Metastable Atrial State Underlies the Primary Genetic Substrate for MYL4 Mutation-Associated Atrial Fibrillation.

BACKGROUND: Atrial fibrillation (AF) is the most common clinical arrhythmia and is associated with heart failure, stroke, and increased mortality. The myocardial substrate for AF is poorly understood because of limited access to primary human tissue and mechanistic questions around existing in vitro or in vivo models. METHODS: Using an MYH6:mCherry knock-in reporter line, we developed a protocol to generate and highly purify human pluripotent stem cell-derived cardiomyocytes displaying physiological and molecular characteristics of atrial cells. We modeled human MYL4 mutants, one of the few definitive genetic causes of AF. To explore non-cell-autonomous components of AF substrate, we also created a zebrafish Myl4 knockout model, which exhibited molecular, cellular, and physiologic abnormalities that parallel those in humans bearing the cognate mutations. RESULTS: There was evidence of increased retinoic acid signaling in both human embryonic stem cells and zebrafish mutant models, as well as abnormal expression and localization of cytoskeletal proteins, and loss of intracellular nicotinamide adenine dinucleotide and nicotinamide adenine dinucleotide + hydrogen. To identify potentially druggable proximate mechanisms, we performed a chemical suppressor screen integrating multiple human cellular and zebrafish in vivo endpoints. This screen identified Cx43 (connexin 43) hemichannel blockade as a robust suppressor of the abnormal phenotypes in both models of MYL4 (myosin light chain 4)-related atrial cardiomyopathy. Immunofluorescence and coimmunoprecipitation studies revealed an interaction between MYL4 and Cx43 with altered localization of Cx43 hemichannels to the lateral membrane in MYL4 mutants, as well as in atrial biopsies from unselected forms of human AF. The membrane fraction from MYL4-/- human embryonic stem cell derived atrial cells demonstrated increased phospho-Cx43, which was further accentuated by retinoic acid treatment and by the presence of risk alleles at the Pitx2 locus. PKC (protein kinase C) was induced by retinoic acid, and PKC inhibition also rescued the abnormal phenotypes in the atrial cardiomyopathy models. CONCLUSIONS: These data establish a mechanistic link between the transcriptional, metabolic and electrical pathways previously implicated in AF substrate and suggest novel avenues for the prevention or therapy of this common arrhythmia.

Behavioral Treatment for Veterans with Obesity: 24-Month Weight Outcomes from the ASPIRE-VA Small Changes Randomized Trial.

BACKGROUND: Small Changes (SC) is a weight management approach that demonstrated superior 12-month outcomes compared to the existing MOVE!® Weight Management Program at two Veterans Affairs (VA) sites. However, approaches are needed to help graduates of treatment continue to lose or maintain their weight over the longer term. OBJECTIVE: The purpose of the present study was to examine the effectiveness of a second year of low-intensity SC support compared to support offered by the usual care MOVE! programs. DESIGN: Following participation in the year-long Aspiring to Lifelong Health in VA (ASPIRE-VA) randomized controlled trial, participants were invited to extend their participation in their assigned program for another year. Three programs were extended to include six SC sessions delivered via telephone (ASPIRE-Phone) or an in-person group (ASPIRE-Group), or 12 sessions offered by the MOVE! programs. PARTICIPANTS: Three hundred thirty-two overweight/obese veterans who consented to extend their participation in the ASPIRE-VA trial by an additional year. MAIN MEASURES: Twenty-four-month weight change (kg). KEY RESULTS: Twenty-four months after baseline, participants in all three groups had modest weight loss (-1.40 kg [-2.61 to -0.18] in the ASPIRE-Group, -2.13 kg [-3.43 to -0.83] in ASPIRE-Phone, and -1.78 kg [-3.07 to -0.49] in MOVE!), with no significant differences among the three groups. Exploratory post hoc analyses revealed that participants diagnosed with diabetes initially benefited from the ASPIRE-Group program (-2.6 kg [-4.37 to 0.83]), but experienced significant weight regain during the second year (+2.8 kg [0.92-4.69]) compared to those without diabetes. CONCLUSIONS: Participants in all three programs lost weight and maintained a statistically significant, though clinically modest, amount of weight loss over a 24-month period. Although participants in the ASPIRE-Group initially had greater weight loss, treatment was not sufficient to sustain weight loss through the second year, particularly in veterans with diabetes. Consistent, continuous-care treatment is needed to address obesity in the VA.

