Faculty Bibliography

IMPORTANCE:Adolescents and young people have been historically understudied populations, and previous studies indicate that during epidemics, these populations, especially in low- and middle-income countries (LMICs), are at high risk of developing mental disturbances. OBJECTIVE:To identify the existing evidence regarding the association of mental health with outbreaks of the influenza A (H1N1), Zika, Ebola, and SARS-CoV-2 virus in exposed youth and adolescents in LMICs. EVIDENCE REVIEW:Across 6 databases (Embase, Cochrane Library, PubMed, PsycINFO, Scopus, and Web of Science), the mental health outcomes of adolescents and youth (aged 10-24 years) associated with 4 major pandemic outbreaks from January 2009 to January 2021 in LMICs were reviewed. A group of 3 authors at each stage carried out the screening, selection, and quality assessment using Joanna Briggs Institute checklists. The social determinants of adolescent well-being framework was used as a guide to organizing the review. FINDINGS:A total of 57 studies fulfilled the search criteria, 55 related to the SARS-CoV-2 (COVID-19) pandemic and 2 covered the H1N1 influenza epidemics. There were no studies associated with Zika or Ebola outbreaks that met screening criteria. The studies reported high rates of anxiety and depressive symptoms among adolescents, including posttraumatic stress disorder, general stress, and health-related anxiety. Potential risk factors associated with poor mental health outcomes included female sex; home residence in areas with strict lockdown limitations on social and physical movement; reduced physical activity; poor parental, family, or social support; previous exposure to COVID-19 infection; or being part of an already vulnerable group (eg, previous psychiatric conditions, childhood trauma, or HIV infection). CONCLUSIONS AND RELEVANCE:Results of this systematic scoping review suggest that the COVID-19 pandemic and H1N1 epidemic were associated with adverse mental health among adolescents and youth from LMICs. Vulnerable youth and adolescents may be at higher risk of developing mental health-related complications, requiring more responsive interventions and further research. Geographically localized disease outbreaks such as Ebola, Zika, and H1N1 influenza are highly understudied and warrant future investigation.

Background Angiotensin receptor neprilysin inhibitors (ARNI) reduce mortality and hospitalization for patients with heart failure. However, relatively high copayments for ARNI may contribute to suboptimal adherence, thus potentially limiting their benefits. Methods and Results We conducted a retrospective cohort study within a large, multi-site health system. We included patients with: ARNI prescription between November 20, 2020 and June 30, 2021; diagnosis of heart failure or left ventricular ejection fraction ≤40%; and available pharmacy or pharmacy benefit manager copayment data. The primary exposure was copayment, categorized as $0, $0.01 to $10, $10.01 to $100, and >$100. The primary outcome was prescription fill nonadherence, defined as the proportion of days covered <80% over 6 months. We assessed the association between copayment and nonadherence using multivariable logistic regression, and nonbinarized proportion of days covered using multivariable Poisson regression, adjusting for demographic, clinical, and neighborhood-level covariates. A total of 921 patients met inclusion criteria, with 192 (20.8%) having $0 copayment, 228 (24.8%) with $0.01 to $10 copayment, 206 (22.4%) with $10.01 to $100, and 295 (32.0%) with >$100. Patients with higher copayments had higher rates of nonadherence, ranging from 17.2% for $0 copayment to 34.2% for copayment >$100 (P<0.001). After multivariable adjustment, odds of nonadherence were significantly higher for copayment of $10.01 to $100 (odds ratio [OR], 1.93 [95% CI, 1.15-3.27], P=0.01) or >$100 (OR, 2.58 [95% CI, 1.63-4.18], P<0.001), as compared with $0 copayment. Similar associations were seen when assessing proportion of days covered as a proportion. Conclusions We found higher rates of not filling ARNI prescriptions among patients with higher copayments, which persisted after multivariable adjustment. Our findings support future studies to assess whether reducing copayments can increase adherence to ARNI and improve outcomes for heart failure.

