Latent class mediator for multiple indicators of mediation.

This paper demonstrates the utility of latent classes in evaluating the effect of an intervention on an outcome through multiple indicators of mediation. These indicators are observed intermediate variables that identify an underlying latent class mediator, with each class representing a different mediating pathway. The use of a latent class mediator allows us to avoid modeling the complex interactions between the multiple indicators and ensures the decomposition of the total mediating effects into additive effects from individual mediating pathways, a desirable feature for evaluating multiple indicators of mediation. This method is suitable when the goal is to estimate the total mediating effects that can be decomposed into the additive effects of distinct mediating pathways. Each indicator may be involved in multiple mediation pathways and at the same time multiple indicators may contribute to a single mediating pathway. The relative importance of each pathway may vary across subjects. We applied this method to the analysis of the first 6 months of data from a 2-year clustered randomized trial for adults in their first episode of schizophrenia. Four indicators of mediation are considered: individual resiliency training; family psychoeducation; supported education and employment; and a structural assessment for medication. The improvement in symptoms was found to be mediated by the latent class mediator derived from these four service indicators. Simulation studies were conducted to assess the performance of the proposed model and showed that the simultaneous estimation through the maximum likelihood yielded little bias when the entropy of the indicators was high.

Severity of reduced bone mineral density and risk of fractures in long-term survivors of childhood leukemia and lymphoma undergoing guideline-recommended surveillance for bone health.

BACKGROUND: Survivors of childhood leukemia/lymphoma are at increased risk for reduced bone mineral density (BMD). The authors sought to determine the frequency of reduced BMD detected by off-therapy surveillance, factors associated with reduced BMD, and the association of reduced BMD with fractures. METHODS: This cross-sectional study included childhood leukemia/lymphoma survivors attending 2 survivorship clinics who received guideline-recommended BMD surveillance ≥2 years post-therapy with dual-energy x-ray absorptiometry (from January 1, 2004 to August 31, 2016). Lumbar spine BMD z-scores were height-for-age-adjusted. Low and very low BMD were >1 SD and >2 SDs below norms, respectively. Treatment, chronic conditions, and fractures were abstracted from medical records. Logistic regression was used to examine the association of low BMD with patient/treatment factors and fractures. RESULTS: In total, 542 patients (51.5% female) with a mean age of 15.5 years (range, 4.4-52.2 years) who were 6 years post-therapy (range, 2.0-35.1 years) were evaluated, including 116 who reported post-therapy fractures. Lumbar spine low BMD was identified in 17.2% of survivors, and very low BMD was identified in 3.5% of survivors, but frequencies varied considerably between subgroups; 10.8% of survivors aged 15 to 19 years at diagnosis had very low BMD. In multivariable analyses, older age at diagnosis, white race, and being underweight were significantly associated with low BMD. Survivors with low BMD had greater odds of nondigit fractures (odds ratio, 2.2; 95% CI, 1.3-3.7) and specifically long-bone fractures (odds ratio, 2.7; 95% CI, 1.5-4.7). CONCLUSIONS: In this study of childhood leukemia/lymphoma survivors undergoing guideline-recommended dual-energy x-ray absorptiometry surveillance, patients who were older at diagnosis, white, and underweight were at the highest risk for lumbar spine low BMD. Low BMD was associated with a greater risk of fractures, emphasizing the clinical importance of surveillance.

How do Housing Subsidies Improve Quality of Life Among Homeless Adults? A Mediation Analysis.

Supported housing, combining rent subsidies with intensive case management, is associated with improvements in quality of life of homeless adults, but factors mediating their impact on quality of life have not been studied. Twelve-month outcome data from a randomized trial of the Housing and Urban Development- Veterans Affairs Supported Housing program (HUD-VASH) showed that access to a housing rent subsidy plus intensive case management (ICM) was associated with greater improvement in subjective quality of life than ICM alone. Multiple mediation analyses were applied to identify variables that significantly mediated the relationship between receipt of housing voucher and improvements in quality of life. Significant mediating covariates were those whose 95% bias-corrected confidence intervals, when added to the model predicting improvement in quality of life, did not overlap zero. Increases in the number of days housed, size of social network, and availability of emotional support appear to mediate improvement in quality of life and account for 71% of the benefit attributable to having a rent subsidy. Improvement in subjective quality of life though housing subsidies is mediated by gains in both material and psychosocial factors. Mediating factors deserve special attention in supported housing services.