Noninvasive Scale Measurement of Stroke Volume and Cardiac Output Compared With the Direct Fick Method: A Feasibility Study.

Background Objective markers of cardiac function are limited in the outpatient setting and may be beneficial for monitoring patients with chronic cardiac conditions. We assess the accuracy of a scale, with the ability to capture ballistocardiography, electrocardiography, and impedance plethysmography signals from a patient's feet while standing on the scale, in measuring stroke volume and cardiac output compared with the gold-standard direct Fick method. Methods and Results Thirty-two patients with unexplained dyspnea undergoing level 3 invasive cardiopulmonary exercise test at a tertiary medical center were included in the final analysis. We obtained scale and direct Fick measurements of stroke volume and cardiac output before and immediately after invasive cardiopulmonary exercise test. Stroke volume and cardiac output from a cardiac scale and the direct Fick method correlated with r=0.81 and r=0.85, respectively (P<0.001 each). The mean absolute error of the scale estimated stroke volume was -1.58 mL, with a 95% limits of agreement of -21.97 to 18.81 mL. The mean error for the scale estimated cardiac output was -0.31 L/min, with a 95% limits of agreement of -2.62 to 2.00 L/min. The changes in stroke volume and cardiac output before and after exercise were 78.9% and 96.7% concordant, respectively, between the 2 measuring methods. Conclusions In a proof-of-concept study, this novel scale with cardiac monitoring abilities may allow for noninvasive, longitudinal measures of cardiac function. Using the widely accepted form factor of a bathroom scale, this method of monitoring can be easily integrated into a patient's lifestyle.

A Method to Quantify Mean Hypertension Treatment Daily Dose Intensity Using Health Care System Data.

Importance: Simple measures of hypertension treatment, such as achievement of blood pressure (BP) targets, ignore the intensity of treatment once the BP target is met. High-intensity treatment involves increased treatment burden and can be associated with potential adverse effects in older adults. A method was previously developed to identify older patients receiving intense hypertension treatment by low BP and number of BP medications using national Veterans Health Administration and Medicare Part D administrative pharmacy data to evaluate which BP medications a patient is likely taking on any given day. Objective: To further develop and validate a method to more precisely quantify dose intensity of hypertension treatment using only health system administrative pharmacy fill data. Design, Setting, and Participants: Observational, cross-sectional study of 319 randomly selected older veterans in the national Veterans Health Administration health care system who were taking multiple BP-lowering medications and had a total of 3625 ambulatory care visits from July 1, 2011, to June 30, 2013. Measure development and medical record review occurred January 1, 2017, through November 30, 2018, and data analysis was conducted from December 1, 2019, to August 31, 2020. Main Outcomes and Measures: For each BP-lowering medication, a moderate hypertension daily dose (HDD) was defined as half the maximum dose above which no further clinical benefit has been demonstrated by that medication in hypertension trials. Patients' total HDD was calculated using pharmacy data (pharmacy HDDs), accounting for substantial delays in refills (>30 days) when a patient's pill supply was stretched (eg, cutting existing pills in half). As an external comparison, the pharmacy HDDs were correlated with doses manually extracted from clinicians' visit notes (clinically noted HDDs). How well the pharmacy HDDs correlated with clinically noted HDDs was calculated (using C statistics). To facilitate interpretation, HDDs were described in association with the number of medications. Results: A total of 316 patients (99.1%) were male; the mean (SD) age was 75.6 (7.2) years. Pharmacy HDDs were highly correlated (r = 0.92) with clinically noted HDDs, with a mean (SD) of 2.7 (1.8) for pharmacy HDDs and 2.8 (1.8) for clinically noted HDDs. Pharmacy HDDs correlated with high-intensity, clinically noted HDDs ranging from a C statistic of 92.8% (95% CI, 92.0%-93.7%) for 2 or more clinically noted HDDs to 88.1% (95% CI, 85.5%-90.6%) for 6 or more clinically noted HDDs. Conclusions and Relevance: This study suggests that health system pharmacy data may be used to accurately quantify hypertension regimen dose intensity. Together with clinic-measured BP, this tool can be used in future health system-based research or quality improvement efforts to fine-tune, manage, and optimize hypertension treatment in older adults.

