Childhood adversity, adult stress, and the risk of major depression or generalized anxiety disorder in US soldiers: a test of the stress sensitization hypothesis.

BACKGROUND: The stress sensitization theory hypothesizes that individuals exposed to childhood adversity will be more vulnerable to mental disorders from proximal stressors. We aimed to test this theory with respect to risk of 30-day major depressive episode (MDE) and generalized anxiety disorder (GAD) among new US Army soldiers. METHODS: The sample consisted of 30 436 new soldier recruits in the Army Study to Assess Risk and Resilience (Army STARRS). Generalized linear models were constructed, and additive interactions between childhood maltreatment profiles and level of 12-month stressful experiences on the risk of 30-day MDE and GAD were analyzed. RESULTS: Stress sensitization was observed in models of past 30-day MDE (χ2 8 = 17.6, p = 0.025) and GAD (χ2 8 = 26.8, p = 0.001). This sensitization only occurred at high (3+) levels of reported 12-month stressful experiences. In pairwise comparisons for the risk of 30-day MDE, the risk difference between 3+ stressful experiences and no stressful experiences was significantly greater for all maltreatment profiles relative to No Maltreatment. Similar results were found with the risk for 30-day GAD with the exception of the risk difference for Episodic Emotional and Sexual Abuse, which did not differ statistically from No Maltreatment. CONCLUSIONS: New soldiers are at an increased risk of 30-day MDE or GAD following recent stressful experiences if they were exposed to childhood maltreatment. Particularly in the military with an abundance of unique stressors, attempts to identify this population and improve stress management may be useful in the effort to reduce the risk of mental disorders.

Predicting non-familial major physical violent crime perpetration in the US Army from administrative data.

BACKGROUND: Although interventions exist to reduce violent crime, optimal implementation requires accurate targeting. We report the results of an attempt to develop an actuarial model using machine learning methods to predict future violent crimes among US Army soldiers. METHOD: A consolidated administrative database for all 975 057 soldiers in the US Army in 2004-2009 was created in the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS). Of these soldiers, 5771 committed a first founded major physical violent crime (murder-manslaughter, kidnapping, aggravated arson, aggravated assault, robbery) over that time period. Temporally prior administrative records measuring socio-demographic, Army career, criminal justice, medical/pharmacy, and contextual variables were used to build an actuarial model for these crimes separately among men and women using machine learning methods (cross-validated stepwise regression, random forests, penalized regressions). The model was then validated in an independent 2011-2013 sample. RESULTS: Key predictors were indicators of disadvantaged social/socioeconomic status, early career stage, prior crime, and mental disorder treatment. Area under the receiver-operating characteristic curve was 0.80-0.82 in 2004-2009 and 0.77 in the 2011-2013 validation sample. Of all administratively recorded crimes, 36.2-33.1% (male-female) were committed by the 5% of soldiers having the highest predicted risk in 2004-2009 and an even higher proportion (50.5%) in the 2011-2013 validation sample. CONCLUSIONS: Although these results suggest that the models could be used to target soldiers at high risk of violent crime perpetration for preventive interventions, final implementation decisions would require further validation and weighing of predicted effectiveness against intervention costs and competing risks.

Understanding the elevated suicide risk of female soldiers during deployments.

