Genome-wide association study identifies four pan-ancestry loci for suicidal ideation in the Million Veteran Program.

Suicidal ideation (SI) often precedes and predicts suicide attempt and death, is the most common suicidal phenotype and is over-represented in veterans. The genetic architecture of SI in the absence of suicide attempt (SA) is unknown, yet believed to have distinct and overlapping risk with other suicidal behaviors. We performed the first GWAS of SI without SA in the Million Veteran Program (MVP), identifying 99,814 SI cases from electronic health records without a history of SA or suicide death (SD) and 512,567 controls without SI, SA or SD. GWAS was performed separately in the four largest ancestry groups, controlling for sex, age and genetic substructure. Ancestry-specific results were combined via meta-analysis to identify pan-ancestry loci. Four genome-wide significant (GWS) loci were identified in the pan-ancestry meta-analysis with loci on chromosomes 6 and 9 associated with suicide attempt in an independent sample. Pan-ancestry gene-based analysis identified GWS associations with DRD2, DCC, FBXL19, BCL7C, CTF1, ANNK1, and EXD3. Gene-set analysis implicated synaptic and startle response pathways (q's<0.05). European ancestry (EA) analysis identified GWS loci on chromosomes 6 and 9, as well as GWS gene associations in EXD3, DRD2, and DCC. No other ancestry-specific GWS results were identified, underscoring the need to increase representation of diverse individuals. The genetic correlation of SI and SA within MVP was high (rG = 0.87; p = 1.09e-50), as well as with post-traumatic stress disorder (PTSD; rG = 0.78; p = 1.98e-95) and major depressive disorder (MDD; rG = 0.78; p = 8.33e-83). Conditional analysis on PTSD and MDD attenuated most pan-ancestry and EA GWS signals for SI without SA to nominal significance, with the exception of EXD3 which remained GWS. Our novel findings support a polygenic and complex architecture for SI without SA which is largely shared with SA and overlaps with psychiatric conditions frequently comorbid with suicidal behaviors.

A genome-wide association study of suicide attempts in the million veterans program identifies evidence of pan-ancestry and ancestry-specific risk loci.

To identify pan-ancestry and ancestry-specific loci associated with attempting suicide among veterans, we conducted a genome-wide association study (GWAS) of suicide attempts within a large, multi-ancestry cohort of U.S. veterans enrolled in the Million Veterans Program (MVP). Cases were defined as veterans with a documented history of suicide attempts in the electronic health record (EHR; N = 14,089) and controls were defined as veterans with no documented history of suicidal thoughts or behaviors in the EHR (N = 395,064). GWAS was performed separately in each ancestry group, controlling for sex, age and genetic substructure. Pan-ancestry risk loci were identified through meta-analysis and included two genome-wide significant loci on chromosomes 20 (p = 3.64 × 10-9) and 1 (p = 3.69 × 10-8). A strong pan-ancestry signal at the Dopamine Receptor D2 locus (p = 1.77 × 10-7) was also identified and subsequently replicated in a large, independent international civilian cohort (p = 7.97 × 10-4). Additionally, ancestry-specific genome-wide significant loci were also detected in African-Americans, European-Americans, Asian-Americans, and Hispanic-Americans. Pathway analyses suggested over-representation of many biological pathways with high clinical significance, including oxytocin signaling, glutamatergic synapse, cortisol synthesis and secretion, dopaminergic synapse, and circadian rhythm. These findings confirm that the genetic architecture underlying suicide attempt risk is complex and includes both pan-ancestry and ancestry-specific risk loci. Moreover, pathway analyses suggested many commonly impacted biological pathways that could inform development of improved therapeutics for suicide prevention.

Family Caregivers of Veterans Experience Clinically Significant Levels of Distress Prepandemic and During Pandemic: Implications for Caregiver Support Services.

