Patient safety in the era of the 80-hour workweek.

OBJECTIVE: In 2003, duty-hour regulations (DHR) were initially implemented for residents in the United States to improve patient safety and protect resident's well-being. The effect of DHR on patient safety remains unclear. The study objective was to evaluate the effect of DHR on patient safety. DESIGN: Using an interrupted time series analysis, we analyzed selected patient safety indicators (PSIs) for 376 million discharges in teaching (T) vs nonteaching (NT) hospitals before and after implementation of DHR in 2003 that restricted resident work hours to 80 hours per week. The PSIs evaluated were postoperative pulmonary embolus or deep venous thrombosis (PEDVT), iatrogenic pneumothorax (PTx), accidental puncture or laceration, postoperative wound dehiscence (WD), postoperative hemorrhage or hematoma, and postoperative physiologic or metabolic derangement. Propensity scores were used to adjust for differences in patient comorbidities between T and NT hospitals and between discharge quarters. The primary outcomes were differences in the PSI rates before and after DHR implementation. The PSI differences between T and NT institutions were the secondary outcome. SETTING: T and NT hospitals in the United States. PARTICIPANTS: Participants were 376 million patient discharges from 1998 to 2007 in the Nationwide Inpatient Sample. RESULTS: Declining rates of PTx in both T and NT hospitals preintervention slowed only in T hospitals postintervention (p = 0.04). Increasing PEDVT rates in both T and NT hospitals increased further only in NT hospitals (p = 0.01). There were no differences in the PSI rates over time for hemorrhage or hematoma, physiologic or metabolic derangement, accidental puncture or laceration, or WD. T hospitals had higher rates than NT hospitals both preintervention and postintervention for all the PSIs except WD. CONCLUSIONS: Trends in rates for 2 of the 6 PSIs changed significantly after DHR implementation, with PTx rates worsening in T hospitals and PEDVT rates worsening in NT hospitals. Lack of consistent patterns of change suggests no measurable effect of the policy change on these PSIs.

60-Hz frequency effect on gait in Parkinson's disease with subthalamic nucleus deep brain stimulation.

OBJECTIVE: Gait dysfunction is common in advancing Parkinson's disease and has a disappointing response to dopamine replacement and subthalamic nucleus deep brain stimulation programming parameters. Low-frequency stimulation, less than 130 Hz in combination with increased voltage, has been shown to decrease freezing episodes and number of steps with little impact on overall performance measured by the Unified Parkinson's Disease Rating Scale. This was in the setting of delivering the same total energy, which required both a change in voltage and frequency. We wanted to determine if the benefit came from low frequency alone. MATERIALS AND METHODS: We enrolled 20 Parkinson's patients who were at least three months in postbilateral subthalamic deep brain stimulation and reported gait changes. Subjects held their Parkinson's medications overnight, and following a baseline evaluation, they were randomly assigned to both 60 and 130 Hz stimulation in a blinded fashion with all other parameters held constant. Each subject was set at each frequency twice during the study, with a 60-min stimulation interval prior to each gait evaluation. RESULTS: There was no significant difference between the two frequencies, with the primary outcome measure of stride length. Two of the 20 patients reported a significant subjective improvement in their gait with no statistical difference in their outcomes. There also was less tremor control at 60 Hz. CONCLUSION: We were unable to demonstrate improved gait with lower frequency stimulation as suggested by prior studies. This may have been because of the decreased energy delivered from the lower frequency and unchanged voltage.

Reducing blood culture contamination in the emergency department: an interrupted time series quality improvement study.