Validation of a Health System Measure to Capture Intensive Medication Treatment of Hypertension in the Veterans Health Administration.

Importance: Blood pressure (BP) targets are the main measure of high-quality hypertension care in health systems. However, BP alone does not reflect intensity of pharmacological treatment, which should be carefully managed in older patients. Objectives: To develop and validate an electronic health record (EHR) data-only algorithm using pharmacy and BP data to capture intensive hypertension care (IHC), defined as 3 or more BP medications and BP less than 120 mm Hg, and to identify conditions associated with greater IHC, either through greater algorithm false-positive IHC, or by contributing clinically to delivering more IHC. Design, Setting, and Participants: This cross-sectional study was conducted among 319 randomly selected patients aged 65 years or older receiving IHC from the Veterans Health Administration (VHA) from July 1, 2011, to June 30, 2013. Data were collected from a total of 3625 primary care visits. Data were analyzed from January 2017 to March 2020. Exposures: Calibration and measurement of the algorithm for IHC (algorithm IHC). Main Outcomes and Measures: For each primary care visit, the reference standard, clinical IHC, was determined by detailed review of free-text clinical notes. The correlation in BP medication count between the EHR-only algorithm vs the reference standard and the sensitivity and specificity of the algorithm IHC were calculated. In addition, presence vs absence of contributing conditions acting in combination with hypertension management were measured to examine incidence of IHC associated with contributing conditions, including an acute condition that lowered BP (eg, dehydration), another condition requiring a BP target lower than the standard 140 mm Hg (eg, diabetes), or the patient needing a BP-lowering medication for a nonhypertension condition (eg, ß-blocker for atrial fibrillation) resulting in low BP. Results: Among 319 patients with 3625 visits (mean [SD] age, 75.6 [7.2] years; 3592 [99.1%] men), 911 visits (25.1%) had clinical IHC by the reference standard. The algorithm for determining medication count was highly correlated with the reference standard (r = 0.84). Sensitivity of detecting clinical IHC was 92.2% (95% CI, 89.3%-95.1%), and specificity was 97.2% (95% CI, 96.1%-98.3%), suggesting that clinical IHC can be identified from routinely collected data. Only 75 visits (2.1%) were algorithm IHC false positives, 55 visits (1.5%) involved IHC with contributing conditions, and 125 visits (3.5%) involved either false-positive or IHC with contributing conditions. Among select contributing conditions, congestive heart failure (37 patients [5.2%]) was most associated with a prespecified combined false-positive or IHC with contributing conditions rate higher than 5%. Conclusions and Relevance: These findings suggest that health system data can be used reliably to estimate IHC.

Mental health and behavioral weight loss: 24-month outcomes in Veterans.

BACKGROUND: Individuals with mental health (MH) disorders have an increased risk of being overweight/obese; however research on behavioral weight loss interventions has been limited. A priori hypothesis was that Veterans with serious mental illness (SMI) and/or affective disorders (AD) would lose significantly less weight and have a different pattern of weight loss than Veterans without these diagnoses. METHODS: Secondary data analysis of ASPIRE-VA study, three-arm randomized, effectiveness weight loss trial among Veterans (n=409) categorized by MH diagnoses: 1) SMI, 2) AD without SMI, or 3) No SMI/No AD. Linear mixed-effects model analyzed weight changes from baseline thru 24 months. RESULTS: SMI and AD were diagnosed in 10% (n=41) and 31% (n=125). Participants attended approximately 15 sessions from baseline to 24 months. On average, participants lost a modest amount of weight over 24 months regardless of MH diagnosis. Longitudinally, no statistically significant differences were found in weight loss patterns by MH diagnosis. Unadjusted average weight loss (kg) was 1.6±4.0 at 3 months (n=373), 1.9±6.5 at 12 months (n=361), 1.5±7.8 at 18 months (n=289), and 1.4±8.0 at 24 months (n=279). LIMITATIONS: ASPIRE-VA study was not designed or powered to detect weight loss differences among MH diagnostic groups. CONCLUSIONS: Veterans achieved and maintained modest weight loss, through 24 months, with the three behavioral weight loss interventions. Contrary to our hypotheses, the amount and pattern of weight loss did not differ by MH diagnosis. Greater inclusion of individuals with MH diagnoses may be warranted in behavioral weight loss interventions not specifically tailored for them.