BACKGROUND: The Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS) has found that the proportional elevation in the US Army enlisted soldier suicide rate during deployment (compared with the never-deployed or previously deployed) is significantly higher among women than men, raising the possibility of gender differences in the adverse psychological effects of deployment. METHOD: Person-month survival models based on a consolidated administrative database for active duty enlisted Regular Army soldiers in 2004-2009 (n = 975,057) were used to characterize the gender × deployment interaction predicting suicide. Four explanatory hypotheses were explored involving the proportion of females in each soldier's occupation, the proportion of same-gender soldiers in each soldier's unit, whether the soldier reported sexual assault victimization in the previous 12 months, and the soldier's pre-deployment history of treated mental/behavioral disorders. RESULTS: The suicide rate of currently deployed women (14.0/100,000 person-years) was 3.1-3.5 times the rates of other (i.e. never-deployed/previously deployed) women. The suicide rate of currently deployed men (22.6/100,000 person-years) was 0.9-1.2 times the rates of other men. The adjusted (for time trends, sociodemographics, and Army career variables) female:male odds ratio comparing the suicide rates of currently deployed v. other women v. men was 2.8 (95% confidence interval 1.1-6.8), became 2.4 after excluding soldiers with Direct Combat Arms occupations, and remained elevated (in the range 1.9-2.8) after adjusting for the hypothesized explanatory variables. CONCLUSIONS: These results are valuable in excluding otherwise plausible hypotheses for the elevated suicide rate of deployed women and point to the importance of expanding future research on the psychological challenges of deployment for women.

Occupational differences in US Army suicide rates.

BACKGROUND: Civilian suicide rates vary by occupation in ways related to occupational stress exposure. Comparable military research finds suicide rates elevated in combat arms occupations. However, no research has evaluated variation in this pattern by deployment history, the indicator of occupation stress widely considered responsible for the recent rise in the military suicide rate. METHOD: The joint associations of Army occupation and deployment history in predicting suicides were analysed in an administrative dataset for the 729 337 male enlisted Regular Army soldiers in the US Army between 2004 and 2009. RESULTS: There were 496 suicides over the study period (22.4/100 000 person-years). Only two occupational categories, both in combat arms, had significantly elevated suicide rates: infantrymen (37.2/100 000 person-years) and combat engineers (38.2/100 000 person-years). However, the suicide rates in these two categories were significantly lower when currently deployed (30.6/100 000 person-years) than never deployed or previously deployed (41.2-39.1/100 000 person-years), whereas the suicide rate of other soldiers was significantly higher when currently deployed and previously deployed (20.2-22.4/100 000 person-years) than never deployed (14.5/100 000 person-years), resulting in the adjusted suicide rate of infantrymen and combat engineers being most elevated when never deployed [odds ratio (OR) 2.9, 95% confidence interval (CI) 2.1-4.1], less so when previously deployed (OR 1.6, 95% CI 1.1-2.1), and not at all when currently deployed (OR 1.2, 95% CI 0.8-1.8). Adjustment for a differential 'healthy warrior effect' cannot explain this variation in the relative suicide rates of never-deployed infantrymen and combat engineers by deployment status. CONCLUSIONS: Efforts are needed to elucidate the causal mechanisms underlying this interaction to guide preventive interventions for soldiers at high suicide risk.

Sociodemographic and career history predictors of suicide mortality in the United States Army 2004-2009.

BACKGROUND: The US Army suicide rate has increased sharply in recent years. Identifying significant predictors of Army suicides in Army and Department of Defense (DoD) administrative records might help focus prevention efforts and guide intervention content. Previous studies of administrative data, although documenting significant predictors, were based on limited samples and models. A career history perspective is used here to develop more textured models. METHOD: The analysis was carried out as part of the Historical Administrative Data Study (HADS) of the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS). De-identified data were combined across numerous Army and DoD administrative data systems for all Regular Army soldiers on active duty in 2004-2009. Multivariate associations of sociodemographics and Army career variables with suicide were examined in subgroups defined by time in service, rank and deployment history. RESULTS: Several novel results were found that could have intervention implications. The most notable of these were significantly elevated suicide rates (69.6-80.0 suicides per 100 000 person-years compared with 18.5 suicides per 100 000 person-years in the total Army) among enlisted soldiers deployed either during their first year of service or with less than expected (based on time in service) junior enlisted rank; a substantially greater rise in suicide among women than men during deployment; and a protective effect of marriage against suicide only during deployment. CONCLUSIONS: A career history approach produces several actionable insights missed in less textured analyses of administrative data predictors. Expansion of analyses to a richer set of predictors might help refine understanding of intervention implications.