OBJECTIVES: Blood culture contamination is a common problem in the emergency department (ED) that leads to unnecessary patient morbidity and health care costs. The study objective was to develop and evaluate the effectiveness of a quality improvement (QI) intervention for reducing blood culture contamination in an ED. METHODS: The authors developed a QI intervention to reduce blood culture contamination in the ED and then evaluated its effectiveness in a prospective interrupted times series study. The QI intervention involved changing the technique of blood culture specimen collection from the traditional clean procedure to a new sterile procedure, with standardized use of sterile gloves and a new materials kit containing a 2% chlorhexidine skin antisepsis device, a sterile fenestrated drape, a sterile needle, and a procedural checklist. The intervention was implemented in a university-affiliated ED and its effect on blood culture contamination evaluated by comparing the biweekly percentages of blood cultures contaminated during a 48-week baseline period (clean technique) and 48-week intervention period (sterile technique), using segmented regression analysis with adjustment for secular trends and first-order autocorrelation. The goal was to achieve and maintain a contamination rate below 3%. RESULTS: During the baseline period, 321 of 7,389 (4.3%) cultures were contaminated, compared to 111 of 6,590 (1.7%) during the intervention period (p < 0.001). In the segmented regression model, the intervention was associated with an immediate 2.9% (95% confidence interval [CI] = 2.2% to 3.2%) absolute reduction in contamination. The contamination rate was maintained below 3% during each biweekly interval throughout the intervention period. CONCLUSIONS: A QI assessment of ED blood culture contamination led to development of a targeted intervention to convert the process of blood culture collection from a clean to a fully sterile procedure. Implementation of this intervention led to an immediate and sustained reduction of contamination in an ED with a high baseline contamination rate.

Initiation of tumor necrosis factor α antagonists and risk of fractures in patients with selected rheumatic and autoimmune diseases.

OBJECTIVE: We tested the hypothesis that initiation of tumor necrosis factor α (TNFα) antagonists reduced the risk of fractures compared to nonbiologic comparators in patients with autoimmune diseases. METHODS: Using 4 large administrative databases, we assembled retrospective cohorts of patients with autoimmune diseases who initiated either a TNFα antagonist or a nonbiologic medication. We identified 3 mutually exclusive disease groups: rheumatoid arthritis (RA), inflammatory bowel disease (IBD), and a combined group: psoriasis (PsO), psoriatic arthritis (PsA), or ankylosing spondylitis (AS). We used baseline covariate data to calculate propensity scores (PS) for each disease group and used Cox regression to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs). We compared the risk of combined hip, radius/ulna, humerus, or pelvic fractures between PS-matched cohorts of new users of TNFα antagonists and nonbiologic comparators. RESULTS: We identified 9,020, 2,014, and 2,663 new PS-matched episodes of TNFα antagonist and nonbiologic comparator use in RA, IBD, and PsO-PsA-AS cohorts, respectively. The risk of combined fractures was similar between new users of TNFα antagonists and nonbiologic comparators for each disease (HR 1.17, 95% CI 0.91-1.51; HR 1.49, 95% CI 0.72-3.11; and HR 0.92, 95% CI 0.47-1.82 for RA, IBD, and PsO-PsA-AS, respectively). In RA, the risk of combined fractures was associated with an average daily dosage of prednisone equivalents >10 mg/day at baseline compared with no glucocorticoid (HR 1.54, 95% CI 1.03-2.30). CONCLUSION: The risk of fractures did not differ between initiators of a biologic agent and a nonbiologic comparator for any disease studied. Among RA patients, use of >10 mg/day of prednisone equivalents at baseline increased the fracture risk.

Nearly complete elimination of the 7-valent pneumococcal conjugate vaccine serotypes in Tennessee.

BACKGROUND: Invasive pneumococcal disease (IPD) rates decreased after 7-valent pneumococcal conjugate vaccine (PCV) introduction in 2000. We assessed whether previously described decreases were sustained. METHODS: Active laboratory-based surveillance identified IPD cases in 5 Tennessee Counties. For each case, clinical data were collected, and antibiotic susceptibility testing and serotyping were performed. Penicillin resistance was defined as intermediate- or high-level resistance to penicillin. Serotypes were classified as PCV7, PCV13 (6 additional serotypes not in PCV7), pneumococcal polysaccharide vaccine (PPV23, 11 additional serotypes not in PCV13 and nonvaccine serotypes. Total and penicillin-resistant IPD rates were calculated for persons <2, 2-14 and ≥15 years of age before (1998 to 1999) and after (2001 to 2008) PCV7 introduction. RESULTS: Annual IPD rates in children <2 years of age declined by 75% after PCV7 introduction (P < 0.001). Annual IPD rates in children 2-14 years of age declined by 51% after PCV7 introduction (P < 0.001). IPD rates in persons ≥15 of age years initially decreased 40% from 22 to 13 per 100,000 person-years (from 1998 through 2004), and then increased to 18 per 100,000 person-years in 2008. Both IPD and penicillin-resistant IPD PCV7 serotypes were almost completely eliminated in all age groups by 2008. During 2005 to 2008, 52.5%, 58% and 38% of IPD serotypes in children <2, 2-14 and ≥15 years of age, respectively, were the additional 6 serotypes in PCV13. CONCLUSIONS: Overall, 9 years after PCV7 introduction both penicillin-susceptible and resistant IPD rates PCV7 serotypes have been nearly eliminated in Tennessee in all age groups. Total IPD rates remain reduced in children <15 years of age, whereas total IPD rates in persons ≥15 years of age have approached pre-PCV7 rates due to modest increases in nonvaccine serotypes.

