QIL1-dependent assembly of MICOS complex-lethal mutation in C19ORF70 resulting in liver disease and severe neurological retardation.

Seven subunits of the mitochondrial contact site and cristae junction (CJ) organizing system (MICOS) in humans have been recently described in function and structure. QIL1 (also named MIC13) is a small complex that is crucial for the maintenance and assembling of MICOS. A novel mutation of an essential splice site in the C19orf70 gene encoding QIL1 induces severe mitochondrial encephalopathy, hepatopathy and lactate acidosis consistent with psychomotor retardation. In addition, bilateral kidney stones were observed. Disassembly of MICOS complex subunits displays lack of MIC10-MIC26-MIC27-QIL1 subcomplex, resulting in aberrant cristae structure and a loss of cristae junctions and contact sites. In liver and muscle tissue, the activity of the respiratory chain complexes (OXPHOS) was severely impaired. Defects in MICOS complex do not only affect mitochondrial architecture, but also mitochondrial fusion, metabolic signalling, lipid trafficking and cellular electric homeostasis.

Risperidone olanzapine drug outcomes studies in schizophrenia (RODOS): efficacy and tolerability results of an international naturalistic study.

The Risperidone Olanzapine Drug Outcomes studies in Schizophrenia (RODOS) programme was an international series of naturalistic studies designed to evaluate drug use patterns and outcomes. RODOS consisted of retrospective chart reviews performed in patients who had been admitted to hospital and treated in 61 centres in nine countries. The analysed population consisted of 1901 patients with diagnoses of schizophrenia or schizoaffective disorder. The mean (SD) daily doses of risperidone and olanzapine were 5.3 (2.6) mg/day and 14.5 (5.1) mg/day, respectively. Patients treated with risperidone stayed an average of 3.8 days less in hospital compared to those receiving olanzapine (time to discharge was 43.6 days versus 47.4 days, respectively; P = 0.004). Risperidone was rated as effective in significantly more patients than olanzapine (84% versus 79%; P = 0.01). The time to onset of efficacy was significantly shorter with risperidone than with olanzapine (P < 0.001). The numbers of adverse events in the two treatment groups were not significantly different (13% risperidone, 11% olanzapine; P = 0.1). Correcting for small but statistically significant baseline differences between the two treatment groups did not produce a substantive change in the magnitude or significance of any outcome parameter. In conclusion, the clinical outcomes reported by RODOS suggest that risperidone may be more effective as a first-line therapy drug for schizophrenia than olanzapine.

Risperidone olanzapine drug outcomes studies in schizophrenia (RODOS): health economic results of an international naturalistic study.

We report the health economic data from the Risperidone Olanzapine Drug Outcomes studies in Schizophrenia (RODOS) programme. Details of the efficacy and tolerability data from RODOS are available in a companion paper. The population analysed during RODOS consisted of 1901 patients with diagnoses of schizophrenia or schizoaffective disorder. The mean +/- SD daily dose of olanzapine treatment was 14.5 +/- 5.1 mg compared to 5.3 +/- 2.6 mg for risperidone. Use of concomitant neuroleptics (risperidone, 65%; olanzapine, 62%; P = 0.2) and other concomitant drugs (risperidone, 76%; olanzapine, 73%; P = 0.2) was similar in both groups. The mean +/- SD total costs of all inpatient drugs was significantly (P < 0.001) higher for olanzapine (US$ 297.5 +/- 305.1) than risperidone (US$159.9 +/- 183.3). Although this difference in the average total costs in part reflects the longer treatment duration for olanzapine compared to risperidone (34 days versus 31 days), the cost difference remained when looking at costs on a daily basis. The mean +/- SD daily cost of all inpatient drugs was also significantly (P < 0.001) higher for olanzapine (US$7.7 +/- 4.0) than for risperidone (US$ 4.6 +/- 2.9). These findings were very consistent across all nine countries. The results from RODOS suggest that treatment costs are significantly higher with olanzapine than with risperidone without any clinical benefit to offset this.

Management patterns and costs of acute ischemic stroke : an international study. For the Stroke Economic Analysis Group.

BACKGROUND AND PURPOSE: [corrected] With the ever-increasing pressure on healthcare budgets, we witness a growing demand for evidence of the economic implications of care across many therapeutic areas. Stroke is no exception. METHODS: Detailed information on healthcare use was collected in conjunction with two 12-week international trials designed primarily to assess the safety and efficacy of a new potential neuroprotective agent. The information was gathered prospectively by means of a customized resource use instrument that included both acute and long-term inpatient management as well as community care. In this report, the results pertaining to the 1341 acute ischemic stroke patients are described. RESULTS: More than 70% of the mean cost ($13 668) was explained by the initial hospitalization, which averaged 24 days. The total cost and its components varied according to patient age, the presence of comorbidities, and several indicators of disease severity. Pronounced country differences could be observed in the management of this fairly homogeneous patient group. CONCLUSIONS: This study provides a comprehensive picture of the healthcare services used for the treatment and rehabilitation of stroke victims, presented with respect to various patient and disease characteristics. It is expected that researchers evaluating the cost-efficiency of specific stroke treatments will benefit from the detailed information presented in this report.

Equity in the delivery of health care in Europe and the US.

This paper presents a comparison of horizontal equity in health care utilization in 10 European countries and the US. It does not only extend previous work by using more recent data from a larger set of countries, but also uses new methods and presents disaggregated results by various types of care. In all countries, the lower-income groups are more intensive users of the health care system. But after indirect standardization for need differences, there is little or no evidence of significant inequity in the delivery of health care overall, though in half of the countries, significant pro-rich inequity emerges for physician contacts. This seems to be due mainly to a higher use of medical specialist services by higher-income groups and a higher use of GP care among lower-income groups. These findings appear to be fairly general and emerge in countries with very diverse characteristics regarding access and provider incentives.