Including information about co-morbidity in estimates of disease burden: results from the World Health Organization World Mental Health Surveys.

BACKGROUND: The methodology commonly used to estimate disease burden, featuring ratings of severity of individual conditions, has been criticized for ignoring co-morbidity. A methodology that addresses this problem is proposed and illustrated here with data from the World Health Organization World Mental Health Surveys. Although the analysis is based on self-reports about one's own conditions in a community survey, the logic applies equally well to analysis of hypothetical vignettes describing co-morbid condition profiles. METHOD: Face-to-face interviews in 13 countries (six developing, nine developed; n=31 067; response rate=69.6%) assessed 10 classes of chronic physical and nine of mental conditions. A visual analog scale (VAS) was used to assess overall perceived health. Multiple regression analysis with interactions for co-morbidity was used to estimate associations of conditions with VAS. Simulation was used to estimate condition-specific effects. RESULTS: The best-fitting model included condition main effects and interactions of types by numbers of conditions. Neurological conditions, insomnia and major depression were rated most severe. Adjustment for co-morbidity reduced condition-specific estimates with substantial between-condition variation (0.24-0.70 ratios of condition-specific estimates with and without adjustment for co-morbidity). The societal-level burden rankings were quite different from the individual-level rankings, with the highest societal-level rankings associated with conditions having high prevalence rather than high individual-level severity. CONCLUSIONS: Plausible estimates of disorder-specific effects on VAS can be obtained using methods that adjust for co-morbidity. These adjustments substantially influence condition-specific ratings.

Measuring the incremental cost of clinical cancer research.

PURPOSE: To summarize evidence on the costs of treating patients in clinical trials and to describe the Cost of Cancer Treatment Study, an ongoing effort to produce generalizable estimates of the incremental costs of government-sponsored cancer trials. METHODS: A retrospective study of costs will be conducted with 1,500 cancer patients recruited from a randomly selected sample of institutions in the United States. Patients accrued to either phase II or phase III National Cancer Institute-sponsored clinical trials during a 15-month period will be asked to participate in a study of their health care utilization (n = 750). Costs will be measured approximately 1 year after their trial enrollment from a combination of billing records, medical records, and an in-person survey questionnaire. Similar data will be collected for a comparable group of cancer patients not in trials (n = 750) to provide an estimate of the incremental cost. RESULTS: Evidence suggests insurers limit access to trials because of cost concerns. Public and private efforts are underway to change these policies, but their permanent status is unclear. Previous studies found that treatment costs in clinical trials are similar to costs of standard therapy. However, it is difficult to generalize from these studies because of the unique practice settings, insufficient sample sizes, and the exclusion of potentially important costs. CONCLUSION: Denials of coverage for treatment in a clinical trial limit patient access to trials and could impede clinical research. Preliminary estimates suggest changes to these policies would not be expensive, but these results are not generalizable. The Cost of Cancer Treatment Study is an ongoing effort to provide generalizable estimates of the incremental treatment cost of phase II and phase III cancer trials. The results should be of great interest to insurers and the research community as they consider permanent ways to finance cancer trials.

Long-term effectiveness of disseminating quality improvement for depression in primary care.

BACKGROUND: This article addresses whether dissemination of short-term quality improvement (QI) interventions for depression to primary care practices improves patients' clinical outcomes and health-related quality of life (HRQOL) over 2 years, relative to usual care (UC). METHODS: The sample included 1299 patients with current depressive symptoms and 12-month, lifetime, or no depressive disorder from 46 primary care practices in 6 managed care organizations. Clinics were randomized to UC or 1 of 2 QI programs that included training local experts and nurse specialists to provide clinician and patient education, assessment, and treatment planning, plus either nurse care managers for medication follow-up (QI-meds) or access to trained psychotherapists (QI-therapy). Outcomes were assessed every 6 months for 2 years. RESULTS: For most outcomes, differences between intervention and UC patients were not sustained for the full 2 years. However, QI-therapy reduced overall poor outcomes compared with UC by about 8 percentage points throughout 2 years, and by 10 percentage points compared with QI-meds at 24 months. Both interventions improved patients' clinical and role outcomes, relative to UC, over 12 months (eg, a 10-11 and 6-7 percentage point difference in probable depression at 6 and 12 months, respectively). CONCLUSIONS: While most outcome improvements were not sustained over the full 2 study years, findings suggest that flexible dissemination of short-term, QI programs in managed primary care can improve patient outcomes well after program termination. Models that support integrated psychotherapy and medication-based treatment strategies in primary care have the potential for relatively long-term patient benefits.