Increasing use of atypical antipsychotics and anticonvulsants during pregnancy.

PURPOSE: To quantify maternal use of atypical antipsychotics, typical antipsychotics, anticonvulsants, and lithium during pregnancy. METHODS: Tennessee birth and death records were linked to Tennessee Medicaid data to conduct a retrospective cohort study of 296,817 women enrolled in Tennessee Medicaid throughout pregnancy who had a live birth or fetal death from 1985 to 2005. RESULTS: During the study time period, the adjusted rate of use of any study medication during pregnancy increased from nearly 14 to 31 per 1000 pregnancies (ß = 0.08, 95% CI = 0.07, 0.09). Significant increases were reported in use of anticonvulsants alone among mothers with pain and other psychiatric disorders, atypical antipsychotics alone among mothers with bipolar disorders, schizophrenia, unipolar depressive disorders, and other psychiatric disorders, and more than one studied medication for mothers with epilepsy, pain disorders, bipolar disorders, unipolar depressive disorders, and other psychiatric disorders. Significant decreases were reported in use of lithium alone and typical antipsychotics alone for all clinically meaningful diagnosis groups. CONCLUSIONS: There was a substantial increase in use of atypical antipsychotics alone, anticonvulsants alone, and medications from multiple studied categories among Tennessee Medicaid-insured pregnant women during the study period. Further examination of the maternal and fetal consequences of exposure to these medications during pregnancy is warranted.

Adherence to transcranial Doppler screening guidelines among children with sickle cell disease.

BACKGROUND: Little is known about adherence to guidelines recommending yearly screening with transcranial Doppler (TCD) ultrasonography to detect stroke risk for children with severe sickle cell disease. The objective was to determine the proportion of children with hemoglobin SS (HbSS) or sickle-ß(0) -thalassemia (HbSß(0) ) aged 2-16 years who received recommended TCD screening from 1997 to 2008, and to identify factors associated with adherence. PROCEDURE: A retrospective cohort study included patients enrolled in Tennessee Medicaid with HbSS or HbSß(0) who received care at the two largest sickle cell centers in Tennessee. The outcome of interest was adherence with guidelines for annual screening TCD's, identified from computer claims and validated through medical record review. The cumulative rate of children who received a TCD per year was calculated using the Kaplan-Meier method. Cox proportional hazards regression was used to examine the association of child, family, and health care use characteristics with receiving a TCD. RESULTS: Among 338 TCD eligible at-risk children, 232 (68.6%) had at least one TCD during the study period. The yearly cumulative incidence of annual TCD's increased from 2.5% in 1997 to 68.3% in 2008. In multivariate models, calendar year, maternal education, and increased number of sickle cell related outpatient visits were associated with an increased rate of receiving a TCD. CONCLUSIONS: Publicly insured children with HbSS or HbSß(0) had increasing adherence with TCD screening guidelines between 1997 and 2008, though 31% had no TCD at all during follow-up. Increasing number of sickle cell related outpatient visits was associated with increasing adherence to screening guidelines.

Trends in the use of antiepileptic drugs among pregnant women in the US, 2001-2007: a medication exposure in pregnancy risk evaluation program study.