The Association Between Motor Skills and Academic Achievement Among Pediatric Survivors of Acute Lymphoblastic Leukemia.

OBJECTIVE: Assess the association between fine motor (FM) and visual-motor integration (VMI) skills and academic achievement in pediatric acute lymphoblastic leukemia (ALL) survivors. METHODS: In this 28-site cross-sectional study of 256 children in first remission, a mean of 8.9 ± 2.2 years after treatment for standard-risk precursor-B ALL, validated measures of FM, VMI, reading, math, and intelligence were administered at mean follow-up age of 12.8 ± 2.5 years. RESULTS: VMI was significantly associated with written math calculation ability (p < .0069) after adjusting for intelligence (p < .0001). VMI was more strongly associated with math in those with lower intelligence (p = .0141). Word decoding was also significantly associated with VMI but with no effect modification by intelligence. FM skills were not associated with either reading or math achievement. CONCLUSION: These findings suggest that VMI is associated with aspects of math and reading achievement in leukemia survivors. These skills may be amenable to intervention.

Preoperative serum brain natriuretic peptide and risk of acute kidney injury after cardiac surgery.

BACKGROUND: Acute kidney injury (AKI) after cardiac surgery is associated with poor outcomes and is difficult to predict. We conducted a prospective study to evaluate whether preoperative brain natriuretic peptide (BNP) levels predict postoperative AKI among patients undergoing cardiac surgery. METHODS AND RESULTS: The Translational Research Investigating Biomarker Endpoints in Acute Kidney Injury (TRIBE-AKI) study enrolled 1139 adults undergoing cardiac surgery at 6 hospitals from 2007 to 2009 who were selected for high AKI risk. Preoperative BNP was categorized into quintiles. AKI was common with the use of Acute Kidney Injury Network definitions; at least mild AKI was a ≥0.3-mg/dL or 50% rise in creatinine (n=407, 36%), and severe AKI was either a doubling of creatinine or the requirement of acute renal replacement therapy (n=58, 5.1%). In analyses adjusted for preoperative characteristics, preoperative BNP was a strong and independent predictor of mild and severe AKI. Compared with the lowest BNP quintile, the highest quintile had significantly higher risk of at least mild AKI (risk ratio, 1.87; 95% confidence interval, 1.40-2.49) and severe AKI (risk ratio, 3.17; 95% confidence interval, 1.06-9.48). After adjustment for clinical predictors, the addition of BNP improved the area under the curve to predict at least mild AKI (0.67-0.69; P=0.02) and severe AKI (0.73-0.75; P=0.11). Compared with clinical parameters alone, BNP modestly improved risk prediction of AKI cases into lower and higher risk (continuous net reclassification index; at least mild AKI: risk ratio, 0.183; 95% confidence interval, 0.061-0.314; severe AKI: risk ratio, 0.231; 95% confidence interval, 0.067-0.506). CONCLUSIONS: Preoperative BNP level is associated with postoperative AKI in high-risk patients undergoing cardiac surgery. If confirmed in other types of patients and surgeries, preoperative BNP may be a valuable component of future efforts to improve preoperative risk stratification and discrimination among surgical candidates.

Urinary cystatin C and acute kidney injury after cardiac surgery.

