-
[show abstract]
[hide abstract]
ABSTRACT: PURPOSE: When using claims data, dichotomous covariates (C) are often assumed to be absent unless a claim for the condition is observed. When available historical data differs among subjects, investigators must choose between using all available historical data versus data from a fixed window to assess C. Our purpose was to compare estimation under these two approaches. METHODS: We simulated cohorts of 20 000 subjects with dichotomous variables representing exposure (E), outcome (D), and a single time-invariant C, as well as varying availability of historical data. C was operationally defined under each paradigm and used to estimate the adjusted risk ratio of E on D via Mantel-Haenszel methods. RESULTS: In the base case scenario, less bias and lower mean square error were observed using all available information compared with a fixed window; differences were magnified at higher modeled confounder strength. Upon introduction of an unmeasured covariate (F), the all-available approach remained less biased in most circumstances and rendered estimates that better approximated those that were adjusted for the true (modeled) value of C in all instances. CONCLUSIONS: In most instances considered, operationally defining time-invariant dichotomous C based on all available historical data, rather than on data observed over a commonly shared fixed historical window, results in less biased estimates. Copyright © 2013 John Wiley & Sons, Ltd.
Pharmacoepidemiology and Drug Safety 03/2013; · 2.53 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Dabigatran, an oral thrombin inhibitor, and rivaroxaban and apixaban, oral factor Xa inhibitors, have been found to be safe and effective in reducing stroke risk in patients with atrial fibrillation. We sought to compare the efficacy and safety of the 3 new agents based on data from their published warfarin-controlled randomized trials, using the method of adjusted indirect comparisons.
We included findings from 44 535 patients enrolled in 3 trials of the efficacy of dabigatran (Randomized Evaluation of Long-Term Anticoagulation Therapy [RELY]), apixaban (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation [ARISTOTLE]), and rivaroxaban (Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation [ROCKET-AF]), each compared with warfarin. The primary efficacy end point was stroke or systemic embolism; the safety end point we studied was major hemorrhage. To address a lack of comparability between trial populations caused by the restriction of ROCKET-AF to high-risk patients, we conducted a subgroup analysis in patients with a CHADS(2) score ≥3. We found no statistically significant efficacy differences among the 3 drugs, although apixaban and dabigatran were numerically superior to rivaroxaban. Apixaban produced significantly fewer major hemorrhages than dabigatran and rivaroxaban.
An indirect comparison of new anticoagulants based on existing trial data indicates that in patients with a CHADS(2) score ≥3 dabigatran 150 mg, apixaban 5 mg, and rivaroxaban 20 mg resulted in statistically similar rates of stroke and systemic embolism, but apixaban had a lower risk of major hemorrhage compared with dabigatran and rivaroxaban. Until head-to-head trials or large-scale observational studies that reflect routine use of these agents are available, such adjusted indirect comparisons based on trial data are one tool to guide initial therapeutic choices.
Circulation Cardiovascular Quality and Outcomes 07/2012; 5(4):480-6. · 4.91 Impact Factor
-
Peter M Wahl,
Joshua J Gagne,
Thomas E Wasser,
Debra F Eisenberg,
J Keith Rodgers,
Gregory W Daniel,
Marcus Wilson,
Sebastian Schneeweiss,
Jeremy A Rassen, Amanda R Patrick,
Jerry Avorn,
Rhonda L Bohn
[show abstract]
[hide abstract]
ABSTRACT: Several efforts are under way to develop and test methods for prospective drug safety monitoring using large, electronic claims databases. Prospective monitoring systems must incorporate signalling algorithms and techniques to mitigate confounding in order to minimize false positive and false negative signals due to chance and bias.
The aim of the study was to describe a prototypical targeted active safety monitoring system and apply the framework to three empirical examples.