BACKGROUND: Little is known about the extent of antiepileptic drug (AED) use in pregnancy, particularly for newer agents. Our objective was to assess whether AED use has increased among pregnant women in the US, 2001-2007. METHODS: We analysed data from the Medication Exposure in Pregnancy Risk Evaluation Program (MEPREP) database, 1 January 2001 to 31 December 2007. We identified liveborn deliveries among women, aged 15-45 years on delivery date, who were members of MEPREP health plans (n=585615 deliveries). Pregnancy exposure to AEDs, determined through outpatient pharmacy dispensing files. Older AEDs were available for clinical use before 1993; other agents were considered newer AEDs. Information on sociodemographic and medical/reproductive factors was obtained from linked birth certificate files. Maternal diagnoses were identified based on ICD-9 codes. RESULTS: Prevalence of AED use during pregnancy increased between 2001 (15.7 per 1000 deliveries) and 2007 (21.9 per 1000 deliveries), driven primarily by a fivefold increase in the use of newer AEDs. Thirteen per cent of AED-exposed deliveries involved a combination of two or more AEDs. Psychiatric disorders were the most prevalent diagnoses, followed by epileptic and pain disorders, among AED users regardless of AED type, year of conception or gestational period. CONCLUSIONS: AED use during pregnancy increased between 2001 and 2007, driven by a fivefold increase in the use of newer AEDs. Nearly one in eight AED-exposed deliveries involved the concomitant use of more than one AED. Additional investigations of the reproductive safety of newer AEDs may be needed.

Changes to the financial responsibility for juvenile court ordered psychiatric evaluations reduce inpatient services utilization: an interrupted time series study.

BACKGROUND: The purpose of the current study was to evaluate the impact of a July 2008 Tennessee Court of Appeals opinion that shifted financial responsibility for juvenile court ordered psychiatric evaluations from the State to the County. METHODS: We used de-identified administrative data from the Tennessee Department of Mental Health and mid-year population estimates from the U.S. Census Bureau from July 1, 2006 to June 30, 2010, and an interrupted time series design with segmented regression analysis to quantify the impact of the implementation of the Court opinion. RESULTS: In the study period, there were 2,176 referrals for juvenile court ordered psychiatric evaluations in Tennessee; of these, 74.1% were inpatient evaluations. The Court opinion was associated with a decrease of 9.4 (95% C.I. = 7.9-10.8) inpatient and increase of 1.2 (95% C.I. = 0.4-2.1) outpatient evaluations per 100,000 Tennessee youth aged 12 to 19 years per month. CONCLUSIONS: The Court opinion that shifted financial responsibility for juvenile court ordered psychiatric evaluations from the State to the County was associated with a sudden and significant decrease in inpatient psychiatric evaluations, and more modest increase in outpatient evaluations.

Azithromycin and the risk of cardiovascular death.

BACKGROUND: Although several macrolide antibiotics are proarrhythmic and associated with an increased risk of sudden cardiac death, azithromycin is thought to have minimal cardiotoxicity. However, published reports of arrhythmias suggest that azithromycin may increase the risk of cardiovascular death. METHODS: We studied a Tennessee Medicaid cohort designed to detect an increased risk of death related to short-term cardiac effects of medication, excluding patients with serious noncardiovascular illness and person-time during and shortly after hospitalization. The cohort included patients who took azithromycin (347,795 prescriptions), propensity-score-matched persons who took no antibiotics (1,391,180 control periods), and patients who took amoxicillin (1,348,672 prescriptions), ciprofloxacin (264,626 prescriptions), or levofloxacin (193,906 prescriptions). RESULTS: During 5 days of therapy, patients taking azithromycin, as compared with those who took no antibiotics, had an increased risk of cardiovascular death (hazard ratio, 2.88; 95% confidence interval [CI], 1.79 to 4.63; P<0.001) and death from any cause (hazard ratio, 1.85; 95% CI, 1.25 to 2.75; P=0.002). Patients who took amoxicillin had no increase in the risk of death during this period. Relative to amoxicillin, azithromycin was associated with an increased risk of cardiovascular death (hazard ratio, 2.49; 95% CI, 1.38 to 4.50; P=0.002) and death from any cause (hazard ratio, 2.02; 95% CI, 1.24 to 3.30; P=0.005), with an estimated 47 additional cardiovascular deaths per 1 million courses; patients in the highest decile of risk for cardiovascular disease had an estimated 245 additional cardiovascular deaths per 1 million courses. The risk of cardiovascular death was significantly greater with azithromycin than with ciprofloxacin but did not differ significantly from that with levofloxacin. CONCLUSIONS: During 5 days of azithromycin therapy, there was a small absolute increase in cardiovascular deaths, which was most pronounced among patients with a high baseline risk of cardiovascular disease. (Funded by the National Heart, Lung, and Blood Institute and the Agency for Healthcare Quality and Research Centers for Education and Research on Therapeutics.).