BACKGROUND: Acute kidney injury (AKI) is common after cardiac surgery and is associated with adverse patient outcomes. Urinary cystatin C (CysC) level is a biomarker of proximal tubule function and may increase earlier in AKI than serum creatinine level. STUDY DESIGN: Prospective cohort study. SETTINGS & PARTICIPANTS: The TRIBE AKI (Translational Research Investigating Biomarker Endpoints in AKI) Consortium prospectively enrolled 1,203 adults and 299 children and adolescents at 8 institutions in 2007-2009. INDEX TEST: Urinary CysC (in milligrams per liter) within the first 12 hours after surgery. OUTCOME: Serum creatinine-based AKI was defined as AKI Network stage 1 (mild AKI) and doubling of serum creatinine from the preoperative value or need for dialysis during hospitalization (severe AKI). OTHER MEASUREMENTS: Analyses were adjusted for characteristics used clinically for AKI risk stratification, including age, sex, race, estimated glomerular filtration rate, diabetes, hypertension, heart failure, nonelective surgery, cardiac catheterization within 72 hours, type of surgery, myocardial infarction, and cardiopulmonary bypass time longer than 120 minutes. RESULTS: Urinary CysC level measured in the early postoperative period (0-6 and 6-12 hours postoperatively) correlated with both mild and severe AKI in adults and children. However, after analyses were adjusted for other factors, the effect was attenuated for both forms of AKI in both cohorts. LIMITATIONS: Limited numbers of patients with severe AKI and in-hospital dialysis treatment. CONCLUSIONS: Urinary CysC values are not associated significantly with the development of AKI after cardiac surgery in adults and children.

Biomarkers predict progression of acute kidney injury after cardiac surgery.

Being able to predict whether AKI will progress could improve monitoring and care, guide patient counseling, and assist with enrollment into trials of AKI treatment. Using samples from the Translational Research Investigating Biomarker Endpoints in AKI study (TRIBE-AKI), we evaluated whether kidney injury biomarkers measured at the time of first clinical diagnosis of early AKI after cardiac surgery can forecast AKI severity. Biomarkers included urinary IL-18, urinary albumin to creatinine ratio (ACR), and urinary and plasma neutrophil gelatinase-associated lipocalin (NGAL); each measurement was on the day of AKI diagnosis in 380 patients who developed at least AKI Network (AKIN) stage 1 AKI. The primary end point (progression of AKI defined by worsening AKIN stage) occurred in 45 (11.8%) patients. Using multivariable logistic regression, we determined the risk of AKI progression. After adjustment for clinical predictors, compared with biomarker values in the lowest two quintiles, the highest quintiles of three biomarkers remained associated with AKI progression: IL-18 (odds ratio=3.0, 95% confidence interval=1.3-7.3), ACR (odds ratio=3.4, 95% confidence interval=1.3-9.1), and plasma NGAL (odds ratio=7.7, 95% confidence interval=2.6-22.5). Each biomarker improved risk classification compared with the clinical model alone, with plasma NGAL performing the best (category-free net reclassification improvement of 0.69, P<0.0001). In conclusion, biomarkers measured on the day of AKI diagnosis improve risk stratification and identify patients at higher risk for progression of AKI and worse patient outcomes.

Effects of Electroconvulsive Therapy on Functional Outcomes Among Medicare Patients With Comorbid Depression and Dementia: A Nationwide 1-Year Follow-Up Study.

Objective: Current treatments for behavioral and psychological symptoms of dementia (BPSD) are of limited efficacy. Electroconvulsive therapy (ECT) is an effective and safe treatment for a range of psychiatric disorders, with some limited data suggesting a role in treating BPSD. We sought to expand this growing literature by examining-in a rigorous way with a larger sample size than in previous reports-the potential of ECT as a treatment for comorbid depression and dementia.Methods: Drawing on nationally representative 2014-2015 Medicare claims data, propensity score methods were used to create two comparable cohorts consisting of ECT-treated patients (n = 147) and controls (n = 415) who were hospitalized with a principal psychiatric diagnosis. Functional outcomes were compared before and after hospitalization (when ECT was initiated for the ECT cohort).Results: Both cohorts generally declined in all functional outcomes over the time period observed. The ECT cohort had a slower rate of functional decline in bathing (Cohen d = -0.05 vs 0.38; P < .001) and transferring (d = 0.18 vs 0.45; P = .031) compared to matched controls. In multivariate analysis, ECT patients also fared better in the overall activities of daily living summary score at 180 days (coefficient = -0.10; 95% CI, -0.19 to 0.01), though these effects were small. No difference was seen in cognition or ambulation.Discussion: Receiving ECT does not worsen the trajectory of functional outcomes compared to not receiving ECT in older adults with comorbid depression. Randomized clinical trials are needed to more definitively examine the causal effect of ECT on functional outcomes of individuals with dementia.