We performed sequential, targeted safety monitoring in three known drug/adverse event (AE) pairs: (i) paroxetine/upper gastrointestinal (UGI) bleed; (ii) lisinopril/angioedema; (iii) ciprofloxacin/Achilles tendon rupture (ATR). Data on new users of the drugs of interest were extracted from the HealthCore Integrated Research Database. New users were matched by propensity score to new users of comparator drugs in each example. Analyses were conducted sequentially to emulate prospective monitoring. Two signalling rules--a maximum sequential probability ratio test and an effect estimate-based approach--were applied to sequential, matched cohorts to identify signals within the system.
Signals were identified for all three examples: paroxetine/UGI bleed in the seventh monitoring cycle, within 2 calendar years of sequential data; lisinopril/angioedema in the second cycle, within the first monitoring year; ciprofloxacin/ATR in the tenth cycle, within the fifth year.
In this proof of concept, our targeted, active monitoring system provides an alternative to systems currently in the literature. Our system employs a sequential, propensity score-matched framework and signalling rules for prospective drug safety monitoring and identified signals for all three adverse drug reactions evaluated.
Drug Safety 04/2012; 35(5):407-16. · 3.63 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: A previous study suggested an increased risk of preeclampsia among women treated with selective serotonin reuptake inhibitors (SSRIs). Using population-based health-care utilization databases from British Columbia (1997-2006), the authors conducted a study of 69,448 pregnancies in women with depression. They compared risk of preeclampsia in women using SSRIs, serotonin-norepinephrine reuptake inhibitors (SNRIs), or tricyclic antidepressants (TCAs) between gestational weeks 10 and 20 with risk in depressed women not using antidepressants. Among prepregnancy antidepressant users, the authors compared the risk in women who continued antidepressants between gestational weeks 10 and 24 with the risk in those who discontinued. Relative risks and 95% confidence intervals were estimated. The risk of preeclampsia in depressed women not treated with antidepressants (2.4%) was similar to that in women without depression (2.3%). Compared with women with untreated depression, women treated with SSRI, SNRI, and TCA monotherapy had adjusted relative risks of 1.22 (95% confidence interval (CI): 0.97, 1.54), 1.95 (95% CI: 1.25, 3.03), and 3.23 (95% CI: 1.87, 5.59), respectively. Within prepregnancy antidepressant users, the relative risk for preeclampsia among continuers compared with discontinuers was 1.32 (95% CI: 0.95, 1.84) for SSRI, 3.43 (95% CI: 1.77, 6.65) for SNRI, and 3.26 (95% CI: 1.04, 10.24) for TCA monotherapy. Study results suggest that women who use antidepressants during pregnancy, especially SNRIs and TCAs, have an elevated risk of preeclampsia. These associations may reflect drug effects or more severe depression.
American journal of epidemiology 03/2012; 175(10):988-97. · 5.59 Impact Factor
-
Daniel H Solomon,
Maura D Iversen,
Jerry Avorn,
Timothy Gleeson,
M Alan Brookhart, Amanda R Patrick,
Laura Rekedal,
William H Shrank,
Joyce Lii,
Elena Losina,
Jeffrey N Katz
[show abstract]
[hide abstract]
ABSTRACT: Multiple studies demonstrate poor adherence to medication regimens prescribed for chronic illnesses, including osteoporosis, but few interventions have been proven to enhance adherence. We examined the effectiveness of a telephone-based counseling program rooted in motivational interviewing to improve adherence to a medication regimen for osteoporosis.
We conducted a 1-year randomized controlled clinical trial. Participants were recruited from a large pharmacy benefits program for Medicare beneficiaries. All potentially eligible individuals had been newly prescribed a medication for osteoporosis. Consenting participants were randomized to a program of telephone-based counseling (n = 1046) using a motivational interviewing framework or a control group (n = 1041) that received mailed educational materials. Medication regimen adherence was the primary outcome compared across treatment arms and was measured as the median (interquartile range) medication possession ratio, calculated as the ratio of days with filled prescriptions to total days of follow-up.