BACKGROUND: Of the 26.4 million family caregivers in the United States, nearly 40% report high levels of emotional strain and subjective burden. However, for the 5 million caregivers of Veterans, little is known about the experiences of caregivers of Veterans during the coronavirus disease 2019 (COVID-19) pandemic. OBJECTIVE: The aim was to examine pandemic-related changes of caregiver well-being outcomes. RESEARCH DESIGN, SUBJECTS, AND MEASURES: Using a pre/post design and longitudinal data of individual caregivers captured pre-COVID-19 and during COVID-19, we use multilevel generalized linear mixed models to examine pandemic-related changes to caregiver well-being (n=903). The primary outcome measures include Zarit Subjective Burden, Center for Epidemiologic Studies Short Depression Scale, perceived financial strain, life chaos, and loneliness. RESULTS: During the pandemic, we observe slight improvements for caregivers across well-being measures except for perceived financial strain. Before the pandemic, we observed that caregivers screened positive for clinically significant caregiver burden and probable depression. While we do not observe worsening indicators of caregiver well-being during the COVID-19 pandemic, the average predicted values of indicators of caregiver well-being remain clinically significant for caregiving subjective burden and depression. CONCLUSIONS: These findings illuminate pandemic-related impacts of caregivers receiving support through the Veterans Affairs (VA) pre-COVID and during the COVID-19 pandemic while caring for a population of frail, older care-recipients with a high burden of mental illness and other chronic conditions. Considering the long-term impacts of the pandemic to increase morbidity and the expected increased demand for caregivers in an aging population, these consistently high levels of distress despite receiving support highlight the need for interventions and policy reform to systematically support caregivers more broadly.

Evaluation of a geriatrics primary care model using prospective matching to guide enrollment.

BACKGROUND: Few definitive guidelines exist for rigorous large-scale prospective evaluation of nonrandomized programs and policies that require longitudinal primary data collection. In Veterans Affairs (VA) we identified a need to understand the impact of a geriatrics primary care model (referred to as GeriPACT); however, randomization of patients to GeriPACT vs. a traditional PACT was not feasible because GeriPACT has been rolled out nationally, and the decision to transition from PACT to GeriPACT is made jointly by a patient and provider. We describe our study design used to evaluate the comparative effectiveness of GeriPACT compared to a traditional primary care model (referred to as PACT) on patient experience and quality of care metrics. METHODS: We used prospective matching to guide enrollment of GeriPACT-PACT patient dyads across 57 VA Medical Centers. First, we identified matches based an array of administratively derived characteristics using a combination of coarsened exact and distance function matching on 11 identified key variables that may function as confounders. Once a GeriPACT patient was enrolled, matched PACT patients were then contacted for recruitment using pre-assigned priority categories based on the distance function; if eligible and consented, patients were enrolled and followed with telephone surveys for 18 months. RESULTS: We successfully enrolled 275 matched dyads in near real-time, with a median time of 7 days between enrolling a GeriPACT patient and a closely matched PACT patient. Standardized mean differences of < 0.2 among nearly all baseline variables indicates excellent baseline covariate balance. Exceptional balance on survey-collected baseline covariates not available at the time of matching suggests our procedure successfully controlled many known, but administratively unobserved, drivers of entrance to GeriPACT. CONCLUSIONS: We present an important process to prospectively evaluate the effects of different treatments when randomization is infeasible and provide guidance to researchers who may be interested in implementing a similar approach. Rich matching variables from the pre-treatment period that reflect treatment assignment mechanisms create a high quality comparison group from which to recruit. This design harnesses the power of national administrative data coupled with collection of patient reported outcomes, enabling rigorous evaluation of non-randomized programs or policies.

Transportation as a barrier to colorectal cancer care.

BACKGROUND: Transportation barriers limit access to cancer care services and contribute to suboptimal clinical outcomes. Our objectives were to describe the frequency of Veterans reporting and the factors associated with transportation barriers to or from colorectal cancer (CRC) care visits. METHODS: Between November 2015 and September 2016, Veterans with incident stage I, II, or III CRC completed a mailed survey to assess perceived barriers to recommended care. Participants who reported difficulty with transportation to or from CRC care appointments were categorized as experiencing transportation barriers. We assessed pairwise correlations between transportation barriers, transportation-related factors (e.g., mode of travel), and chaotic lifestyle (e.g., predictability of schedules), and used logistic regression to examine the association between the reporting of transportation difficulties, distance traveled to the nearest Veterans Affairs (VA) facility, and life chaos. RESULTS: Of the 115 Veterans included in this analysis, 18% reported experiencing transportation barriers. Distance to the VA was not strongly correlated with the reporting of transportation barriers (Spearman's ρ = 0.12, p = 0.19), but chaotic lifestyle was both positively and significantly correlated with experiencing transportation barriers (Spearman's ρ = 0.22, p = 0.02). Results from the logistic regression model modestly supported the findings from the pairwise correlations, but were not statistically significant. CONCLUSIONS: Transportation is an important barrier to or from CRC care visits, especially among Veterans who experience greater life chaos. Identifying Veterans who experience chaotic lifestyles would allow for timely engagement in behavioral interventions (e.g., organizational skills training) and with support services (e.g., patient navigation).

Family Caregiver Skills Training to Improve Experiences of Care: a Randomized Clinical Trial.