Volume-outcome effects for children undergoing resection of renal malignancies.

INTRODUCTION: Adults undergoing oncologic resections at low-volume centers experience increased perioperative morbidity and mortality. The volume-outcome effect has not been extensively studied in pediatric oncologic resections. METHODS: To clarify volume-outcome effects in pediatric oncologic resections, we analyzed resection of renal malignancies in children less than 15 y of age. We conducted a cross-sectional analysis of hospital discharges included in the health care utilization project kids' inpatient database from 1997 to 2009, examining in-hospital operative complications, length of stay (LOS), and inflation-adjusted hospital charges. Hospital volume was expressed as low (n = 1-2), medium (n = 3-4), and high (n > 4) annual volume of resections. RESULTS: One thousand five hundred thirty-eight patients underwent renal malignancy resection. Of these, 527 patients had resection in low-, 422 in medium-, and 589 in high-volume hospitals. Relative to low-volume hospitals, those resected in medium-volume hospitals had an odds ratio of 0.62 (95% confidence interval 0.39-0.99, P = 0.046) for operative complication and those in high-volume hospitals had an odds ratio of 1.02 (95% confidence interval 0.63-1.65, P = 0.95). There was no detectable association with LOS (P = 0.113) or inflation-adjusted charges (P = 0.331). CONCLUSIONS: The number of complications, total charges, and LOS attributable to resection of a childhood renal malignancy did not differ among high-, medium-, or low-operative volume hospitals, although oncologic outcomes could not be determined because of the limited nature of this administrative database.

ED crowding and the use of nontraditional beds.

BACKGROUND AND OBJECTIVES: In an effort to compensate for crowding, many emergency departments (EDs) evaluate and treat patients in nontraditional settings such as gurneys in hallways and conference rooms. The impact of this practice on ED evaluation time is unknown. RESEARCH DESIGN AND SUBJECTS: A historical cohort of adult ED visits to an academic hospital between August 1, 2009 and August 1, 2010, was used to evaluate the relationship between ED bed assignment (traditional, hallway, or conference room bed) and mean ED evaluation time, defined as the time spent in an ED bed before admission or discharge. Chief complaints were categorized into the 5 most frequent categories: abdominal/genitourinary, joint/muscle, general (fever, malaise), head/neck, and other. Multiple linear regression and marginal prediction were used to calculate the mean ED evaluation times for each bed type, overall, and by chief complaint category. RESULTS: During the study period, 15 073 patient visits met the inclusion criteria. After adjustment for patient and ED factors, assignments to hallway and conference room beds were associated with increases in a mean ED evaluation time of 13.3 minutes (95% confidence interval, 13.2-13.3) and 10.9 minutes (95% confidence interval, 10.8-10.9), respectively, compared with the traditional bed ED evaluation time. This varied by chief complaint category. CONCLUSIONS: Use of nontraditional beds is associated with increases in mean ED evaluation time; however, these increases are small and may be further minimized by restricting the use of nontraditional beds to patients with specific chief complaints. Nontraditional beds may have a role in improving ED throughput during times of crowding.

The impact of beta-blocker therapy on anemia after traumatic brain injury.

BACKGROUND: An increase in endogenous catecholamine levels after traumatic brain injury (TBI) is well described. Animal studies suggest that postinjury anemia is exacerbated by a persistent hyperadrenergic state. This study aims to determine if beta-blocker (BB) exposure affects anemia after TBI. STUDY DESIGN AND METHODS: We reviewed a Level I trauma registry for patients with TBI, examining markers of anemia between patients who received BB with those who did not. RESULTS: A total of 174 patients were exposed to BB (BB+) and 245 were not exposed (BB-). The mean age in the BB+ group was 50 years (vs. 36 years in BB- group, p < 0.001). The mean injury severity score was 33.6 for the BB+ group (vs. 30.8 for BB- group, p = 0.01). While BB+ patients were more likely to receive a transfusion (60.9% vs. 35.1%, p < 0.001), BB+ patients reached their nadir hemoglobin (Hb) at a later day of hospitalization and their rate of decrease in Hb was significantly slower (both p < 0.001). Choosing Hb cutoffs for anemia of both 7 and 10 g/dL, Kaplan-Meier demonstrated a significant delay in time to anemia. CONCLUSION: This study suggests beta-blockade delays anemia after TBI. Elaboration of this effect may demonstrate an additional benefit of beta-blockade after head injury.