The groups were balanced at baseline, with a mean age of 78 years; 93.8% were female. In an intention-to-treat analysis, median adherence was 49% (interquartile range, 7%-88%) in the intervention arm and 41% (2%-86%) in the control arm (P = .07, Kruskal-Wallis test). There were no differences in self-reported fractures.
In this randomized controlled trial, we did not find a statistically significant improvement in adherence to an osteoporosis medication regimen using a telephonic motivational interviewing intervention.
Archives of internal medicine 02/2012; 172(6):477-83. · 11.46 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Little is known about the use of warfarin in hemodialysis (HD) patients with atrial fibrillation (AF). We studied temporal trends of AF among older HD patients, and of warfarin use among those with AF.
We linked US Medicare and prescription claims from older patients undergoing HD in 2 Eastern US states. We established annual cohorts of prevalent HD patients; AF was ascertained from >2 claims (>7 days apart) in the same year, with a diagnosis code indicating AF. Among those with AF, we defined current and past warfarin use. Demographic and clinical characteristics were also ascertained for each cohort. We used repeated-measures logistic regression to define the odds of AF and of current or past versus absence of warfarin use.
Of 6,563 unique patients, 2,185 were determined to have AF. The prevalence of AF increased from 26% in 1998 to 32% in 2005. In 2005, current warfarin use was present in 24% of AF patients and past use in 25%; 51% had no evidence of any warfarin use. No significant trends in utilization were observed from 1998 through 2005. Patients aged =85 years and nonwhites were less likely to have received warfarin; most comorbidities were not associated with warfarin use except for patients with past pulmonary embolism or deep venous thrombosis who were more likely than those without such history.
While the prevalence of AF has been increasing among older HD patients, warfarin use was low and unchanged over time, perhaps reflecting the lack of evidence supporting its use.
Journal of nephrology 12/2011; 25(3):341-53. · 1.65 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Adherence to osteoporosis treatment is low. Although new therapies and behavioral interventions may improve medication adherence, questions are likely to arise regarding their cost-effectiveness.
Our objectives were to develop and validate a model to simulate the clinical outcomes and costs arising from various osteoporosis medication adherence patterns among women initiating bisphosphonate treatment and to estimate the cost-effectiveness of a hypothetical intervention to improve medication adherence.
We constructed a computer simulation using estimates of fracture rates, bisphosphonate treatment effects, costs, and utilities for health states drawn from the published literature. Probabilities of transitioning on and off treatment were estimated from administrative claims data.
Patients were women initiating bisphosphonate therapy from the general community.
We evaluated a hypothetical behavioral intervention to improve medication adherence.
Changes in 10-yr fracture rates and incremental cost-effectiveness ratios were evaluated.
A hypothetical intervention with a one-time cost of $250 and reducing bisphosphonate discontinuation by 30% had an incremental cost-effectiveness ratio (ICER) of $29,571 per quality-adjusted life year in 65-yr-old women initiating bisphosphonates. Although the ICER depended on patient age, intervention effectiveness, and intervention cost, the ICERs were less than $50,000 per quality-adjusted life year for the majority of intervention cost and effectiveness scenarios evaluated. Results were sensitive to bisphosphonate cost and effectiveness and assumptions about the rate at which intervention and treatment effects decline over time.
Our results suggests that behavioral interventions to improve osteoporosis medication adherence will likely have favorable ICERs if their efficacy can be sustained.
The Journal of clinical endocrinology and metabolism 07/2011; 96(9):2762-70. · 6.50 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Sudden cardiac death constitutes the leading cause of death in patients receiving dialysis. Little is known about the trends in implantable cardioverter-defibrillator (ICD) use and the outcomes of such device placement.
Retrospective cohort study.
US long-term dialysis patients who received an ICD in 1994-2006. PREDICTORS, OUTCOMES, & MEASUREMENTS: ICD utilization rates and incident rates of all-cause mortality, device infections, and other device-related procedures were measured. We compared mortality between recipients and otherwise similar patients who did not receive such a device using high-dimensional propensity score matching. We also examined the associations of demographics, dialysis type, baseline comorbid conditions, cardiovascular events at the time of admission, and recent infection with the study outcomes.
