Search

Introduction Studies have reported higher risks of mortality for patients with schizophrenia, compared to the general population. This study aimed to evaluate the risk of all-cause, sudden death, and cardiovascular mortality among patients with schizophrenia in terms of types of antipsychotics. Methods A retrospective cohort study assessed the risk of mortality among antipsychotic-treated patients with schizophrenia. The study linked the Taiwan National Health Insurance (NHI) claims and National Register of Death databases from 2001 to 2015. Patients were hierarchically assigned to the following index antipsychotic treatment groups: atypical long acting injection (LAI), typical LAI, atypical oral, and typical oral. Results A total of 68,159 antipsychotic-treated patients with schizophrenia were analyzed. Under the hierarchical grouping, the largest percentages of patients were on atypical oral antipsychotic regimens (65.51%), followed by typical oral (14.00%), typical LAI (12.84%), and atypical LAI (7.65%). Typical oral patients had the highest incidence of all-cause mortality of 27.48 per 1000 patient-years and the atypical LAI group had the lowest incidence (13.95 per 1000 patient-years). Compared to typical oral users, there were lower risks of all-cause mortality for users of atypical LAI (aHR = 0.62, 95% CI: 0.47–0.81), typical LAI (aHR = 0.65, 95% CI: 0.55–0.78), and atypical orals (aHR = 0.55, 95% CI: 0.49–0.62). Conclusion Compared to typical oral users, we found a lower risk of all-cause mortality, sudden death, and cardiovascular mortality among schizophrenia users of LAIs and oral atypicals. Further research is warranted to characterize the risk of mortality among users of more recently available LAIs in the Asia Pacific region and elsewhere.

Background Systemic lupus erythematosus (SLE) is a chronic autoimmune disease of unknown origin. The objective of this research was to develop phenotype algorithms for SLE suitable for use in epidemiological studies using empirical evidence from observational databases. Methods We used a process for empirically determining and evaluating phenotype algorithms for health conditions to be analyzed in observational research. The process started with a literature search to discover prior algorithms used for SLE. We then used a set of Observational Health Data Sciences and Informatics (OHDSI) open-source tools to refine and validate the algorithms. These included tools to discover codes for SLE that may have been missed in prior studies and to determine possible low specificity and index date misclassification in algorithms for correction. Results We developed four algorithms using our process: two algorithms for prevalent SLE and two for incident SLE. The algorithms for both incident and prevalent cases are comprised of a more specific version and a more sensitive version. Each of the algorithms corrects for possible index date misclassification. After validation, we found the highest positive predictive value estimate for the prevalent, specific algorithm (89%). The highest sensitivity estimate was found for the sensitive, prevalent algorithm (77%). Conclusion We developed phenotype algorithms for SLE using a data-driven approach. The four final algorithms may be used directly in observational studies. The validation of these algorithms provides researchers an added measure of confidence that the algorithms are selecting subjects correctly and allows for the application of quantitative bias analysis.

Objective Antipsychotics may increase serum prolactin, which has particularly been observed with risperidone. Further, hyperprolactinemia has been linked to osteoporosis-related fractures. Therefore, we investigated fracture risk in a nationwide cohort exposed to antipsychotics. Methods Swedish registers were used to identify adults with two consecutive dispensations of risperidone (n = 38 211), other atypical antipsychotics not including paliperidone (n = 60 691), or typical antipsychotics (n = 17 445) within three months between 2006 and 2013. An osteoporosis-related fracture was defined as a non-open hip/femur fracture in primary analyses. Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results Risperidone users were on average older (mean age of 68, 44, and 63 years for risperidone, other atypical antipsychotics, and typical antipsychotics respectively). Compared with other atypical antipsychotics, there was no association between risperidone and osteoporosis-related fractures in the overall (HR = 1.04, CI: 0.91-1.19) or age-stratified analyses. A significantly increased risk of typical antipsychotics (HR = 1.24, CI: 1.07-1.45) compared with other atypical antipsychotics remained for ages >45 years. Conclusion Risperidone does not appear to be associated with an increased risk of osteoporosis-related fracture compared with other atypical antipsychotic agents as a group. For typical antipsychotics, a moderately elevated risk of hip fractures was noted compared with other atypical antipsychotics, possibly because of residual confounding.