Development and validation of the ASPIRE-VA coaching fidelity checklist (ACFC): a tool to help ensure delivery of high-quality weight management interventions.

Practical and valid instruments are needed to assess fidelity of coaching for weight loss. The purpose of this study was to develop and validate the ASPIRE Coaching Fidelity Checklist (ACFC). Classical test theory guided ACFC development. Principal component analyses were used to determine item groupings. Psychometric properties, internal consistency, and inter-rater reliability were evaluated for each subscale. Criterion validity was tested by predicting weight loss as a function of coaching fidelity. The final 19-item ACFC consists of two domains (session process and session structure) and five subscales (sets goals and monitor progress, assess and personalize self-regulatory content, manages the session, creates a supportive and empathetic climate, and stays on track). Four of five subscales showed high internal consistency (Cronbach alphas > 0.70) for group-based coaching; only two of five subscales had high internal reliability for phone-based coaching. All five sub-scales were positively and significantly associated with weight loss for group- but not for phone-based coaching. The ACFC is a reliable and valid instrument that can be used to assess fidelity and guide skill-building for weight management interventionists.

Weight loss among women and men in the ASPIRE-VA behavioral weight loss intervention trial.

OBJECTIVE: Weight loss was examined among women and men veterans in a clinical trial comparing Aspiring for Lifelong Health (ASPIRE), a "small changes" weight loss program using either mixed-sex group-visit or telephone-based coaching, to MOVE!(®) , the usual mixed-sex group-based program. METHODS: Linear mixed-effects models were used to calculate adjusted percent weight change at 12 months by sex and compare outcomes across arms within sex. RESULTS: Analyses included 72 women (ASPIRE-Phone = 26; ASPIRE-Group = 26; MOVE! = 20) and 409 men (ASPIRE-Phone = 136; ASPIRE-Group = 134; MOVE! = 139). At 12 months, women displayed significant weight loss from baseline in ASPIRE-Group (-2.6%) and MOVE! (-2.7%), but not ASPIRE-Phone (+0.2%). Between-arm differences in weight change among women were: ASPIRE-Group versus ASPIRE-Phone, -2.8% (P = 0.15); MOVE! versus ASPIRE-Phone, -2.8% (P = 0.20); and ASPIRE-Group versus MOVE!, 0.0% (P = 1.0). At 12 months, men lost significant weight from baseline across arms (ASPIRE-Phone, -1.5%; ASPIRE-Group, -2.5%; MOVE!, -1.0%). Between-arm differences in weight change among men were: ASPIRE-Group versus ASPIRE-Phone, -0.9% (P = 0.23); MOVE! versus ASPIRE-Phone, +0.5% (P = 0.76); ASPIRE-Group versus MOVE!, -1.5% (P = 0.03). CONCLUSIONS: Mixed-sex, group-based programs can result in weight loss for both women and men veterans.

Effect of race and sex on primary care physicians' diagnosis and treatment of late-life depression.