OBJECTIVE: To evaluate the effectiveness of Helping Invested Families Improve Veterans' Experiences Study (HI-FIVES), a skills training program for caregivers of persons with functional or cognitive impairments. DESIGN: A two-arm RCT. SETTING: Single Veterans Affairs Medical Center. PARTICIPANTS: Patients and their primary caregivers referred in the past 6 months to home and community-based services or geriatrics clinic. INTERVENTION: All caregivers received usual care. Caregivers in HI-FIVES also received five training calls and four group training sessions. MAIN MEASURES: Cumulative patient days at home 12 months post-randomization, defined as days not in an emergency department, inpatient hospital, or post-acute facility. Secondary outcomes included patients' total VA health care costs, caregiver and patient rating of the patient's experience of VA health care, and caregiver depressive symptoms. RESULTS: Of 241 dyads, caregivers' (patients') mean age was 61 (73) years, 54% (53%) Black and 89% (4%) female. HI-FIVES was associated with a not statistically significant 9% increase in the rate of days at home (95% CI 0.72, 1.65; mean difference 1 day over 12 months). No significant differences were observed in health care costs or caregiver depressive symptoms. Model-estimated mean baseline patient experience of VA care (scale of 0-10) was 8.43 (95% CI 8.16, 8.70); the modeled mean difference between HI-FIVES and controls at 3 months was 0.29 (p = .27), 0.31 (p = 0.26) at 6 months, and 0.48 (p = 0.03) at 12 months. For caregivers, it was 8.34 (95% CI 8.10, 8.57); the modeled mean difference at 3 months was 0.28 (p = .18), 0.53 (p < .01) at 6 months, and 0.46 (p = 0.054) at 12 months. CONCLUSIONS: HI-FIVES did not increase patients' days at home; it showed sustained improvements in caregivers' and patients' experience of VA care at clinically significant levels, nearly 0.5 points. The training holds promise in increasing an important metric of care quality-reported experience with care.

Medication non-adherence after myocardial infarction: an exploration of modifying factors.

BACKGROUND: Medication non-adherence is a major impediment to the management of cardiovascular disease risk factors. A better understanding of the modifying factors underlying medication non-adherence among individuals with known cardiovascular disease may inform approaches for addressing non-adherence. OBJECTIVE: The purpose of this study was to identify demographic and patient characteristics, medical comorbidities, psychosocial factors, and health belief-related factors associated with medication non-adherence among patients with known cardiovascular disease. DESIGN: We performed secondary analysis of baseline data from a randomized trial. PATIENTS: The study included 405 patients with a diagnosis of hypertension and history of acute myocardial infarction that was diagnosed within a three-year period prior to enrollment. MAIN MEASURES: Baseline demographics and patient characteristics, medical comorbidities, psychosocial factors, health belief-related factors, and patient-reported medication non-adherence were analyzed. KEY RESULTS: Of 405 patients, 173 (42.7 %) reported medication non-adherence. Factors associated with non-adherence in bivariate analysis included younger age, non-white race, having less than 12 years of education, smoking, financial insecurity, identifying as nervous or tense, higher life chaos score, greater worry about having a myocardial infarction, and greater worry about having a stroke. Using multivariable modeling, we determined that age (OR 0.97 per additional year, 95 % CI, 0.95-0.99), life chaos (OR 1.06 per additional point, 95 % CI, 1.00-1.11), and worry about stroke (OR 1.12 per additional point, 95 % CI, 1.01-1.25) remained significantly associated with self-reported medication non-adherence. CONCLUSIONS: We found that worry about having a stroke, higher life chaos, and younger age were all significantly associated with self-reported medication non-adherence in patients with cardiovascular disease and a history of myocardial infarction. Further research exploring these factors as targets for intervention is needed, as is additional research examining modifiable causes of medication non-adherence among patients with cardiovascular disease.

Nurse-led behavioral management of diabetes and hypertension in community practices: a randomized trial.

