Krista F. Huybrechts

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.

Antidepressant Use in Pregnancy and the Risk of Cardiac Defects

BACKGROUND Whether the use of selective serotonin-reuptake inhibitors (SSRIs) and other antidepressants during pregnancy is associated with an increased risk of congenital cardiac defects is uncertain. In particular, there are concerns about a possible association between paroxetine use and right ventricular outflow tract obstruction and between sertraline use and ventricular septal defects. METHODS We performed a cohort study nested in the nationwide Medicaid Analytic eXtract for the period 2000 through 2007. The study included 949,504 pregnant women who were enrolled in Medicaid during the period from 3 months before the last menstrual period through 1 month after delivery and their liveborn infants. We compared the risk of major cardiac defects among infants born to women who took antidepressants during the first trimester with the risk among infants born to women who did not use antidepressants, with an unadjusted analysis and analyses that restricted the cohort to women with depression and that used propensity-score adjustment to control for depression severity and other potential confounders. RESULTS A total of 64,389 women (6.8%) used antidepressants during the first trimester. Overall, 6403 infants who were not exposed to antidepressants were born with a cardiac defect (72.3 infants with a cardiac defect per 10,000 infants), as compared with 580 infants with exposure (90.1 per 10,000 infants). Associations between antidepressant use and cardiac defects were attenuated with increasing levels of adjustment for confounding. The relative risks of any cardiac defect with the use of SSRIs were 1.25 (95% confidence interval [CI], 1.13 to 1.38) in the unadjusted analysis, 1.12 (95% CI, 1.00 to 1.26) in the analysis restricted to women with depression, and 1.06 (95% CI, 0.93 to 1.22) in the fully adjusted analysis restricted to women with depression. We found no significant association between the use of paroxetine and right ventricular outflow tract obstruction (relative risk, 1.07; 95% CI, 0.59 to 1.93) or between the use of sertraline and ventricular septal defects (relative risk, 1.04; 95% CI, 0.76 to 1.41). CONCLUSIONS The results of this large, population-based cohort study suggested no substantial increase in the risk of cardiac malformations attributable to antidepressant use during the first trimester. (Funded by the Agency for Healthcare Research and Quality and the National Institutes of Health.).

Management Patterns and Costs of Acute Ischemic Stroke: An International Study

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 (

Effects of Adjusting for Instrumental Variables on Bias and Precision of Effect Estimates

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.

Antidepressant Use Late in Pregnancy and Risk of Persistent Pulmonary Hypertension of the Newborn

Recent theoretical studies have shown that conditioning on an instrumental variable (IV), a variable that is associated with exposure but not associated with outcome except through exposure, can increase both bias and variance of exposure effect estimates. Although these findings have obvious implications in cases of known IVs, their meaning remains unclear in the more common scenario where investigators are uncertain whether a measured covariate meets the criteria for an IV or rather a confounder. The authors present results from two simulation studies designed to provide insight into the problem of conditioning on potential IVs in routine epidemiologic practice. The simulations explored the effects of conditioning on IVs, near-IVs (predictors of exposure that are weakly associated with outcome), and confounders on the bias and variance of a binary exposure effect estimate. The results indicate that effect estimates which are conditional on a perfect IV or near-IV may have larger bias and variance than the unconditional estimate. However, in most scenarios considered, the increases in error due to conditioning were small compared with the total estimation error. In these cases, minimizing unmeasured confounding should be the priority when selecting variables for adjustment, even at the risk of conditioning on IVs.

Increase in prescription opioid use during pregnancy among Medicaid-enrolled women.

