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BACKGROUND: Buprenorphine is an effective treatment for opioid use disorder (OUD); however, buprenorphine initiation can be complicated by withdrawal symptoms including precipitated withdrawal. There has been increasing interest in using low dose initiation (LDI) strategies to reduce this withdrawal risk. As there are limited data on withdrawal symptoms during LDI, we characterize withdrawal symptoms in people with daily fentanyl use who underwent initiation using these strategies as outpatients. METHODS: We conducted a retrospective chart review of patients with OUD using daily fentanyl who were prescribed 7-day or 4-day LDI at 2 substance use disorder treatment clinics in San Francisco. Two addiction medicine experts assessed extracted chart documentation for withdrawal severity and precipitated withdrawal, defined as acute worsening of withdrawal symptoms immediately after taking buprenorphine. A third expert adjudicated disagreements. Data were analyzed using descriptive statistics. RESULTS: There were 175 initiations in 126 patients. The mean age was 37 (SD 10 years). 71% were men, 26% women, and 2% non-binary. 21% identified as Black, 16% Latine, and 52% white. 60% were unstably housed and 75% had Medicaid insurance. Substance co-use included 74% who used amphetamines, 29% cocaine, 22% benzodiazepines, and 19% alcohol. Follow up was available for 118 (67%) initiations. There was deviation from protocol instructions in 22% of these initiations with follow up. 31% had any withdrawal, including 21% with mild symptoms, 8% moderate and 2% severe. Precipitated withdrawal occurred in 10 cases, or 8% of initiations with follow up. Of these, 7 had deviation from protocol instructions; thus, there were 3 cases with follow up (3%) in which precipitated withdrawal occurred without protocol deviation. CONCLUSIONS: Withdrawal was relatively common in our cohort but was mostly mild, and precipitated withdrawal was rare. Deviation from instructions, structural barriers, and varying fentanyl use characteristics may contribute to withdrawal. Clinicians should counsel patients who use fentanyl that mild withdrawal symptoms are likely during LDI, and there is still a low risk for precipitated withdrawal. Future studies should compare withdrawal across initiation types, seek ways to support patients in initiating buprenorphine, and qualitatively elicit patients withdrawal experiences.

IntroductionAlthough dementia-related proteinopathy has a strong negative impact on public health, and is highly heritable, understanding of the related genetic architecture is incomplete.MethodsWe applied multidimensional generalized partial credit modeling (GPCM) to test genetic associations with dementia-related proteinopathies. Data were analyzed to identify candidate single nucleotide variants for the following proteinopathies: Aβ, tau, α-synuclein, and TDP-43.ResultsFinal included data comprised 966 participants with neuropathologic and WGS data. Three continuous latent outcomes were constructed, corresponding to TDP-43-, Aβ/Tau-, and α-synuclein-related neuropathology endophenotype scores. This approach helped validate known genotype/phenotype associations: for example, TMEM106B and GRN were risk alleles for TDP-43 pathology; and GBA for α-synuclein/Lewy bodies. Novel suggestive proteinopathy-linked alleles were also discovered, including several (SDHAF1, TMEM68, and ARHGEF28) with colocalization analyses and/or high degrees of biologic credibility.DiscussionA novel methodology using GPCM enabled insights into gene candidates for driving misfolded proteinopathies.HighlightsLatent factor scores for proteinopathies were estimated using a generalized partial credit model. The three latent continuous scores corresponded well with proteinopathy severity. Novel genes associated with proteinopathies were identified. Several genes had high degrees of biologic credibility for dementia risk factors.

BackgroundPrior work has found relationships between childhood social adversity and biomarkers of stress, but knowledge gaps remain. To help address these gaps, we explored associations between social adversity and biomarkers of inflammation (interleukin-1β [IL-1β], IL-6, IL-8, tumor necrosis factor-alpha [TNF-α], and salivary cytokine hierarchical "clusters" based on the three interleukins), neuroendocrine function (cortisol, cortisone, dehydroepiandrosterone, testosterone, and progesterone), neuromodulation (N-arachidonoylethanolamine, stearoylethanolamine, oleoylethanolamide, and palmitoylethanolamide), and epigenetic aging (Pediatric-Buccal-Epigenetic clock).MethodsWe collected biomarker samples of children ages 0-17 recruited from an acute care pediatrics clinic and examined their associations with caregiver-endorsed education, income, social risk factors, and cumulative adversity. We calculated regression-adjusted means for each biomarker and compared associations with social factors using Wald tests. We used logistic regression to predict being in the highest cytokine cluster based on social predictors.ResultsOur final sample included 537 children but varied based on each biomarker. Cumulative social adversity was significantly associated with having higher levels of all inflammatory markers and with cortisol, displaying a U-shaped distribution. There were no significant relationships between cumulative social adversity and cortisone, neuromodulation biomarkers or epigenetic aging.ConclusionOur findings support prior work suggesting that social stress exposures contribute to increased inflammation in children.ImpactOur study is one of the largest studies examining associations between childhood social adversity and biomarkers of inflammation, neuroendocrine function, neuromodulation, and epigenetic aging. It is one of the largest studies to link childhood social adversity to biomarkers of inflammation, and the first of which we are aware to link cumulative social adversity to cytokine clusters. It is also one of the largest studies to examine associations between steroids and epigenetic aging among children, and one of the only studies of which we are aware to examine associations between social adversity and endocannabinoids among children.Clinical trial registrationNCT02746393.

BACKGROUND: Female genital fistula is a traumatic debilitating injury, frequently caused by prolonged obstructed labor, affecting between 500,000-2 million women in lower-resource settings. Vesicovaginal fistula causes urinary incontinence, and other morbidity may occur during fistula development. Women with fistula are stigmatized, limit social and economic engagement, and experience psychiatric morbidity. Improved surgical access has reduced fistula consequences yet post-repair risks impacting quality of life and well-being include fistula repair breakdown or recurrence and ongoing or changing urine leakage or incontinence. Limited evidence on risk factors contributing to adverse outcomes hinders interventions to mitigate adverse events. This study aims to quantify these adverse risks and inform clinical and counseling interventions to optimize womens health and quality of life following fistula repair through: identifying predictors and characteristics of post-repair fistula breakdown and recurrence (Objective 1) and post-repair incontinence (Objective 2), and to identify feasible and acceptable intervention strategies (Objective 3). METHODS: This mixed-methods study incorporates a prospective cohort of women with successful vesicovaginal fistula repair at approximately 12 fistula repair centers in Uganda (Objectives 1-2) followed by qualitative inquiry among key stakeholders (Objective 3). Cohort participants will have a baseline visit at the time of surgery followed by data collection at 2 weeks, 6 weeks, 3 months and quarterly thereafter for 3 years. Primary predictors to be evaluated include patient-related factors, fistula-related factors, fistula repair-related factors, and post-repair behaviors and exposures, collected via structured questionnaire at all data collection points. Clinical exams will be conducted at baseline, 2 weeks post-surgery, and for outcome confirmation at symptom development. Primary outcomes are fistula repair breakdown or fistula recurrence and post-repair incontinence. In-depth interviews will be conducted with cohort participants (n ~ 40) and other key stakeholders (~ 40 including family, peers, community members and clinical/social service providers) to inform feasibility and acceptability of recommendations. DISCUSSION: Participant recruitment is underway. This study is expected to identify key predictors that can directly improve fistula repair and post-repair programs and womens outcomes, optimizing health and quality of life. Furthermore, our study will create a comprehensive longitudinal dataset capable of supporting broad inquiry into post-fistula repair health. Trial Registration ClinicalTrials.gov Identifier: NCT05437939.