The aim of this study was to investigate the risk of falls and fractures among older adults receiving atypical antipsychotics.An emulation analysis of a previously published study was performed using the US Truven MarketScan Medicare Supplemental database (MDCR). In addition, modified analyses were implemented to evaluate alternative confounding control strategies that (1) included all covariates used to fit propensity score models in outcome models and (2) required patients to have a mental health condition diagnosis and a health care visit within 90 days prior to the index date.The MDCR emulation analyses yielded similar results as the previous study. For the previous study and our emulation analysis, the results were: nonvertebral osteoporotic fractures (odds ratio [OR], 1.51; 95% confidence interval [CI], 1.41-1.60; and OR, 1.49; 95% CI, 1.37-1.63, respectively), hip fractures (OR, 1.67; 95% CI, 1.53-1.81; and OR, 1.59; 95% CI, 1.43-1.77, respectively), any fracture (OR, 1.29; 95% CI, 1.24-1.34; and OR, 1.32; 95% CI, 1.23-1.41, respectively), and falls (OR, 1.54; 95% CI, 1.47-1.61; and OR, 1.45; 95% CI, 1.11-1.89, respectively). However, in modified analyses, no associations were significant. The primary change that resulted in the attenuation of associations was the requirement for patients to have a mental health condition diagnosis and a health care visit prior to the index date.Our MDCR emulation analysis yielded similar results as a previous study; however, in modified analyses, the associations between fractures and falls and atypical antipsychotics were no longer significant. The contrast of results between the emulation and modified analyses may be due to the analytic approach used to compare patients (and potential confounding by indication). Further research is warranted to evaluate these associations.

A recently published analysis of population-based claims data from Ontario, Canada reported higher risks of acute kidney injury (AKI) and related outcomes among older adults who were new users of atypical antipsychotics (AAPs) compared with unexposed patients. In light of these findings, the objective of the current study was to further investigate the risks of AKI and related outcomes among older adults receiving AAPs. A replication of the previously published analysis was performed using the US Truven MarketScan Medicare Supplemental database (MDCR) among patients aged 65 years and older. Compared with non-users of AAPs, the study compared the risk of AKI and related outcomes with users of AAPs (quetiapine, risperidone, olanzapine, aripiprazole, or paliperidone) using a 1-to-1 propensity score matched analysis. In addition, we performed adapted analyses that: (1) included all covariates used to fit propensity score models in outcome models; and (2) required patients to have a diagnosis of schizophrenia, bipolar disorder, or major depression and a healthcare visit within 90 days prior to the index date. AKI effect estimates [as odds ratios (ORs) with 95% confidence intervals (CIs)] were significantly elevated in our MDCR replication analyses (OR 1.45, 95% CI 1.32–1.60); however, in adapted analyses, associations were not significant (OR 0.91, 95% CI 0.78–1.07)). In analyses of AKI and related outcomes, results were mostly consistent between the previously published and the MDCR replication analyses. The primary change that attenuated associations in adapted analyses was the requirement for patients to have a mental health condition and a healthcare visit prior to the index date. The MDCR analysis yielded similar results when the methodology of the previously published analysis was replicated, but, in adapted analyses, we did not find significantly higher risks of AKI and related outcomes. The contrast of results between our replication and adapted analyses may be due to the analytic approach used to compare patients (and potential confounding by indication). Further research is warranted to evaluate these associations, while also examining methods to account for differences in older adults who do and do not use these medications.

SUMMARY. In patients with chronic hepatitis C virus (HCV) infection, steatosis and fibrosis have been shown to be inversely associated with total cholesterol (TC) and low- density lipoprotein cholesterol. Steatosis and fibrosis have also been found to be associated with triglyceride (TG) levels; though, the direction of the relationship is inconsistent across studies. The objective of this study was to assess whether viral level and histological factors are associated with the serum lipid profile in a treatment-naive cohort with chronic HCV genotype 1 infection. Participants were from the prospective Study of Viral Resistance to Antiviral Ther- apy (Virahep-C). Fasting lipid profiles were analysed for 160 African Americans and 170 Caucasian Americans. Linear regression was used to evaluate associations of each lipid with viral load and liver disease. TG levels were significantly and directly associated with HCV levels (P = 0.0034) and steatosis (P < 0.0001). Other lipid parameters were signifi- cantly lower in those with fibrosis (HDLc (P = 0.001) and TC levels (P = 0.004)) than in those without fibrosis. In patients with HCV genotype 1 infection, more severe liver disease was associated with lower lipid levels, with the exception of TG levels that were directly related to steatosis. The direct relationship between viral load and TG levels is consistent with proposed the mechanisms of very low den- sity lipoprotein/HCV particle secretion. In contrast, the direct relationship between TG level and steatosis is inconsistent with posited mechanisms of HCV-induced steatosis, a possi- ble reflection of HCV genotype 1 infection and a metabolic aetiology of steatosis.