BACKGROUND: Several trials have demonstrated the efficacy of nurse telephone case management for diabetes (DM) and hypertension (HTN) in academic or vertically integrated systems. Little is known about the real-world potency of these interventions. OBJECTIVE: To assess the effectiveness of nurse behavioral management of DM and HTN in community practices among patients with both diseases. DESIGN: The study was designed as a patient-level randomized controlled trial. PARTICIPANTS: Participants included adult patients with both type 2 DM and HTN who were receiving care at one of nine community fee-for-service practices. Subjects were required to have inadequately controlled DM (hemoglobin A1c [A1c] ≥ 7.5%) but could have well-controlled HTN. INTERVENTIONS: All patients received a call from a nurse experienced in DM and HTN management once every two months over a period of two years, for a total of 12 calls. Intervention patients received tailored DM- and HTN- focused behavioral content; control patients received non-tailored, non-interactive information regarding health issues unrelated to DM and HTN (e.g., skin cancer prevention). MAIN OUTCOMES AND MEASURES: Systolic blood pressure (SBP) and A1c were co-primary outcomes, measured at 6, 12, and 24 months; 24 months was the primary time point. RESULTS: Three hundred seventy-seven subjects were enrolled; 193 were randomized to intervention, 184 to control. Subjects were 55% female and 50% white; the mean baseline A1c was 9.1% (SD = 1%) and mean SBP was 142 mmHg (SD = 20). Eighty-two percent of scheduled interviews were conducted; 69% of intervention patients and 70% of control patients reached the 24-month time point. Expressing model estimated differences as (intervention--control), at 24 months, intervention patients had similar A1c [diff = 0.1 %, 95 % CI (-0.3, 0.5), p = 0.51] and SBP [diff = -0.9 mmHg, 95% CI (-5.4, 3.5), p = 0.68] values compared to control patients. Likewise, DBP (diff = 0.4 mmHg, p = 0.76), weight (diff = 0.3 kg, p = 0.80), and physical activity levels (diff = 153 MET-min/week, p = 0.41) were similar between control and intervention patients. Results were also similar at the 6- and 12-month time points. CONCLUSIONS: In nine community fee-for-service practices, telephonic nurse case management did not lead to improvement in A1c or SBP. Gains seen in telephonic behavioral self-management interventions in optimal settings may not translate to the wider range of primary care settings.

Willingness of Patients to Use Computers for Health Communication and Monitoring Following Myocardial Infarction.

We describe the computer use characteristics of 406 post-myocardial infarction (MI) patients and their willingness to engage online for health communication and monitoring. Most participants were computer users (n = 259; 63.8%) and half (n = 209; 51.5%) read health information online at least monthly. However, most participants did not go online to track health conditions (n = 283; 69.7%), look at medical records (n = 287; 70.7%), or e-mail doctors (n = 351; 86.5%). Most participants would consider using a Web site to e-mail doctors (n = 275; 67.7%), share medical information with doctors (n = 302; 74.4%), send biological data to their doctor (n = 308; 75.9%), look at medical records (n = 321; 79.1%), track health conditions (n = 331; 81.5%), and read about health conditions (n = 332; 81.8%). Sharing health information online with family members (n = 181; 44.6%) or for support groups (n = 223; 54.9%) was not of much interest. Most post-MI participants reported they were interested in communicating with their provider and tracking their health conditions online. Because patients with a history of MI tend to be older and are disproportionately minority, researchers and clinicians must be careful to design interventions that embrace post-MI patients of diverse backgrounds that both improve their access to care and health outcomes.

Differences in osteoarthritis self-management support intervention outcomes according to race and health literacy.

We explored whether the effects of a telephone-based osteoarthritis (OA) self-management support intervention differed by race and health literacy. Participants included 515 veterans with hip and/or knee OA. Linear mixed models assessed differential effects of the intervention compared with health education (HE) and usual care (UC) on pain (Arthritis Impact Measurement Scales-2 [AIMS2] and Visual Analogue Scale), function (AIMS2 mobility and walking/bending), affect (AIMS2) and arthritis self-efficacy by: (i) race (white/non-white), (ii) health literacy (high/low) and (iii) race by health literacy. AIMS2 mobility improved more among non-whites than whites in the intervention compared with HE and UC (P = 0.02 and 0.008). AIMS2 pain improved more among participants with low than high literacy in the intervention compared with HE (P = 0.05). However, we found a differential effect of the intervention on AIMS2 pain compared with UC according to the combination of race and health literacy (P = 0.05); non-whites with low literacy in the intervention had the greatest improvement in pain. This telephone-based OA intervention may be particularly beneficial for patients with OA who are racial/ethnic minorities and have low health literacy. These results warrant further research designed specifically to assess whether this type of intervention can reduce OA disparities.

Informing a home time measure reflective of quality of life: A data driven investigation of time frames and settings of health care utilization.

