Perceived Discrimination and Cardiometabolic Risk Among US Hispanics/Latinos in the HCHS/SOL Sociocultural Ancillary Study.

BACKGROUND: Metabolic syndrome (MetS) is a group of cardiovascular risk factors including elevated blood pressure, elevated triglycerides, decreased high-density lipoprotein cholesterol, impaired fasting glucose, and abdominal obesity, which disproportionately affects Hispanics/Latinos. The present study examined associations between perceived discrimination and MetS in Hispanic/Latino adults from various background groups (i.e., Dominican, Central American, Cuban, Mexican, Puerto Rican, South American). METHODS: Data were obtained from 5174 Hispanics/Latinos who participated in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) Sociocultural Ancillary Study. MetS components and covariates were measured at a baseline examination, and perceived discrimination was assessed within 9 months of baseline. Path analysis modeled associations of perceived discrimination with MetS prevalence and each of the six components of MetS, controlling for age, sex, income, acculturation, physical activity, diet, smoking, and alcohol use. RESULTS: Among the full cohort, perceived discrimination was not associated with MetS prevalence in any of the models evaluated. Higher perceived discrimination at work/school was associated with larger waist circumference. When examining background groups separately, higher perceived ethnicity-associated threat was related to increased MetS prevalence only among individuals of Central American background. Differential patterns of association between perceived discrimination and MetS components were found for different background groups. CONCLUSIONS: Overall results suggested that perceived discrimination was not strongly or consistently associated with MetS among Hispanics/Latinos.

Incorporating Patient Preferences into Estimation of Optimal Individualized Treatment Rules.

Precision medicine seeks to provide treatment only if, when, to whom, and at the dose it is needed. Thus, precision medicine is a vehicle by which healthcare can be made both more effective and efficient. Individualized treatment rules operationalize precision medicine as a map from current patient information to a recommended treatment. An optimal individualized treatment rule is defined as maximizing the mean of a pre-specified scalar outcome. However, in settings with multiple outcomes, choosing a scalar composite outcome by which to define optimality is difficult. Furthermore, when there is heterogeneity across patient preferences for these outcomes, it may not be possible to construct a single composite outcome that leads to high-quality treatment recommendations for all patients. We simultaneously estimate the optimal individualized treatment rule for all composite outcomes representable as a convex combination of the (suitably transformed) outcomes. For each patient, we use a preference elicitation questionnaire and item response theory to derive the posterior distribution over preferences for these composite outcomes and subsequently derive an estimator of an optimal individualized treatment rule tailored to patient preferences. We prove that as the number of subjects and items on the questionnaire diverge, our estimator is consistent for an oracle optimal individualized treatment rule wherein each patient's preference is known a priori. We illustrate the proposed method using data from a clinical trial on antipsychotic medications for schizophrenia.

Spirometry Reference Equations from the HCHS/SOL (Hispanic Community Health Study/Study of Latinos).

RATIONALE: Accurate reference values for spirometry are important because the results are used for diagnosing common chronic lung diseases such as asthma and chronic obstructive pulmonary disease, estimating physiologic impairment, and predicting all-cause mortality. Reference equations have been established for Mexican Americans but not for others with Hispanic/Latino backgrounds. OBJECTIVES: To develop spirometry reference equations for adult Hispanic/Latino background groups in the United States. METHODS: The HCHS/SOL (Hispanic Community Health Study/Study of Latinos) recruited a population-based probability sample of 16,415 Hispanics/Latinos aged 18-74 years living in the Bronx, Chicago, Miami, and San Diego. Participants self-identified as being of Puerto Rican, Cuban, Dominican, Mexican, or Central or South American background. Spirometry was performed using standardized methods with central quality control monitoring. Spirometric measures from a subset of 6,425 never-smoking participants without respiratory symptoms or disease were modeled as a function of sex, age, height, and Hispanic/Latino background to produce background-specific reference equations for the predicted value and lower limit of normal. MEASUREMENTS AND MAIN RESULTS: Dominican and Puerto Rican Americans had substantially lower predicted and lower limit of normal values for FVC and FEV1 than those in other Hispanic/Latino background groups and also than Mexican American values from NHANES III (Third National Health and Nutrition Examination Survey). CONCLUSIONS: For patients of Dominican and Puerto Rican background who present with pulmonary symptoms in clinical practice, use of background-specific spirometry reference equations may provide more appropriate predicted and lower limit of normal values, enabling more accurate diagnoses of abnormality and physiologic impairment.

