionnaire completed. Eighty-five of 86 (99%) patients had warning signs, and 27 (31%) were classified as severe. Median age was 34 years (range, 8 to 91 years); 48 (56%) were female. Patients acquired dengue most frequently in the Caribbean (n = 27 [31%]) and Southeast Asia (n = 20 [23%]). Frequent reasons for travel were tourism (45%) and visiting friends and relatives (30%). Twenty-one of 84 (25%) patients had comorbidities. Seventy-eight (91%) patients were hospitalized. One patient died of nondengue-related illnesses. Common laboratory findings and signs were thrombocytopenia (78%), elevated aminotransferase (62%), bleeding (52%), and plasma leakage (20%). Among severe cases, ophthalmologic pathology (n = 3), severe liver disease (n = 3), myocarditis (n = 2), and neurologic symptoms (n = 2) were reported. Of 44 patients with serologic data, 32 confirmed cases were classified as primary dengue (IgM+/IgG−) and 12 as secondary (IgM−/IgG+) dengue. Limitations: Data for some variables could not be retrieved by chart review for some patients. The generalizability of our observations may be limited. Conclusion: Complicated dengue is relatively rare in travelers. Clinicians should monitor patients with dengue closely for warning signs that may indicate progression to severe disease. Risk factors for developing complications of dengue in travelers need further prospective study. Primary Funding Source: Centers for Disease Control and Prevention, International Society of Travel Medicine, Public Health Agency of Canada, and GeoSentinel Foundation.

Disparities in Guideline-Recommended Statin Use for Prevention of Atherosclerotic Cardiovascular Disease by Race, Ethnicity, and Gender: A Nationally Representative Cross-Sectional Analysis of Adults in the United States: Annals of Internal Medicine: Vol 176, No 8

Background: Although statins are a class I recommendation for prevention of atherosclerotic cardiovascular disease and its complications, their use is suboptimal. Differential underuse may mediate disparities in cardiovascular health for systematically marginalized persons. Objective: To estimate disparities in statin use by race–ethnicity–gender and to determine whether these potential disparities are explained by medical appropriateness of therapy and structural factors. Design: Cross-sectional analysis. Setting: National Health and Nutrition Examination Survey from 2015 to 2020. Participants: Persons eligible for statin therapy based on 2013 and 2018 American College of Cardiology/American Heart Association blood cholesterol guidelines. Measurements: The independent variable was race–ethnicity–gender. The outcome of interest was use of a statin. Using the Institute of Medicine framework for examining unequal treatment, we calculated adjusted prevalence ratios (aPRs) to estimate disparities in statin use adjusted for age, disease severity, access to health care, and socioeconomic status relative to non-Hispanic White men. Results: For primary prevention, we identified a lower prevalence of statin use that was not explained by measurable differences in disease severity or structural factors among non-Hispanic Black men (aPR, 0.73 [95% CI, 0.59 to 0.88]) and non-Mexican Hispanic women (aPR, 0.74 [CI, 0.53 to 0.95]). For secondary prevention, we identified a lower prevalence of statin use that was not explained by measurable differences in disease severity or structural factors for non-Hispanic Black men (aPR, 0.81 [CI, 0.64 to 0.97]), other/multiracial men (aPR, 0.58 [CI, 0.20 to 0.97]), Mexican American women (aPR, 0.36 [CI, 0.10 to 0.61]), non-Mexican Hispanic women (aPR, 0.57 [CI, 0.33 to 0.82), non-Hispanic White women (aPR, 0.69 [CI, 0.56 to 0.83]), and non-Hispanic Black women (aPR, 0.75 [CI, 0.57 to 0.92]). Limitation: Cross-sectional data; lack of geographic, language, or statin-dose data. Conclusion: Statin use disparities for several race–ethnicity–gender groups are not explained by measurable differences in medical appropriateness of therapy, access to health care, and socioeconomic status. These residual disparities may be partially mediated by unobserved processes that contribute to health inequity, including bias, stereotyping, and mistrust. Primary Funding Source: National Institutes of Health.

Association Between Vascular 18F-Fluorodeoxyglucose Uptake at Diagnosis and Change in Aortic Dimensions in Giant Cell Arteritis: A Cohort Study: Annals of Internal Medicine: Vol 176, No 10

Background: Previous studies have shown that patients with giant cell arteritis (GCA) who have vascular 18F-fluorodeoxyglucose (FDG) uptake at diagnosis are at increased risk for thoracic aortic complications. Objective: To measure the association between vascular FDG uptake at diagnosis and the change in aortic dimensions. Design: Prospective cohort study. Setting: University Hospitals Leuven. Patients: 106 patients with GCA and FDG positron emission tomography (PET) imaging 3 days or less after initiation of glucocorticoids. Measurements: Patients had PET and computed tomography (CT) imaging at diagnosis and CT imaging yearly for a maximum of 10 years. The PET scans were scored 0 to 3 in 7 vascular areas and summed to a total vascular score (TVS). The PET scan results were positive when FDG uptake was grade 2 or greater in any large vessel. The association between vascular FDG uptake and aortic dimensions was estimated by linear mixed-effects models with random intercept and slope. Results: When compared with patients with a negative PET scan result, those with a positive scan result had a greater increase in the diameter of the ascending aorta (difference in 5-year progression, 1.58 mm [95% CI, 0.41 to 2.74 mm]), the diameter of the descending aorta (1.32 mm [CI, 0.38 to 2.26 mm]), and the volume of the thoracic aorta (20.5 cm³ [CI, 4.5 to 36.5 cm³]). These thoracic aortic dimensions were also positively associated with TVS. Patients with a positive PET scan result had a higher risk for thoracic aortic aneurysms (adjusted hazard ratio, 10.21 [CI, 1.25 to 83.3]). Limitation: The lengthy inclusion and follow-up period resulted in missing data and the use of different PET machines. Conclusion: Higher TVS was associated with greater yearly increase in thoracic aortic dimensions. Performing PET imaging at diagnosis may help to estimate the risk for aortic aneurysm formation. Primary Funding Source: None.