9,528 patients received an ICD in 1994-2006, with >88% placed after 2000. Almost all ICD use in the 1990s was for secondary prevention, however, half the patients received ICDs for apparent primary prevention in 2006. Mortality rates after implantation were high (448 deaths/1,000 patient-years) and most deaths were cardiovascular. Postimplantation infection rates were high, especially in the first year after implantation (988 events/1,000 patient-years) and were predicted by diabetes and recent infection. Patients receiving ICDs for secondary prevention had an overall 14% (95% CI, 9%-19%) lower mortality risk compared with propensity-matched controls, but these benefits seemed to be restricted to the early postimplantation time.
Lack of clinical data, especially for laboratory and heart function studies. Residual confounding by indication.
ICD use in dialysis patients is increasing, but rates of all-cause and cardiovascular mortality remain high in dialysis patients receiving these devices. Device infections are common, particularly in patients with recent infections. Randomized trials of ICDs are needed to determine the efficacy, safety, and risk-benefit ratio of these devices in dialysis patients.
American Journal of Kidney Diseases 06/2011; 58(3):409-17. · 5.43 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To explore the "healthy user" and "healthy adherer" effects-hypothetical sources of bias thought to arise when patients who initiate and adhere to preventive therapies are more likely to engage in healthy behaviors than are other subjects.
The authors examined the association between statin initiation and adherence, and the subsequent use of preventive health services and incidence of clinical outcomes unlikely to be associated with the need for, or use of, a statin among older enrollees in two state-sponsored drug benefit programs.
After adjustment for demographic and clinical covariates, patients who initiated statin use were more likely to receive recommended preventive services than noninitiators matched on age, sex, and state (hazard ratio [HR]: 1.10, 1.06-1.14 for males, HR: 1.09, 1.07-1.11 for females) and appeared to have a lower risk of a range of adverse outcomes (HR: 0.87, 0.85-0.89) thought to be unrelated to statin use. Adherence to a statin regimen was also associated with increased rates of preventive service use and a decreased rate of adverse clinical outcomes (HR: 0.93, 0.88-0.99).
These results suggest that patients initiating and adhering to chronic preventive drug therapies are more likely to engage in other health-promoting behaviors. Failure to account for this relationship may introduce bias in any epidemiologic study evaluating the effect of a preventive therapy on clinical outcomes.
Value in Health 06/2011; 14(4):513-20. · 2.19 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To examine the effect of variable selection strategies on the performance of propensity score (PS) methods in a study of statin initiation, mortality, and hip fracture assuming a true mortality reduction of < 15% and no effect on hip fracture.
We compared seniors initiating statins with seniors initiating glaucoma medications. Out of 202 covariates with a prevalence > 5%, PS variable selection strategies included none, a priori, factors predicting exposure, and factors predicting outcome. We estimated hazard ratios (HRs) for statin initiation on mortality and hip fracture from Cox models controlling for various PSs.
During 1 year follow-up, 2693 of 55,610 study subjects died and 496 suffered a hip fracture. The crude HR for statin initiators was 0.64 for mortality and 0.46 for hip fracture. Adjusting for the non-parsimonious PS yielded effect estimates of 0.83 (95%CI:0.75-0.93) and 0.72 (95%CI:0.56-0.93). Including in the PS only covariates associated with a greater than 20% increase or reduction in outcome rates yielded effect estimates of 0.84 (95%CI:0.75-0.94) and 0.76 (95%CI:0.61-0.95), which were closest to the effects predicted from randomized trials.
Due to the difficulty of pre-specifying all potential confounders of an exposure-outcome association, data-driven approaches to PS variable selection may be useful. Selecting covariates strongly associated with exposure but unrelated to outcome should be avoided, because this may increase bias. Selecting variables for PS based on their association with the outcome may help to reduce such bias.