Circadian and power spectral changes of RR and QT intervals during treatment of patients with angina pectoris with nadolol providing evidence for differential autonomic modulation of heart rate and ventricular repolarization.

This study evaluates the effects of autonomic manipulation by chronic beta blockade with nadolol on the circadian and power spectral changes of heart rate and QT interval. It was hypothesized that differential innervation of the atria and ventricles by sympathetic and parasympathetic fibers may produce differential effects on heart rate and QT interval variabilities. Holter recordings of 12 male patients (age 63 +/- 7 years) with stable angina were analyzed before and after 3 weeks of nadolol therapy. The QT intervals were individually normalized by an exponential formula to study the circadian variation of QTc. Power spectra of RR and uncorrected QT intervals were obtained by fast-Fourier analysis from 256 consecutive sinus beats during the day at maximal heart rate and during the night at minimal heart rate. Frequency-specific variability was determined from areas under the spectral plots. Both heart rate and QTc exhibited significant circadian patterns (p < 0.01) in opposite phase with each other. Mean heart rate was significantly reduced with nadolol (81 +/- 12 vs 67 +/- 12 beats/min, p < 0.001), with greater reduction during daytime. The mean QTc was unexpectedly reduced after nadolol treatment, with borderline significance (p = 0.06). The RR variability in the frequency range of 0.05 to 0.25 Hz was significantly increased with nadolol at 3:00 A.M. (p < 0.01) but not at 1:00 P.M. The QT variability in the same frequency range of was not significantly increased with nadolol. The power spectra of RR and QT intervals were dissimilar except at the lower frequencies around 0.05 Hz.(ABSTRACT TRUNCATED AT 250 WORDS)

Circadian rhythmicity of rate-normalized QT interval in hypothyroidism and its significance for development of class III antiarrhythmic agents.

Lengthening of repolarization and refractoriness occurs in hypothyroidism; it is associated with a reduced probability of arrhythmias, with the converse occurring in hyperthyroidism. Because the QT interval and its circadian rhythmicity relative to heart rate is poorly defined in man, we used our new computer-assisted technique to measure QT interval in our analysis of 24-hour Holter tapes before and after (8 to 12 weeks) thyroxine (T4) replacement in 10 patients with hypothyroidism; the findings were compared to those in 6 normal control subjects. QTc interval was prolonged (p less than 0.02) and heart rate decreased (p less than 0.005) during the hypothyroid state. Data were analyzed for circadian rhythmicity by repeated-measures analysis. Circadian variation in QTc and heart rate was statistically significant during hypothyroid and euthyroid states (p less than 0.001) as well as in control subjects, but the circadian rhythmicity of QTc interval and heart rate were out of phase; the maximum prolongation of QTc occurred between midnight and 6 A.M., at a time when heart was at its lowest. QTc interval remained significantly prolonged after 8 to 12 weeks of T4 replacement, when biochemical indexes of hypothyroidism had returned to normal values. The computer-assisted QTc interval determination technique that we used, and our data on the circadian rhythmicity of QTc and heart rate, have significant implications for the development of new class III antiarrhythmic agents.

Race differences in labor force attachment and disability status.