OBJECTIVE: To evaluate short- and long-term measures of health care utilization-days in the emergency department (ED), inpatient (IP) care, and rehabilitation in a post-acute care (PAC) facility-to understand how home time (i.e., days alive and not in an acute or PAC setting) corresponds to quality of life (QoL). DATA SOURCES: Survey data on community-residing veterans combined with multipayer administrative data on health care utilization. STUDY DESIGN: VA or Medicare health care utilization, quantified as days of care received in the ED, IP, and PAC in the 6 and 18 months preceding survey completion, were used to predict seven QoL-related measures collected during the survey. Elastic net machine learning was used to construct models, with resulting regression coefficients used to develop a weighted utilization variable. This was then compared with an unweighted count of days with any utilization. PRINCIPAL FINDINGS: In the short term (6 months), PAC utilization emerged as the most salient predictor of decreased QoL, whereas no setting predominated in the long term (18 months). Results varied by outcome and time frame, with some protective effects observed. In the 6-month time frame, each weighted day of utilization was associated with a greater likelihood of activity of daily living deficits (0.5%, 95% CI: 0.1%-0.9%), as was the case with each unweighted day of utilization (0.6%, 95% CI: 0.3%-1.0%). The same was true in the 18-month time frame (for both weighted and unweighted, 0.1%, 95% CI: 0.0%-0.3%). Days of utilization were also significantly associated with greater rates of instrumental ADL deficits and fair/poor health, albeit not consistently across all models. Neither measure outperformed the other in direct comparisons. CONCLUSIONS: These results can provide guidance on how to measure home time using multipayer administrative data. While no setting predominated in the long term, all settings were significant predictors of QoL measures.

Identification of Novel, Replicable Genetic Risk Loci for Suicidal Thoughts and Behaviors Among US Military Veterans.

Importance: Suicide is a leading cause of death; however, the molecular genetic basis of suicidal thoughts and behaviors (SITB) remains unknown. Objective: To identify novel, replicable genomic risk loci for SITB. Design, Setting, and Participants: This genome-wide association study included 633 778 US military veterans with and without SITB, as identified through electronic health records. GWAS was performed separately by ancestry, controlling for sex, age, and genetic substructure. Cross-ancestry risk loci were identified through meta-analysis. Study enrollment began in 2011 and is ongoing. Data were analyzed from November 2021 to August 2022. Main Outcome and Measures: SITB. Results: A total of 633 778 US military veterans were included in the analysis (57 152 [9%] female; 121 118 [19.1%] African ancestry, 8285 [1.3%] Asian ancestry, 452 767 [71.4%] European ancestry, and 51 608 [8.1%] Hispanic ancestry), including 121 211 individuals with SITB (19.1%). Meta-analysis identified more than 200 GWS (P < 5 × 10-8) cross-ancestry risk single-nucleotide variants for SITB concentrated in 7 regions on chromosomes 2, 6, 9, 11, 14, 16, and 18. Top single-nucleotide variants were largely intronic in nature; 5 were independently replicated in ISGC, including rs6557168 in ESR1, rs12808482 in DRD2, rs77641763 in EXD3, rs10671545 in DCC, and rs36006172 in TRAF3. Associations for FBXL19 and AC018880.2 were not replicated. Gene-based analyses implicated 24 additional GWS cross-ancestry risk genes, including FURIN, TSNARE1, and the NCAM1-TTC12-ANKK1-DRD2 gene cluster. Cross-ancestry enrichment analyses revealed significant enrichment for expression in brain and pituitary tissue, synapse and ubiquitination processes, amphetamine addiction, parathyroid hormone synthesis, axon guidance, and dopaminergic pathways. Seven other unique European ancestry-specific GWS loci were identified, 2 of which (POM121L2 and METTL15/LINC02758) were replicated. Two additional GWS ancestry-specific loci were identified within the African ancestry (PET112/GATB) and Hispanic ancestry (intergenic locus on chromosome 4) subsets, both of which were replicated. No GWS loci were identified within the Asian ancestry subset; however, significant enrichment was observed for axon guidance, cyclic adenosine monophosphate signaling, focal adhesion, glutamatergic synapse, and oxytocin signaling pathways across all ancestries. Within the European ancestry subset, genetic correlations (r > 0.75) were observed between the SITB phenotype and a suicide attempt-only phenotype, depression, and posttraumatic stress disorder. Additionally, polygenic risk score analyses revealed that the Million Veteran Program polygenic risk score had nominally significant main effects in 2 independent samples of veterans of European and African ancestry. Conclusions and Relevance: The findings of this analysis may advance understanding of the molecular genetic basis of SITB and provide evidence for ESR1, DRD2, TRAF3, and DCC as cross-ancestry candidate risk genes. More work is needed to replicate these findings and to determine if and how these genes might impact clinical care.

Participant evaluation of a telephone-based osteoarthritis self-management program, 2006-2009.