OBJECTIVE:A previous study of a reading aloud intervention in Brazil, called Universidade do Bebê (UBB), demonstrated impacts on parenting and child outcomes for families with toddlers and preschoolers, even for parents with low literacy, and cognitive stimulation mediated effects on child outcomes. In a new study, we sought to determine whether similar results would be found when UBB was provided beginning in pregnancy through early toddlerhood, including (1) impacts on parenting and child development, (2) variation in impact on parenting and child outcomes by parent literacy level, and (3) indirect impacts on child outcomes through cognitive stimulation. METHOD/METHODS:Women with low income who were either pregnant or with children aged 0 to 24 months were randomized to UBB or control groups. UBB consisted of monthly workshops focused on reading aloud complemented by a book-lending library. Participants were evaluated at baseline and approximately 11 months later (M = 11.0, SD = 0.4; range 9.9-12.2 months) on parenting (cognitive stimulation, beliefs about early reading, screen time, and discipline) and child development. RESULTS:Four hundred families (n = 200 UBB) were randomized; 286 (71.5%; n = 150 UBB) received 11-month follow-up. UBB families showed increased cognitive stimulation (Cohen's d = 0.92) and awareness about the importance of early reading (d = 0.90) than controls, with no differences by parent literacy level. UBB was associated with reduced screen time and increased vocabulary, but only for families with low parent literacy. UBB effects on child outcomes were mediated by cognitive stimulation. CONCLUSION/CONCLUSIONS:The findings support implementation of reading aloud programs beginning in pregnancy and early childhood.

OBJECTIVE:To characterize and compare glucose-lowering medication use in type 2 diabetes in the U.S., Sweden, and Israel, including adoption of newer medications and prescribing patterns. RESEARCH DESIGN AND METHODS/METHODS:We used data from the National Health and Nutrition Examination Survey (NHANES) from the U.S., the Stockholm CREAtinine Measurements (SCREAM) project from Sweden, and Maccabi Healthcare Services (Maccabi) from Israel. Specific pharmacotherapy for type 2 diabetes between 2007 and 2018 was examined. RESULTS:Use of glucose-lowering medications among patients with type 2 diabetes was substantially lower in NHANES and SCREAM than in Maccabi (66.0% in NHANES, 68.4% in SCREAM, and 88.1% in Maccabi in 2017-2018). Among patients who took at least one glucose-lowering medication in 2017-2018, metformin use was also lower in NHANES and SCREAM (74.1% in NHANES, 75.9% in SCREAM, and 92.6% in Maccabi) whereas sulfonylureas use was greater in NHANES (31.5% in NHANES, 16.0% in SCREAM, and 14.9% in Maccabi). Adoption of dipeptidyl peptidase 4 inhibitors and sodium-glucose cotransporter 2 inhibitors (SGLT2i) was slower in NHANES and SCREAM than in Maccabi. History of atherosclerotic cardiovascular disease, heart failure, reduced kidney function, or albuminuria was not consistently associated with greater use of SGLT2i or glucagon-like peptide 1 receptor agonists (GLP1RA) across the three countries. CONCLUSIONS:There were substantial differences in real-world use of glucose-lowering medications across the U.S., Sweden, and Israel, with more optimal pharmacologic management in Israel. Variation in access to care and medication cost across countries may have contributed to these differences. SGLT2i and GLP1RA use in patients at high risk was limited in all three countries during this time period.

BACKGROUND:Spectral-domain (SD-) optical coherence tomography (OCT) can reliably measure axonal (peripapillary retinal nerve fiber layer [pRNFL]) and neuronal (macular ganglion cell + inner plexiform layer [GCIPL]) thinning in the retina. Measurements from 2 commonly used SD-OCT devices are often pooled together in multiple sclerosis (MS) studies and clinical trials despite software and segmentation algorithm differences; however, individual pRNFL and GCIPL thickness measurements are not interchangeable between devices. In some circumstances, such as in the absence of a consistent OCT segmentation algorithm across platforms, a conversion equation to transform measurements between devices may be useful to facilitate pooling of data. The availability of normative data for SD-OCT measurements is limited by the lack of a large representative world-wide sample across various ages and ethnicities. Larger international studies that evaluate the effects of age, sex, and race/ethnicity on SD-OCT measurements in healthy control participants are needed to provide normative values that reflect these demographic subgroups to provide comparisons to MS retinal degeneration. METHODS:Participants were part of an 11-site collaboration within the International Multiple Sclerosis Visual System (IMSVISUAL) consortium. SD-OCT was performed by a trained technician for healthy control subjects using Spectralis or Cirrus SD-OCT devices. Peripapillary pRNFL and GCIPL thicknesses were measured on one or both devices. Automated segmentation protocols, in conjunction with manual inspection and correction of lines delineating retinal layers, were used. A conversion equation was developed using structural equation modeling, accounting for clustering, with healthy control data from one site where participants were scanned on both devices on the same day. Normative values were evaluated, with the entire cohort, for pRNFL and GCIPL thicknesses for each decade of age, by sex, and across racial groups using generalized estimating equation (GEE) models, accounting for clustering and adjusting for within-patient, intereye correlations. Change-point analyses were performed to determine at what age pRNFL and GCIPL thicknesses exhibit accelerated rates of decline. RESULTS:The healthy control cohort (n = 546) was 54% male and had a wide distribution of ages, ranging from 18 to 87 years, with a mean (SD) age of 39.3 (14.6) years. Based on 346 control participants at a single site, the conversion equation for pRNFL was Cirrus = -5.0 + (1.0 × Spectralis global value). Based on 228 controls, the equation for GCIPL was Cirrus = -4.5 + (0.9 × Spectralis global value). Standard error was 0.02 for both equations. After the age of 40 years, there was a decline of -2.4 μm per decade in pRNFL thickness ( P < 0.001, GEE models adjusting for sex, race, and country) and -1.4 μm per decade in GCIPL thickness ( P < 0.001). There was a small difference in pRNFL thickness based on sex, with female participants having slightly higher thickness (2.6 μm, P = 0.003). There was no association between GCIPL thickness and sex. Likewise, there was no association between race/ethnicity and pRNFL or GCIPL thicknesses. CONCLUSIONS:A conversion factor may be required when using data that are derived between different SD-OCT platforms in clinical trials and observational studies; this is particularly true for smaller cross-sectional studies or when a consistent segmentation algorithm is not available. The above conversion equations can be used when pooling data from Spectralis and Cirrus SD-OCT devices for pRNFL and GCIPL thicknesses. A faster decline in retinal thickness may occur after the age of 40 years, even in the absence of significant differences across racial groups.