Serum cystatin C- versus creatinine-based definitions of acute kidney injury following cardiac surgery: a prospective cohort study.

BACKGROUND: The primary aim of this study was to compare the sensitivity and rapidity of acute kidney injury (AKI) detection by cystatin C level relative to creatinine level after cardiac surgery. STUDY DESIGN: Prospective cohort study. SETTINGS & PARTICIPANTS: 1,150 high-risk adult cardiac surgery patients in the TRIBE-AKI (Translational Research Investigating Biomarker Endpoints for Acute Kidney Injury) Consortium. PREDICTOR: Changes in serum creatinine and cystatin C levels. OUTCOME: Postsurgical incidence of AKI. MEASUREMENTS: Serum creatinine and cystatin C were measured at the preoperative visit and daily on postoperative days 1-5. To allow comparisons between changes in creatinine and cystatin C levels, AKI end points were defined by the relative increases in each marker from baseline (25%, 50%, and 100%) and the incidence of AKI was compared based on each marker. Secondary aims were to compare clinical outcomes among patients defined as having AKI by cystatin C and/or creatinine levels. RESULTS: Overall, serum creatinine level detected more cases of AKI than cystatin C level: 35% developed a ≥25% increase in serum creatinine level, whereas only 23% had a ≥25% increase in cystatin C level (P < 0.001). Creatinine level also had higher proportions meeting the 50% (14% and 8%; P < 0.001) and 100% (4% and 2%; P = 0.005) thresholds for AKI diagnosis. Clinical outcomes generally were not statistically different for AKI cases detected by creatinine or cystatin C level. However, for each AKI threshold, patients with AKI confirmed by both markers had a significantly higher risk of the combined mortality/dialysis outcome compared with patients with AKI detected by creatinine level alone (P = 0.002). LIMITATIONS: There were few adverse clinical outcomes, limiting our ability to detect differences in outcomes between subgroups of patients based on their definitions of AKI. CONCLUSIONS: In this large multicenter study, we found that cystatin C level was less sensitive for AKI detection than creatinine level. However, confirmation by cystatin C level appeared to identify a subset of patients with AKI with a substantially higher risk of adverse outcomes.

Postoperative biomarkers predict acute kidney injury and poor outcomes after pediatric cardiac surgery.

Acute kidney injury (AKI) occurs commonly after pediatric cardiac surgery and associates with poor outcomes. Biomarkers may help the prediction or early identification of AKI, potentially increasing opportunities for therapeutic interventions. Here, we conducted a prospective, multicenter cohort study involving 311 children undergoing surgery for congenital cardiac lesions to evaluate whether early postoperative measures of urine IL-18, urine neutrophil gelatinase-associated lipocalin (NGAL), or plasma NGAL could identify which patients would develop AKI and other adverse outcomes. Urine IL-18 and urine and plasma NGAL levels peaked within 6 hours after surgery. Severe AKI, defined by dialysis or doubling in serum creatinine during hospital stay, occurred in 53 participants at a median of 2 days after surgery. The first postoperative urine IL-18 and urine NGAL levels strongly associated with severe AKI. After multivariable adjustment, the highest quintiles of urine IL-18 and urine NGAL associated with 6.9- and 4.1-fold higher odds of AKI, respectively, compared with the lowest quintiles. Elevated urine IL-18 and urine NGAL levels associated with longer hospital stay, longer intensive care unit stay, and duration of mechanical ventilation. The accuracy of urine IL-18 and urine NGAL for diagnosis of severe AKI was moderate, with areas under the curve of 0.72 and 0.71, respectively. The addition of these urine biomarkers improved risk prediction over clinical models alone as measured by net reclassification improvement and integrated discrimination improvement. In conclusion, urine IL-18 and urine NGAL, but not plasma NGAL, associate with subsequent AKI and poor outcomes among children undergoing cardiac surgery.