We used the first wave of the Health and Retirement Survey to study the effect of health on the labor force activity of black and white men and women in their 50s. The evidence we present confirms the notion that health is an extremely important determinant of early labor force exit. Our estimates suggest that health differences between blacks and whites can account for most of the racial gap in labor force attachment for men. For women, when participation rates are comparable, our estimates imply that black women would be substantially more likely to work than white women were it not for the marked health differences. We also found for both men and women that poor health has a substantially larger effect on labor force behavior for blacks. The evidence suggests that these differences result from black/white differences in access to the resources necessary to retire.

Race, socioeconomic status, and health: accounting for race differences in health.

This article uses the Asset and Health Dynamics Among the Oldest Old (AHEAD) study to examine the extent to which observed differences in the prevalence of chronic conditions and functional limitations between Black and White adults (aged 70+) in the United States can be attributed to differences in various aspects of socioeconomic status (SES) between these groups. We use linear and logistic regression techniques to model the relationships between health outcomes and SES. Our findings indicate that race differences in measurable socioeconomic characteristics indeed explain a substantial fraction, but in general not all, of Black/White differences in health status. While our findings do not suggest that low SES directly "causes" poor health, any more than being Black does so, they do suggest that research and policy intended to address the deficit in health status among Blacks (when compared to Whites) in the U.S. would be well-served to begin with the deficit in wealth, education, and other SES measures.

Costs and utilization of substance abuse care in a privately insured population under managed care.

OBJECTIVE: Cost and utilization patterns of substance abuse and mental health treatment under private, employer-sponsored, managed behavioral health care plans were examined. METHODS: Data were from claims made in 1995 in 93 behavioral health care plans covering 617,133 members. Rates of use of mental health and substance abuse care were determined, as were payments by insurers and patients for the two types of care. Means were calculated per plan member and per user of either of these service types. RESULTS: Approximately .3 percent of plan members used any substance abuse services; 5.2 percent used mental health services. However, among substance abuse patients, average costs were more than twice as high as average costs for mental health patients. For substance abuse treatment, the annual cost per user was $2,188, compared with $979 for users of mental health care. Annual per-member costs were $6.51 for substance abuse treatment and $50.08 for mental health care. Higher costs for substance abuse treatment reflected greater rates of use of both inpatient and intensive outpatient treatment. Overall, substance abuse costs represented 13 percent of insurance payments for behavioral health care and perhaps .4 percent of the cost of health insurance overall. CONCLUSIONS: Substance abuse coverage accounts for a small fraction of insurance payments for behavioral health coverage and a very small fraction of insurance payments for both physical and behavioral health care.

A study comparing the immunologic responses of swine to pseudorabies viral antigens based on the ELISA, serum virus neutralization, and latex agglutination tests.

A study of pseudorabies virus (PRV)-vaccinated pigs comparing the immune responses detected by the latex agglutination test (LAT) with responses detected by other routine tests for pseudorabies antibodies indicated that LAT was more sensitive than either the enzyme-linked immunosorbent assay (ELISA) or the serum virus neutralization test (SVNT). The LAT detected antibodies sooner than ELISA and SVNT in unvaccinated pigs after challenge with virulent PRV. The specificities of the 3 tests were found to be near 100%. The LAT is a good alternative to SVNT or ELISA for detection of PRV-specific antibodies.

How expensive are unlimited substance abuse benefits under managed care?

Substance abuse (SA) care has been excluded from recent federal and state legislation mandating equal benefits for mental health and medical care ("parity"), largely because of cost concerns. This article studies how many patients are affected by SA coverage limits and the likely implications of limits on insurance payments, using 1996-97 claims from 25 managed care plans with unlimited SA benefits. Changing even stringent limits on annual SA benefits has a small absolute effect on overall insurance costs under managed care, even though a large percentage of SA patients are affected. Removing an annual limit of $10,000 per year on SA care is estimated to increase insurance payments by about 6 cents per member per year, removing a limit of $1,000 increases payments by about $3.40. As long as care is comprehensively managed, "parity" for SA in employer-sponsored health plans is not very costly.

Health plan choice and information about out-of-pocket costs: an experimental analysis.