Is there a link between wealth and cardiovascular disease risk factors among Hispanic/Latinos? Results from the HCHS/SOL sociocultural ancillary study.

OBJECTIVE: To examine the relationship between wealth and cardiovascular disease risk factors among Hispanic/Latinos of diverse backgrounds. DESIGN: This cross-sectional study used data from 4971 Hispanic/Latinos, 18-74 years, who participated in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) baseline exam and the HCHS/SOL Sociocultural Ancillary Study. Three objectively measured cardiovascular disease risk factors (hypertension, hypercholesterolemia, and obesity) were included. Wealth was measured using an adapted version of the Home Affluence Scale, which included questions regarding the ownership of a home, cars, computers, and recent vacations. RESULTS: After adjusting for traditional socioeconomic indicators (income, employment, education), and other covariates, we found that wealth was not associated with hypertension, hypercholesterolemia or obesity. Analyses by sex showed that middle-wealth women were less likely to have hypercholesterolemia or obesity. Analyses by Hispanic/Latino background groups showed that while wealthier Central Americans were less likely to have obesity, wealthier Puerto Ricans were more likely to have obesity. CONCLUSION: This is the first study to explore the relationship between wealth and health among Hispanic/Latinos of diverse backgrounds, finding only partial evidence of this association. Future studies should utilize more robust measures of wealth, and address mechanisms by which wealth may impact health status among Hispanic/Latinos of diverse backgrounds in longitudinal designs.

Pulmonary Disease and Age at Immigration among Hispanics. Results from the Hispanic Community Health Study/Study of Latinos.

RATIONALE: Asthma has been reported to be more prevalent among Hispanics of Puerto Rican heritage than among other Hispanics and among Hispanics born in the United States or who immigrated as children than among those who came as adults; however, direct comparisons across Hispanic groups are lacking. OBJECTIVES: To test whether asthma is more prevalent among Hispanics of Puerto Rican heritage than among other Hispanic groups, whether asthma is associated with age of immigration, and whether chronic obstructive pulmonary disease varies by heritage in a large, population-based cohort of Hispanics in the United States. METHODS: The Hispanic Community Health Study/Study of Latinos researchers recruited a population-based probability sample of 16,415 Hispanics/Latinos, 18-74 years of age, in New York City, Chicago, Miami, and San Diego. Participants self-reported Puerto Rican, Cuban, Dominican, Mexican, Central American, or South American heritage; birthplace; and, if relevant, age at immigration. A respiratory questionnaire and standardized spirometry were performed with post-bronchodilator measures for those with airflow limitation. MEASUREMENTS AND MAIN RESULTS: The prevalence of physician-diagnosed asthma among Puerto Ricans (36.5%; 95% confidence interval, 33.6-39.5%) was higher than among other Hispanics (odds ratio, 3.9; 95% confidence interval, 3.3-4.6). Hispanics who were born in the mainland United States or had immigrated as children had a higher asthma prevalence than those who had immigrated as adults (19.6, 19.4, and 14.1%, respectively; P < 0.001). Current asthma, bronchodilator responsiveness, and wheeze followed similar patterns. Chronic obstructive pulmonary disease prevalence was higher among Puerto Ricans (14.1%) and Cubans (9.8%) than among other Hispanics (<6.0%), but it did not vary across Hispanic heritages after adjustment for smoking and prior asthma (P = 0.22), by country of birth, or by age at immigration. CONCLUSIONS: Asthma was more prevalent among Puerto Ricans, other Hispanics born in the United States, and those who had immigrated as children than among other Hispanics. In contrast, the higher prevalence of chronic obstructive pulmonary disease among Puerto Ricans and Cubans was largely reflective of differential smoking patterns and asthma.

Comparison of serum, EDTA plasma and P100 plasma for luminex-based biomarker multiplex assays in patients with chronic obstructive pulmonary disease in the SPIROMICS study.