PurposePersistent gastrointestinal (GI) symptoms are frequently experienced by colon cancer survivors and may help identify patients with higher utilization of healthcare services. To assess the relationship between GI symptoms and specialty care utilization among colon cancer survivors.MethodsA prospective longitudinal cohort study at an academic medical center of 126 adults surgically treated for stage I-IV colon cancer between February 2017 and June 2022. Participants reported GI symptoms through the EORTC QLQ-C30 and QLQ-CR29 at enrollment and as frequently as every 6 months for 5 years. Main outcome measures were visits, telephone encounters, and secure messages with a medical provider within specialty oncology clinics within 6 months after each survey completion. Generalized linear mixed regression model for repeated measurements with random trajectory for each participant was performed to estimate the associations between symptoms and healthcare use. Models were adjusted for demographics, clinical and surgical factors, and timing in relation to onset of the COVID-19 pandemic.ResultsIn the 6 months after each survey time point, patients averaged 1.2 visits, 0.5 telephone encounters, and 3.2 patient-initiated messages. In adjusted models, those with any abdominal pain (RR 1.45; p = 0.002), buttock pain (RR 1.30; p = 0.050), or increased stool frequency (RR 1.26; p = 0.046) had more clinic visits in the following 6 months than those without these symptoms. Including these three symptoms in one model revealed that only abdominal pain was statistically significantly associated with increased clinic visits (RR 1.36; p = 0.016). Patients with any blood or mucus in stool (RR 2.46; p = 0.009) had significantly more telephone encounters, and those with any abdominal pain (RR 1.65; p = 0.002) had significantly more patient-initiated messages than those without these symptoms.ConclusionsOur findings identify GI symptoms associated with increased use of oncologic specialty care among colon cancer survivors, with abdominal pain as an important predictor of utilization.Implications for cancer survivorsEarly identification and anticipatory management of colon cancer survivors experiencing abdominal pain may decrease healthcare utilization.

IntroductionThis study aimed to understand whether older adults' longitudinal completion of assessments in an online Alzheimer's disease and related dementias (ADRD)-related registry is influenced by self-reported medical conditions.MethodsBrain Health Registry (BHR) is an online cognitive aging and ADRD-related research registry that includes longitudinal health and cognitive assessments. Using logistic regressions, we examined associations between longitudinal registry completion outcomes and self-reported (1) number of medical conditions and (2) eight defined medical condition groups (cardiovascular, metabolic, immune system, ADRD, current psychiatric, substance use/abuse, acquired, other specified conditions) in adults aged 55+ (N = 23,888). Longitudinal registry completion outcomes were assessed by the completion of the BHR initial questionnaire (first questionnaire participants see at each visit) at least twice and completion of a cognitive assessment (Cogstate Brief Battery) at least twice. Models included ethnocultural identity, education, age, and subjective memory concern as covariates.ResultsWe found that the likelihood of longitudinally completing the initial questionnaire was negatively associated with reporting a diagnosis of ADRD and current psychiatric conditions but was positively associated with reporting substance use/abuse and acquired medical conditions. The likelihood of longitudinally completing the cognitive assessment task was negatively associated with number of reported medical conditions, as well as with reporting cardiovascular conditions, ADRD, and current psychiatric conditions. Previously identified associations between ethnocultural identity and longitudinal assessment completion in BHR remained after accounting for the presence of medical conditions.DiscussionThis post hoc analysis provides novel, initial evidence that older adults' completion of longitudinal assessments in an online registry is associated with the number and types of participant-reported medical conditions. Our findings can inform future efforts to make online studies with longitudinal health and cognitive assessments more usable for older adults with medical conditions. The results need to be interpreted with caution due to selection biases, and the under-inclusion of minoritized communities.

BackgroundA female genital fistula, primarily caused by prolonged obstructed labor or after cesarean delivery in resource-limited countries, affects 500,000 to 2,000,000 women worldwide. Fistula is preventable with timely access to high-quality obstetrical care. Access to surgical repair of a female genital fistula has greatly increased over time. However, research surrounding postrepair reintegration, the process of returning to an individual's normal life, remains limited, and further efforts are needed to understand the factors shaping women's ability to rebuild their relationships and lives following repair.ObjectiveThis study aimed to characterize the 12-month reintegration trajectory after female genital fistula repair by participant sociodemographic and clinical characteristics.Study designThis study analyzed quantitative survey and medical record data of women (N=60) participating in a longitudinal cohort study assessing recovery after genital fistula repair in Uganda, with baseline and 4 quarterly follow-up assessments in 12 months. The primary outcome of reintegration was assessed using a 19-item postfistula repair reintegration instrument (range, 0-100) where a higher score represents better reintegration. Predictors of interest included parity and living children, quality of life, depressive symptoms at baseline, self-esteem, stigma, trauma, physical symptoms, and social support. We described participant baseline characteristics using means and proportions and estimated a series of mixed-effects linear regression models, including interactions of characteristics with time to understand how these characteristics influence reintegration trajectory in the 12 months after repair.ResultsThe participants' physical and psychosocial morbidities at baseline were high; more than 80% of participants reported fistula-related physical symptoms, 82% of participants described their general health as poor, and measures of self-esteem, overall social support, and overall quality of life were low. The mean reintegration score at baseline was 33 (standard deviation, 20), which increased to 78 (standard deviation, 19) at 12 months after fistula repair. The participant sociodemographic characteristics statistically associated with reintegration included any living children (β, 1.08; 95% confidence interval, -0.08 to 2.23). Moreover, psychosocial factors significantly affected reintegration with steeper trajectories for women with depressive symptoms (β, 0.89; 95% confidence interval, 0.02-1.75) or women experiencing internalized stigma (β, 0.05; 95% confidence interval, -0.00 to 0.11) and less steep for those with higher self-esteem (β, -0.11; 95% confidence interval, -0.24 to 0.01), overall social support (β, -0.06; 95% confidence interval, -0.12 to -0.01), and partner support (β, -0.21; 95% confidence interval, -0.35 to -0.07).ConclusionUnderstanding the prominent factors associated with differences in reintegration trajectories across the year after genital fistula surgery has the potential to inform interventions that mitigate challenges and improve women's postrepair recovery experiences.

Mechanisms of resilience against tau pathology in individuals across the Alzheimer's disease spectrum are insufficiently understood. Longitudinal data are necessary to reveal which factors relate to preserved cognition (i.e. cognitive resilience) and brain structure (i.e. brain resilience) despite abundant tau pathology, and to clarify whether these associations are cross-sectional or longitudinal. We used a longitudinal study design to investigate the role of several demographic, biological and brain structural factors in yielding cognitive and brain resilience to tau pathology as measured with PET. In this multicentre study, we included 366 amyloid-β-positive individuals with mild cognitive impairment or Alzheimer's disease dementia with baseline 18F-flortaucipir-PET and longitudinal cognitive assessments. A subset (n = 200) additionally underwent longitudinal structural MRI. We used linear mixed-effects models with global cognition and cortical thickness as dependent variables to investigate determinants of cognitive resilience and brain resilience, respectively. Models assessed whether age, sex, years of education, APOE-ε4 status, intracranial volume (and cortical thickness for cognitive resilience models) modified the association of tau pathology with cognitive decline or cortical thinning. We found that the association between higher baseline tau-PET levels (quantified in a temporal meta-region of interest) and rate of cognitive decline (measured with repeated Mini-Mental State Examination) was adversely modified by older age (Stβinteraction = -0.062, P = 0.032), higher education level (Stβinteraction = -0.072, P = 0.011) and higher intracranial volume (Stβinteraction = -0.07, P = 0.016). Younger age, higher education and greater cortical thickness were associated with better cognitive performance at baseline. Greater cortical thickness was furthermore associated with slower cognitive decline independent of tau burden. Higher education also modified the negative impact of tau-PET on cortical thinning, while older age was associated with higher baseline cortical thickness and slower rate of cortical thinning independent of tau. Our analyses revealed no (cross-sectional or longitudinal) associations for sex and APOE-ε4 status on cognition and cortical thickness. In this longitudinal study of clinically impaired individuals with underlying Alzheimer's disease neuropathological changes, we identified education as the most robust determinant of both cognitive and brain resilience against tau pathology. The observed interaction with tau burden on cognitive decline suggests that education may be protective against cognitive decline and brain atrophy at lower levels of tau pathology, with a potential depletion of resilience resources with advancing pathology. Finally, we did not find major contributions of sex to brain nor cognitive resilience, suggesting that previous links between sex and resilience might be mainly driven by cross-sectional differences.