ADHD medications and risk of serious cardiovascular events in young and middle-aged adults.

CONTEXT: More than 1.5 million US adults use stimulants and other medications labeled for treatment of attention-deficit/hyperactivity disorder (ADHD). These agents can increase heart rate and blood pressure, raising concerns about their cardiovascular safety. OBJECTIVE: To examine whether current use of medications prescribed primarily to treat ADHD is associated with increased risk of serious cardiovascular events in young and middle-aged adults. DESIGN, SETTING, AND PARTICIPANTS: Retrospective, population-based cohort study using electronic health care records from 4 study sites (OptumInsight Epidemiology, Tennessee Medicaid, Kaiser Permanente California, and the HMO Research Network), starting in 1986 at 1 site and ending in 2005 at all sites, with additional covariate assessment using 2007 survey data. Participants were adults aged 25 through 64 years with dispensed prescriptions for methylphenidate, amphetamine, or atomoxetine at baseline. Each medication user (n = 150,359) was matched to 2 nonusers on study site, birth year, sex, and calendar year (443,198 total users and nonusers). MAIN OUTCOME MEASURES: Serious cardiovascular events, including myocardial infarction (MI), sudden cardiac death (SCD), or stroke, with comparison between current or new users and remote users to account for potential healthy-user bias. RESULTS: During 806,182 person-years of follow-up (median, 1.3 years per person), 1357 cases of MI, 296 cases of SCD, and 575 cases of stroke occurred. There were 107,322 person-years of current use (median, 0.33 years), with a crude incidence per 1000 person-years of 1.34 (95% CI, 1.14-1.57) for MI, 0.30 (95% CI, 0.20-0.42) for SCD, and 0.56 (95% CI, 0.43-0.72) for stroke. The multivariable-adjusted rate ratio (RR) of serious cardiovascular events for current use vs nonuse of ADHD medications was 0.83 (95% CI, 0.72-0.96). Among new users of ADHD medications, the adjusted RR was 0.77 (95% CI, 0.63-0.94). The adjusted RR for current use vs remote use was 1.03 (95% CI, 0.86-1.24); for new use vs remote use, the adjusted RR was 1.02 (95% CI, 0.82-1.28); the upper limit of 1.28 corresponds to an additional 0.19 events per 1000 person-years at ages 25-44 years and 0.77 events per 1000 person-years at ages 45-64 years. CONCLUSIONS: Among young and middle-aged adults, current or new use of ADHD medications, compared with nonuse or remote use, was not associated with an increased risk of serious cardiovascular events. Apparent protective associations likely represent healthy-user bias.

ADHD drugs and serious cardiovascular events in children and young adults.

BACKGROUND: Adverse-event reports from North America have raised concern that the use of drugs for attention deficit-hyperactivity disorder (ADHD) increases the risk of serious cardiovascular events. METHODS: We conducted a retrospective cohort study with automated data from four health plans (Tennessee Medicaid, Washington State Medicaid, Kaiser Permanente California, and OptumInsight Epidemiology), with 1,200,438 children and young adults between the ages of 2 and 24 years and 2,579,104 person-years of follow-up, including 373,667 person-years of current use of ADHD drugs. We identified serious cardiovascular events (sudden cardiac death, acute myocardial infarction, and stroke) from health-plan data and vital records, with end points validated by medical-record review. We estimated the relative risk of end points among current users, as compared with nonusers, with hazard ratios from Cox regression models. RESULTS: Cohort members had 81 serious cardiovascular events (3.1 per 100,000 person-years). Current users of ADHD drugs were not at increased risk for serious cardiovascular events (adjusted hazard ratio, 0.75; 95% confidence interval [CI], 0.31 to 1.85). Risk was not increased for any of the individual end points, or for current users as compared with former users (adjusted hazard ratio, 0.70; 95% CI, 0.29 to 1.72). Alternative analyses addressing several study assumptions also showed no significant association between the use of an ADHD drug and the risk of a study end point. CONCLUSIONS: This large study showed no evidence that current use of an ADHD drug was associated with an increased risk of serious cardiovascular events, although the upper limit of the 95% confidence interval indicated that a doubling of the risk could not be ruled out. However, the absolute magnitude of such an increased risk would be low. (Funded by the Agency for Healthcare Research and Quality and the Food and Drug Administration.).