BACKGROUND: As a part of the longitudinal Chronic Obstructive Pulmonary Disease (COPD) study, Subpopulations and Intermediate Outcome Measures in COPD study (SPIROMICS), blood samples are being collected from 3200 subjects with the goal of identifying blood biomarkers for sub-phenotyping patients and predicting disease progression. To determine the most reliable sample type for measuring specific blood analytes in the cohort, a pilot study was performed from a subset of 24 subjects comparing serum, Ethylenediaminetetraacetic acid (EDTA) plasma, and EDTA plasma with proteinase inhibitors (P100). METHODS: 105 analytes, chosen for potential relevance to COPD, arranged in 12 multiplex and one simplex platform (Myriad-RBM) were evaluated in duplicate from the three sample types from 24 subjects. The reliability coefficient and the coefficient of variation (CV) were calculated. The performance of each analyte and mean analyte levels were evaluated across sample types. RESULTS: 20% of analytes were not consistently detectable in any sample type. Higher reliability and/or smaller CV were determined for 12 analytes in EDTA plasma compared to serum, and for 11 analytes in serum compared to EDTA plasma. While reliability measures were similar for EDTA plasma and P100 plasma for a majority of analytes, CV was modestly increased in P100 plasma for eight analytes. Each analyte within a multiplex produced independent measurement characteristics, complicating selection of sample type for individual multiplexes. CONCLUSIONS: There were notable detectability and measurability differences between serum and plasma. Multiplexing may not be ideal if large reliability differences exist across analytes measured within the multiplex, especially if values differ based on sample type. For some analytes, the large CV should be considered during experimental design, and the use of duplicate and/or triplicate samples may be necessary. These results should prove useful for studies evaluating selection of samples for evaluation of potential blood biomarkers.

Effectiveness of atypical antipsychotic drugs in patients with Alzheimer's disease.

BACKGROUND: Second-generation (atypical) antipsychotic drugs are widely used to treat psychosis, aggression, and agitation in patients with Alzheimer's disease, but their benefits are uncertain and concerns about safety have emerged. We assessed the effectiveness of atypical antipsychotic drugs in outpatients with Alzheimer's disease. METHODS: In this 42-site, double-blind, placebo-controlled trial, 421 outpatients with Alzheimer's disease and psychosis, aggression, or agitation were randomly assigned to receive olanzapine (mean dose, 5.5 mg per day), quetiapine (mean dose, 56.5 mg per day), risperidone (mean dose, 1.0 mg per day), or placebo. Doses were adjusted as needed, and patients were followed for up to 36 weeks. The main outcomes were the time from initial treatment to the discontinuation of treatment for any reason and the number of patients with at least minimal improvement on the Clinical Global Impression of Change (CGIC) scale at 12 weeks. RESULTS: There were no significant differences among treatments with regard to the time to the discontinuation of treatment for any reason: olanzapine (median, 8.1 weeks), quetiapine (median, 5.3 weeks), risperidone (median, 7.4 weeks), and placebo (median, 8.0 weeks) (P=0.52). The median time to the discontinuation of treatment due to a lack of efficacy favored olanzapine (22.1 weeks) and risperidone (26.7 weeks) as compared with quetiapine (9.1 weeks) and placebo (9.0 weeks) (P=0.002). The time to the discontinuation of treatment due to adverse events or intolerability favored placebo. Overall, 24% of patients who received olanzapine, 16% of patients who received quetiapine, 18% of patients who received risperidone, and 5% of patients who received placebo discontinued their assigned treatment owing to intolerability (P=0.009). No significant differences were noted among the groups with regard to improvement on the CGIC scale. Improvement was observed in 32% of patients assigned to olanzapine, 26% of patients assigned to quetiapine, 29% of patients assigned to risperidone, and 21% of patients assigned to placebo (P=0.22). CONCLUSIONS: Adverse effects offset advantages in the efficacy of atypical antipsychotic drugs for the treatment of psychosis, aggression, or agitation in patients with Alzheimer's disease. (ClinicalTrials.gov number, NCT00015548 [ClinicalTrials.gov].).

Results of phase 3 of the CATIE schizophrenia trial.