BackgroundIndividual behaviours are associated with prostate cancer (PC) progression. Behavioural scores, comprised of multiple risk factors, allow assessment of the combined impact of multiple behaviours.MethodsWe examined the association between six a priori scores and risk of PC progression and mortality among 2156 men with PC in the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) cohort: two scores developed based on the PC survivorship literature ('2021 Score [+ Diet]'); a score developed based on pre-diagnostic PC literature ('2015 Score'); and three scores based on US recommendations for cancer prevention ('WCRF/AICR Score') and survival ('ACS Score [+ Alcohol]'). Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for progression and PC mortality via parametric survival models (interval censoring) and Cox models, respectively.ResultsOver a median (IQR) of 6.4 (1.3, 13.7) years, we observed 192 progression and 73 PC mortality events. Higher (i.e., healthier) 2021 Score + Diet and WCRF/AICR Scores were inversely associated with risk of PC progression (2021 + Diet: HRcontinuous = 0.76, 95% CI: 0.63-0.90.Wcrf/aicrHRcontinuous = 0.83, 95% CI: 0.67-1.02) and mortality (2021 + Diet: HRcontinuous = 0.65, 95% CI: 0.45-0.93.Wcrf/aicrHRcontinuous = 0.71; 95% CI: 0.57-0.89). The ACS Score + Alcohol was only associated with progression (HRcontinuous = 0.89, 95% CI: 0.81-0.98) while the 2021 Score was only associated with PC mortality (HRcontinuous = 0.62, 95% CI: 0.45-0.85). The 2015 was not associated with PC progression or mortality.ConclusionFindings strengthen the evidence that behavioural modifications following a prostate cancer diagnosis may improve clinical outcomes.

Introduction and Objective: Prior literature had demonstrated increased stone burden and higher rates of staged surgery in individuals of lower socioeconomic status (SES). Low SES individuals are more likely to experience delays in definitive stone surgery after initial presentation to the emergency department (ED) for kidney stones. This study aims to investigate the relationship between delays in definitive kidney stone surgery and the subsequent need for percutaneous nephrolithotomy (PNL) and/or staged surgical procedures using a statewide data set. Methods: This retrospective cohort study gathered longitudinal data from 2009 to 2018 using the California Department of Health Care Access and Information data set. Patient demographic characteristics, comorbidities, diagnosis/procedure codes, and distance were analyzed. Complex stone surgery was defined as initial PNL and/or undergoing more than one procedure within 365 days of initial intervention. Results: A total of 1,816,093 billing encounters from 947,798 patients were screened, resulting in 44,835 patients with ED visits for kidney stones followed by a urologic stone procedure. Multivariable analysis revealed that relative to patients who underwent surgery within 1 month of initial ED visit for stone disease, patients were at increased odds of undergoing complex surgery if waiting ≥6 months (odds ratio [OR] 1.18, p = 0.022), ≥1 year (OR 1.29, p

After introducing guidelines for breast cancer screening in 2003, Mexico began to prioritize the implementation of mammography screening nationally. Since then, there have been no studies assessing changes in mammography in Mexico using the two-year prevalence interval that corresponds to national guidelines for screening frequency. The present study analyzes the Mexican Health and Aging Study (MHAS), a national population-based panel study of adults aged 50 and older, to evaluate changes in 2-year mammography prevalence among women aged 50 to 69 across five survey waves from 2001 to 2018 (n = 11,773). We calculated unadjusted and adjusted mammography prevalence by survey year and health insurance type. Overall prevalence increased substantially from 2003 to 2012 and leveled off in the period from 2012 to 2018 (2001: 20.2 % [95 % CI 18.3, 22.1]; 2003: 22.7 % [20.4, 25.0]; 2012: 56.5 % [53.2, 59.7]; 2015: 62.0 % [58.8, 65.2]; 2018: 59.4 % [56.7,62.1]; unadjusted prevalence). Prevalence was higher among respondents with social security insurance, who are more likely to work in the formal economy, than among respondents without social security, who are more likely to work in the informal economy or be unemployed. The overall prevalence estimates observed were higher than previously published estimates of mammography prevalence in Mexico. More research is needed to confirm findings regarding two-year mammography prevalence in Mexico and to better understand the causes of observed disparities.

BackgroundRecent endeavors emphasize the importance of understanding early barriers to liver transplantation (LT) by consistently collecting data on patient demographics, socioeconomic factors, and geographic social deprivation indices.MethodsIn this retrospective single-center cohort study of 1657 adults referred for LT evaluation, we assessed the association between community-level vulnerability and individual socioeconomic status measures on the rate of waitlisting and transplantation. Patients' addresses were linked to Social Vulnerability Index (SVI) at the census tract-level to characterize community-level vulnerability. Descriptive statistics were used to describe patient characteristics. Multivariable cause-specific HRs were used to assess the association between community-level vulnerability, individual measures of the socioeconomic status, and LT evaluation outcomes (waitlist and transplantation).ResultsAmong the 1657 patients referred for LT during the study period, 54% were waitlisted and 26% underwent LT. A 0.1 increase in overall SVI correlated with an 8% lower rate of waitlisting (HR 0.92, 95% CI 0.87-0.96, p < 0.001), with socioeconomic status, household characteristics, housing type and transportation, and racial and ethnic minority status domains contributing significantly to this association. Patients residing in more vulnerable communities experienced a 6% lower rate of transplantation (HR 0.94, 95% CI 0.91- 0.98, p = 0.007), with socioeconomic status and household characteristic domain of SVI significantly contributing to this association. At the individual level, both government insurance and employment status were associated with lower rates of waitlisting and transplantation. There was no association with mortality prior to waitlisting or mortality while on the waitlist.ConclusionOur findings indicate that both individual and community measures of the socioeconomic status (overall SVI) are associated with LT evaluation outcomes. Furthermore, we identified individual measures of neighborhood deprivation associated with both waitlisting and transplantation.

PurposeWe sought to analyze biologic, clinical, and prognostic differences according to pattern of failure at the time of first relapse in neuroblastoma.Patients and methodsChildren

BackgroundInflammatory and insulin pathways have been linked to prostate cancer; postdiagnostic behaviors activating these pathways may lead to poor outcomes. The empirical dietary inflammatory pattern (EDIP), empirical dietary index for hyperinsulinemia (EDIH), and empirical dietary index for insulin resistance (EDIR), and associated lifestyle indices (ELIH, ELIR) predict biomarkers of inflammation (EDIP: IL6, TNFaR2, CRP) and insulin secretion (EDIH/ELIH: c-peptide; EDIR/ELIR: TAG:HDL) from whole foods and behaviors.MethodsAssociations of these indices with time to prostate cancer progression (primary, n = 2,056) and prostate cancer-specific mortality (PCSM; secondary, n = 2,447) were estimated among men diagnosed with nonmetastatic prostate cancer in the Cancer of the Prostate Strategic Urologic Research Endeavor cohort diet and lifestyle sub-study. Because the true (versus clinically documented) date of progression is unobserved, we used parametric (Weibull) survival models to accommodate interval-censoringand estimated adjusted HR and 95% confidence intervals (CI) for prostate cancer progression per 1-SD increase in index. Cox proportional hazards models were used to estimate PCSM associations.ResultsDuring a median [interquartile range (IQR)] 6.4 years (IQR, 1.3-12.7), 192 progression and 73 PCSM events were observed. Inflammatory (EDIP: HR, 1.27; CI, 1.17-1.37), hyperinsulinemic (EDIH: HR, 1.24; CI, 1.05-1.46. ELIH: HR, 1.34; CI, 1.17-1.54), and insulin-resistant (EDIR: HR, 1.22; CI, 1.00-1.48. ELIR: HR, 1.36; CI, 1.12-1.64) indices were positively associated with risk of prostate cancer progression. There was no evidence of associations between the indices and PCSM.ConclusionsBoth inflammatory and insulinemic dietary and lifestyle patterns are associated with risk of prostate cancer progression.ImpactFor men with prostate cancer, consuming dietary patterns that limit chronic systemic inflammation and insulin hypersecretion may improve survivorship, especially when coupled with active lifestyle and healthy body weight. See related commentary by Kucuk, p. 1673.