Approximately one half of patients who undergo antiviral therapy for chronic hepatitis C virus (HCV) genotype 1 infection do not respond to treatment. African Americans (AAs) are less responsive to treatment than Caucasian Americans (CAs), but the reasons for this disparity are largely unknown. Recent studies suggest that serum lipids may be associated with treatment response. The aims of this study were to evaluate baseline and changes in serum lipids during therapy, determine whether serum lipids are associated with virological response, and assess whether these measures explain the racial difference in efficacy. The study participants were from Virahep-C, a prospective study of treatment-naïve patients with genotype 1 HCV infection who received peginterferon (PEG-IN) alfa-2a plus ribavirin therapy for up to 48 weeks. Fasting serum lipids were analyzed at baseline and during and after therapy in 160 AAs and 170 CAs. A relative risk (RR) model was employed to evaluate characteristics associated with sustained virological response (SVR). Antiviral therapy was associated with changes in serum lipids during and after antiviral therapy, with the changes differing by race and the amount of PEG-IFN taken. Baseline lipid measures independently associated with higher rates of SVR were lower triglyceride and higher low-density lipoprotein cholesterol, with an interaction between high-density lipoprotein cholesterol (HDLc) and gender. Lipid measures did not contribute significantly to an explanation of the racial difference in SVR.Serum lipids are associated with SVR, although these paramaters did not explain the racial difference in treatment response. The results of this study are compatible with proposed biological mechanisms of HCV entry, replication, and secretion, and may underscore new potential therapeutic targets for HCV eradication.

Assessment of histological stage is an integral part of disease management in patients infected with the hepatitis C virus (HCV). The aim of this study was to develop a model incorporating objective clinical and laboratory parameters to estimate the probability of severe fibrosis (i.e., Ishak fibrosis > or = 3) in previously untreated African American (AA) and Caucasian American (CA) patients with HCV genotype 1. The Ishak fibrosis scores of 205 CA and 194 AA patients enrolled in the Viral Resistance to Antiviral Therapy of Chronic Hepatitis C study (Virahep-C) were modeled using simple and multiple logistic regression. The model was then validated in an independent cohort of 461 previously untreated patients with HCV. The distribution of fibrosis scores was similar in the AA and CA patients as was the proportion of patients with severe fibrosis (35% vs. 39%, P = .47). After accounting for the number of portal areas in the biopsy, patient age, serum aspartate aminotransferase, alkaline phosphatase, and platelet count were independently associated with severe fibrosis in the overall cohort, and the relationship with fibrosis was similar in both the AA and CA subgroups. The area under the receiver operating characteristic curve (AUROC) of the Virahep-C model (0.837) was significantly better than in other published models (P = .0003). The AUROC of the Virahep-C model was 0.851 in the validation population. In conclusion, a model consisting of widely available clinical and laboratory features predicted severe hepatic fibrosis equally well in AA and CA patients with HCV genotype 1 and was superior to other published models. The excellent performance of the Virahep-C model in an external validation cohort suggests the findings are replicable and potentially generalizable.

Objectives: To describe the economic impact on families of caring for children with special health care needs (CSHCN), and to determine the relative contributions of socioeconomic and health-related factors to these impacts on families in the State of New Hampshire. Methods: Seven hundred and fifty families with CSHCN in New Hampshire were interviewed in the National Survey of Children with Special Health Needs. Among respondents with CSHCN, univariate and bivariate analyses were conducted to examine economic impact and independent factors (income, insurance type, and impact of condition). Multiple logistic and linear regression models were used to examine relationships between impact and independent factors, controlling for race/ethnicity. Results: Compared to typical children, CSHCN were more likely to have public insurance (12% and 21%, respectively) and less likely to live in higher income families (56% and 48%, respectively). Among CSHCN, nearly one-quarter were greatly affected by their condition, 31% had inadequate insurance, families of 21% had financial problems, parents of 27% had to cut work hours, and almost 15% needed professional care coordination. Adjusting for other factors in regression models, the impact of the condition was associated with all measures of impact, insurance type was associated with out-of-pocket costs, and income was associated with the total number of impacts. Parents of children who are usually or always affected by their conditions were 14 times more likely than those who are never affected to need care coordination. Conclusion: A family’s need for support services, and particularly for care coordination, may depend less on the family’s means than on the impact of their child’s condition.