Changes in cotherapies after initiation of disease-modifying antirheumatic drug therapy in patients with rheumatoid arthritis.

Objective. We hypothesized that initiation of a new disease-modifying antirheumatic drug (DMARD) for treatment of rheumatoid arthritis (RA) would decrease the use of corticosteroids, nonsteroidal antiinflammatory drugs (NSAIDs), and narcotics.Methods. Using administrative databases, we assembled 4 retrospective cohorts of RA patients (1998-2005) and identified 5 groups initiating DMARD regimens: methotrexate (MTX) with (new MTX) or without (first MTX) use of other nonbiologic DMARDs in the previous year; new hydroxychloroquine (HCQ) and/or sulfasalazine (SSZ; new HCQ/SSZ)and new leflunomide (new LEF), both with previous use of MTX; and new tumor necrosis factor α (TNFα) antagonists(new anti-TNF). We compared within-person differences in any use of cotherapies (≥ prescription) between the 6 months before and the 6-12 months after DMARD initiation.Results. Among 32,476 DMARD initiators, the prevalence of corticosteroid, NSAID, and narcotic use increased by 15%, 5%,and 6%, respectively, in the 6 months before initiation compared to the previous 6 months, suggesting worsening of the disease. In the 6-12 months after initiation for most initiator groups, more patients stopped using corticosteroids and NSAIDs than started, with overall decreases of 8.9% (95% confidence interval [95% CI] 8.4-9.4%) for corticosteroids and 12.9% (95%CI 12.3-13.4%) for NSAIDs. The proportion of narcotic users changed little (overall decrease of 2.5%; 95% CI 1.9-3.0%).Conclusion. Use of all 3 cotherapies increased in the 6 months before initiation of new DMARD regimens for RA. Use of corticosteroids and NSAIDs decreased modestly 6-12 months after initiation, but there was only a very small decrease in narcotic use. These differential changes require further study.

Positive predictive value of automated database records for diabetic ketoacidosis (DKA) in children and youth exposed to antipsychotic drugs or control medications: a Tennessee Medicaid Study.

BACKGROUND: Diabetic ketoacidosis (DKA) is a potentially life-threatening complication of treatment with some atypical antipsychotic drugs in children and youth. Because drug-associated DKA is rare, large automated health outcomes databases may be a valuable data source for conducting pharmacoepidemiologic studies of DKA associated with exposure to individual antipsychotic drugs. However, no validated computer case definition of DKA exists. We sought to assess the positive predictive value (PPV) of a computer case definition to detect incident cases of DKA, using automated records of Tennessee Medicaid as the data source and medical record confirmation as a "gold standard." METHODS: The computer case definition of DKA was developed from a retrospective cohort study of antipsychotic-related type 2 diabetes mellitus (1996-2007) in Tennessee Medicaid enrollees, aged 6-24 years. Thirty potential cases with any DKA diagnosis (ICD-9 250.1, ICD-10 E1x.1) were identified from inpatient encounter claims. Medical records were reviewed to determine if they met the clinical definition of DKA. RESULTS: Of 30 potential cases, 27 (90%) were successfully abstracted and adjudicated. Of these, 24 cases were confirmed by medical record review (PPV 88.9%, 95% CI 71.9 to 96.1%). Three non-confirmed cases presented acutely with severe hyperglycemia, but had no evidence of acidosis. CONCLUSIONS: Diabetic ketoacidosis in children and youth can be identified in a computerized Medicaid database using our case definition, which could be useful for automated database studies in which drug-associated DKA is the outcome of interest.

Comparative effectiveness of antibiotic treatment strategies for pediatric skin and soft-tissue infections.