IMPORTANCE The association between selective serotonin reuptake inhibitor (SSRI) antidepressant use during pregnancy and risk of persistent pulmonary hypertension of the newborn (PPHN) has been controversial since the US Food and Drug Administration issued a public health advisory in 2006. OBJECTIVE To examine the risk of PPHN associated with exposure to different antidepressant medication classes late in pregnancy. DESIGN AND SETTING Cohort study nested in the 2000-2010 Medicaid Analytic eXtract for 46 US states and Washington, DC. Last follow-up date was December 31, 2010. PARTICIPANTS A total of 3,789,330 pregnant women enrolled in Medicaid from 2 months or fewer after the date of last menstrual period through at least 1 month after delivery. The source cohort was restricted to women with a depression diagnosis and logistic regression analysis with propensity score adjustment applied to control for potential confounders. EXPOSURES FOR OBSERVATIONAL STUDIES: SSRI and non-SSRI monotherapy use during the 90 days before delivery vs no use. MAIN OUTCOMES AND MEASURES Recorded diagnosis of PPHN during the first 30 days after delivery. RESULTS A total of 128,950 women (3.4%) filled at least 1 prescription for antidepressants late in pregnancy: 102,179 (2.7%) used an SSRI and 26,771 (0.7%) a non-SSRI. Overall, 7630 infants not exposed to antidepressants were diagnosed with PPHN (20.8; 95% CI, 20.4-21.3 per 10,000 births) compared with 322 infants exposed to SSRIs (31.5; 95% CI, 28.3-35.2 per 10,000 births), and 78 infants exposed to non-SSRIs (29.1; 95% CI, 23.3-36.4 per 10,000 births). Associations between antidepressant use and PPHN were attenuated with increasing levels of confounding adjustment. For SSRIs, odds ratios were 1.51 (95% CI, 1.35-1.69) unadjusted and 1.10 (95% CI, 0.94-1.29) after restricting to women with depression and adjusting for the high-dimensional propensity score. For non-SSRIs, the odds ratios were 1.40 (95% CI, 1.12-1.75) and 1.02 (95% CI, 0.77-1.35), respectively. Upon restriction of the outcome to primary PPHN, the adjusted odds ratio for SSRIs was 1.28 (95% CI, 1.01-1.64) and for non-SSRIs 1.14 (95% CI, 0.74-1.74). CONCLUSIONS AND RELEVANCE Evidence from this large study of publicly insured pregnant women may be consistent with a potential increased risk of PPHN associated with maternal use of SSRIs in late pregnancy. However, the absolute risk was small, and the risk increase appears more modest than suggested in previous studies.

Long term cost-of-illness in stroke: an international review.

OBJECTIVE: To report the prevalence of prescription opioid use and evaluate the trends in a large cohort of Medicaid-enrolled pregnant women. METHODS: A cohort of pregnancies was identified using data from the Medicaid Analytical eXtract for the period of 2000–2007. Dispensing of opioids, as a class and separately for individual agents, was evaluated using claims from filled prescriptions. Variations in patterns of prescription opioid fills were examined by demographic characteristics, by geographic region, and over time. Median number of opioid prescriptions dispensed and cumulative days of availability for prescription opioids during pregnancy were reported. RESULTS: The study population consisted of more than 1.1 million women with completed pregnancies from 46 U.S. states and Washington, DC. One of five women from our cohort (21.6%) filled a prescription for an opioid during pregnancy; this proportion increased from 18.5% in 2000 to 22.8% in 2007. Substantial regional variation was seen with the proportion of women who filled a prescription during pregnancy, ranging between 9.5% and 41.6% across the states. Codeine and hydrocodone were the most commonly prescribed opioids. Among women filling at least one opioid prescription, the median (interquartile range) number of prescriptions filled was 1 (1–2) and the median (interquartile range) cumulative days of opioid availability during pregnancy were 5 (3–13) days. CONCLUSION: We observed high and increasing number of filled prescriptions for opioids during pregnancy among Medicaid-enrolled women. These findings call for further safety evaluations of these drugs and their effects on the developing fetus to inform clinical practice. LEVEL OF EVIDENCE: II

Risk of death and hospital admission for major medical events after initiation of psychotropic medications in older adults admitted to nursing homes

An international review of the costs of stroke was conducted to explore data sources, and cost variables as well as to compare estimates of the annual aggregated cost (prevalence-based) and total per patient long-term cost (incidence-based) of care.Dutch, English, French, German, Italian and Spanish literature was searched using the keywords stroke, ischaemic stroke, haemorrhagic stroke, cerebrovascular accident, cerebral infarction, cost(s), economics, and cost analysis. Criteria for study inclusion were: provides estimates of direct and/or indirect costs of stroke, published after 1989, methods described in adequate detail, and for studies of long-term costs, estimates based on a minimum 5 years of care following the event. Cost estimates are presented in original currencies and US dollars.Among studies representing Australia, New Zealand, Western Europe and North America, six prevalence studies reported total annual aggregated costs of

Safety and effectiveness of dabigatran and warfarin in routine care of patients with atrial fibrillation

US7975 (1988 values) to

The Barthel Index and modified Rankin Scale as prognostic tools for long-term outcomes after stroke: a qualitative review of the literature

US54 546 (1993 values) per patient; eight incidence-based studies reported total long-term per patient costs of