Early postoperative serum cystatin C predicts severe acute kidney injury following pediatric cardiac surgery.

In this multicenter, prospective study of 288 children (half under 2 years of age) undergoing cardiac surgery, we evaluated whether the measurement of pre- and postoperative serum cystatin C (CysC) improves the prediction of acute kidney injury (AKI) over that obtained by serum creatinine (SCr). Higher preoperative SCr-based estimated glomerular filtration rates predicted higher risk of the postoperative primary outcomes of stage 1 and 2 AKI (adjusted odds ratios (ORs) 1.5 and 1.9, respectively). Preoperative CysC was not associated with AKI. The highest quintile of postoperative (within 6 h) CysC predicted stage 1 and 2 AKI (adjusted ORs of 6 and 17.2, respectively). The highest tertile of percent change in CysC independently predicted AKI, whereas the highest tertile of SCr predicted stage 1 but not stage 2 AKI. Postoperative CysC levels independently predicted longer duration of ventilation and intensive care unit length of stay, whereas the postoperative SCr change only predicted longer intensive care unit stay. Thus, postoperative serum CysC is useful to risk-stratify patients for AKI treatment trials. More research, however, is needed to understand the relation between preoperative renal function and the risk of AKI.

Insurance Status and Continuity for Young Adults With First-Episode Psychosis.

OBJECTIVE: Insurance status and continuity may affect access to and quality of care. The authors characterized patterns of and changes in insurance status over 1 year among people with first-episode psychosis (FEP), comparing insurance patterns with adults of similar age in the general population. METHODS: Longitudinal data on insurance status and predictors of insurance status among adults with FEP were obtained from RAISE-ETP (Recovery After an Initial Schizophrenia Episode-Early Treatment Program) study participants with complete 1-year data (N=288). The frequencies of insurance status and transitions are presented. Bivariate comparisons were used to assess the impact of the comprehensive coordinated care intervention in RAISE-ETP on insurance changes. These data were compared with contemporaneous longitudinal data in the 2011 Medical Expenditures Panel Study. RESULTS: The RAISE-ETP experimental intervention did not significantly change insurance status. At baseline, levels of uninsurance (47%) and public insurance (31%) were higher among RAISE-ETP participants than among a similar age group in the general public (29% and 13%, respectively). Insurance transitions were common among people with FEP, although 79% of those with public insurance at baseline also had public insurance at 1 year. Of studied RAISE-ETP participants, 60% had a period of uninsurance during the year studied. CONCLUSIONS: Compared with a national sample, people with FEP were more likely to use public insurance but still had high persistence of 12-month uninsurance. That over half of the RAISE-ETP participants had a period of uninsurance suggests that more research is needed on whether these periods affect treatment continuity and medication adherence.

Association of ECT With Risks of All-Cause Mortality and Suicide in Older Medicare Patients.

OBJECTIVE: This observational study examined the effects of electroconvulsive therapy (ECT) on suicide and all-cause mortality risk in older psychiatric patients. METHODS: Participants were Medicare-insured psychiatric inpatients age 65 or older. Patients receiving ECT were exact-matched to control subjects (in a 1:3 ratio) on age, gender, principal hospital diagnosis, past-year psychiatric hospitalizations, past-year suicide attempts, and Elixhauser comorbidity index. Cox proportional hazard models were risk-adjusted for race, year of hospitalization, rural-urban continuum code, year of index hospitalization, median income of zip code, and all matched covariates to estimate hazard ratios with 95% confidence intervals. RESULTS: A total of 10,460 patients in the ECT group and 31,160 in the control group were included in the analyses (total N=41,620; 65.4% female; mean age, 74.7 years [SD=7.09]). Compared with the control group, patients receiving ECT had lower all-cause mortality for up to 1 year following hospital discharge (adjusted hazard ratio=0.61, 95% CI=0.56, 0.66). For death by suicide, 1-year survival analysis showed no group difference. A significant association was observed with suicide in the first months following ECT, but this pattern waned over time (1 month: hazard ratio=0.44, 95% CI=0.21, 0.91; 2 months: hazard ratio=0.52, 95% CI=0.29, 0.92; 3 months: hazard ratio=0.56, 95% CI=0.37, 0.92; 6 months: 0.87, 95% CI=0.59, 1.28; 12 months: 0.92, 95% CI=0.68, 1.25). CONCLUSIONS: In this observational study, ECT was associated with lower 1-year all-cause mortality and with short-lived protective effects on suicide risk. These findings support greater consideration of ECT for inpatients with mood disorders at short-term risk of suicide.