OBJECTIVE: To compare the effectiveness of clindamycin, trimethoprim-sulfamethoxazole, and ß-lactams for the treatment of pediatric skin and soft-tissue infections (SSTIs). METHODS: A retrospective cohort of children 0 to 17 years of age who were enrolled in Tennessee Medicaid, experienced an incident SSTI between 2004 and 2007, and received treatment with clindamycin (reference), trimethoprim-sulfamethoxazole, or a ß-lactam was created. Outcomes included treatment failure and recurrence, defined as an SSTI within 14 days and between 15 and 365 days after the incident SSTI, respectively. Adjusted models stratified according to drainage status were used to estimate the risk of treatment failure and time to recurrence. RESULTS: Among the 6407 children who underwent drainage, there were 568 treatment failures (8.9%) and 994 recurrences (22.8%). The adjusted odds ratios for treatment failure were 1.92 (95% confidence interval [CI]: 1.49-2.47) for trimethoprim-sulfamethoxazole and 2.23 (95% CI: 1.71-2.90) for ß-lactams. The adjusted hazard ratios for recurrence were 1.26 (95% CI: 1.06-1.49) for trimethoprim-sulfamethoxazole and 1.42 (95% CI: 1.19-1.69) for ß-lactams. Among the 41 094 children without a drainage procedure, there were 2435 treatment failures (5.9%) and 5436 recurrences (18.2%). The adjusted odds ratios for treatment failure were 1.67 (95% CI: 1.44-1.95) for trimethoprim-sulfamethoxazole and 1.22 (95% CI: 1.06-1.41) for ß-lactams; the adjusted hazard ratios for recurrence were 1.30 (95% CI: 1.18-1.44) for trimethoprim-sulfamethoxazole and 1.08 (95% CI: 0.99-1.18) for ß-lactams. CONCLUSIONS: Compared with clindamycin, use of trimethoprim-sulfamethoxazole or ß-lactams was associated with increased risks of treatment failure and recurrence. Associations were stronger for those with a drainage procedure.

Performance of disease risk scores, propensity scores, and traditional multivariable outcome regression in the presence of multiple confounders.

Propensity scores are widely used in cohort studies to improve performance of regression models when considering large numbers of covariates. Another type of summary score, the disease risk score (DRS), which estimates disease probability conditional on nonexposure, has also been suggested. However, little is known about how it compares with propensity scores. Monte Carlo simulations were conducted comparing regression models using the DRS and the propensity score with models that directly adjust for all of the individual covariates. The DRS was calculated in 2 ways: from the unexposed population and from the full cohort. Compared with traditional multivariable outcome regression models, all 3 summary scores had comparable performance for moderate correlation between exposure and covariates and, for strong correlation, the full-cohort DRS and propensity score had comparable performance. When traditional methods had model misspecification, propensity scores and the full-cohort DRS had superior performance. All 4 models were affected by the number of events per covariate, with propensity scores and traditional multivariable outcome regression least affected. These data suggest that, for cohort studies for which covariates are not highly correlated with exposure, the DRS, particularly that calculated from the full cohort, is a useful tool.

Use of drugs known to cause fetal harm among women delivering infants in Haiti.

OBJECTIVE: To estimate the prevalence of use of fetal-harm drugs among women who received postpartum care in hospitals in Haiti and to identify groups of women at higher risk for potentially harmful medication exposures. METHODS: Women who received postpartum care in 2 large hospitals in Port-au-Prince, Haiti, from August 18 to December 1, 2008, were surveyed in Creole about their use of medications in pregnancy, including fetal-harm drugs. RESULTS: We surveyed 482 women who had a median age of 26 years. Approximately 75% reported using at least 1 medicine in pregnancy, with the most common being amoxicillin (n = 127), acetaminophen (n = 109), metronidazole (n = 79), and misoprostol (n = 38). More than 13% used fetal-harm drugs, including misoprostol and tetracycline. Unmarried women (adjusted relative risk [RR] 2.2; 95% confidence interval [CI], 1.0-4.7) and separated women (adjusted RR 4.6; CI, 1.8-11.9) were more likely than married women to report use of fetal-harm drugs. In addition, women with 4 or more children were more likely to report use of medications known to cause fetal harm (adjusted RR 4.3; CI, 1.9-9.9). CONCLUSION: Women who delivered infants in Haiti commonly report use of fetal-harm drugs. The public health implications of these findings are broad and relate to complex issues such as pregnancy planning and regulation of medications to prevent potentially harmful exposures.