International trends in clozapine use: a study in 17 countries.

OBJECTIVE: There is some evidence that clozapine is significantly underutilised. Also, clozapine use is thought to vary by country, but so far no international study has assessed trends in clozapine prescribing. Therefore, this study aimed to assess clozapine use trends on an international scale, using standardised criteria for data analysis. METHOD: A repeated cross-sectional design was applied to data extracts (2005-2014) from 17 countries worldwide. RESULTS: In 2014, overall clozapine use prevalence was greatest in Finland (189.2/100 000 persons) and in New Zealand (116.3/100 000), and lowest in the Japanese cohort (0.6/100 000), and in the privately insured US cohort (14.0/100 000). From 2005 to 2014, clozapine use increased in almost all studied countries (relative increase: 7.8-197.2%). In most countries, clozapine use was highest in 40-59-year-olds (range: 0.6/100 000 (Japan) to 344.8/100 000 (Finland)). In youths (10-19 years), clozapine use was highest in Finland (24.7/100 000) and in the publicly insured US cohort (15.5/100 000). CONCLUSION: While clozapine use has increased in most studied countries over recent years, clozapine is still underutilised in many countries, with clozapine utilisation patterns differing significantly between countries. Future research should address the implementation of interventions designed to facilitate increased clozapine utilisation.

Outpatient calcium-channel blockers and the risk of postpartum haemorrhage: a cohort study.

OBJECTIVE: To determine whether outpatient exposure to calcium-channel blockers (CCBs) at the time of delivery is associated with an increased risk for postpartum haemorrhage (PPH). DESIGN: Cohort study. SETTING: United States of America. POPULATION OR SAMPLE: Medicaid beneficiaries. METHODS: We identified a cohort of 9750 patients with outpatient prescriptions for CCBs, methyldopa, or labetalol for pre-existing or gestational hypertension whose days of supply overlapped with delivery; 1226 were exposed to CCBs. The risk of PPH was compared in those exposed to CCBs to those exposed to methyldopa or labetalol. Propensity score matching and stratification were used to address potential confounding. MAIN OUTCOME MEASURES: The occurrence of PPH during the delivery hospitalisation. RESULTS: There were 27 patients exposed to CCBs (2.2%) and 232 patients exposed to methyldopa or labetalol (2.7%) who experienced PPH. After accounting for confounders, there was no meaningful association between CCB exposure and PPH in the propensity score matched (odds ratio 0.77, 95% CI 0.50-1.18) or stratified (odds ratio 0.79, 95% CI 0.53-1.19) analyses. Similar results were obtained across multiple sensitivity analyses. CONCLUSIONS: The outpatient use of CCBs in late pregnancy for the treatment of hypertension does not increase the risk of PPH.

Differential risk of death in older residents in nursing homes prescribed specific antipsychotic drugs: population based cohort study.

OBJECTIVE: To assess risks of mortality associated with use of individual antipsychotic drugs in elderly residents in nursing homes. DESIGN: Population based cohort study with linked data from Medicaid, Medicare, the Minimum Data Set, the National Death Index, and a national assessment of nursing home quality. SETTING: Nursing homes in the United States. PARTICIPANTS: 75,445 new users of antipsychotic drugs (haloperidol, aripiprazole, olanzapine, quetiapine, risperidone, ziprasidone). All participants were aged ≥ 65, were eligible for Medicaid, and lived in a nursing home in 2001-5. MAIN OUTCOME MEASURES: Cox proportional hazards models were used to compare 180 day risks of all cause and cause specific mortality by individual drug, with propensity score adjustment to control for potential confounders. RESULTS: Compared with risperidone, users of haloperidol had an increased risk of mortality (hazard ratio 2.07, 95% confidence interval 1.89 to 2.26) and users of quetiapine a decreased risk (0.81, 0.75 to 0.88). The effects were strongest shortly after the start of treatment, remained after adjustment for dose, and were seen for all causes of death examined. No clinically meaningful differences were observed for the other drugs. There was no evidence that the effect measure modification in those with dementia or behavioural disturbances. There was a dose-response relation for all drugs except quetiapine. CONCLUSIONS: Though these findings cannot prove causality, and we cannot rule out the possibility of residual confounding, they provide more evidence of the risk of using these drugs in older patients, reinforcing the concept that they should not be used in the absence of clear need. The data suggest that the risk of mortality with these drugs is generally increased with higher doses and seems to be highest for haloperidol and least for quetiapine.

Predicting treatment costs after acute ischemic stroke on the basis of patient characteristics at presentation and early dysfunction.