Barriers to the Implementation of Electroconvulsive Therapy (ECT): Results From a Nationwide Survey of ECT Practitioners.

OBJECTIVE: Electroconvulsive therapy (ECT) is an effective treatment for major depressive disorder; yet, its use is confined to <1% of individuals with this disorder. The authors aimed to examine barriers to ECT from the perspective of the provider. METHODS: Qualitative interviews were conducted with U.S.-based ECT providers to identify potential barriers. A quantitative survey was created asking providers to rank-order barriers to starting a new ECT service or expanding existing services. RESULTS: Survey responses were received from 192 physicians. Respondents were representative of all ECT providers found in the Medicare Provider Utilization and Payment Database with respect to gender and geographic distribution. Approximately one-third (N=58, 30%) of survey respondents graduated from one of 12 residency programs. Programs with dedicated hospital space were more likely to have larger services than those borrowing surgical recovery space (χ2=25.87, df=1, p<0.001). The most prominent provider-reported barriers to expanding an existing ECT service were lack of physical space, stigma on the part of patients, and transportation difficulties. The most prominent barriers to initiating a new service were lack of well-trained colleagues and ECT practitioners, lack of a champion within the institution, and lack of physical space. Wide geographic variation was found in the availability of ECT, with the highest concentration of ECT providers per 1 million individuals found in New England (6.4), and the lowest found in the West South Central (1.1). CONCLUSIONS: Coordinated efforts to overcome identified barriers may allow ECT to be more broadly implemented. Investments in education may increase the number of competent practitioners.

An 18-month longitudinal study of suicidality in patients diagnosed with schizophrenia.

BACKGROUND: Suicide kills over 30,000 people annually in the US. Schizophrenia increases the risk, even in psychiatric populations. Identifying high-risk groups within this patient population is central to suicide prevention. We tested the effects of known and putative risk factors for suicide in a clinically recognizable population with symptoms of schizophrenia and unstable illness. METHODS: We studied 1439 subjects with schizophrenia participating in the NIMH-funded Clinical Antipsychotic Treatment for Intervention Effectiveness (CATIE) trial and followed for 18 months. The dependent variable was moderate to severe self-reported suicidal thinking and self-reported suicide attempts. The independent variables comprised potential risk factors for suicidality including measures of clinical change during follow-up. Proportional hazards models of time to first suicidality generated bivariate and multivariate hazard ratios (HRs). RESULTS: Altogether 96 patients (7.6%) experienced moderate to severe suicidality in the course of 18 months. Multivariate analyses showed that baseline moderate or severe suicidality was the strongest correlate of subsequent moderate or severe suicidality (HR 5.1). An increase in a subject's depression score during follow-up was also independently and strongly associated with suicidality (HR 3.5). A change in psychotic symptoms was not. CONCLUSIONS: Depression and despair may be more important risk factors for suicidality among people with schizophrenia than psychotic decompensation. Strategies for prevention that seek to identify groups at high risk of suicide should focus on these variables, as well as the effect of prior suicidality.

Characterization of the Quality of Electroconvulsive Therapy Among Older Medicare Beneficiaries.