Pharmacoepidemiology and Drug Safety 03/2011; 20(6):551-9. · 2.53 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: We sought to evaluate the cost-effectiveness of applying the JUPITER (Justification for the Use of statins in Prevention: an Intervention Trial Evaluating Rosuvastatin) trial results into clinical practice.
The JUPITER trial found that rosuvastatin reduces vascular events in apparently healthy subjects with elevated high-sensitivity C-reactive protein (hs-CRP) but normal low-density lipoprotein (LDL) cholesterol levels. The implications of expanding treatment recommendations based on these results have not been evaluated.
We constructed a cost-effectiveness model of men ≥ 50 years and women ≥ 60 years with LDL cholesterol levels of <130 mg/dl and no known cardiovascular disease. We compared: 1) hs-CRP testing followed by rosuvastatin treatment for patients with hs-CRP levels ≥ 2.0 mg/l; and 2) usual care (i.e., no testing and no treatment). Estimates of treatment effectiveness were based on the JUPITER trial and were varied in sensitivity analyses.
Among patients with LDL <130 mg/dl and hs-CRP levels ≥ 2.0 mg/l, rosuvastatin had an incremental cost-effectiveness of $25,198 per quality-adjusted life year (QALY) gained compared to usual care. If the effectiveness of rosuvastatin were 50% of that observed in JUPITER, the incremental cost-effectiveness ratio would increase to $50,871 per QALY. Implementing this strategy only in patients with a Framingham risk score ≥ 10% yielded an incremental cost-effectiveness of $14,205 per QALY. Among such intermediate-risk patients, a JUPITER-based strategy becomes cost-saving at a rosuvastatin price of < $0.86 per day.
Rosuvastatin treatment for JUPITER-eligible patients appears to be cost-effective, particularly among those with a Framingham risk score ≥ 10%.
Journal of the American College of Cardiology 02/2011; 57(7):784-91. · 14.16 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: A half million Americans have ESRD, which puts them at high risk for cardiovascular disease and poor outcomes. Little is known about the epidemiology of atrial fibrillation among patients with ESRD. We analyzed data from annual cohorts (1992 to 2006) of prevalent hemodialysis patients from the United States Renal Data System. In each cohort, we searched 1 year of medical claims for relevant diagnosis codes to determine the prevalence of atrial fibrillation. Among 2.5 million patient observations, 7.7% had atrial fibrillation, with the prevalence increasing 3-fold from 3.5% (1992) to 10.7% (2006). The number of affected patients increased from 3620 to 23,893 (6.6-fold) during this period. Older age, male gender, and several comorbid conditions were associated with increased risk for atrial fibrillation. Compared with otherwise similar Caucasians, the prevalence of atrial fibrillation rates was substantially lower for blacks, Asians, and Native Americans. One-year mortality was twice as high among hemodialysis patients with atrial fibrillation compared with those without (39% versus 19%), and this increased risk was constant during the 15 years of the study. In conclusion, the prevalence of diagnosed atrial fibrillation among patients receiving hemodialysis in the United States is increasing, varies by race, and remains associated with substantially increased mortality. Identifying potentially modifiable risk factors for incident atrial fibrillation requires further investigation.
Journal of the American Society of Nephrology 02/2011; 22(2):349-57. · 9.66 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The current emphasis on comparative effectiveness research will provide practicing physicians with increasing volumes of observational evidence about preventive care. However, numerous highly publicized observational studies of the effect of prevention on health outcomes have reported exaggerated relationships that were later contradicted by randomized controlled trials. A growing body of research has identified sources of bias in observational studies that are related to patient behaviors or underlying patient characteristics, known as the healthy user effect, the healthy adherer effect, confounding by functional status or cognitive impairment, and confounding by selective prescribing. In this manuscript we briefly review observational studies of prevention that have appeared to reach incorrect conclusions. We then describe potential sources of bias in these studies and discuss study designs, analytical methods, and sensitivity analyses that may mitigate bias or increase confidence in the results reported. More careful consideration of these sources of bias and study designs by providers can enhance evidence-based decision-making.