Aging into later life is often accompanied by social disconnection, anxiety, and sadness. Negative emotions are self-focused states with detrimental effects on aging and longevity. Awe-a positive emotion elicited when in the presence of vast things not immediately understood-reduces self-focus, promotes social connection, and fosters prosocial actions by encouraging a small self. We investigated the emotional benefits of a novel awe walk intervention in healthy older adults. Sixty participants took weekly 15-min outdoor walks for 8 weeks; participants were randomly assigned to an awe walk group, which oriented them to experience awe during their walks, or to a control walk group. Participants took photographs of themselves during each walk and rated their emotional experience. Each day, they reported on their daily emotional experience outside of the walk context. Participants also completed pre- and postintervention measures of anxiety, depression, and life satisfaction. Compared with participants who took control walks, those who took awe walks experienced greater awe during their walks and exhibited an increasingly small self in their photographs over time. They reported greater joy and prosocial positive emotions during their walks and displayed increasing smile intensity over the study. Outside of the walk context, participants who took awe walks reported greater increases in daily prosocial positive emotions and greater decreases in daily distress over time. Postintervention anxiety, depression, and life satisfaction did not change from baseline in either group. These results suggest cultivating awe enhances positive emotions that foster social connection and diminishes negative emotions that hasten decline. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Women's nutritional status remains poor in South Asia, impacting maternal and infant health outcomes. Women's household status is also low, as evidenced by eating behaviours. We started with triadic qualitative interviews with newly married women, husbands and mothers-in-law to explore the link between women's status and eating patterns, followed by longitudinal data from a cohort of 200 newly married women in rural Nepal to measure associations over time. Quantitative data were collected every 6 months for 18 months (four rounds of data) between 2018 and 2020. Interviews suggested that household relationships, women's status, and how much and what types of food she was given were intricately linked. Using mixed effects logistic regression models, we explore the association between markers of changing women's status (becoming pregnant, giving birth and working outside the home) on two outcomes (eating last always/usually and achieving minimum dietary diversity). We also explore for interaction between women's status and household food insecurity. Pregnancy increases women's dietary diversity, but this is not sustained post-partum. Women who work outside the home are less likely to eat last in the household. Food insecurity is associated with both the order of household eating and dietary diversity. Interactions between food insecurity and giving birth suggested that women who give birth in food insecure households are more likely to eat last in the household. Changes in women's household status are associated with some improvements in dietary diversity and order of household eating, but the associations are not long-lasting and depend on food security status.

To identify predictors of when systematic biopsy leads to a higher overall prostate cancer grade compared to targeted biopsy. 918 consecutive patients who underwent prostate MRI followed by MRI/US fusion biopsy and systematic biopsies from January 2015 to November 2019 at a single academic medical center were retrospectively identified. The outcome was upgrade of PCa by systematic biopsy, defined as cases when systematic biopsy led to a Gleason Grade (GG) ≥ 2 and greater than the maximum GG detected by targeted biopsy. Generalized linear regression and conditional logistic regression were used to analyze predictors of upgrade. At the gland level, the presence of an US-visible lesion was associated with decreased upgrade (OR 0.64, 95% CI 0.44-0.93, p = 0.02). At the sextant level, upgrade was more likely to occur through the biopsy of sextants with MRI-visible lesions (OR 2.58, 95% CI 1.87-3.63, p

Study objectivesTo evaluate the effects of digital cognitive behavior therapy for insomnia (dCBT-I) delivered during pregnancy on subjective sleep outcomes, depressive symptoms, and anxiety symptoms through 6 months postpartum.MethodsPeople up to 28 weeks gestation (N = 208) with insomnia were randomized to 6 weekly sessions of dCBT-I or standard care. We report follow-up data at 3 and 6 months postpartum. The primary outcome was insomnia symptom severity. Secondary sleep outcomes included global sleep quality and insomnia caseness. Mental health outcomes included depressive and anxiety symptom severity. We evaluated between-condition differences in change from baseline for each postpartum timepoint and categorical outcomes.ResultsdCBT-I participants did not experience significantly greater improvements in insomnia symptom severity relative to standard care participants, but they did experience higher rates of insomnia remission and lower rates of insomnia caseness at 6 months postpartum. dCBT-I participants experienced greater improvements in depressive symptom severity from baseline to both postpartum timepoints, and in anxiety symptom severity from baseline to 3 months postpartum. The proportion of participants with probable major depression at 3 months postpartum was significantly higher among standard care (18%) than dCBT-I (4%, p = 0.006) participants; this between-condition difference was pronounced among the subset (n = 143) with minimal depressive symptoms at baseline (18% vs 0%).ConclusiondCBT-I use during pregnancy leads to enduring benefits for postpartum insomnia remission. Findings provide strong preliminary evidence that dCBT-I use during pregnancy may prevent postpartum depression and anxiety, which is notable when considering the high frequency and importance of these problems.Clinical Trials: ClinicalTrials.gov, https://clinicaltrials.gov/ct2/show/NCT02805998, NCT02805998.

Background and aimsRacial/ethnic minority children have worse liver transplant (LT) outcomes. We evaluated whether neighborhood socioeconomic deprivation affected associations between race/ethnicity and wait-list mortality.Approach and resultsWe included children (age

Naming of nouns and verbs can be selectively impaired in neurological disorders, but the specificity of the neural and cognitive correlates of such dissociation remains unclear. Functional imaging and stroke research sought to identify cortical regions selectively recruited for nouns versus verbs, yet findings are inconsistent. The present study investigated this issue in neurodegenerative diseases known to selectively affect different brain networks, thus providing new critical evidence of network specificity. We examined naming performances on nouns and verbs in 146 patients with different neurodegenerative syndromes (Primary Progressive Aphasia - PPA, Alzheimer's disease - AD, and behavioral variant Frontotemporal Dementia - FTD) and 30 healthy adults. We then correlated naming scores with MRI-derived cortical thickness values as well as with performances in semantic and syntactic tasks, across all subjects. Results indicated that patients with the semantic variant PPA named significantly fewer nouns than verbs. Instead, nonfluent/agrammatic PPA patients named fewer verbs than nouns. Across all subjects, performance on nouns (adjusted for verbs) specifically correlated with cortical atrophy in left anterior temporal regions, and performance on verbs (adjusted for nouns) with atrophy in left inferior and middle frontal, inferior parietal and posterior temporal regions. Furthermore, lower lexical-semantic abilities correlated with deficits in naming both nouns and verbs, while lower syntactic abilities only correlated with naming verbs. Our results show that different neural and cognitive mechanisms underlie naming of specific grammatical categories in neurodegenerative diseases. Importantly, our findings showed that verb processing depends on a widespread perisylvian networks, suggesting that some regions might be involved in processing different types of action knowledge. These findings have important implications for early differential diagnosis of neurodegenerative disorders.