OBJECTIVES: To examine primary care physician (PCP) contributions toward racial and sex differences in the diagnosis and treatment of late-life depression. DESIGN: Survey using a computerized instrument incorporating video interviews and text, with volunteer PCPs randomly assigned to one of four standardized video vignettes of an elderly patient depicting late-life depression. Vignettes differed only in the patient/actor's race (white/African-American) or sex. SETTING: American Academy of Family Physicians meeting, San Diego, California, 2002. PARTICIPANTS: One hundred seventy-eight U.S.-practicing postresidency PCPs who were asked to participate in a clinical decision-making study. MEASUREMENTS: The computerized survey instrument assessed PCPs' diagnoses, first-line treatment and management recommendations, and judgment of personal characteristics/behaviors for the patients in the vignettes. RESULTS: Eighty-five percent of all PCPs correctly diagnosed the elderly patient(s) with major depression. There were no significant differences in the diagnosis of depression, treatment recommendations, or PCP assessment of most patient characteristics by the race or sex of the patient/actor in the vignette, but PCP characteristics, most notably the location of medical school training (U.S. vs international), affected the likelihood of a depression diagnosis and treatment recommendations. CONCLUSION: Given standardized symptom-pictures, PCPs are just as likely to diagnose and treat depression in African-American as in white older people, suggesting that bias based simply on apparent patient race is not a likely explanation for the lower rates of depression diagnosis and treatment in older African Americans. PCPs who have trained at international medical schools may benefit from targeted training initiatives on the diagnosis and treatment of late-life depression.

Race, gender, and psychiatrists' diagnosis and treatment of major depression among elderly patients.

OBJECTIVE: This study examined psychiatrists' contributions to racial and gender disparities in diagnosis and treatment among elderly persons. METHODS: Psychiatrists who volunteered to participate in the study were randomly assigned to one of four video vignettes depicting an elderly patient with late-life depression. The vignettes differed only in terms of the race of the actor portraying the patient (white or African American) and gender. The study participants were 329 psychiatrists who attended the 2002 annual meeting of the American Psychiatric Association. RESULTS: Eighty-one percent of the psychiatrists assigned the elderly patient a diagnosis of major depression. Patients' race and gender was not associated with significant differences in the diagnoses of major depression, assessment of most patient characteristics, or recommendations for managing the disorder. However, psychiatrists' characteristics, particularly the location of the medical school at which the psychiatrist was trained (United States versus international), were significantly associated with a number of variables. CONCLUSIONS: Given standardized symptom pictures, psychiatrists are no less likely to diagnose or treat depression among African-American elderly patients than among other patients, which suggests that bias based simply on race is not a likely explanation for racial differences in diagnosis and treatments found in earlier clinical studies. The impact of psychiatrists' having trained at international medical schools on diagnosis, treatment, and judgment of several patient attributes may indicate the need for targeted educational initiatives for aging and cultural competency.

Poor antipsychotic adherence among patients with schizophrenia: medication and patient factors.

Many patients with schizophrenia are poorly adherent with antipsychotic medications. The newer, atypical antipsychotics may be more acceptable to patients and result in increased adherence. We used national Department of Veterans Affairs (VA) pharmacy data to examine whether patients receiving atypical agents are more adherent with their medication and explored patient factors associated with adherence. Patients who received a diagnosis of schizophrenia or schizoaffective disorder between October 1, 1998, and September 30, 1999, were identified in the VA National Psychosis Registry. We calculated medication possession ratios (MPRs) for patients filling prescriptions for one (n = 49,003) or two (n = 14,211) antipsychotics during the year. We examined cross-sectional relationships among adherence, type of antipsychotic, and patient characteristics and explored adherence among patients switching antipsychotics during the year. Among patients receiving one antipsychotic, 40 percent had MPRs < 0.8, indicating poor adherence. African-Americans and younger patients were more likely to be poorly adherent. Cross-sectionally, patients on atypical agents were more likely to be poorly adherent (41.5%) than patients on conventional agents (37.8%). However, among a small group of patients switching from a conventional to an atypical agent (n = 1,661) during the year, the percentage who were poorly adherent decreased from 46 percent to 40 percent. We describe the continuum of antipsychotic adherence among a large sample of patients with schizophrenia and confirm that poor adherence is common. African-Americans and younger patients are particularly at risk. Unfortunately, atypical antipsychotics may not be associated with substantial improvements in adherence. More intensive interventions are likely needed.

Small-changes obesity treatment among veterans: 12-month outcomes.