OBJECTIVE: The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study examined the comparative effectiveness of antipsychotic treatments for individuals with chronic schizophrenia. Patients who had discontinued antipsychotic treatment in phases 1 and 2 were eligible for phase 3, in which they selected one of nine antipsychotic regimens with the help of their study doctor. We describe the characteristics of the patients who selected each treatment option and their outcomes. METHOD: Two hundred and seventy patients entered phase 3. The open-label treatment options were monotherapy with oral aripiprazole, clozapine, olanzapine, perphenazine, quetiapine, risperidone, ziprasidone, long-acting injectable fluphenazine decanoate, or a combination of any two of these treatments. RESULTS: Few patients selected fluphenazine decanoate (n=9) or perphenazine (n=4). Similar numbers selected each of the other options (range 33-41). Of the seven common choices, those who selected clozapine and combination antipsychotic treatment were the most symptomatic, and those who selected aripiprazole and ziprasidone had the highest body mass index. Symptoms improved for all groups, although the improvements were modest for the groups starting with relatively mild levels of symptoms. Side effect profiles of the medications varied considerably but medication discontinuations due to intolerability were rare (7% overall). CONCLUSIONS: Patients and their doctors made treatment selections based on clinical factors, including severity of symptoms, response to prior treatments, and physical health status. Fluphenazine decanoate was rarely used among those with evidence of treatment non-adherence and clozapine was underutilized for those with poor previous response. Combination antipsychotic treatment warrants further study.

Effectiveness of antipsychotic drugs in patients with chronic schizophrenia.

BACKGROUND: The relative effectiveness of second-generation (atypical) antipsychotic drugs as compared with that of older agents has been incompletely addressed, though newer agents are currently used far more commonly. We compared a first-generation antipsychotic, perphenazine, with several newer drugs in a double-blind study. METHODS: A total of 1493 patients with schizophrenia were recruited at 57 U.S. sites and randomly assigned to receive olanzapine (7.5 to 30 mg per day), perphenazine (8 to 32 mg per day), quetiapine (200 to 800 mg per day), or risperidone (1.5 to 6.0 mg per day) for up to 18 months. Ziprasidone (40 to 160 mg per day) was included after its approval by the Food and Drug Administration. The primary aim was to delineate differences in the overall effectiveness of these five treatments. RESULTS: Overall, 74 percent of patients discontinued the study medication before 18 months (1061 of the 1432 patients who received at least one dose): 64 percent of those assigned to olanzapine, 75 percent of those assigned to perphenazine, 82 percent of those assigned to quetiapine, 74 percent of those assigned to risperidone, and 79 percent of those assigned to ziprasidone. The time to the discontinuation of treatment for any cause was significantly longer in the olanzapine group than in the quetiapine (P<0.001) or risperidone (P=0.002) group, but not in the perphenazine (P=0.021) or ziprasidone (P=0.028) group. The times to discontinuation because of intolerable side effects were similar among the groups, but the rates differed (P=0.04); olanzapine was associated with more discontinuation for weight gain or metabolic effects, and perphenazine was associated with more discontinuation for extrapyramidal effects. CONCLUSIONS: The majority of patients in each group discontinued their assigned treatment owing to inefficacy or intolerable side effects or for other reasons. Olanzapine was the most effective in terms of the rates of discontinuation, and the efficacy of the conventional antipsychotic agent perphenazine appeared similar to that of quetiapine, risperidone, and ziprasidone. Olanzapine was associated with greater weight gain and increases in measures of glucose and lipid metabolism.

Extrapyramidal side-effects of antipsychotics in a randomised trial.

BACKGROUND: There are claims that second-generation antipsychotics produce fewer extrapyramidal side-effects (EPS) compared with first-generation drugs. AIMS: To compare the incidence of treatment-emergent EPS between second-generation antipsychotics and perphenazine in people with schizophrenia. METHOD: Incidence analyses integrated data from standardised rating scales and documented use of concomitant medication or treatment discontinuation for EPS events. Mixed model analyses of change in rating scales from baseline were also conducted. RESULTS: There were no significant differences in incidence or change in rating scales for parkinsonism, dystonia, akathisia or tardive dyskinesia when comparing second-generation antipsychotics with perphenazine or comparing between second-generation antipsychotics. Secondary analyses revealed greater rates of concomitant antiparkinsonism medication among individuals on risperidone and lower rates among individuals on quetiapine, and lower rates of discontinuation because of parkinsonism among people on quetiapine and ziprasidone. There was a trend for a greater likelihood of concomitant medication for akathisia among individuals on risperidone and perphenazine. CONCLUSIONS: The incidence of treatment-emergent EPS and change in EPS ratings indicated that there are no significant differences between second-generation antipsychotics and perphenazine or between second-generation antipsychotics in people with schizophrenia.

The effectiveness of antipsychotic medications in patients who use or avoid illicit substances: results from the CATIE study.