BACKGROUND: Electroconvulsive therapy (ECT) is an important therapy for treatment-resistant depression and is especially effective for elderly individuals with depression. This is the first US nationally representative description of ECT in the elderly. METHODS: Using 2014-2015 Medicare claims data, we compared elderly individuals with major depressive disorder (using ICD-9 and ICD-10 codes) who received ECT with those who did not on demographic and clinical measures. We characterized treatment patterns by setting and the proportion of individuals receiving index and continuation/maintenance courses, subtherapeutic courses of ECT, and post-ECT follow-up care. RESULTS: Of all Medicare beneficiaries aged 65 years and older diagnosed with depression in 2014-2015, 7,817 (0.41%) received 1 or more ECT sessions. Compared to the general population of elderly Medicare beneficiaries with depression, recipients of ECT were slightly younger and more likely to be male, non-Hispanic, and white and live in a zip code with a higher median income. Among those who received any ECT, 33.7% received < 5 total treatments. Of those who received an index ECT treatment, 33.7% received a continuation/maintenance course of ECT, while 60.9% received some form of post-ECT follow-up treatment (additional ECT or new psychotropic medication). Receipt of psychotherapy was the strongest predictor of those who received ≥ 5 ECT treatments (adjusted odds ratio = 1.43; 95% CI, 1.22 to 1.67). CONCLUSIONS: Despite substantial evidence of efficacy, ECT use remains rare among elderly patients with depression. Findings suggest a potential need for efforts to increase the proportion of patients receiving adequate courses of ECT and evidence-based post-ECT follow-up care.

Correlates of Future Violence in People Being Treated for Schizophrenia.

OBJECTIVE: Violent behavior is infrequent among individuals with schizophrenia but is clinically important. The purpose of this study was to provide data on the correlates of violence, which may allow better risk assessment and care. METHODS: A total of 1,435 individuals with schizophrenia who participated in the National Institute of Mental Health's Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study and were followed for 18 months were examined. The dependent variables were self-reported injurious and noninjurious violence during follow-up. The independent variables, assessed at study entry, comprised participants' recent injurious and noninjurious violence, demographic and background variables, childhood risk factors, clinical condition, current circumstances, and recent contact with hospitals and prisons. Proportional hazards models of time to first injurious violence were used to generate bivariable and multivariable hazard ratios for all participants and, separately, for participants with no injurious violence at study entry. RESULTS: Seventy-seven participants (5.4%) reported engaging in injurious violence during follow-up, and 119 (8.3%) reported engaging in exclusively noninjurious violence. In the multivariable analysis, baseline injurious violence (hazard ratio=4.02), recent violent victimization (hazard ratio=3.52), severity of drug use (hazard ratio=2.93), baseline noninjurious violence (hazard ratio=2.72), childhood sexual abuse (hazard ratio=1.85), and medication nonadherence (hazard ratio=1.39) were associated with future injurious violence. For participants with no history of injurious violence at study entry, baseline noninjurious violence was the strongest predictor (hazard ratio=3.02). Recent violent victimization was no longer a significant correlate. The remaining correlates and the strength of their association with future injurious violence were similar to those for all participants. CONCLUSIONS: This is the first longitudinal multivariable analysis of predictors of injurious violence in a large cohort of patients with schizophrenia followed over 18 months. The results revealed simultaneous strong effects of baseline injurious violence and recent violent victimization on future injurious violent behavior. Among clinical variables, poor medication adherence, but not baseline symptoms of psychosis or depression, significantly predicted injurious violence. Treatment strategies to reduce risk should emphasize medication adherence.

Predictors of Hospitalization of Individuals With First-Episode Psychosis: Data From a 2-Year Follow-Up of the RAISE-ETP.

