Faculty Bibliography

BACKGROUND:Oppositional Defiant Disorders (ODDs) and other Disruptive Behavior Disorders (DBDs) are common among children and adolescents in poverty-impacted communities in sub-Saharan Africa. Without early intervention, its progression into adulthood can result in dire consequences. We examined the impact of a manualized family strengthening intervention called Amaka Amasanyufu designed to reduce ODDs and other DBDs among school-going children residing in low-resource communities in Uganda. METHODS:We used longitudinal data from the SMART Africa-Uganda study (2016-2022). Public primary schools were randomized to: (1) Control condition (receiving usual care comprising generalized psychosocial functioning literature), 10 schools; (2) intervention delivered via parent peers (Amaka-parents), 8 schools or; (3) intervention delivered via community healthcare workers (Amaka-community), 8 schools. All the participants were blinded. At baseline, 8- and 16-weeks postintervention initiation, caregivers completed the Iowa Conners Scale, which measured Oppositional Defiant Disorder (ODD) and Impairment Rating Scale to evaluate children's overall impairment and impaired functioning with peers, siblings, and parents; impaired academic progress, self-esteem, and family functioning. Three-level linear mixed-effects models were fitted to each outcome. Pairwise comparisons of postbaseline group means within each time point were performed using Sidak's adjustment for multiple comparisons. Only children positive for ODD and other DBDs were analyzed. RESULTS:Six hundred and thirty-six children screened positive for ODDs and other DBDs (Controls: n = 243; Amaka-parents: n = 194; Amaka-community: n = 199). At 8 weeks, Amaka-parents' children had significantly lower mean scores for overall impairment compared to controls, (mean difference: -0.71, p = .001), while Amaka-community children performed better on ODD (mean difference: -0.84, p = .016). At 16 weeks, children in both groups were performing better on ODD and IRS than controls, and there were no significant differences between the two intervention groups. CONCLUSIONS:The Amaka Amasanyufu intervention was efficacious in reducing ODD and impaired functioning relative to usual care. Hence, the Amaka Amasanyufu intervention delivered either by Amaka-community or Amaka-parents has the potential to reduce negative behavioral health outcomes among young people in resource-limited settings and improve family functioning. TRIAL REGISTRATION/BACKGROUND:ClinicalTrials.gov, ID: NCT03081195. Registered on 16 March 2017.

BACKGROUND:Patients with prostate cancer suffer significant sexual dysfunction after treatment which negatively affects them and their partners psychologically, and strain their relationships. AIM/OBJECTIVE:We convened an international panel with the aim of developing guidelines that will inform clinicians, patients and partners about the impact of prostate cancer therapies (PCT) on patients' and partners' sexual health, their relationships, and about biopsychosocial rehabilitation in prostate cancer (PC) survivorship. METHODS:The guidelines panel included international expert researchers and clinicians, and a guideline methodologist. A systematic review of the literature, using the Ovid MEDLINE, Scopus, CINAHL, PsychINFO, LGBT Life, and Embase databases was conducted (1995-2022) according to the Cochrane Handbook for Systematic Reviews of Interventions. Study selection was based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Each statement was assigned an evidence strength (A-C) and a recommendation level (strong, moderate, conditional) based on benefit/risk assessment. Data synthesis included meta-analyses of studies deemed of sufficient quality (3), using A Measurement Tool to Assess Systematic Reviews (AMSTAR). OUTCOMES/RESULTS:Guidelines for sexual health care for patients with prostate cancer were developed, based on available evidence and the expertise of the international panel. RESULTS:The guidelines account for patients' cultural, ethnic, and racial diversity. They attend to the unique needs of individuals with diverse sexual orientations and gender identities. The guidelines are based on literature review, a theoretical model of sexual recovery after PCT, and 6 principles that promote clinician-initiated discussion of realistic expectations of sexual outcomes and mitigation of sexual side-effects through biopsychosocial rehabilitation. Forty-seven statements address the psychosexual, relationship, and functional domains in addition to statements on lifestyle modification, assessment, provider education, and systemic challenges to providing sexual health care in PC survivorship. CLINICAL IMPLICATIONS/CONCLUSIONS:The guidelines provide clinicians with a comprehensive approach to sexual health care for patients with prostate cancer. STRENGTHS & LIMITATIONS/UNASSIGNED:The strength of the study is the comprehensive evaluation of existing evidence on sexual dysfunction and rehabilitation in prostate cancer that can, along with available expert knowledge, best undergird clinical practice. Limitation is the variation in the evidence supporting interventions and the lack of research on issues facing patients with prostate cancer in low and middle-income countries. CONCLUSION/CONCLUSIONS:The guidelines document the distressing sexual sequelae of PCT, provide evidence-based recommendations for sexual rehabilitation and outline areas for future research. Wittmann D, Mehta A, McCaughan E, et al. Guidelines for Sexual Health Care for Prostate Cancer Patients: Recommendations of an International Panel. J Sex Med 2022;19:1655-1669.