OBJECTIVE: This double-blind study compared a second generation (atypical) antipsychotic drugs compared to a representative older agent for patients with schizophrenia who use or avoid illicit substances. METHODS: Schizophrenic subjects were recruited at 57 U.S. sites and randomly assigned to olanzapine, perphenazine, quetiapine, risperidone or ziprasidone for up to 18 months. The primary aim of this analysis was to delineate differences between the overall effectiveness of these five treatments among patients who used or did not use illicit substances. RESULTS: There were no significant differences between treatment groups in time to all-cause treatment discontinuation among patients who use illicit drugs (median 3.3 to 6.8 months). Among non-users time to treatment discontinuation was significantly longer for patients treated with olanzapine (median 13.0 months) than perphenazine ( 5.9 months), risperidone (5.6 months), or quetiapine (5.0 months); time to discontinuation for ziprasidone (4.3 months) was even shorter, although the latter difference was not significant. The difference between risperidone and quetiapine, although small, was significant. All remaining differences were non-significant. Similar results were found for discontinuation due to inefficacy. There were no differences between illicit users and non-users in symptom reduction and global improvement, after adjustment for differential duration of treatment. Differences in discontinuation results were attenuated by non-compliance, but the trends persisted after controlling for treatment compliance. CONCLUSIONS: Among patients with chronic schizophrenia who avoid use of illicit drugs, olanzapine was more effective than other antipsychotics as reflected by longer time to all-cause discontinuation, but illicit substance abuse attenuated this advantage, reinforcing the need for concurrent substance abuse treatment.

Change in metabolic syndrome parameters with antipsychotic treatment in the CATIE Schizophrenia Trial: prospective data from phase 1.

BACKGROUND: The metabolic syndrome (MS) is associated with increased risk for diabetes mellitus and coronary heart disease, and is highly prevalent among schizophrenia patients. Given concerns over antipsychotic metabolic effects, this analysis explored MS status and outcomes in phase 1 of the CATIE Schizophrenia Trial. METHODS: The change in proportion of subjects with MS and individual criteria was compared between antipsychotic treatment groups, along with mean changes for individual criteria. Primary analyses examined subjects with fasting laboratory assessments at baseline and 3 months. Other analyses examined 3-month changes in MS status, waist circumference (WC), HDL cholesterol and blood pressure in all subjects, metabolic changes at the end of phase 1 participation (EOP), and repeated measures changes in HDL, blood pressure (BP) and WC over phase 1. RESULTS: At 3 months, there were no significant between-drug differences for the change in proportion of subjects meeting MS status or individual MS criteria in the smaller fasting cohort (n = 281) or for those meeting criteria for parameters not dependent on fasting status (BP, HDL, WC) among all subjects (n=660). Among all subjects whose MS status could be determined at 3 months (n=660), MS prevalence increased for olanzapine (from 34.8% to 43.9%), but decreased for ziprasidone (from 37.7% to 29.9%) (p=.001). Although effect sizes varied across subgroups, at 3 months olanzapine and quetiapine had the largest mean increase in waist circumference (0.7 in. for both) followed by risperidone (0.4 in.), compared to no change for ziprasidone (0.0 in.) and a decrease in waist circumference for perphenazine (-0.4 in.). Olanzapine also demonstrated significantly different changes in fasting triglycerides at 3 months (+21.5 mg/dl) compared to ziprasidone (-32.1 mg/dl). EOP exposure data was obtained, on average, nine months from baseline for all metabolic variables. Results from EOP and repeated measures analyses were consistent with those at 3 months for mean changes in WC and fasting triglycerides, but between group differences emerged for HDL and SBP. CONCLUSIONS: This large non-industry sponsored study confirms the differential metabolic effects between antipsychotics. Clinicians are advised to monitor all metabolic parameters, including WC, HDL and serum triglycerides, during antipsychotic treatment.

Antipsychotic effects on estimated 10-year coronary heart disease risk in the CATIE schizophrenia study.

