Comparative effectiveness of second generation long-acting injectable antipsychotics based on nationwide database research in Hungary.

BACKGROUND: Schizophrenia is a severe condition that affects approximately 1% of the population. Certain elements of antipsychotic treatment can only be examined in large population, thus the need for population-based real-world analyses has been increasing. PATIENTS AND METHODS: Hungarian National Health Fund database includes all healthcare data of the population of Hungary. All patients diagnosed with schizophrenia between 01.01.2006 and 31.12.2015 were included in the study. We analyzed all patients with newly initiated second-generation antipsychotic during the inclusion period (01.01.2012-31.12.2013). Patients were followed for 2 years. All-cause treatment discontinuation served as the primary outcome of the study. Patients with newly initiated long-acting injectable treatments were further investigated in stratified analyses based on their previous treatment. RESULTS: 106,624 patients had schizophrenia diagnosis during the study period. 12,232 patients met the inclusion criteria for newly initiating second-generation antipsychotic during the inclusion period. The proportion of patients still on treatment after 1 year for oral treatments varied between 17% (oral risperidone) and 31% (oral olanzapine) while the analogous data for long acting injectables were between 32% (risperidone long acting) and 64% (paliperidone long acting one monthly). The 2-year data were similarly in favor of long-actings. Median time to discontinuation in the oral group varied between 57 days (clozapine) and 121 days (olanzapine). The median time to discontinuation for long-actings was significantly longer: between 176 and 287 days; in case of paliperidone long acting, median was not reached during the observation period. Patients receiving long-acting treatment switched from another long-acting remained on the newly initiated treatment significantly longer than those switched from orals. CONCLUSION: Our results indicate the superiority of second generation long-acting antipsychotics with regard to rates of treatment discontinuation and periods of persistence to the assigned medication.

Mortality and the relationship of somatic comorbidities to mortality in schizophrenia. A nationwide matched-cohort study.

AIM: We conducted a matched-cohort study to assess mortality in schizophrenia and the relationship of mortality with comorbid somatic conditions and suicide attempts. METHOD: A full-population register-based prospective matched-cohort study was performed including all eligible patients with schizophrenia in Hungary between 01/01/2005 and 31/12/2013. Control subjects were individually matched to patients with schizophrenia at a 5:1 ratio. The principal outcome measure was death due to any reason. A non-parametric approach was used for descriptive statistical purposes, the Kaplan-Meier model for survival analysis, and the Cox proportional-hazards regression model for inferential statistics. RESULTS: Patients with schizophrenia (n=65,169) had substantially higher risk of all-cause mortality than the control subjects (n=325,435) (RR=2.4; P<0.0001). Comorbidities and suicide attempts were associated with significantly increased mortality in both groups. As compared to the controls, 20-year old males with schizophrenia had a shorter life expectancy by 11.5years, and females by 13.7years; the analogous numbers for 45-year old schizophrenics were 8.1 and 9.6years, respectively. CONCLUSIONS: A significant mortality gap - mainly associated with somatic comorbidities - was detected between patients with schizophrenia and individually matched controls. Improved medical training to address the disparity in mortality, and many other factors including lack of resources, access to and model of medical care, lifestyle, medication side effects, smoking, stigma, need for early intervention and adequate health care organization could help to better address the physical health needs of patients with schizophrenia.

Drug survival of biologic therapy in a large, disease-based registry of patients with psoriasis: results from the Psoriasis Longitudinal Assessment and Registry (PSOLAR).

BACKGROUND: Drug survival is a marker for treatment sustainability in chronic diseases such as psoriasis. OBJECTIVE: The aim of these analyses was to assess survival of biologic treatments in the PSOriasis Longitudinal Assessment and Registry (PSOLAR). METHODS: PSOLAR is a large, prospective, international, disease-based registry of patients with psoriasis receiving (or eligible for) systemic therapy in a real-world setting. Drug survival is defined as the time from initiation to discontinuation (stop/switch) of biologic therapy on registry. The number of patients who discontinued each treatment and the duration of therapy were recorded. Using Kaplan-Meier survival curves and Cox-regression analyses [hazard ratios (HR) and 95% confidence intervals (CIs)], time to discontinuation was compared across cohorts undergoing first-, second- or third-line treatment with ustekinumab, infliximab, adalimumab or etanercept. RESULTS: As of the 2013 data cut, 12 095 patients with psoriasis were enrolled in PSOLAR. Of the 4000 patients initiating any new biologic therapy, approximately 3500 started a first-line, second-line or third-line biologic therapy during the registry. Lack of effectiveness was the most common reason for discontinuation across biologic therapies. Based on the multivariate analysis, significantly shorter times to discontinuation were observed for infliximab [HR (95%CI) = 2.73 (1.48-5.04), P = 0.0014]; adalimumab [4.16 (2.80-6.20), P < 0.0001]; and etanercept [4.91 (3.28-7.35) P < 0.0001] compared with ustekinumab [reference treatment]) for first-line biologic use; results were similar for treatment effects for second/third-line therapies. Although limited in power, analyses in patients with concurrent psoriatic arthritis confirmed by a rheumatologist reflect observations in the overall psoriasis population. CONCLUSION: Drug survival was superior for ustekinumab compared with infliximab, adalimumab and etanercept in patients with psoriasis.

Source of tryptone in growth medium affects oxidative stress resistance in Escherichia coli.

AIMS: To investigate the influence of the source of tryptone in the growth medium on the resistance of Escherichia coli to various types of oxidative stress. METHODS AND RESULTS: Cultures of Escherichia coli MG1655 were grown in Luria-Bertani (LB) medium at 37 degrees C to stationary phase, harvested, and subsequently subjected to various types of oxidative stress. A marked difference in oxidative stress sensitivity was observed depending on the origin of the tryptone in the LB medium used to grow the cultures. Cells harvested from LB containing tryptone from source x (LBx) were more sensitive to inactivation by the superoxide generating compound plumbagin and by t-butyl peroxide, and to growth inhibition by the lactoperoxidase enzyme system, than cells harvested from LB containing tryptone from source y (LBy). By monitoring expression of a panel of stress gene promotors linked to the gfp (green fluorescent protein) gene, and using Delta2-22 alkaline phosphatase as a probe for disulphide bridge formation from protein sulphydryl groups, it was demonstrated that a greater cytoplasmic oxidative stress existed in cells during growth in LBy than in LBx. CONCLUSIONS: Depending on the source of tryptone, bacteria may experience different levels of oxidative stress in tryptone-containing nonselective growth media. Although these levels of oxidative stress are subinhibitory, they may trigger a stress response that makes the bacteria more resistant to a subsequent exposure to a lethal or inhibitory level of oxidative stress. SIGNIFICANCE AND IMPACT OF THE STUDY: This work highlights the importance of controlling very subtle differences in composition of nonselective growth media in studies on bacterial physiology.