Journal of General Internal Medicine 01/2011; 26(5):546-50. · 2.83 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Suicidal behavior has gained attention as an adverse outcome of prescription drug use. Hospitalizations for intentional self-harm, including suicide, can be identified in administrative claims databases using external cause of injury codes (E-codes). However, rates of E-code completeness in US government and commercial claims databases are low due to issues with hospital billing software.
To develop an algorithm to identify intentional self-harm hospitalizations using recorded injury and psychiatric diagnosis codes in the absence of E-code reporting.
We sampled hospitalizations with an injury diagnosis (ICD-9 800-995) from two databases with high rates of E-coding completeness: 1999-2001 British Columbia, Canada data and the 2004 US Nationwide Inpatient Sample. Our gold standard for intentional self-harm was a diagnosis of E950-E958. We constructed algorithms to identify these hospitalizations using information on type of injury and presence of specific psychiatric diagnoses.
The algorithm that identified intentional self-harm hospitalizations with high sensitivity and specificity was a diagnosis of poisoning, toxic effects, open wound to elbow, wrist, or forearm, or asphyxiation; plus a diagnosis of depression, mania, personality disorder, psychotic disorder, or adjustment reaction. This had a sensitivity of 63%, specificity of 99% and positive predictive value (PPV) of 86% in the Canadian database. Values in the US data were 74, 98, and 73%. PPV was highest (80%) in patients under 25 and lowest those over 65 (44%).
The proposed algorithm may be useful for researchers attempting to study intentional self-harm in claims databases with incomplete E-code reporting, especially among younger populations.
Pharmacoepidemiology and Drug Safety 10/2010; 19(12):1263-75. · 2.53 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: A US Food and Drug Administration advisory has warned that antidepressants may be associated with an increased risk of suicidal thoughts and behaviors in adolescents. This prompted a meta-analysis of trials in adults that found no overall increase in risk, but individual agents could not be studied.
To assess the risk of suicide and suicide attempts associated with individual antidepressant agents.
Cohort study of incident users of antidepressant agents.
Population-based health care utilization data of all residents of British Columbia, Canada, aged 18 years and older between January 1, 1997, and December 31, 2005.
British Columbia residents who had antidepressant therapy initiated and had a recorded diagnosis of depression.
Initiation of various antidepressant medications.
Combined suicide death or hospitalization due to self-harm.
In a population of 287,543 adults aged 18 years and older with antidepressant therapy initiated, we observed outcome rates ranging from 4.41/1000 person-years to 9.09/1000 person-years. Most events occurred in the first 6 months after treatment initiation. After extensive propensity score adjustment, we found no clinically meaningful variation in the risk of suicide and suicide attempt between antidepressant agents compared with fluoxetine hydrochloride initiation: citalopram hydrobromide, hazard ratio = 1.00 (95% confidence interval, 0.63-1.57); fluvoxamine maleate, hazard ratio = 0.98 (95% confidence interval, 0.63-1.51); paroxetine hydrochloride, hazard ratio = 1.02 (95% confidence interval, 0.77-1.35); and sertraline hydrochloride, hazard ratio = 0.75 (95% confidence interval, 0.53-1.05). Compared with selective serotonin reuptake inhibitors as a drug class, other classes including serotonin-norepinephrine reuptake inhibitors, tricyclic agents, and other newer and atypical agents had a similar risk. Restriction to patients with no antidepressant use in the past 3 years further reduced apparent differences between groups.
Our finding of equal event rates across antidepressant agents supports the US Food and Drug Administration's decision to treat all antidepressants alike in their advisory. Treatment decisions should be based on efficacy, and clinicians should be vigilant in monitoring after initiating therapy with any antidepressant agent.