OBJECTIVE: Persons with schizophrenia die earlier than the general population, in large part due to cardiovascular disease. The study objective was to examine effects of different antipsychotic treatments on estimates of 10-year coronary heart disease (CHD) risk calculated by the Framingham Heart Study formula. METHOD: Change in 10-year risk for CHD was compared between treatment groups in 1125 patients followed for 18 months or until treatment discontinuation in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Schizophrenia Trial. RESULTS: The covariate-adjusted mean change in 10-year CHD risk differed significantly between treatments. Olanzapine was associated with a 0.5% (SE 0.3) increase and quetiapine, a 0.3% (SE 0.3) increase; whereas risk decreased in patients treated with perphenazine, -0.5% (SE 0.3), risperidone, -0.6% (SE 0.3), and ziprasidone -0.6% (SE 0.4). The difference in 10-year CHD risk between olanzapine and risperidone was statistically significant (p=0.004). Differences in estimated 10-year CHD risk between drugs were most marked in the tertile of subjects with a baseline CHD risk of at least 10%. Among individual CHD risk factors used in the Framingham formula, only total and HDL cholesterol levels differed between treatments. CONCLUSIONS: These results indicate that the impact on 10-year CHD risk differs significantly between antipsychotic agents, with olanzapine producing the largest elevation in CHD risk of the agents studied in CATIE.

Impact of antipsychotic treatment on nonfasting triglycerides in the CATIE Schizophrenia Trial phase 1.

BACKGROUND: Recent literature documents a stronger association between nonfasting triglycerides (TG) and cardiovascular risk compared to fasting TG. Given concerns over antipsychotic effects on serum TG, this analysis explored changes in nonfasting TG in phase 1 of the CATIE Schizophrenia Trial. METHODS: Change in nonfasting TG, adjusted for baseline value, was compared between antipsychotic treatment groups using subjects with nonfasting laboratory assessments at baseline and 3 months. RESULTS: Among the 246 subjects there were significant treatment differences in 3-month change from baseline (p=0.009). The greatest increases in median and adjusted mean nonfasting TG levels were seen among those randomized to quetiapine (mean+54.7 mg/dl, median+26 mg/dl) and olanzapine (mean+23.4 mg/dl, median+26.5 mg/dl), while ziprasidone was neutral (mean+0.0 mg/dl, median+8 mg/dl), and decreases were seen with risperidone (mean -18.4 mg/dl, median -6.5 mg/dl) and perphenazine (mean -1.3 mg/dl, median -22 mg/dl). Pairwise comparisons indicated a significant between-group difference for perphenazine vs. olanzapine (p=0.002) and a trend for perphenazine vs. quetiapine (p=0.006). CONCLUSIONS: This analysis provides further evidence for differential antipsychotic metabolic liabilities, and confirms signals for the effects of olanzapine and quetiapine on serum TG seen in earlier CATIE analyses. Future consensus recommendations will clarify the role of nonfasting TG monitoring in routine clinical practice.

Neurocognitive effects of antipsychotic medications in patients with chronic schizophrenia in the CATIE Trial.

CONTEXT: Neurocognitive impairment in schizophrenia is severe and is an important predictor of functional outcome. The relative effect of the second-generation (atypical) antipsychotic drugs and older agents on neurocognition has not been comprehensively determined. OBJECTIVE: To compare the neurocognitive effects of several second-generation antipsychotics and a first-generation antipsychotic, perphenazine. DESIGN: Randomized, double-blind study of patients with schizophrenia assigned to receive treatment with olanzapine, perphenazine, quetiapine fumarate, or risperidone for up to 18 months as reported previously by Lieberman et al. Ziprasidone hydrochloride was included after its approval by the Food and Drug Administration. SETTING: Fifty-seven sites participated, including academic sites and treatment mental health facilities representative of the community. PATIENTS: From a cohort of 1460 patients in the treatment study, 817 completed neurocognitive testing immediately prior to randomization and then after 2 months of treatment. MAIN OUTCOME MEASURES: The primary outcome was change in a neurocognitive composite score after 2 months of treatment. Secondary outcomes included neurocognitive composite score change at 6 months and 18 months after continued treatment and changes in neurocognitive domains. RESULTS: At 2 months, treatment resulted in small neurocognitive improvements of z = 0.13 for olanzapine (P<.002), 0.25 for perphenazine (P<.001), 0.18 for quetiapine (P<.001), 0.26 for risperidone (P<.001), and 0.12 for ziprasidone (P<.06), with no significant differences between groups. Results at 6 months were similar. After 18 months of treatment, neurocognitive improvement was greater in the perphenazine group than in the olanzapine and risperidone groups. Neurocognitive improvement predicted longer time to treatment discontinuation, independently from symptom improvement, in patients treated with quetiapine or ziprasidone. CONCLUSIONS: After 2 months of antipsychotic treatment, all groups had a small but significant improvement in neurocognition. There were no differences between any pair of agents, including the typical drug perphenazine. These results differ from the majority of previous studies, and the possible reasons are discussed.