INTRODUCTION: Self-management support interventions can help improve osteoarthritis outcomes but are underused. Little is known about how participants evaluate the helpfulness of these programs. We describe participants' evaluations of a telephone-based, osteoarthritis self-management support intervention that yielded improved outcomes in a clinical trial. METHODS: Participants were 140 people in the intervention arm of the trial who completed an end-of-trial survey. We used mixed methods to describe participants' perceived helpfulness of the program and its components. We compared ratings of helpfulness according to participant characteristics and analyzed themes from open-ended responses with a constant comparison approach. We calculated Pearson correlation coefficients between perceived helpfulness and changes in pain, function, affect, and self-efficacy. RESULTS: The average rating of overall helpfulness on a scale from 1 to 10 was 7.6 (standard deviation, 2.3), and more than 80% of participants agreed that each component (phone calls, educational material, setting goals and action plans) was helpful. Participants had better perceived helpfulness ratings than their counterparts if they were nonwhite, had limited health literacy, had no college education, had perceived inadequate income, were older, had a spouse or were living together in a committed relationship, and had greater symptom duration and less pain. Ratings of helpfulness increased with greater improvement in outcomes. Participants frequently mentioned the health educator's calls as being helpful for staying on task with self-management behaviors. CONCLUSION: Participants viewed this intervention and each of its components as helpful for improving osteoarthritis symptoms. In addition to the improvements in objective outcomes seen in the clinical trial, these results provide further support for the dissemination of self-management support interventions.

Which domains of spirituality are associated with anxiety and depression in patients with advanced illness?

BACKGROUND: Anxiety and depression are common in seriously ill patients and may be associated with spiritual concerns. Little research has examined how concerns in different domains of spirituality are related to anxiety and depression. OBJECTIVE: To examine the association of spiritual history and current spiritual well-being with symptoms of anxiety and depression in patients with advanced illness. DESIGN: Cross-sectional cohort study PARTICIPANTS: Two hundred and ten patients with advanced illness, of whom 1/3 were diagnosed with cancer, 1/3 COPD, and 1/3 CHF. The mean age of the sample was 66 years, and 91% were Christian. MEASUREMENTS: Outcome measures were the Profile of Mood States' Anxiety Subscale (POMS) and 10-item Center for Epidemiologic Studies Depression Scale (CESD). Predictors were three subscales of the Spiritual History Scale measuring past religious help-seeking and support, past religious participation, and past negative religious experiences and two subscales of the Functional Assessment of Chronic Illness Therapy Spiritual Well-Being Scale measuring the role of faith in illness and meaning, peace, and purpose in life. We conducted multiple regression analyses, controlling for demographics, disease type and severity, self-rated religiousness/spirituality, and frequency of religious attendance and devotion. RESULTS: In adjusted analyses, greater spiritual well-being, including both beliefs about the role of faith in illness and meaning, peace, and purpose in life were associated with fewer symptoms of anxiety (P ≤ 0.001) and depression (P < 0.001). Greater past negative religious experiences were associated with more symptoms of anxiety (P = 0.04) and depression (P = 0.004). No other measures of spiritual history were associated with the outcomes. CONCLUSIONS: In this diverse sample of seriously ill patients, current spiritual well-being and past negative religious experiences were associated with symptoms of anxiety and depression. Healthcare providers should consider asking about current spiritual well-being and past negative religious experiences in their assessment of seriously ill patients with symptoms of anxiety and depression.

Telephone-based self-management of osteoarthritis: A randomized trial.

BACKGROUND: Osteoarthritis is a leading cause of pain and disability, and self-management behaviors for osteoarthritis are underutilized. OBJECTIVE: To examine the effectiveness of a telephone-based self-management intervention for hip or knee osteoarthritis in a primary care setting. DESIGN: Randomized clinical trial with equal assignment to osteoarthritis self-management, health education (attention control), and usual care control groups. (ClinicalTrials.gov registration number: NCT00288912) SETTING: Primary care clinics in a Veterans Affairs Medical Center. PATIENTS: 515 patients with symptomatic hip or knee osteoarthritis. INTERVENTION: The osteoarthritis self-management intervention involved educational materials and 12 monthly telephone calls to support individualized goals and action plans. The health education intervention involved nonosteoarthritis educational materials and 12 monthly telephone calls related to general health screening topics. MEASUREMENTS: The primary outcome was score on the Arthritis Impact Measurement Scales-2 pain subscale (range, 0 to 10). Pain was also assessed with a 10-cm visual analog scale. Measurements were collected at baseline and 12 months. RESULTS: 461 participants (90%) completed the 12-month assessment. The mean Arthritis Impact Measurement Scales-2 pain score in the osteoarthritis self-management group was 0.4 point lower (95% CI, -0.8 to 0.1 point; P = 0.105) than in the usual care group and 0.6 point lower (CI, -1.0 to -0.2 point; P = 0.007) than in the health education group at 12 months. The mean visual analog scale pain score in the osteoarthritis self-management group was 1.1 points lower (CI, -1.6 to -0.6 point; P < 0.001) than in the usual care group and 1.0 point lower (CI, -1.5 to -0.5 point; P < 0.001) than in the health education group. Health care use did not differ across the groups. LIMITATION: The study was conducted at 1 Veterans Affairs Medical Center, and the sample consisted primarily of men. CONCLUSION: A telephone-based osteoarthritis self-management program produced moderate improvements in pain, particularly compared with a health education control group. PRIMARY FUNDING SOURCE: U.S. Department of Veterans Affairs Health Services Research and Development Service.