OBJECTIVE: Despite treatment advances in other domains, inpatient psychiatric hospitalization rates for individuals with first-episode psychosis remain high. Even with early intervention services, a third or more of individuals are hospitalized over the first 2 years of treatment. Reducing hospitalization is desirable from the individual's perspective and for public health reasons because hospitalization costs are a major component of treatment costs. METHODS: Univariate and multivariate baseline and time-varying covariate analyses were conducted to identify predictors of hospitalization in the Recovery After an Initial Schizophrenia Episode-Early Treatment Program (RAISE-ETP) study, a 2-year cluster randomized trial for participants experiencing a first episode of psychosis who were outpatients at study entry. The trial compared an early intervention treatment model (NAVIGATE) with usual community care at 34 clinics across the United States. RESULTS: RAISE-ETP enrolled 404 participants of whom 382 had one or more postbaseline assessments that included hospitalization data. Thirty-four percent of NAVIGATE and 37% of usual-care participants were hospitalized during the trial. Risk analyses revealed significant predictors of hospitalization to be the number of hospitalizations before study entry; duration of untreated psychosis; and time-varying days of substance misuse, presence of positive symptoms, and beliefs about the value of medication. CONCLUSIONS: These results indicate that hospital use may be decreased by reducing the duration of untreated psychosis and prior hospitalizations, minimizing residual symptoms, preventing substance misuse, and facilitating adherence to medication taking. Addressing these factors could enhance the impact of first-episode early intervention treatment models and also enhance outcomes of people with first-episode psychosis treated using other models.

Accounting for group differences in study retention in a randomized trial of specialized treatment for first episode psychosis.

BACKGROUND: Schizophrenia is a chronic disabling disorder for which current treatments are only partially effective. While the evaluation of novel interventions is a high priority, loss to follow-up is a major threat to validity. METHODS: Pattern mixture modeling is a statistical technique that incorporates information on patterns of retention that may bias comparisons between randomized treatment groups. This study used pattern mixture mixed model (PMMM) in the analysis of outcomes of a two-year cluster-randomized trial, the Recovery after an Initial Schizophrenia Episode-Early Treatment Program, which compared a coordinated specialty care intervention called NAVIGATE to usual community care (CC). PMM-adjusted outcome differences between NAVIGATE and CC were estimated by the weighted-average of effects across the retention patterns. RESULTS: Compared to the original analysis, PMMM improved model fit and the estimated effectiveness of NAVIGATE as compared to CC. On the Quality of Life Scale NAVIGATE effectiveness increased by 1.50 points (25.4%); on the Positive and Negative Syndrome Scale, by 1.72 points (39.8%), and on the Calgary Depression Scale by 0.49 points (62.1%). PMMM did not improve model fit for employment days, substance use days, or hospital days. CONCLUSION: Use of PMMM improved model fit and increased the estimated differences between NAVIGATE and CC for major outcomes. Patients with differential retention patterns may have different outcome trajectories. PMMM is a useful tool for addressing potential biases arising from these differences.

Supported employment and education in comprehensive, integrated care for first episode psychosis: Effects on work, school, and disability income.

BACKGROUND: Participation in work and school are central objectives for first episode psychosis (FEP) programs, but evidence effectiveness has been mixed in studies not focused exclusively on supported employment and education (SEE). Requirements for current motivation to work or go to school limit the generalizability of such studies. METHODS: FEP participants (N=404) at thirty-four community treatment clinics participated in a cluster randomized trial that compared usual Community Care (CC) to NAVIGATE, a comprehensive, team-based treatment program that included ≥5h of SEE services per week, , grounded in many of the principles of the Individual Placement and Support model of supported employment combined with supported education services. All study participants were offered SEE regardless of their initial interest in work or school. Monthly assessments over 24months recorded days of employment and attendance at school, days of participation in SEE, and both employment and public support income (including disability income). General Estimation Equation models were used to compare CC and NAVIGATE on work and school participation, employment and public support income, and the mediating effect of receiving ≥3 SEE visits on these outcomes. RESULTS: NAVIGATE treatment was associated with a greater increase in participation in work or school (p=0.0486) and this difference appeared to be mediated by SEE. No group differences were observed in earnings or public support payments. CONCLUSION: A comprehensive, team-based FEP treatment approach was associated with greater improvement in work or school participation, and this effect appears to be mediated, in part, by participation in SEE.