Objective we evaluated whether memory recall following an extended (1 week) delay predicts cognitive and brain structural trajectories in older adultsMethodClinically normal older adults (52-92 years old) were followed longitudinally for up to 8 years after completing a memory paradigm at baseline [Story Recall Test (SRT)] that assessed delayed recall at 30 min and 1 week. Subsets of the cohort underwent neuroimaging (N = 134, mean age = 75) and neuropsychological testing (N = 178-207, mean ages = 74-76) at annual study visits occurring approximately 15-18 months apart. Mixed-effects regression models evaluated if baseline SRT performance predicted longitudinal changes in gray matter volumes and cognitive composite scores, controlling for demographics.ResultsWorse SRT 1-week recall was associated with more precipitous rates of longitudinal decline in medial temporal lobe volumes (p = .037), episodic memory (p = .003), and executive functioning (p = .011), but not occipital lobe or total gray matter volumes (demonstrating neuroanatomical specificity; p > .58). By contrast, SRT 30-min recall was only associated with longitudinal decline in executive functioning (p = .044).ConclusionsMemory paradigms that capture longer-term recall may be particularly sensitive to age-related medial temporal lobe changes and neurodegenerative disease trajectories. (JINS, 2020, xx, xx-xx).

IntroductionThis study investigated the extent to which subjective and objective data from an online registry can be analyzed using machine learning methodologies to predict the current brain amyloid beta (Aβ) status of registry participants.MethodsWe developed and optimized machine learning models using data from up to 664 registry participants. Models were assessed on their ability to predict Aβ positivity using the results of positron emission tomography as ground truth.ResultsStudy partner-assessed Everyday Cognition score was preferentially selected for inclusion in the models by a feature selection algorithm during optimization.DiscussionOur results suggest that inclusion of study partner assessments would increase the ability of machine learning models to predict Aβ positivity.

Objective: We aimed to test the hypothesis that elevated neocortical β-amyloid (Aβ), a hallmark feature of Alzheimer's disease (AD), predicts sex-specific cognitive trajectories in clinically normal older adults, with women showing greater risk of decline than men. Method: Florbetapir Aβ positron emission tomography (PET) was acquired in 149 clinically normal older adults (52% female, Mage = 74). Participants underwent cognitive testing at baseline and during annual follow-up visits over a timespan of up to 5.14 years. Mixed-effects regression models evaluated whether relations between baseline neocortical Standardized Uptake Value Ratio (SUVR) and composite scores of episodic memory, executive functioning, and processing speed were moderated by sex (male/female) and apolipoprotein E (APOE) status (ε4 carrier/noncarrier). Results: Higher baseline SUVR was associated with longitudinal decline in episodic memory in women (b = -1.32, p < .001) but not men (b = -0.30, p = .28). Female APOE ε4 carriers with elevated SUVR showed particularly precipitous declines in episodic memory (b = -4.33, p < .001) whereas other cognitive domains were spared. SUVR did not predict changes in executive functioning or processing speed, regardless of sex (ps >.63), though there was a main effect of SUVR on processing speed (b = 2.50, p = .003). Conclusions: Clinically normal women with elevated Aβ are more vulnerable to episodic memory decline than men. Understanding sex-related differences in AD, particularly in preclinical stages, is crucial for guiding precision medicine approaches to early detection and intervention. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

IntroductionAssessment of functional status is associated with risk of cognitive decline and diagnosis of dementia, and can be assessed by participants and study partners (SPs).MethodsIn 770 older adults enrolled in the Imaging Dementia-Evidence for Amyloid Scanning (IDEAS) study and the online Brain Health Registry (BHR), we estimated associations between online assessments and clinical variables related to Alzheimer's disease (AD) risk.ResultsWorse online learning scores and SP-reported functional decline were associated with higher probability of AD dementia diagnosis and poor in-clinic cognitive assessment, and with higher odds of amyloid beta (Aβ) positivity when combined with participants' report of less decline. SP report of functional decline conferred predictive value independent of online cognitive assessments. Participants underreported decline compared to SPs.DiscussionThe results support the validity of online assessments and their greater utilization in healthcare and research settings. Online SP-reported functional decline is an indicator of dementia and AD risk.

BackgroundCentral nervous system levels of tumor necrosis factor-alpha (TNF-α), a pro-inflammatory cytokine, regulate the neuroinflammatory response and may play a role in age-related neurodegenerative diseases. The longitudinal relation between peripheral levels of TNF-α and typical brain aging is understudied. We hypothesized that within-person increases in systemic TNF-α would track with poorer brain health outcomes in functionally normal adults.MethodsPlasma-based TNF-α concentrations (pg/mL; fasting morning draws) and magnetic resonance imaging were acquired in 424 functionally intact adults (mean age = 71) followed annually for up to 8.4 years (mean follow-up = 2.2 years). Brain outcomes included total gray matter volume and white matter hyperintensities. Cognitive outcomes included composites of memory, executive functioning, and processing speed, as well as Mini-Mental State Examination total scores. Longitudinal mixed-effects models were used, controlling for age, sex, education, and total intracranial volume, as appropriate.ResultsTNF-α concentrations significantly increased over time (p < .001). Linear increases in within-person TNF-α were longitudinally associated with declines in gray matter volume (p < .001) and increases in white matter hyperintensities (p = .003). Exploratory analyses suggested that the relation between TNF-α and gray matter volume was curvilinear (TNF-α 2p = .002), such that initial increases in inflammation were associated with more precipitous atrophy. There was a negative linear relationship of within-person changes in TNF-α to Mini-Mental State Examination scores over time (p = .036) but not the cognitive composites (all ps >.05).ConclusionSystemic inflammation, as indexed by plasma TNF-α, holds potential as a biomarker for age-related declines in brain health.

IntroductionThis study aimed to predict brain amyloid beta (Aβ) status in older adults using collected information from an online registry focused on cognitive aging.MethodsAβ positron emission tomography (PET) was obtained from multiple in-clinic studies. Using logistic regression, we predicted Aβ using self-report variables collected in the Brain Health Registry in 634 participants, as well as a subsample (N = 533) identified as either cognitively unimpaired (CU) or mild cognitive impairment (MCI). Cross-validated area under the curve (cAUC) evaluated the predictive performance.ResultsThe best prediction model included age, sex, education, subjective memory concern, family history of Alzheimer's disease, Geriatric Depression Scale Short-Form, self-reported Everyday Cognition, and self-reported cognitive impairment. The cross-validated AUCs ranged from 0.62 to 0.66. This online model could help reduce between 15.2% and 23.7% of unnecessary Aβ PET scans in CU and MCI populations.DisucssionThe findings suggest that a novel, online approach could aid in Aβ prediction.

ObjectivesDevelopment and pilot evaluation of a personalized decision support intervention to help men with early-stage prostate cancer choose among active surveillance, surgery, and radiation.MethodsWe developed a decision aid featuring long-term survival and side effects data, based on focus group input and stakeholder endorsement. We trained premedical students to administer the intervention to newly diagnosed men with low-risk prostate cancer seen at the University of California, San Francisco. Before the intervention, and after the consultation with a urologist, we administered the Decision Quality Instrument for Prostate Cancer (DQI-PC). We hypothesized increases in two knowledge items from the DQI-PC: How many men diagnosed with early-stage prostate cancer will eventually die of prostate cancer? How much would waiting 3 months to make a treatment decision affect chances of survival? Correct answers were: "Most will die of something else" and "A little or not at all."ResultsThe development phase involved 6 patients, 1 family member, 2 physicians, and 5 other health care providers. In our pilot test, 57 men consented, and 44 received the decision support intervention and completed knowledge surveys at both timepoints. Regarding the two knowledge items of interest, before the intervention, 35/56 (63%) answered both correctly, compared to 36/44 (82%) after the medical consultation (P = .04 by chi-square test).ConclusionsThe intervention was associated with increased patient knowledge. Data from this pilot have guided the development of a larger scale randomized clinical trial to improve decision quality in men with prostate cancer being treated in community settings.

