Validation of a hybrid approach to standardize immunophenotyping analysis in large population studies: The Health and Retirement Study.

Traditional manual gating strategies are often time-intensive, place a high burden on the analyzer, and are susceptible to bias between analyzers. Several automated gating methods have shown to exceed performance of manual gating for a limited number of cell subsets. However, many of the automated algorithms still require significant manual interventions or have yet to demonstrate their utility in large datasets. Therefore, we developed an approach that utilizes a previously published automated algorithm (OpenCyto framework) with a manually created hierarchically cell gating template implemented, along with a custom developed visualization software (FlowAnnotator) to rapidly and efficiently analyze immunophenotyping data in large population studies. This approach allows pre-defining populations that can be analyzed solely by automated analysis and incorporating manual refinement for smaller downstream populations. We validated this method with traditional manual gating strategies for 24 subsets of T cells, B cells, NK cells, monocytes and dendritic cells in 931 participants from the Health and Retirement Study (HRS). Our results show a high degree of correlation (r ≥ 0.80) for 18 (78%) of the 24 cell subsets. For the remaining subsets, the correlation was low (<0.80) primarily because of the low numbers of events recorded in these subsets. The mean difference in the absolute counts between the hybrid method and manual gating strategy of these cell subsets showed results that were very similar to the traditional manual gating method. We describe a practical method for standardization of immunophenotyping methods in large scale population studies that provides a rapid, accurate and reproducible alternative to labor intensive manual gating strategies.

Field Application of Digital Technologies for Health Assessment in the 10,000 Families Study.

BACKGROUND: We field tested new-to-market portable, digital applications to assess hearing, pulmonary, and cognitive function to determine the feasibility of implementing these applications across a range of age groups in the pilot phase of the 10,000 Families Study (10KFS), a new Minnesota family-based prospective cohort study. METHODS: We followed manufacturer recommended protocols for audiometry (SHOEBOX Inc), spirometry (NuvoAir), and the digital clock drawing test (dCDT; Digital Cognition Technologies Inc). RESULTS: These digital devices were low cost and readily implemented in a 2.5-hour health fair visit with minimal training (2-3 hours) of study staff. To date, we have performed these measurements on 197 eligible 10KFS participants during an in-person clinic visit. A total of 37 children (age 4-17 years), 107 adults (18-64 years), and 53 seniors (≥65 years) were eligible to undergo hearing and pulmonary assessments. Children were less likely to successfully complete the hearing test (76%) compared with adults (86%) and seniors (89%). However, successful completion of the pulmonary assessment was high across all groups: 100% of children and seniors and 98% of adults. The dCDT was performed among those over the age of 40, and completion rates were 92% for those aged 41-64 and 94% for those ≥65 years. CONCLUSIONS: Our field testing indicates these digital applications are easy and cost-effective to implement in epidemiologic studies. IMPACT: Digital applications provide exciting opportunities to collect data in population studies. Issues related to data privacy, data access, and reproducibility of measurements need to be addressed before deploying digital applications in epidemiologic studies.See all articles in this CEBP Focus section, "Modernizing Population Science."

The association between comorbidity and outcome in pathological gambling: a prospective follow-up of recent quitters.

A naturalistic sample of pathological gamblers (N = 101) who recently quit gambling was followed prospectively for a year (follow-up rate 80%). Lifetime mood disorders were identified in 61% of participants and 73% and 48% had lifetime alcohol use and drug use disorders, respectively. Current prevalence rates, however, were much lower. Current mood disorders were found for 20% and 7% had a current alcohol disorder and 7% a current drug use disorder. Age of onset for substance use disorders was earlier than gambling disorders but mood disorders were equally likely to predate or follow gambling disorders. Lifetime mood disorder was associated with a longer time to achieve 3 months of stable abstinence. Participants who were currently in treatment or attending Gamblers Anonymous and the small number of participants with current alcohol disorders were also more likely to achieve abstinence earlier. The results underscore the importance of increasing our understanding of the role of comorbid disorders in the recovery process from gambling problems.

Underreporting of behavioral problems in older hospitalized patients.

This descriptive study examined reports of behavioral problems among older patients hospitalized in acute care medical settings. Greater numbers of behavioral problems were reported by nursing staff on the Neuropsychiatric Inventory-Questionnaire than were documented in medical charts over the same time period. Such underreporting may have clinical and administrative implications.

Mixed anxiety and depression in older adults: clinical characteristics and management.