Clergy-laity support and patients' mood during serious illness: a cross-sectional epidemiologic study.

OBJECTIVES: Religious participation is positively associated with mental health, but attendance at worship services declines during serious illness. This study assessed whether home visits by clergy or laity provide benefits to seriously ill patients who may have difficulty attending religious services. METHOD: A cross-sectional study design nested in an observational epidemiologic cohort study was used. The regionally representative sample of patients had metastatic lung, colorectal, breast, and prostate cancer (n = 70); Class III and IV congestive heart failure (n = 70); or chronic obstructive pulmonary disease with hypercapnea (n = 70) and were observed regarding clergy-laity support in their natural environments. DEPENDENT VARIABLE: 10-item Center for Epidemiologic Studies - Depression Scale. INDEPENDENT VARIABLE: A one-item question measuring how much helpful support patients received from clergy or other persons from church, temple, synagogue, or mosque. Covariates: demographic, health, social support, religiousness. RESULTS: Depressed mood was negatively associated with clergy-laity support in a non-linear pattern. Depressed mood was also positively associated with functional deficits and a lifetime history of difficulties related to religious involvement. SIGNIFICANCE OF RESULTS: In lieu of worship attendance when people are sick, home visits by members of a patient's religious community may bolster mood by providing continuity of instrumental, emotional, and spiritual support.

Time to diagnosis in the National Registry of Veterans with Amyotrophic Lateral Sclerosis.

Our objective was to determine the interval from symptom onset to diagnosis, and to evaluate associated factors in a cohort of U.S. Veterans with motor neuron diseases. We retrospectively evaluated 1359 patients enrolled in the National Registry of Veterans with Amyotrophic Lateral Sclerosis (ALS). The main outcome measures were time from symptom onset to first diagnosis and to second opinion. Predictor variables included age at symptom onset, year of symptom onset, race, onset site, final diagnosis, number of diagnostic tests performed and clinical sites visited. Median time to first diagnosis was 11 months; median time to second opinion was two months. In a multivariable model, more recent calendar year of symptom onset, younger age, bulbar onset and a diagnosis of ALS versus non-ALS motor neuron disease were all significantly associated with a shorter time to first diagnosis. Later year of symptom onset and white race were significantly associated with a shorter time to second opinion. While the interval from symptom onset to diagnosis, and many of the associated factors are similar between our large cohort of U.S. Veterans with ALS and other smaller published cohorts, we found that the diagnostic interval among U.S. Veterans has significantly decreased over time.

Family Caregivers of Veterans Experience High Levels of Burden, Distress, and Financial Strain.