ObjectiveIdentifying individuals at risk for cognitive decline, Mild Cognitive Impairment (MCI), and dementia due to Alzheimer's disease (AD) is a critical need. Functional decline is associated with risk and can be efficiently assessed by participants and study partners (SPs). We tested the hypothesis that SP-reported functional decline is an independent predictor of dementia risk and cognitive decline.MethodsIn 1048 older adults in the Alzheimer's Disease Neuroimaging Initiative (ADNI), we measured associations between Everyday Cognition Scale scores (ECog, self- and SP-reported versions) and (1) baseline and longitudinal change in neuropsychological test (NPT scores) across multiple cognitive domains; (2) diagnostic conversion to MCI or dementia. Models included Mini Mental Status Exam (MMSE) score and ApoE ε4 genotype (APOE) as predictors. Model fits were compared with and without predictors of interest included.ResultsSP-reported ECog was the strongest predictor of cognitive decline across multiple domains, as well as diagnostic conversion. Self-reported ECog was associated with baseline NPT scores in some cognitive domains, and diagnostic conversion to MCI in participants with biomarker evidence for AD (elevated brain β-amyloid, Aβ). Models including SP-reported ECog were significantly stronger at predicting outcomes.ConclusionsSP-reported functional decline is an independent indicator of cognitive decline and dementia risk, even when accounting for cognitive screening, genetic risk, demographics, and self-report decline. The results provide a rationale for greater utilization of SP-reported functional decline to identify those at risk for dementia due to AD and other causes.

Neurodegenerative diseases appear to progress by spreading via brain connections. Here we evaluated this transneuronal degeneration hypothesis by attempting to predict future atrophy in a longitudinal cohort of patients with behavioral variant frontotemporal dementia (bvFTD) and semantic variant primary progressive aphasia (svPPA). We determined patient-specific "epicenters" at baseline, located each patient's epicenters in the healthy functional connectome, and derived two region-wise graph theoretical metrics to predict future atrophy: (1) shortest path length to the epicenter and (2) nodal hazard, the cumulative atrophy of a region's first-degree neighbors. Using these predictors and baseline atrophy, we could accurately predict longitudinal atrophy in most patients. The regions most vulnerable to subsequent atrophy were functionally connected to the epicenter and had intermediate levels of baseline atrophy. These findings provide novel, longitudinal evidence that neurodegeneration progresses along connectional pathways and, further developed, could lead to network-based clinical tools for prognostication and disease monitoring.

BackgroundThe association of obesity at diagnosis with prostate cancer progression is uncertain. This study aimed to examine the relationship between body mass index (BMI; 18.5-

BackgroundHispanic subjects with cystic fibrosis (CF) have increased morbidity and mortality than non-Hispanic white subjects. The ethnic disparity in mortality varies by region. Factors influencing pulmonary function vary by both ethnicity and region.ObjectiveTo determine if the ethnic difference in pulmonary function varies by region.MethodsThis retrospective cohort study compared differences in longitudinal pulmonary function (percent-predicted forced vital capacity [FVC], forced expiratory volume in 1 second [FEV1 ], forced expiratory flow at 25% to 75% [FEF25-75 ], FEV1 /FVC, and FEV1 decline) between Hispanic and non-Hispanic white subjects with CF by Census region of the United States (West, South, Midwest, and Northeast). Subjects were of ages 6 to 25 years and in the CF Foundation Patient Registry from 2008 to 2013. We used linear mixed effects models with subject-specific slopes and intercepts, adjusting for 14 demographic and clinical variables.ResultsOf 14 932 subjects, 1433 (9.6%) were Hispanic and 13 499 (90.4%) were non-Hispanic white. Hispanic subjects' FEV1 was 9.0% (8.3%-9.8%) lower than non-Hispanic white subjects in the West, while Hispanic subjects' FEV1 was only 4.0% (3.0%-5.0%) lower in the Midwest, 4.4% (3.1%-5.7%) lower in the Northeast, and 4.4% (3.2%-5.5%) lower in the South. Similarly, FVC and FEF25-75 were lower among Hispanic subjects compared to non-Hispanic white subjects in all US regions, with the biggest differences in the West. Only in the West was FEV1 /FVC significantly lower in Hispanic subjects (-0.019; -0.022 to -0.015). FEV1 decline was not significantly different between ethnicities in any region.ConclusionsIn CF, Hispanic subjects have lower pulmonary function than non-Hispanic white subjects in all geographic regions with the largest difference in occurring in the West.

BackgroundRacial disparities in guideline-based, appropriate treatment (ApT) may be a significant driving force for differences in survival for people with nonmetastatic muscle-invasive bladder cancer (MIBC). We hypothesize that receipt of ApT is influenced by factors such as race and socioeconomic status, irrespective of neighborhood-level differences in healthcare, variations in practice patterns, and clinical characteristics of patients with nonmetastatic MIBC.MethodsWithin the National Cancer Database, we identified individuals diagnosed with MIBC between 2004 and 2013. Multivariable logistic regression and mixed effects modelling was used to examine predictors of ApT, clustered within institutions.ResultsA total of 51,350 individuals had clinically staged nonmetastatic, lymph node-negative MIBC. Black individuals comprised 6.4% of the cohort. Mean age was 72.6 years (SD 11.6) with a male predominance (71.4%). Less than half received ApT (42.6%). Fewer black individuals received ApT compared with white individuals (37% vs. 43%, P < 0.001). When clustered by institution, the odds of ApT were 21% lower for black individuals [odds ratio (OR), 0.79; 95% confidence interval (CI), 0.73-0.87] compared with white individuals with nonmetastatic MIBC. When restricted to higher volume centers with more diverse populations, black individuals had 25% lower odds of ApT (OR, 0.75; 95% CI, 0.61-0.91; P < 0.01), compared with white counterparts.ConclusionsRacial disparities in treatment persisted after accounting for various clinical factors and social determinants of health. Future efforts should focus on addressing racial bias to improve disparities in bladder cancer treatment.ImpactIf we are not delivering evidence-based care due to these biases (after accounting for access and biology), then it is expected that patients will experience inferior outcomes.

Previous studies indicate that repetition is affected in primary progressive aphasia (PPA), particularly in the logopenic variant, due to limited auditory-verbal short-term memory (avSTM). We tested repetition of phrases varied by length (short, long) and meaning (meaningful, non-meaningful) in 58 participants (22 logopenic, 19 nonfluent, and 17 semantic variants) and 21 healthy controls using a modified Bayles repetition test. We evaluated the relation between cortical thickness and repetition performance and whether sub-scores could discriminate PPA variants. Logopenic participants showed impaired repetition across all phrases, specifically in repeating long phrases and any phrases that were non-meaningful. Nonfluent, semantic, and healthy control participants only had difficulty repeating long, non-meaningful phrases. Poor repetition of long phrases was associated with cortical thinning in left temporo-parietal areas across all variants, highlighting the importance of these areas in avSTM. Finally, Bayles repetition phrases can assist classification in PPA, discriminating logopenic from nonfluent/semantic participants with 89% accuracy.