What CATIE found: results from the schizophrenia trial.

The authors provide an overview of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) sponsored by the National Institute of Mental Health. CATIE was designed to compare a proxy first-generation antipsychotic, perphenazine, to several newer drugs. In phase 1 of the trial, consenting patients were randomly assigned to receive olanzapine, perphenazine, quetiapine, risperidone, or ziprasidone for up to 18 months on a double-blind basis. Patients with tardive dyskinesia were excluded from being randomly assigned to perphenazine and were assigned to one of the four second-generation antipsychotics in phase 1A. Clozapine was included in phase 2 of the study. Overall, olanzapine had the longest time to discontinuation in phase 1, but it was associated with significant weight and metabolic concerns. Perphenazine was not significantly different in overall effectiveness, compared with quetiapine, risperidone, and ziprasidone. Also, perphenazine was found to be the most cost-effective drug. Clozapine was confirmed as the most effective drug for individuals with a poor symptom response to previous antipsychotic drug trials, although clozapine was also associated with troublesome adverse effects. There were no differences in neurocognitive or psychosocial functioning in response to medications. Subsequent randomizations suggest that a poor response to an initial medication may mean that a different medication will be more effective or better tolerated. Although the CATIE results are controversial, they are broadly consistent with most previous antipsychotic drug trials and meta-analyses; however, the results may not generalize well to patients at high risk of tardive dyskinesia. Patient characteristics and clinical circumstances affected drug effectiveness; these patient factors are important in making treatment choices.

Serologic Reactivity Reflects Clinical Expression of Ulcerative Colitis in Children.

Background: In contrast to pediatric Crohn's disease (CD), little is known in pediatric ulcerative colitis (UC) about the relationship between disease phenotype and serologic reactivity to microbial and other antigens. Aim: The aim of this study was to examine disease phenotype and serology in a well-characterized inception cohort of children newly diagnosed with UC during the PROTECT Study (Predicting Response to Standardized Pediatric Colitis Therapy). Methods: Patients were recruited from 29 participating centers. Demographic, clinical, laboratory, and serologic (pANCA, ASCA IgA/IgG, Anti-CBir1, and Anti-OmpC) data were obtained from children 4-17 years old with UC. Results: Sixty-five percent of the patients had positive serology for pANCA, with 62% less than 12 years old and 66% 12 years old or older. Perinuclear anti-neutrophil cytoplasmic antibodies did not correspond to a specific phenotype though pANCA ≥100, found in 19%, was strongly associated with pancolitis (P = 0.003). Anti-CBir1 was positive in 19% and more common in younger children with 32% less than 12 years old as compared with 14% 12 years old or older (P < 0.001). No association was found in any age group between pANCA and Anti-CBir1. Relative rectal sparing was more common in +CBir1, 16% versus 7% (P = 0.02). Calprotectin was lower in Anti-CBir1+ (Median [IQR] 1495 mcg/g [973-3333] vs 2648 mcg/g [1343-4038]; P = 0.04). Vitamin D 25-OH sufficiency was associated with Anti-CBir1+ (P = 0.0009). Conclusions: The frequency of pANCA in children was consistent with adult observations. High titer pANCA was associated with more extensive disease, supporting the idea that the magnitude of immune reactivity may reflect disease severity. Anti-CBir1+ was more common in younger ages, suggesting host-microbial interactions may differ by patient age.

Effects of antipsychotic medications on psychosocial functioning in patients with chronic schizophrenia: findings from the NIMH CATIE study.

OBJECTIVE: This study examined the relative effects of the second-generation antipsychotic drugs and an older representative agent on psychosocial functioning in patients with chronic schizophrenia. METHOD: Consenting patients were enrolled in the NIMH Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) project. In phase 1, patients were randomly assigned to receive olanzapine, perphenazine, quetiapine, risperidone, or ziprasidone for up to 18 months. Clozapine was included for patients who chose this pathway after discontinuing phase 1 due to inefficacy; all other patients received another second-generation antipsychotic. Psychosocial functioning was assessed using the Quality of Life Scale. RESULTS: Psychosocial functioning modestly improved for the one-third of phase 1 patients who reached the primary Quality of Life Scale analysis endpoint of 12 months (average effect size 0.19 SD units). Although for several of the drugs individually there were significant changes from baseline, overall there were no significant differences between the different agents. Results were similar at 6 and 18 months. There were no significant differences among the treatment groups in the amount of change in the Quality of Life Scale total score or subscale scores at 6, 12, or 18 months. Patients treated with clozapine in the efficacy pathway made comparable gains. Early treatment discontinuations, especially among patients most impaired at baseline, limited the ability to achieve more substantial functional gains. CONCLUSIONS: All antipsychotic treatment groups in all phases made modest improvements in psychosocial functioning. There were no differences among them after 6, 12, or 18 months. More substantial improvements would likely require more intensive adjunctive psychosocial rehabilitation interventions.