BACKGROUND:The diagnosis of multiple sclerosis (MS) requires demyelinating events that are disseminated in time and space. Peripapillary retinal nerve fiber layer (pRNFL) thickness as measured by optical coherence tomography (OCT) distinguishes eyes with a prior history of acute optic neuritis (ON) and may provide evidence to support a demyelinating attack. OBJECTIVE:To investigate whether a deep learning (DL)-based network can distinguish between eyes with prior ON and healthy control (HC) eyes using peripapillary ring scans. METHODS:We included 1033 OCT scans from 415 healthy eyes (213 HC subjects) and 510 peripapillary ring scans from 164 eyes with prior acute ON (140 patients with MS). Data were split into 70% training, 15% validation, and 15% test data. We included 102 OCT scans from 80 healthy eyes (40 HC) and 61 scans from 40 ON eyes (31 MS patients) from an independent second center. Receiver operating characteristic curve analyses with area under the curve (AUC) were used to investigate performance. RESULTS:We used a dilated residual convolutional neural network for the classification. The final network had an accuracy of 0.85 and an AUC of 0.86, whereas pRNFL only had an AUC of 0.77 in recognizing ON eyes. Using data from a second center, the network achieved an accuracy of 0.77 and an AUC of 0.90 compared to pRNFL, which had an AUC of 0.84. INTERPRETATION:DL-based disease classification of prior ON is feasible and has the potential to outperform thickness-based classification of eyes with and without history of prior ON.

BACKGROUND:Adjuvant therapy for high-risk resected melanoma with programmed cell-death 1 blockade results in a median relapse-free survival (RFS) of 5 years. The addition of low dose ipilimumab (IPI) to a regimen of adjuvant nivolumab (NIVO) in CheckMate-915 did not result in increased RFS. A pilot phase II adjuvant study of either standard dose or low dose IPI with NIVO was conducted at two centers to evaluate RFS with correlative biomarker studies. METHODS:Patients with resected stages IIIB/IIIC/IV melanoma received either IPI 3 mg/kg and NIVO 1 mg/kg (cohort 4) or IPI 1 mg/kg and NIVO 3 mg/kg (cohorts 5 and 6) induction therapy every 3 weeks for 12 weeks, followed by maintenance NIVO. In an amalgamated subset of patients across cohorts, peripheral T cells at baseline and on-treatment were assessed by flow cytometry and RNA sequencing for exploratory biomarkers. RESULTS:High rates of grade 3-4 adverse events precluded completion of induction therapy in 50%, 35% and 7% of the patients in cohorts 4, 5 and 6, respectively. At a median of 63.9 months of follow-up, 16/56 patients (29%) relapsed. For all patients, at 5 years, RFS was 71% (95% CI: 60 to 84), and overall survival was 94% (95% CI: 88 to 100). Expansion of CD3+CD4+CD38+CD127-GARP- T cells, an on-treatment increase in CD39 expression in CD8+ T cells, and T-cell expression of phosphorylated signal-transducer-and-activator-of-transcription (STAT)2 and STAT5 were associated with relapse. CONCLUSIONS:Adjuvant IPI/NIVO at the induction doses used resulted in promising relapse-free and overall survival, although with a high rate of grade 3-4 adverse events. Biomarker analyses highlight an association of ectoenzyme-expressing T cells and STAT signaling pathways with relapse, warranting future validation. TRIAL REGISTRATION NUMBER:NCT01176474 and NCT02970981.

Chronic kidney disease (CKD) is defined by a low glomerular filtration rate or high albuminuria, and affects 15-20% of adults globally. CKD increases the risk of various adverse outcomes, but cardiovascular disease (CVD) is of particular relevance because it is the leading cause of death in this clinical population. CKD is associated with several CVD outcomes, including coronary heart disease, stroke, peripheral artery disease, arrhythmias, heart failure and venous thrombosis. Notably, CKD is particularly strongly associated with severe CVD outcomes such as CVD mortality, heart failure and lower extremity amputations. This broad impact of CKD on the cardiovascular system probably reflects the involvement of several pathophysiological mechanisms that link CKD to CVD development - shared risk factors (for example, diabetes and hypertension), changes in bone mineral metabolism, anaemia, volume overload, inflammation and the presence of uraemic toxins. Understanding the status of CKD is crucial for appropriate CVD risk prediction in CKD populations. However, major clinical guidelines are not consistent in their incorporation of CKD measures for CVD risk prediction. Mitigating CVD risk in patients with CKD effectively requires multidisciplinary care that involves nephrologists, cardiologists and other health professionals, as well as further work to address current research and implementation gaps.