The frequent comorbidity of anxiety and depression, particularly among elderly, is widely recognized by clinicians, but the debate continues as to whether the combined diagnostic designation is merited. This article reviews the debate over the mixed diagnosis, discusses treatment implications, and reviews a small treatment study undertaken with elderly patients. Ten community-dwelling, older adults diagnosed with generalized anxiety disorder and subsyndromal depression (n = 6) or generalized anxiety disorder and major depressive disorder (n = 4) were started on a 12-week, open-label trial of nefazodone. Clinicians' ratings on the Clinical Global Impression of Change and patients' self-ratings of symptoms on the Beck Depression Inventory and the Beck Anxiety Inventory identified statistically significant gains in patients' overall pre/post functioning. Nefazodone was efficacious in symptom alleviation in patients with comorbid anxiety and depression. Further double-blind, randomized investigations with newer antidepressant medications are required to extend these preliminary findings with nefazodone.

Assessment of trauma exposure and post-traumatic stress in long-term care veterans: preliminary data on psychometrics and post-traumatic stress disorder prevalence.

This article reports preliminary data on trauma and post-traumatic stress disorder (PTSD) prevalence, as well as test psychometrics, among 35 cognitively intact veterans residing in long-term care settings. Participants received a traumatic event screening, the Mini-Mental Status Examination, Combat Exposure Scale (CES), PTSD Checklist (PCL), and Mississippi Combat PTSD Scale (M-PTSD). Results demonstrated adequate reliability for the CES, PCL, and M-PTSD for use in these settings, with several significant intercorrelations. A high prevalence of trauma exposure was found, in particular combat. Based on the PCL and M-PTSD, although most veterans did not meet full PTSD diagnostic criteria, a moderate proportion met partial criteria. The need for assessment and treatment of trauma exposure and PTSD in Veterans Affairs long-term care settings is emphasized.

Efficacy, safety, and tolerability of sertraline in patients with late-life depression and comorbid medical illness.

OBJECTIVES: To report on the efficacy, safety, and tolerability of sertraline in the treatment of elderly depres-sed patients with and without comorbid medical illness. SETTING: Multicenter. DESIGN: Randomized, double-blind, placebo-controlled study. PARTICIPANTS: A total of 752 patients aged 60 and older with diagnosis of major depressive disorder according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, diagnosis. MEASUREMENTS: Outcome measures included the 17-item Hamilton Depression Scale (HAMD); the Clinical Global Depression-Severity/Improvement (CGI-S/CGI-I); efficacy and safety/adverse event assessments; Quality of Life, Enjoyment, and Satisfaction Questionnaire; and the Medical Outcomes Study 36-Item Short-Form Health Status Survey. RESULTS: In the overall sample, sertraline was superior to placebo on all three primary outcome measures, HAMD, and overall clinical severity and change (CGI-S/CGI-I). Furthermore, therapeutic response to sertraline was comparable in those with or without medical comorbidity, and there were no treatment-by-comorbidity group interactions. Sertraline was also associated with a faster time to response than placebo in the comorbid group (P<.006). Sertraline-treated patients in the comorbid group had similar adverse events and discontinuations when compared to those in the noncomorbid group. CONCLUSION: Sertraline was efficacious in reducing depressive symptomatology, regardless of the presence of comorbid medical illness. Sertraline was safe and well tolerated by patients with or without medical illness.

Cognitive status and behavioral problems in older hospitalized patients.

OBJECTIVES: (a) To determine the quantity and quality of behavioral problems in older hospitalized patients on acute care units; (b) to determine the burden of these behaviors on staff; and (c) to identify predictors of behavioral problems. METHODS: Upon admission, patients performed the Mini-Mental State Exam (MMSE), the Geriatric Depression Scale (GDS), and information was obtained on age, ethnicity, level of education, living arrangement, and psychiatric history. Two days post-admission, a clinical staff member caring for each patient, performed the Neuropsychiatric Inventory-Questionnaire (NPI-Q) to assess patients' behavioral problems and staff distress. PARTICIPANTS AND SETTING : Forty-two patients, over 60 years of age, admitted to medical and surgical units of the Veterans Affairs Hospitals in Palo Alto and San Francisco, participated. RESULTS: Twenty-three of 42 (55%) patients exhibited behavioral problems. Anxiety, depression, irritability, and agitation/aggression were the most frequently observed behaviors. The severity of the behavioral problems was significantly correlated with staff distress. Lower performance on the MMSE at admission was significantly associated with higher NPI-Q ratings. Specifically, of those cases with scores less than or equal to 27 on the MMSE, 66% had behavioral problems during hospitalization, compared to only 31% of those with scores greater than 27. CONCLUSION: Behavioral problems in older hospitalized patients appear to occur frequently, are a significant source of distress to staff, and can result in the need for psychiatric consultation. Assessment of the mental status of older adults at admission to hospital may be valuable in identifying individuals at increased risk for behavioral problems during hospitalization.