Archives of general psychiatry 05/2010; 67(5):497-506. · 12.26 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Real-world adherence to bisphosphonate therapy is poor. Consistent data support a relation between medication adherence and fracture reduction, but relatively little attention has been paid to the effect of the method used to measure adherence on this relation or on the relation between adherence and specific fracture types.
Our objective was to assess the relation between bisphosphonate adherence and the risk of hip, vertebral, distal forearm, and any fracture using different measures of adherence.
We conducted a cohort study using administrative claims data. Adherence was assessed in sequential 60-d periods. In models incorporating time-varying measures of adherence, the adjusted relation between adherence and fracture was examined using several methods for calculating the proportion of days covered (PDC).
Patients included community-dwelling elderly enrolled in a Pennsylvania pharmaceutical assistance program and Medicare initiating an oral bisphosphonate for osteoporosis.
Risk of hip, vertebral, distal forearm, and any osteoporotic fracture was assessed.
Fractures occurred at a rate of 43 per 1000 person-years among the 19,987 patients meeting study eligibility criteria. There was an inverse relation between adherence and fracture rate for all adherence measures and fracture types, excluding distal forearm fractures. High (80-100%) cumulative PDC was associated with a 22% reduction in overall fracture rate, a 23% reduction in hip fracture rate, and 26% reduction in vertebral fracture rate.
We found a consistent relation between adherence with osteoporosis treatment and fracture reduction, regardless of method for measuring PDC. The similarity in results across adherence measures is likely due to the high correlation between them.
The Journal of clinical endocrinology and metabolism 05/2010; 95(7):3251-9. · 6.50 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The objective of this study was to assess the risk of suicide attempts and suicides after initiation of antidepressant medication use by children and adolescents, for individual agents.
We conducted a 9-year cohort study by using population-wide data from British Columbia. We identified new users of antidepressants who were 10 to 18 years of age with a recorded diagnosis of depression. Study outcomes were hospitalization attributable to intentional self-harm and suicide death.
Of 20,906 children who initiated antidepressant therapy, 16,774 (80%) had no previous antidepressant use. During the first year of use, we observed 266 attempted and 3 completed suicides, which yielded an event rate of 27.04 suicidal acts per 1000 person-years (95% confidence interval [CI]: 23.9-30.5 suicidal acts per 1000 person-years). There were no meaningful differences in the rate ratios (RRs) comparing fluoxetine with citalopram (RR: 0.97 [95% CI: 0.54-1.76]), fluvoxamine (RR: 1.05 [95% CI: 0.46-2.43]), paroxetine (RR: 0.80 [95% CI: 0.47-1.37]), and sertraline (RR: 1.02 [95% CI: 0.56-1.84]). Tricyclic agents showed risks similar to those of selective serotonin reuptake inhibitors (RR: 0.92 [95% CI: 0.43-2.00]).
Our finding of equal event rates among antidepressant agents supports the decision of the Food and Drug Administration to include all antidepressants in the black box warning regarding potentially increased suicidality risk for children and adolescents beginning use of antidepressants.
PEDIATRICS 04/2010; 125(5):876-88. · 4.47 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: In 2008, the US Food and Drug Administration mandated warning labeling for anticonvulsant medications regarding the increased risk of suicidal thoughts and behaviors. The decision was based on a meta-analysis not sufficiently large to investigate individual drugs.
To evaluate the risk of suicidal acts and combined suicidal acts or violent death associated with individual anticonvulsants.
A cohort study of the risk of suicidal acts and combined suicidal acts or violent death in patients beginning use of anticonvulsant medications compared with patients initiating a reference anticonvulsant drug.
Patients 15 years and older from the HealthCore Integrated Research Database (HIRD) who began taking an anticonvulsant between July 2001 and December 2006.
Cox proportional hazards models and propensity score-matched analyses were used to evaluate risk of attempted or completed suicide and combined suicidal acts or violent death, controlling for psychiatric comorbidities and other risk factors, among individual anticonvulsants compared with topiramate and secondarily carbamazepine.