Neurodegenerative dementia syndromes are characterized by spreading of pathological protein deposition along syndrome-specific neural networks. Structural and functional MRI measures can assess the integrity of these networks and have been proposed as biomarkers of disease progression for clinical trials. The relationship between in vivo imaging measures and pathological features, at the single subject level, remains largely unknown. Patient-specific maps of atrophy and seed-based intrinsic connectivity disruption, as compared to normal controls, were obtained for 27 patients subsequently diagnosed with progressive supranuclear palsy (n = 16, seven males, age at death 68.9 ± 6.0 years, imaging-to-pathology interval = 670.2 ± 425.1 days) or corticobasal degeneration (n = 11, two males, age at death 66.7 ± 5.4 years, imaging-to-pathology interval = 696.2 ± 482.2 days). A linear mixed effect model with crossed random effects was used to test regional and single-subject level associations between post-mortem regional measures of neurodegeneration and tau inclusion burden, on the one hand, and regional volume loss and seed-based intrinsic connectivity reduction, on the other. A significant association was found between tau inclusion burden and in vivo volume loss, at the regional level and independent of neurodegeneration severity, in both progressive supranuclear palsy [n = 340 regions; beta 0.036; 95% confidence interval (CI): 0.001, 0.072; P = 0.046] and corticobasal degeneration (n = 215 regions; beta 0.044; 95% CI: 0.009, 0.079; P = 0.013). We also found a significant association between post-mortem neurodegeneration and in vivo volume loss in both progressive supranuclear palsy (n = 340 regions; beta 0.155; 95% CI: 0.061, 0.248; P = 0.001) and corticobasal degeneration (n = 215 regions; beta 0.277; 95% CI: 0.104, 0.450; P = 0.002). We found a significant association between regional neurodegeneration and intrinsic connectivity dysfunction in corticobasal degeneration (n = 215 regions; beta 0.074; 95% CI: 0.005, 0.143; P = 0.035), but no other associations between post-mortem measures of tauopathy and intrinsic connectivity dysfunction reached statistical significance. Our data suggest that in vivo structural imaging measures reflect independent contributions from neurodegeneration and tau burden in progressive supranuclear palsy and corticobasal degeneration. Seed-based measures of intrinsic connectivity dysfunction showed less reliable predictive value when used as in vivo biomarkers of tauopathy. The findings provide important guidance for the use of imaging biomarkers as indirect in vivo assays of microscopic pathology.

BackgroundMetagenomic next-generation sequencing (NGS) of cerebrospinal fluid (CSF) has the potential to identify a broad range of pathogens in a single test.MethodsIn a 1-year, multicenter, prospective study, we investigated the usefulness of metagenomic NGS of CSF for the diagnosis of infectious meningitis and encephalitis in hospitalized patients. All positive tests for pathogens on metagenomic NGS were confirmed by orthogonal laboratory testing. Physician feedback was elicited by teleconferences with a clinical microbial sequencing board and by surveys. Clinical effect was evaluated by retrospective chart review.ResultsWe enrolled 204 pediatric and adult patients at eight hospitals. Patients were severely ill: 48.5% had been admitted to the intensive care unit, and the 30-day mortality among all study patients was 11.3%. A total of 58 infections of the nervous system were diagnosed in 57 patients (27.9%). Among these 58 infections, metagenomic NGS identified 13 (22%) that were not identified by clinical testing at the source hospital. Among the remaining 45 infections (78%), metagenomic NGS made concurrent diagnoses in 19. Of the 26 infections not identified by metagenomic NGS, 11 were diagnosed by serologic testing only, 7 were diagnosed from tissue samples other than CSF, and 8 were negative on metagenomic NGS owing to low titers of pathogens in CSF. A total of 8 of 13 diagnoses made solely by metagenomic NGS had a likely clinical effect, with 7 of 13 guiding treatment.ConclusionsRoutine microbiologic testing is often insufficient to detect all neuroinvasive pathogens. In this study, metagenomic NGS of CSF obtained from patients with meningitis or encephalitis improved diagnosis of neurologic infections and provided actionable information in some cases. (Funded by the National Institutes of Health and others; PDAID ClinicalTrials.gov number, NCT02910037.).

BackgroundPeople living with HIV (PLWH) who experience homelessness and unstable housing (HUH) often have fragmented health care. Research that incorporates granular assessments of housing status and primary care visit adherence to understand patterns of acute care utilization can help pinpoint areas for intervention.MethodsWe collected self-reported living situation, categorized as stable (rent/own, hotel/single room occupancy), unstable (treatment/transitional program, staying with friends), or homeless (homeless shelter, outdoors/in vehicle) at an urban safety-net HIV clinic between February and August 2017 and abstracted demographic and clinical information from the medical record. Regression models evaluated the association of housing status on the frequency of acute care visits-urgent care (UC) visits, emergency department (ED) visits, and hospitalizations-and whether suboptimal primary care visit adherence (

Limited access to healthy food caused by food insecurity makes diabetes mellitus (DM) self-management more challenging. Using data from Hunger in America 2014 (n = 60,122 US food pantry users), we sought to understand food preferences and coping strategy utilization (e.g. choosing between paying for food and medical care) among households seeking assistance from US food pantries with and without DM members. The prevalence of wanting and not obtaining fruits, vegetables, dairy, and protein was high among all households. After adjusting for sociodemographic characteristics, households with DM members were more likely to want and not obtain fruits, vegetables, and dairy, and were also more likely to use several coping strategies to increase food access, compared to households without DM members. These results highlight the high demand for healthy food items among clients from US food pantries, particularly among households with DM, as well as the extra burden DM may place on food insecure households.

ObjectiveThe objective of the study is to evaluate the association of intergenerational educational attainment with cardiovascular disease (CVD) risk factors among US Latinos.MethodsWe used cross-sectional data from the Niños Lifestyle and Diabetes Study, an offspring cohort of middle-aged Mexican-Americans whose parents participated in the Sacramento Latino Study on Aging. We collected educational attainment, demographic and health behaviours and measured systolic blood pressure (SBP), fasting glucose and waist circumference. We evaluated the association of parental, offspring and a combined parent-offspring education variable with each CVD risk factor using multivariable regression.ResultsHigher parental education was associated only with smaller offspring waist circumference. In contrast, higher offspring education was associated with lower SBP, fasting glucose and smaller waist circumference. Adjustment for parental health behaviours modestly attenuated these offspring associations, whereas adjustment for offspring health behaviours and income attenuated the associations of offspring education with offspring SBP and fasting glucose but not smaller waist circumference, even among offspring with low parental education.ConclusionsHigher offspring education is associated with lower levels of CVD risk factors in adulthood, despite intergenerational exposure to low parental education.

ObjectivesChronic stress is associated with poorer age-related cognition, but the mechanisms of this relationship are not well understood. Aging increases expression of activated macrophages, leading to exacerbated immune responses to stressors. We examined the impact of stress and aging on macrophage-related inflammation and cognition in clinically normal adults.MethodsThree hundred eighty clinically normal adults were followed longitudinally (age M = 73 years; visit range: 1-8; M = 2.5 visits). Participants completed the Perceived Stress Scale, a neuropsychological battery, and blood draws. Plasma was analyzed for cytokines related to macrophage function (interleukin 6, tumor necrosis factor alpha, macrophage inflammatory protein-1 alpha, macrophage inflammatory protein-1 beta). Linear mixed-effects examined the effects of age, baseline stress, and their interaction predicting macrophage cytokines, adjusting for sex, education, and depressive symptoms. Latent growth curve models assessed the mediating role of macrophage cytokines in the relationship between age and cognition in high or low stress.ResultsBaseline perceived stress interacted with age to predict macrophage cytokines longitudinally. Specifically, high-stress adults demonstrated accelerated age-related elevations in macrophage cytokines across time. Macrophage cytokines negatively tracked with executive functioning longitudinally. Macrophage cytokines mediated 19% of the relationship between age and executive function in high-stress, but not low-stress, adults.ConclusionsOur data provide evidence of accelerated immune aging among individuals with high stress. Elevated macrophage cytokine trajectories mediated the effect of age on executive function only in individuals with high stress, suggesting these constructs may be more tightly linked in elevated stress contexts. Stress interventions are warranted to optimize immune aging, with possible downstream cognitive benefits among even clinically normal adults.

Although leukocyte telomere length (TL) shortens over the lifespan and is associated with diseases of aging, little is known about the relationships between TL, memory, and brain structure. Sixty-nine functionally normal older adults (mean age = 71.7) were assessed at 2 time points (mean interval = 2.9 years). Linear mixed models assessed relationships between TL and hippocampal volume, fractional anisotropy, and mean diffusivity (MD) of the fornix and verbal and visual episodic memory. Unstandardized coefficients are reported in the following, and p values are not corrected for multiple comparisons. A negative baseline trend was observed between TL and fornix MD (b = -0.01, p = 0.06), but no other cross-sectional associations were significant (ps > 0.16). Greater TL shortening at follow-up was associated with greater hippocampal volume loss (b = 27.09, p < 0.001), even after controlling for global volume loss (b = 10.83, p = 0.002). Greater telomere attrition was also associated with larger increases in fornix MD (b = -0.01, p = 0.012) and decreases in fornix fractional anisotropy (b = 0.004, p = 0.002). TL was not associated with changes in episodic memory (ps > 0.23). These relationships may reflect neurobiological influences that affect both TL and brain structure, as well as the effect of TL on brain aging via mechanisms such as cellular senescence and inflammation.