BACKGROUND/OBJECTIVES: To describe the caregiving experiences and physical and emotional needs of family members and friends who provide care to veterans with mental, physical, and cognitive comorbidities. DESIGN: Cross-sectional study. SETTING: National telephone surveys administered from 2017 to 2019. PARTICIPANTS: Family caregivers of veterans enrolled in the Veterans Affairs (VA) Program of General Caregiver Support Services between October 2016 and July 2018 who responded to a telephone survey (N = 1,509; response rate = 39%). MEASUREMENTS: We examined caregiver burden, depressive symptoms, financial strain, satisfaction with care, amount and duration of caregiving, life chaos, loneliness, and integration of caregiver with the healthcare team using validated instruments. We also collected caregiver demographic and socioeconomic characteristics and asked caregivers to identify the veteran's condition(s) and provide an assessment of the veteran's functioning. RESULTS: Average caregiver age was 62.2 (standard deviation [SD] = 13.7) and 69.8 (SD = 15.6) for veterans. Among caregivers, 76.7% identified at White, and 79.9% were married to the veteran. Caregivers reported having provided care for an average of 6.4 years and spending on average 9.6 hours per day and 6.6 days per week providing care. Average Zarit Subjective Burden score was 21.8 (SD = 9.4; range = 0-47), which is well above the cutoff for clinically significant burden (>16). Caregivers reported high levels of depressive symptoms; the sample average Center for Epidemiologic Studies Depression 10-item Scale score was 11.5 (SD = 7.1; range = 0-30). Caregivers also reported high levels of loneliness and financial strain. CONCLUSION: Caregivers who care for veterans with trauma-based comorbidities reported intensive caregiving and significant levels of distress, depressive symptoms, and other negative consequences. These caregivers require comprehensive support services including access to health care, financial assistance, and enhanced respite care. Planned expansion of VA caregiver support has the potential to provide positive benefits for this population and serve as a model for caregiver support programs outside the VA health care system.

Identifying treatment effects of an informal caregiver education intervention to increase days in the community and decrease caregiver distress: a machine-learning secondary analysis of subgroup effects in the HI-FIVES randomized clinical trial.

BACKGROUND: Informal caregivers report substantial burden and depressive symptoms which predict higher rates of patient institutionalization. While caregiver education interventions may reduce caregiver distress and decrease the use of long-term institutional care, evidence is mixed. Inconsistent findings across studies may be the result of reporting average treatment effects which do not account for how effects differ by participant characteristics. We apply a machine-learning approach to randomized clinical trial (RCT) data of the Helping Invested Family Members Improve Veteran's Experiences Study (HI-FIVES) intervention to explore how intervention effects vary by caregiver and patient characteristics. METHODS: We used model-based recursive partitioning models. Caregivers of community-residing older adult US veterans with functional or cognitive impairment at a single VA Medical Center site were randomized to receive HI-FIVES (n = 118) vs. usual care (n = 123). The outcomes included cumulative days not in the community and caregiver depressive symptoms assessed at 12 months post intervention. Potential moderating characteristics were: veteran age, caregiver age, caregiver ethnicity and race, relationship satisfaction, caregiver burden, perceived financial strain, caregiver depressive symptoms, and patient risk score. RESULTS: The effect of HI-FIVES on days not at home was moderated by caregiver burden (p < 0.001); treatment effects were higher for caregivers with a Zarit Burden Scale score ≤ 28. Caregivers with lower baseline Center for Epidemiologic Studies Depression Scale (CESD-10) scores (≤ 8) had slightly lower CESD-10 scores at follow-up (p < 0.001). CONCLUSIONS: Family caregiver education interventions may be less beneficial for highly burdened and distressed caregivers; these caregivers may require a more tailored approach that involves assessing caregiver needs and developing personalized approaches. TRIAL REGISTRATION: ClinicalTrials.gov, ID:NCT01777490. Registered on 28 January 2013.

Clinical aspects of ALS in Gulf War veterans.

The increased incidence of ALS in military veterans of the first Persian Gulf War raised speculation that they may have a 'Persian Gulf' variant of ALS with atypical clinical features. Medical records of military veterans with ALS, previously identified in our epidemiological study, were evaluated for clinical features (age and site of onset, race, unexplained atypical findings) and ventilator-free survival. Comparisons between deployed versus non-deployed cohorts were made with deployment status based on designation by the Department of Defense Manpower Data Center (DMDC) or by self-report. Other than the young age of onset in both cohorts (40.8 years overall mean; 40.1 years for DMDC deployed, 41.2 years for DMDC non-deployed), review of the medical records failed to document any atypical features. After adjusting for bulbar onset, median survival from symptom onset in those > or =40 years of age was 35.5 months (2.96 years) compared to 64.7 months (5.39 years) in the group <40 years of age (hazard ratio (HR)=0.47, 95% CI 0.30-0.73, p=0.0006). After adjusting for age, median survival was 45.4 months (3.78 years) and 54.8 months (4.57 years) in bulbar- versus non-bulbar onset groups, respectively (HR=1.41, 95% CI 0.83-2.39, p=0.20). After adjusting for age and site of onset, deployed veterans had significantly shorter survival than non-deployed (40.2 vs. 57.0 months, HR=0.62, 95% CI 0.40-0.96, p=0.03) using DMDC data. In conclusion, although veterans developing ALS after deployment to the Persian Gulf in 1990-1991 exhibited otherwise typical clinical features, they experienced shorter ventilator-free survival than non-deployed veterans.