BACKGROUND:Despite concerns about increasing trends in depression over the past two decades, little is known about recent trends in depression and mental health (MH) treatment among older adults and whether these trends differ by demographic characteristics. METHODS:We examined data from a US representative sample of noninstitutionalized adults aged ≥65 from the 2010-2019 National Survey on Drug Use and Health (N = 31,502). We estimated trends in the prevalence of past-year major depressive episode (MDE) overall and by demographic characteristics. We also estimated trends in MH treatment among those with past-year MDE. RESULTS:From 2010/11 to 2018/19, the estimated prevalence of past-year MDE among older adults increased from 2.0 % (95 % CI: 1.6-2.6) to 3.2 % (95 % CI: 2.7 to 3.7), a 60.0 % increase (p = 0.013). Increases were detected among men (p = 0.038), White individuals (p = 0.018), those who are widowed (p = 0.003), those with an annual household income of <$20,000 (p = 0.020) or $20,000-$49,000 (p = 0.016), and those with some college degree (p = 0.014). Among those with MDE, there were no significant changes detected in any form of past-year MH treatment. LIMITATIONS/CONCLUSIONS:NSDUH does not assess individuals who are institutionalized, incarcerated, or experiencing homelessness, and thus the prevalence of MDE may be underestimated. CONCLUSIONS:Although the estimated prevalence of depression is increasing among older adults, there has not been a proportional increase in MH treatment among those with depression. These findings call for urgent expansion of treatment services and training of MH professionals with expertise in older adults to meet the needs of this growing, vulnerable population.

Androgen deprivation therapy (ADT) has been hypothesized to protect against COVID-19, but previous observational studies of men with prostate cancer on ADT have been inconsistent regarding mortality risk from coronavirus disease 2019 (COVID-19). Using data from the Prostate Cancer data Base Sweden (PCBaSe), we identified a cohort of 114 547 men with prevalent prostate cancer on the start of follow-up in February 2020, and followed them until 16 December 2020 to evaluate the association between ADT and time to test positive for COVID-19. Among men testing positive for COVID-19, we used regression analyses to estimate the association between ADT and risk of COVID-19-related hospital admission/death from any cause within 30 days of the positive test. In total, 1695 men with prostate cancer tested positive for COVID-19. In crude analyses, exposure to ADT was associated with a 3-fold increased risk of both testing positive for COVID-19 infection and subsequent hospital admission/death. Adjustment for age, comorbidity and prostate cancer risk category substantially attenuated the associations: HR 1.3 (95% CI: 1.1-1.5) for testing positive for COVID-19, and OR 1.4 (95% CI: 1.0-1.9) for risk of subsequent hospital admission/death. In conclusion, although these results suggest increased risks of a positive COVID-19 test, and COVID-19-related hospital admission/death in men on ADT, these findings are likely explained by confounding by old age, cancer-associated morbidity and other comorbidities being more prevalent in men on ADT, rather than a direct effect of the therapy.