OBJECTIVE:Extracorporeal membrane oxygenation (ECMO) is increasingly used as a bridge to lung transplantation. The impact of preoperative ECMO on health-related quality of life (HRQL) and depressive symptoms after lung transplantation remains unknown, however. METHODS:In a single-center prospective cohort study, we assessed HRQL and depressive symptoms before and at 3, 6, and 12 months after lung transplantation using the Short Form 12 Physical and Mental Component Scores (SF12-PCS and SF12-MCS), Airway Questionnaire 20-Revised (AQ20R), EuroQol 5D (EQ5D), and Geriatric Depression Scale (GDS). Changes in HRQL were quantified by segmented linear mixed-effects models controlling for age, sex, diagnosis, preoperative forced expiratory volume in 1 second, 6-minute walk distance, and Lung Allocation Score. We compared changes in HRQL among subjects bridged with ECMO, subjects hospitalized but not on ECMO, and subjects called in for transplantation as outpatients. RESULTS:Out of 189 subjects, 17 were bridged to transplantation with ECMO. In all groups, improvements in HRQL following lung transplantation exceeded the minimally clinically important difference using the SF12-PCS, AQ20R, EQ5D, and GDS. HRQL defined by SF12-MCS did not change after transplantation. Improvements were generally similar among the groups, except for EQ5D, which showed a trend toward less benefit in the outpatients, possibly due to their better HRQL before lung transplantation. CONCLUSIONS:Subjects ill enough to require ECMO as a bridge to lung transplantation appear to achieve similar improvements in HRQL and depressive symptoms as those who do not. It is reassuring to both providers and patients that lung transplantation provides substantial improvements in HRQL, even for those patients who are critically ill in the run up to transplantation.

Diarrhea is a leading cause of death among children aged less than five years globally. Most studies of pediatric diarrhea rely on caregiver-reported stool consistency and frequency to define the disease. Research on the validity of caregiver-reported diarrhea is sparse. We collected stool samples from 2,398 children participating in two clinical trials in the Amhara region of Ethiopia. The consistency of each stool sample was graded by the child's caregiver and two trained laboratory technicians according to an illustrated stool consistency scale. We assessed the reliability of graded stool consistency among the technicians, and then compared the caregiver's grade with the technician's grade. We also tested if the illustrated stool consistency scale could improve the validity of caregiver's report. The weighted kappa measuring the agreement between the two laboratory technicians reached 0.90 after 500 stool samples were graded. The sensitivity of caregiver-reported loose or watery stool was 15.5% (95% confidence interval [CI]: 9.7, 24.2) and the specificity was 98.4% (95% CI 97.1, 99.1). With the illustrated scale, the sensitivity was 68.5% (95% CI: 58.5, 77.1) and the specificity was 86.1% (95% CI: 79.3, 90.9). The results indicate that caregiver-reported stool consistency using the terms "loose or watery" does not accurately describe stool consistency as graded by trained laboratory technicians. Given the predominance of using caregiver-reported stool consistency to define diarrheal disease, the low sensitivity identified in this study suggests that the burden of diarrheal disease may be underestimated and intervention effects could be biased. The illustrated scale is a potential low-lost tool to improve the validity of caregiver-reported stool consistency.

The default mode network (DMN) supports memory functioning and may be sensitive to preclinical Alzheimer's pathology. Little is known, however, about the longitudinal trajectory of this network's intrinsic functional connectivity (FC). In this study, we evaluated longitudinal FC in 111 cognitively normal older human adults (ages 49-87, 46 women/65 men), 92 of whom had at least three task-free fMRI scans (n = 353 total scans). Whole-brain FC and three DMN subnetworks were assessed: (1) within-DMN, (2) between anterior and posterior DMN, and (3) between medial temporal lobe network and posterior DMN. Linear mixed-effects models demonstrated significant baseline age × time interactions, indicating a nonlinear trajectory. There was a trend toward increasing FC between ages 50-66 and significantly accelerating declines after age 74. A similar interaction was observed for whole-brain FC. APOE status did not predict baseline connectivity or change in connectivity. After adjusting for network volume, changes in within-DMN connectivity were specifically associated with changes in episodic memory and processing speed but not working memory or executive functions. The relationship with processing speed was attenuated after covarying for white matter hyperintensities (WMH) and whole-brain FC, whereas within-DMN connectivity remained associated with memory above and beyond WMH and whole-brain FC. Whole-brain and DMN FC exhibit a nonlinear trajectory, with more rapid declines in older age and possibly increases in connectivity early in the aging process. Within-DMN connectivity is a marker of episodic memory performance even among cognitively healthy older adults.SIGNIFICANCE STATEMENT Default mode network and whole-brain connectivity, measured using task-free fMRI, changed nonlinearly as a function of age, with some suggestion of early increases in connectivity. For the first time, longitudinal changes in DMN connectivity were shown to correlate with changes in episodic memory, whereas volume changes in relevant brain regions did not. This relationship was not accounted for by white matter hyperintensities or mean whole-brain connectivity. Functional connectivity may be an early biomarker of changes in aging but should be used with caution given its nonmonotonic nature, which could complicate interpretation. Future studies investigating longitudinal network changes should consider whole-brain changes in connectivity.

Clarifying the mechanisms connecting neurofibrillary tangle (NFT) neurotoxicity to neuronal dysfunction in humans is likely to be pivotal for developing effective treatments for Alzheimer's disease (AD). To model the temporal progression of AD in humans, we used a collection of brains with controls and individuals from each Braak stage to quantitatively investigate the correlation between intraneuronal caspase activation or macroautophagy markers, NFT burden, and neuronal loss, in the dorsal raphe nucleus and locus coeruleus, the earliest vulnerable areas to NFT accumulation. We fit linear regressions with each count as outcomes, with Braak score and age as the predictors. In progressive Braak stages, intraneuronal active caspase-6 positivity increases both alone and overlapping with NFTs. Likewise, the proportion of NFT-bearing neurons showing autophagosomes increases. Overall, caspases may be involved in upstream cascades in AD and are associated with higher NFTs. Macroautophagy changes correlate with increasing NFT burden from early AD stages.

BackgroundHispanic patients with cystic fibrosis (CF) have decreased life expectancy compared to non-Hispanic white patients. Pulmonary function is a main predictor of life expectancy in CF. Ethnic differences in pulmonary function in CF have been understudied. The objective was to compare longitudinal pulmonary function between Hispanic and non-Hispanic white patients with CF.MethodsThis cohort study of 15 018 6-25 years old patients in the CF Foundation Patient Registry from 2008 to 2013 compared FEV1 percent predicted and longitudinal change in FEV1 percent predicted in Hispanic to non-Hispanic white patients. We used linear mixed effects models with patient-specific slopes and intercepts, adjusting for 14 demographic and clinical variables. We did sub-analyses by CFTR class, F508del copies, and PERT use.ResultsHispanic patients had lower FEV1 percent predicted (79.9%) compared with non-Hispanic white patients (85.6%); (-5.8%, 95%CI -6.7% to -4.8%, P  0.05) or between F508del copies (None: -7.6%, Heterozygotes: -5.6%, Homozygotes: -5.3%, P > 0.05).ConclusionsDisparities in pulmonary function exist in Hispanic patients with CF early in life and then persist without improving or worsening over time. It is valuable to investigate the factors contributing to pulmonary function in Hispanic patients with CF.