BACKGROUND: Given the pressure on healthcare budgets, assessing the cost of managing a disease has become a major research focus; yet collection of these data are labor intensive and difficult. Understanding the predictors of cost provides an efficient means of incorporating such information in decision-making concerning new therapies. METHODS: Data from two 12-week multinational trials that collected information on a variety of neurological, functional, and cost parameters for 1341 ischemic stroke patients were examined by means of multiple linear regression. Because the intent is for the model to be predictive, only patient characteristics that can be known at the time of patient presentation or shortly thereafter were evaluated for inclusion in the model. RESULTS: The Barthel Index was the strongest predictor of cost in all models evaluated. Other major predictors, either directly or through their impact on survival, were stroke subtype, neurological impairment, congestive heart failure, and country. A good model fit was obtained, judging by the model statistics (model F:=84, 3 df, P:<0.0001) and the accuracy of the predictions (<3% difference between mean actual and predicted cost). CONCLUSIONS: Through the use of key patient characteristics, this regression model allows for prediction of the cost of stroke care, which may be helpful in the context of therapeutic decisions and budgetary planning purposes. It also provides insight into how specific treatments, through their impact on clinical characteristics, can modify the cost of stroke treatment.

Secondary prevention fallacy: pitfalls in comparing with primary.

A basic tenet of our culture is the idea that preventing ills is better than curing them. This principle is entrenched in many proverbs and popular admonitions: 'A stitch in time saves nine', 'An ounce of prevention is worth a pound of cure'. These well-worn sayings crisply convey our sense that it is preferable to intervene before a bad event occurs than to wait and try to mitigate it afterwards. Yet, economic analyses have demonstrated that in healthcare this does not hold: 'primary prevention' does not provide as good value-for-money as 'secondary prevention'. Is this reversal of folk wisdom correct? Or, instead, is it a result of faults in the application of the relatively new methodology of cost-effectiveness analyses?

Are the WOSCOPS clinical and economic findings generalizable to other populations? A case study for Belgium. The WOSCOPS Economic Analysis Group. West of Scotland Coronary Prevention Study.

AIMS: As the West of Scotland Coronary Prevention Study (WOSCOPS) was conducted in Scotland, a country well-known for its high cardiovascular risk, the generalizability of its findings on pravastatin's clinical and economic effects has been questioned. This study examines the legitimacy of this concern, using Belgium as a case study. METHODS AND RESULTS: Local information on the prevalence and clustering of risk factors in individual patients was used in a risk equation to estimate the reference risk in Belgium. In contrast to prevailing beliefs, this risk was shown to coincide with the trial population's risk. As the relative risk reduction documented in a trial should apply across populations, the health benefits observed in WOSCOPS can clearly be extrapolated. This information in combination with local costs was then used to assess the economic efficiency of primary prevention with pravastatin in Belgium by means of a previously developed model. In parallel with the original estimates for the United Kingdom, the cost-effectiveness ratios remain well within the range of what is considered strong to moderate evidence for adoption and appropriate utilization, over a wide range of input values. CONCLUSION: This study demonstrates that the clinical and economic findings from WOSCOPS can indeed be generalized to other populations.

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.

Stroke treatment economic model (STEM): predicting long-term costs from functional status.

BACKGROUND AND PURPOSE: Stroke is a debilitating disease with long-term social and economic consequences. As new therapies for acute ischemic stroke are forthcoming, there is an increasing need to understand their long-term economic implications. To address this need, a stroke economic model was created. METHODS: The model consists of 3 modules. A short-term module incorporates short-term clinical trial data. A long-term module composed of several Markov submodels predicts patient transitions among various locations over time. The modules are connected via a bridge component that groups the survivors at the end of the short-term module according to their functional status and location. Examples of analyses that can be conducted with this model are provided with the use of data from 2 international trials. For illustration, UK unit costs were estimated. RESULTS: With the trial data in the short-term module, the short-term management cost is estimated to be pound8326 (US $13,649 [USD]). Hospital stay was the major cost driver. By the end of the trials, there was a pronounced difference in the distribution of patient locations between functional groups. It is predicted in the long-term module that the subsequent cost amounts to pound75 985 (124,564 USD) for a major and pound27,995 (45,893 USD) for a minor stroke. CONCLUSIONS: Linking functional recovery at the end of short-term treatment with patients' treatment and residential locations allows this model to estimate the long-term economic impact of stroke interventions. Using patient location instead of the more common natural history as the model foundation allows quantification of the long-term impact to become data driven and hence increases confidence in the results.