BACKGROUND: Weight-loss trials tend to recruit highly selective, non-representative samples. Effective weight-loss approaches are needed for real-world challenging populations. PURPOSE: To test whether a small-changes intervention, delivered in groups or via telephone, promotes greater weight loss than standard obesity treatment in a predominantly male, high-risk Veteran population. Data were collected in 2010-2012 and analyzed in 2013. DESIGN: A three-arm, 12-month randomized pragmatic effectiveness trial. SETTING/PARTICIPANTS: Four-hundred eighty-one overweight/obese participants from two Midwestern Veterans Affairs (VA) Medical Centers were randomly assigned to one of three programs: the 12-month Aspiring to Lifelong Health (ASPIRE) weight-loss program delivered (1) individually over the phone (ASPIRE-Phone) or (2) in-person group sessions (ASPIRE-Group); compared to (3) VA's standard weight-loss program (MOVE!). INTERVENTION: Twenty-eight sessions with a non-clinician coach via telephone or in-person groups using a small-changes obesity treatment approach compared to a 15-30-session standard VA program. MAIN OUTCOME MEASURES: Twelve-month change in weight (kilograms). RESULTS: Participants in all three arms lost significant (p<0.01) weight at 12 months. Participants in the ASPIRE-Group arm lost significantly more weight at 12 months than those in the other two treatment arms (-2.8 kg, 95% CI=-3.8, -1.9, in ASPIRE-Group vs -1.4 kg, 95% CI=-2.4, -0.5, in ASPIRE-Phone and -1.4 kg, 95% CI=-2.3, -0.4) in MOVE!(®). ASPIRE-Group resulted in greater improvements in all other anthropometric measures compared to MOVE! at 12 months (p<0.05) and for all (p<0.05) but waist circumference (p=0.23) compared to ASPIRE-Phone. CONCLUSIONS: Group-based delivery of the ASPIRE weight management program is more effective than MOVE! and the phone-based version of ASPIRE at promoting sustained weight loss in a predominantly male population with multiple comorbidities. The incremental benefits of group-based ASPIRE over the current MOVE! program could yield significant population-level benefits if implemented on a large scale.

A randomized trial of a small changes approach for weight loss in veterans: design, rationale, and baseline characteristics of the ASPIRE-VA trial.

BACKGROUND: Overweight/obesity rates among veterans are higher than the national average. While weight management treatment has been implemented in the Veterans Health Administration (VHA), program data shows low enrollment, participation, and weight loss. This paper presents the design, rationale and baseline characteristics of a multisite, multi-modality, randomized clinical trial assessing an innovative Small Changes (SC) approach on weight loss compared to the current weight management program in the VHA. METHOD: Overweight/obese veterans were recruited from two VHA medical centers. Participants were randomized to either: 1) sc group, 2) SC phone, or 3) usual care. Participants in the SC arms met with health coaches weekly in months 1-3, bi-weekly in months 4-9, and monthly in months 10-12. Usual care participants met weekly for 12 weeks with limited options for follow-up care. The primary outcome is weight at 12 months. Secondary outcomes include physiological, behavioral, psychosocial outcomes along with participation and adherence. RESULTS: Participants include 481 veterans who are middle-aged (M=55.45, SD=10.00), obese (BMI=36.45, SD=6.24), relatively sedentary (M=4721 steps per day; SD=3115), disabled (52%), men (85%) with a large minority of non-white race/ethnicity (43%) and high prevalence of physical co-morbidities (83%) (Charlson Co-morbidity Index M=1.27, SD=1.75) and mental health disorders (57%) at baseline. CONCLUSION: The present study seeks to determine if an SC approach, delivered either via phone or in-person, will result in greater weight loss and program participation and adherence at 12 months compared to usual care.

A small-change approach delivered via telephone promotes weight loss in veterans: results from the ASPIRE-VA pilot study.