The objective of this study was to examine the association between caffeine usage in U.S. adolescents and the frequency that feeling tired in the morning and having difficulty sleeping is reported. In this study we found that feeling tired in the morning and having difficulty sleeping was experienced more commonly in those adolescents that have a high intake of caffeine.

Background & Aims The recommended therapy for chronic hepatitis C, pegylated interferon and ribavirin for 24 or 48 weeks, has many known adverse side effects. The aim of this study was to evaluate the impact of antiviral therapy on male sexual health. Methods As part of the Study of Viral Resistance to Antiviral Therapy of Chronic Hepatitis C (Virahep-C), 260 men treated with pegylated interferon alfa-2a and ribavirin completed self-administered questionnaires concerning sexual desire, sexual function, including erectile and ejaculatory function, and sexual satisfaction before, during, and after treatment. Results Before therapy, 37% of men reported at least some degree of impairment in sexual desire and 44% reported dissatisfaction with their sexual life, while 26% reported impairment in erectile and 22% in ejaculatory function. During therapy, significant declines were observed in all components of sexual health compared with pretreatment. At the end of therapy (24 or 48 weeks), an estimated 38%–48% of men reported that overall sexual function was worse than before treatment. African American patients reported less impairment in sexual desire and satisfaction than Caucasian American patients during therapy. By 24 weeks after treatment, sexual desire and satisfaction improved and were comparable to baseline levels. However, among men who received 48 weeks of therapy, the estimated percentage of men reporting posttreatment erectile or ejaculatory problems remained higher than baseline, although persistent erectile impairment was limited to Caucasian American patients. Conclusions Sexual impairment is common among men with chronic hepatitis C undergoing therapy with pegylated interferon and ribavirin and should be considered as a potential side effect of antiviral therapy.

Combination therapy for chronic hepatitis C is associated with depression, which may lead to worse treatment outcomes. The objectives of this study were to determine the association between patient characteristics and depression before and during treatment and to evaluate the relationship between depression and treatment outcomes.Prospective data from the Viral Resistance to Antiviral Therapy of Chronic Hepatitis C (Virahep-C) study were analyzed (191 African Americans, 203 Caucasians). Depression was defined as a score of23 on the Center for Epidemiologic Studies Depression (CES-D) scale. Scores were taken before treatment, at weeks 4, 12, and 24 of treatment, and 24 weeks after treatment ended. Baseline social support was measured using the Medical Outcomes Study (MOS) Social Support Survey. Associations between baseline patient characteristics and incident depression were assessed with discrete-time Cox proportional hazards models.At baseline, 47 (12%) participants had CES-D scores 23. Univariable analyses indicated that several patient characteristics were associated with baseline depression, including lower social support (P0.0001). On treatment, these patients were more likely to have psychiatric adverse events (AEs) or start new antidepressants (45 vs. 28%, P=0.02) and to have had early treatment discontinuation (38 vs.13%, P0.0001); however, sustained virological response (SVR) rates were similar (38 vs. 40%, P=0.79) to those of participants without baseline depression. The incidence of new-onset depression was 26% by 24 weeks. One-third of patients were started on antidepressants, and no patients attempted suicide. Multivariable analyses indicated that new-onset depression was significantly associated with younger age (P=0.04), lower social support (P0.001), and "feeling depressed, sad, or blue" (P=0.008). Patients who developed depression during treatment were more likely to have a psychiatric AE or begin antidepressants (44 vs. 23%, P0.001) but had lower rates of treatment discontinuation (6 vs. 15%, P=0.02) and comparable rates of SVR compared with patients without depression (47 vs. 38%, P=0.16). There were no differences in the frequency of pretreatment or new-onset depression between African-American and Caucasian participants in this study.In this large prospective analysis, baseline and new-onset depression were associated with patient characteristics and treatment outcomes; however, SVR rates did not differ between depressed and nondepressed patients. The relationship of lower baseline social support with depressive symptoms warrants further investigation.