Many consumers are offered two or more employer-sponsored health insurance plans, and competition among health plans for subscribers is promoted as a mechanism for balancing health care costs and quality. Yet consumers may not receive the information necessary to make informed health plan choices. This study tests the effects on health plan choice of providing supplemental decision-support materials to inform consumers about expected health plan costs. Our main finding is that such information induces consumers to bear more risk, especially those in relatively good health. Thus our results suggest that working-age, privately insured consumers currently may be over-insuring for medical care.

Pseudorabies virus latency and reactivation in vaccinated swine.

Latency and reactivation of pseudorabies virus in swine was studied. Thirty-one pigs were assigned to 5 groups and were given 1 of 4 vaccines; 10 remained unvaccinated controls. All pigs were then challenge exposed with a sublethal dose of virulent pseudorabies virus. One hundred one days after challenge exposure, all pigs were treated with dexamethasone to reactivate the virus. Virus-positive tonsil and nasal mucus isolates were recovered from 29 of the 31 pigs over a 12-day period. Frequency and duration of virus-positivity were significantly (P less than 0.05) and consistently lower among vaccinated pigs than among the unvaccinated controls. It was concluded that vaccination before challenge exposure had little or no effect on the rate of establishment of virus latency, but that vaccination reduced shedding after subsequent reactivation of the virus.

Survival of pseudorabies virus in aerosol.

The survival of pseudorabies virus in an aerosol was studied under different environmental conditions of temperature and relative humidity. Pseudorabies virus decayed logarithmically with mean half-lives of 17.4 (85% relative humidity, 22 C), 18.8 (25% relative humidity, 22 C), 27.3 (85% relative humidity, 4 C), 36.1 (55% relative humidity, 22 C), and 43.6 (55% relative humidity, 4 C) minutes. Virus survival was significantly improved in environments at 55% relative humidity, compared with those at 85% relative humidity (P = 0.017). Rates of survival were improved in environment at 4 C in comparison with those at 22 C. Results suggest that, under the best conditions of this study, the infectivity of pseudorabies virus in an aerosol decreases by 50% in less than 1 hour.

A strain of Pasteurella multocida associated with infections in rabbit colonies.

Pasteurella multocida was isolated from 4 conventional rabbit colonies. Amongst 51 isolates, 48 (94%) belonged to a group of strains with similar morphological, cultural, biochemical and antigenic characteristics; they were named for convenience Lo strains and gave rise to local or ascending infections. All Lo strains were found to be a new serotype, but 8 of them had additional antigenic factors characteristic of known serotypes. The other 3 isolates (6%) were identified as serotype 3, known to have a wide host range: 2 strains were associated with septicaemia and haemotogenic spread, and 1 with snuffles. Diagnostic agglutinating antibodies were present in the sera of adult rabbits. Maternal antibodies were in the sera of adult rabbits. Maternal antibodies were in the sera of rabbits of 3 and 4 weeks old, but by the age of 8 weeks the titres had fallen to an undetectable level.

Survival of pseudorabies virus in the presence of selected diluents and fomites.

Because of the importance of environmental survival of pseudorabies virus to proposals to eradicate the virus from swine in the United States, survival of the virus was studied in various diluents and on combinations of diluents and solid fomites at 25 C. Suspensions of the virus in phosphate-buffered saline and saline G solutions remained infectious for at least 10 days. Infectivity of other virus/diluent suspensions decreased to less than 10 plaque-forming units/ml in 14 days (swine urine), 7 days (well water), 4 days (swine saliva), 2 days (lagoon water and swine nasal washings), and 1 day (swine pit effluent, chlorinated water, and bile). Suspensions of pseudorabies virus in saline G solution and on the solid fomites, whole corn, and steel remained infectious for at least 7 days. Infectivity of other virus/diluent/fomite combinations decreased to less than 10 plaque-forming units/ml in 7 days. The role of the fomites as vehicles for transmission of infection is discussed.