Effectiveness of olanzapine, quetiapine, and risperidone in patients with chronic schizophrenia after discontinuing perphenazine: a CATIE study.

OBJECTIVE: The relative effectiveness of newly started antipsychotic drugs for individuals with schizophrenia may depend on multiple factors, including each patient's previous treatment response and the reason for a new medication trial. This randomized, double-blind study compared olanzapine, quetiapine, and risperidone in patients who had just discontinued the older antipsychotic perphenazine. METHOD: Subjects with schizophrenia (N=114) who had been randomly assigned to and then discontinued perphenazine in phase 1 of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia study were reassigned randomly to double-blinded treatment with olanzapine, 7.5-30.0 mg/day (N=38); quetiapine, 200-800 mg/day (N=38); or risperidone, 1.5-6.0 mg/day (N=38). The primary aim was to determine whether there were differences among these three treatments in effectiveness, as measured by time to treatment discontinuation for any reason. Secondary outcomes included reasons for treatment discontinuation and measures of drug tolerability. RESULTS: The time to treatment discontinuation was longer for patients treated with quetiapine (median, 9.9 months) and olanzapine (7.1 months) than with risperidone (3.6 months). There were no significant differences between treatments on discontinuation due to inefficacy, intolerability, or patient decision. CONCLUSIONS: Among this group of patients with chronic schizophrenia who had just discontinued the older antipsychotic perphenazine, quetiapine and olanzapine were more effective than risperidone, as reflected by longer time to discontinuation for any reason. In the context of other results from the CATIE study, the effectiveness and acceptability of antipsychotic drugs appears to vary considerably according to clinical circumstances.

Association of Serum Lipids and Obstructive Lung Disease in Hispanic/Latino Adults of Diverse Backgrounds.

RATIONALE: Substantial variation in the prevalences of obstructive lung disease exist between Hispanic/Latino heritage groups. Experimental studies have posited biological mechanisms linking serum lipids and lipid-lowering medications with obstructive lung disease. The aim of this study is to examine the associations of serum lipid levels with the prevalences of asthma and chronic obstructive pulmonary disease in the Hispanic Community Health Study/Study of Latinos and how these associations vary by Hispanic/Latino heritage group. METHODS: The Hispanic Community Health Study/Study of Latinos is a population-based probability sample of 16,415 self-identified Hispanic/Latino persons aged 18-74 years recruited between 2008 and 2011 from randomly selected households in four US field centers. The baseline clinical examination included comprehensive biological testing (fasting serum lipid levels), behavioral and socio-demographic assessments, medication inventory including inhalers, and respiratory data including questionnaires for asthma and standardized spirometry with post-bronchodilator measures for identification of obstructive lung disease. MEASUREMENTS AND MAIN RESULTS: Hispanic/Latinos with current asthma had lower age- and statin-use-adjusted mean serum total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels than their non-asthmatic counterparts. In analysis adjusted for age plus gender, ethnicity, cigarette smoking, alcohol intake, body mass index, lipid/cholesterol-lowering medications, age at immigration, health insurance status, and use of oral corticosteroids, increasing serum levels of total cholesterol and low-density lipoprotein cholesterol were associated with lower odds of current asthma in the estimated population. Unlike asthma, Hispanic/Latinos with chronic obstructive pulmonary disease had lower mean high-density lipoprotein than their non- chronic obstructive pulmonary disease counterparts. In the fully adjusted analysis no significant associations were found between lipid levels and prevalent chronic obstructive pulmonary disease. CONCLUSIONS: We showed a modest inverse relationship between serum lipid levels and current asthma. These results highlight some important differences in Hispanics/Latinos and certain serum lipids may be factors or markers of obstructive lung disease.