RATIONALE & OBJECTIVE/UNASSIGNED:The coronavirus disease 2019 (COVID-19) pandemic has had a profound impact on hospitalizations in general and on dialysis patients in particular. This study modeled the impact of COVID-19 on hospitalizations of dialysis patients in 2020. STUDY DESIGN/UNASSIGNED:Retrospective cohort study. SETTING & PARTICIPANTS/UNASSIGNED:Medicare patients on dialysis in calendar year 2020. PREDICTORS/UNASSIGNED:COVID-19 status was divided into 4 stages: COVID1 (first 10 days after initial diagnosis), COVID2 (extends until the Post-COVID stage), Post-COVID (after 21 days with no COVID-19 diagnosis), and Late-COVID (begins after a hospitalization with a COVID-19 diagnosis); demographic and clinical characteristics; and dialysis facilities. OUTCOME/UNASSIGNED:The sequence of hospitalization events. ANALYTICAL APPROACH/UNASSIGNED:A proportional rate model with a nonparametric baseline rate function of calendar time on the study population. RESULTS/UNASSIGNED:A total of 509,609 patients were included in the study, 63,521 were observed to have a SARS-CoV-2 infection, 34,375 became Post-COVID, and 1,900 became Late-COVID. Compared with No-COVID, all 4 stages had significantly greater adjusted risks of hospitalizations with relative rates of 18.50 (95% CI, 18.19-18.81) for COVID1, 2.03 (95% CI, 1.99-2.08) for COVID2, 1.37 (95% CI, 1.35-1.40) for Post-COVID, and 2.00 (95% CI, 1.89-2.11) for Late-COVID. LIMITATIONS/UNASSIGNED:For Medicare Advantage patients, we only had inpatient claim information. The analysis was based on data from the year 2020, and the effects may have changed due to vaccinations, new treatments, and new variants. The COVID-19 effects may be somewhat overestimated due to missing information on patients with few or no symptoms and possible delay in COVID-19 diagnosis. CONCLUSIONS/UNASSIGNED:We discovered a marked time dependence in the effect of COVID-19 on hospitalization of dialysis patients, beginning with an extremely high risk for a relatively short period, with more moderate but continuing elevated risks later, and never returning to the No-COVID level.

Stress, in both intrinsic psychosocial and extrinsic physical environmental forms, can impact the development of, and outcomes in, cardiovascular disease (CVD) through allostatic load. Cortisol is a core hormonal mediator of allostatic load produced in response to various stresses. Alterations in morning serum cortisol and daily diurnal cortisol have been associated with adiposity, dyslipidemia, incident diabetes, and CVDs such as hypertension. The review examines the role of cortisol as a key mechanistic link between stress physiology and cardiometabolic disease. Importantly, we discuss the role of targeting cortisol through pharmacological, behavioral, and environmental interventions to advance health equity in cardiometabolic disease.

PURPOSE/OBJECTIVE:We investigated the relationship between measures of self-reported health and well-being and concurrent and prospective healthcare utilization and costs to assess the added value of these self-reported measures in understanding utilization and cost. METHODS:Kaiser Permanente members (N = 6752) completed a 9-item survey measuring life evaluation, financial situation, social support, meaning and purpose, physical health, and mental health. Responses were linked to medical record information during the period 12 months before and after the survey. RESULTS:Correlations between health and well-being measures and healthcare utilization and cost variables were generally weak, with stronger correlations for future life evaluation and selected health measures (ρ = .20-.33, ps < .001). Better overall life evaluation had a significant but weak association with lower total cost and hospital days in the following year after controlling for age, sex, and race/ethnicity (p < .001). Full multivariate models, adjusting for age, sex, race/ethnicity, prior utilization, and relative risk models, showed weak associations between health and well-being measures and following year total healthcare cost and utilization, though the associations were relatively stronger for the health variables than the well-being variables. CONCLUSION/CONCLUSIONS:Overall, the health and well-being variables added little to no predictive utility for future utilization and cost beyond prior utilization and cost and the inclusion of predictive models based on clinical information. Perceptions of well-being may be associated with factors beyond healthcare utilization. When information about prior use is unavailable, self-reported health items have some predictive utility.

BACKGROUND:Feeding problems are common in early childhood, and some evidence suggests that feeding problems may be associated with psychopathology. Few prospective studies have explored whether toddler feeding problems predict later psychopathology. METHODS:Mothers of 1,136 children from the Upstate KIDS cohort study provided data when children were 2.5 and 8 years of age. Food refusal (picky eating) and mechanical/distress feeding problems and developmental delays were assessed at 2.5 years. Child eating behaviors (enjoyment of food, food fussiness, and emotional under and overeating) and child psychopathology (attention-deficit/hyperactivity (ADHD), oppositional-defiant (OD), conduct disorder (CD), and anxiety/depression) symptoms were assessed at 8 years. RESULTS:Mechanical/distress feeding problems at age 2.5, but not food refusal problems, were associated with ADHD, problematic behavior (OD/CD), and anxiety/depression symptoms at 8 years in models adjusting for eating behaviors at 8 years and child and family covariates. Associations with mechanical/distress feeding problems were larger for ADHD and problematic behavior than anxiety/depression symptoms, though all were modest. Model estimates were similar for boys and girls. CONCLUSIONS:Much of the research on feeding problems focuses on picky eating. This study suggests that early mechanical and mealtime distress problems may serve as better predictors of later psychopathology than food refusal. Parents and pediatricians could monitor children with mechanical/distress feeding problems for signs of developing psychopathology.