OBJECTIVE: High rates of overweight and obesity (70%) among US veterans pose a significant threat of obesity-related chronic disease and disability. The purpose of this pilot study was to demonstrate feasibility and impact of a phone-based small-change weight loss intervention (ASPIRE-VA) with veterans. METHODS: Participants received a pedometer, food log book, and treatment manual outlining the small change program. Participants then scheduled weekly phone calls with a lifestyle coach, during which they reviewed the prior week's goals and developed new goals for the following week. Primary outcome was weight loss measured at 12 weeks, compared to baseline. RESULTS: Fourteen sedentary (4471+/-2315 steps per day), obese (37.0+/-4.2 BMI), middle aged (53.8+/-12.5) male (64%) and female (36%) participants were enrolled. At 12 weeks participants exhibited significant weight loss (-3.8+/-3.6 kg; p=.002) and increased intake of fruits and vegetables (+2.2+/-3.1 daily servings; p=.03); though no change in walking (+786+/-2288 daily steps; p=.24). CONCLUSION: Results suggest that a phone-based small change program is feasible and beneficial for promoting weight loss in overweight/obese veterans. PRACTICE IMPLICATIONS: This telephone-based program has the potential to reduce rates of overweight and obesity among veterans and thus prevent and improve prognosis of associated chronic conditions.

Ethnicity and diagnostic patterns in veterans with psychoses.

BACKGROUND: Differential diagnosis of schizophrenia and bipolar disorder is a challenging but important task. These conditions often exhibit overlapping clinical symptomatology, but have different prognoses and pharmacological management strategies. Factors other than clinical presentation may influence diagnosis. Past studies suggest that ethnicity is one such factor, with variations observed in diagnostic rates of serious mental illness (SMI). With increasing attention paid to provider cultural competency, we investigate current diagnostic practices within a veteran population. METHOD: Controlling for patient need characteristics and illness severity, we examine whether ethnic differences in diagnosis continue to exist. If so, race may adversely enter the evaluation process. A national database of all SMI veterans explores the relationship between ethnicity and diagnosis. The role of symptomatology is also examined. Given minimal variation in veteran socioeconomic status, the Department of Veterans Affairs (VA) provides a natural setting to address this confounding factor. The 1999 National Psychosis Registry provides a sample of 134,523 veterans diagnosed with schizophrenia, schizoaffective disorder, or bipolar disorder. Multinomial logistic regression yielded odds ratios (OR) for being diagnosed with schizophrenia versus bipolar disorder; the schizoaffective versus bipolar risk was likewise assessed, exploring theoretical aspects of a psychosis-affective 'continuum'. RESULTS: Small effects were observed for being male, single or rural resident. However, the demographic characteristic most strongly associated with a schizophrenia diagnosis was race. The OR for African Americans was 4.05, and 3.15 for Hispanics. Similar though less dramatic results were revealed for schizoaffective disorder. CONCLUSIONS: This study confirms continued ethnic disparities in diagnostic patterns, and highlights the importance of recognizing ethnic differences in symptom presentation while emphasizing greater cultural competency.

Pharmacy data identify poorly adherent patients with schizophrenia at increased risk for admission.

BACKGROUND: Health care organizations may be able to use pharmacy data to identify patients with schizophrenia and poor antipsychotic adherence. OBJECTIVE: To determine whether a pharmacy-based measure of outpatient adherence, the medication possession ratio (MPR), is associated with adverse outcomes among patients with schizophrenia, as evidenced by increased psychiatric admission. RESEARCH DESIGN: Cohort study linking pharmacy and utilization data for veterans with schizophrenia. MPRs were calculated by dividing the number of days' supply of antipsychotic medication the veteran had received by the number of days' supply they needed to receive to take their antipsychotic continuously. Using multivariate regression, the relationship between MPRs and psychiatric admission was examined. SUBJECTS: Sixty-seven thousand seventy-nine veterans who received a diagnosis of schizophrenia and had outpatient antipsychotic medication fills between October 1, 1998 and September 30, 1999. RESULTS: Patients with MPRs close to 1.0 had the lowest rates of admission. As patients secured progressively smaller proportions of required antipsychotic medication (and had smaller MPRs), rates of admission climbed. Among patients on one antipsychotic (n = 49,003), patients with poor adherence (MPRs < 0.8) were 2.4 times as likely to be admitted as patients with good adherence (MPRs from 0.8-1.1). 23% of poorly adherent patients but only 10% of adherent patients were admitted. Once admitted, poorly adherent patients had more hospital days. Patients who received excess medication also had higher admission rates. CONCLUSIONS: Many health care systems may be able to use pharmacy data to identify poorly adherent patients with schizophrenia. These patients are at-risk for admission and may benefit from intervention.