The study identified 26 completed suicides, 801 attempted suicides, and 41 violent deaths in 297,620 new episodes of treatment with an anticonvulsant (overall median follow-up, 60 days). The incidence of the composite outcomes of completed suicides, attempted suicides, and violent deaths for anticonvulsants used in at least 100 treatment episodes ranged from 6.2 per 1000 person-years for primidone to 34.3 per 1000 person-years for oxcarbazepine. The risk of suicidal acts was increased for gabapentin (hazard ratio [HR], 1.42; 95% confidence interval [CI], 1.11-1.80), lamotrigine (HR, 1.84; 95% CI, 1.43-2.37), oxcarbazepine (HR, 2.07; 95% CI, 1.52-2.80), tiagabine (HR, 2.41; 95% CI, 1.65-3.52), and valproate (HR, 1.65; 95% CI, 1.25-2.19), compared with topiramate. The analyses including violent death produced similar results. Gabapentin users had increased risk in subgroups of younger and older patients, patients with mood disorders, and patients with epilepsy or seizure when compared with carbamazepine.
This exploratory analysis suggests that the use of gabapentin, lamotrigine, oxcarbazepine, and tiagabine, compared with the use of topiramate, may be associated with an increased risk of suicidal acts or violent deaths.
JAMA The Journal of the American Medical Association 04/2010; 303(14):1401-9. · 30.03 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Depression imposes enormous burdens on the elderly. Despite this, rates of initiation of and adherence to recommended pharmacotherapy are frequently low in this population. Although initiatives such as the Medicare Modernization Act (MMA) have improved seniors' access to antidepressants, there are concerns that the patient cost-sharing incorporated in the MMA may have unintended consequences if it reduces essential drug use. Age-related pharmacokinetic and pharmacodynamic changes could make seniors particularly vulnerable to antidepressant regimens used inappropriately to save costs, increasing their risks of morbidity, hospitalizations, and nursing home placements. Two sequential large-scale "natural experiments'' in British Columbia provide a unique opportunity to evaluate the effect of cost sharing on outcomes and mental health service use among seniors. In January 2002 the province introduced a CAD 25 copay (CAD10 for low-income seniors). In May 2003 this copay policy was replaced by a second policy consisting of an income-based deductible, 25% coinsurance once the deductible was met, and full coverage once an out-of-pocket ceiling was met. The transition between the two policies is analogous to what many U.S. seniors experience when they transition from private insurance requiring copays to Medicare Part D requiring deductibles and coinsurance.
To evaluate whether declines in antidepressant initiation after the introduction of two drug cost-sharing policies in British Columbia were associated with increased use of physician services, hospitalizations, and nursing home admissions among all British Columbia residents aged 65+.
Records of physician service use, inpatient hospitalizations, and residential care admissions were obtained from administrative databases. Population-level patterns over time were plotted, and effects of implementing the cost-sharing policies examined in segmented linear regression models.
Neither policy affected the rates of visits to physicians or psychiatrists for depression, hospitalizations with a depression diagnosis, or long-term care admissions.
The cost-sharing policies studied may have contained non-essential antidepressant use without substantially increasing mental health service utilization. However, it is possible that the policies had effects that we were unable to detect, such as increasing rates of visits to social workers or psychologists or forcing patients to reduce other spending. Further, the sequential implementation of the policy changes, makes it difficult to estimate the effect of a direct change from full coverage to a coinsurance/income-based deductible policy.
It may be possible to design policies to contain non-essential antidepressant use without substantially increasing other service utilization or adverse events. However, because undertreatment remains a serious problem among depressed elderly, well-designed prescription drug policies should be coupled with interventions to address under-treatment.
The Journal of Mental Health Policy and Economics 03/2010; 13(1):37-44. · 0.97 Impact Factor
-
American Journal of Hypertension 02/2010; 23(2):110. · 3.18 Impact Factor
