Characteristics, treatment patterns, health care resource utilization and costs in patients with bullous pemphigoid: A retrospective analysis of US health insurance claims data.

Background: Real-world data describing the impact of incident bullous pemphigoid (BP) on patients and health care resource utilization (HCRU) are limited. Objective: To examine characteristics, treatment patterns, HCRU, and costs for incident BP. Methods: Retrospective analysis of 2015 to 2019 US health insurance claims for patients ≥18 years with an incident BP diagnosis. Patients with BP were matched to those without on demographic and clinical characteristics. Statistics were descriptive. Results: The mean Charlson Comorbidity Index score was higher for patients with BP (n = 1108) than without (n = 4621) at baseline (mean [SD]: 3.3 [2.7] vs 2.8 [2.4]) and during follow-up (5.0 [4.9] vs 3.7 [3.0]). Hypertension, diabetes, skin ulcers, chronic pulmonary disease, dyslipidemia, sleep disorders, and congestive heart failure were higher with BP. Most patients with BP received antibiotics (>80%) and/or corticosteroids (>90%). Hospitalizations were more common (44.0% vs 17.1%) and monthly all-cause health care costs more than double ($3214 vs $1353) in patients with BP than without. Limitations: Diagnoses were based on billing codes. HCRU claims data may not reflect the true number of encounters. Conclusion: Incident BP is associated with considerable morbidity, HCRU, and costs. More effective, targeted treatments are needed to improve quality of life, while minimizing exposure to systemic corticosteroids.

Cardiovascular events and all-cause mortality in patients with chronic obstructive pulmonary disease using olodaterol and other long-acting beta2-agonists.

PURPOSE: We examined the effect of olodaterol on the risk of myocardial ischaemia, cardiac arrhythmia, and all-cause mortality compared with use of other long-acting beta2-agonists (LABAs). Channelling bias was also explored. METHODS: This Danish population-based cohort study used data linked from registries of hospital diagnoses, outpatient dispensings, and deaths. It included patients (aged ≥40 years) with a diagnosis of chronic obstructive pulmonary disease (COPD) who initiated olodaterol or another LABA. Using matching and propensity score (PS) stratification, we calculated adjusted incidence rate ratios (IRRs) using Poisson regression, followed by several additional analyses to evaluate and control channelling bias. RESULTS: The IRRs of cardiac arrhythmias or myocardial ischaemia among users of olodaterol (n = 14 239) compared to users of other LABAs (n = 51 167) ranged from 0.96 to 1.65 in various analyses, although some estimates had low precision. Initial analysis suggested an increased risk for death with olodaterol compared with other LABAs (IRR, 1.63; 95% CI, 1.44-1.84). Because olodaterol prescribing was associated with COPD severity, the mortality association was attenuated by using different methods of tighter confounding control: the IRRs were 1.26 (95% CI, 0.97-1.64) among LABA-naïve LABA/LAMA users without recent COPD hospitalisation; 1.27 (95% CI, 1.03-1.57) in a population with additional trimming from the tails of the PS distribution; and 1.32 (95% CI, 1.19-1.48) after applying overlap-weights analysis. CONCLUSIONS: Olodaterol users had a similar risk for cardiac arrhythmias or myocardial ischaemia as other LABA users. The observed excess all-cause mortality associated with olodaterol use could be due to uncontrolled channelling bias.

Desloratadine Exposure and Incidence of Seizure: A Nordic Post-authorization Safety Study Using a New-User Cohort Study Design, 2001-2015.

INTRODUCTION: A small number of adverse events of seizure in patients using desloratadine (DL) have been reported. The European Medicines Agency requested a post-authorization safety study to investigate whether there is an association between DL exposure and seizure. OBJECTIVE: The aim was to study the association between DL exposure and incidence of first seizure. METHODS: A new-user cohort study of individuals redeeming a first-ever prescription of DL in Denmark, Finland, Norway, and Sweden in 2001-2015 was conducted. DL exposure was defined as days' supply plus a 4-week grace period. DL unexposed periods were initiated 27 weeks after DL prescription redemption. Poisson regression was used to estimate the adjusted incidence rate and adjusted incidence rate ratio (aIRR) of incident seizure. RESULTS: A total of 1,807,347 first-ever DL users were included in the study, with 49.3% male and a mean age of 29.5 years at inclusion; 20.3% were children aged 0-5 years. The adjusted incidence rates of seizure were 21.7 and 31.6 per 100,000 person-years during DL unexposed and exposed periods, respectively. A 46% increased incidence rate of seizure was found during DL exposed periods (aIRR = 1.46, 95% confidence interval [CI] 1.34-1.59). The aIRR ranged from 1.85 (95% CI 1.65-2.08) in children aged 0-5 years to 1.01 in adults aged 20 years or more (95% CI 0.85-1.19). CONCLUSION: This study found an increased incidence rate of seizure during DL exposed periods as compared to unexposed periods among individuals younger than 20 years. No difference in incidence rate of seizure was observed in adults between DL exposed and unexposed.

Risk Factors for Surgical Site Infection After Cholecystectomy.

BACKGROUND: There are limited data on risk factors for surgical site infection (SSI) after open or laparoscopic cholecystectomy. METHODS: A retrospective cohort of commercially insured persons aged 18-64 years was assembled using International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) procedure or Current Procedural Terminology, 4th edition codes for cholecystectomy from December 31, 2004 to December 31, 2010. Complex procedures and patients (eg, cancer, end-stage renal disease) and procedures with pre-existing infection were excluded. Surgical site infections within 90 days after cholecystectomy were identified by ICD-9-CM diagnosis codes. A Cox proportional hazards model was used to identify independent risk factors for SSI. RESULTS: Surgical site infections were identified after 472 of 66566 (0.71%) cholecystectomies; incidence was higher after open (n = 51, 4.93%) versus laparoscopic procedures (n = 421, 0.64%; P < .001). Independent risk factors for SSI included male gender, preoperative chronic anemia, diabetes, drug abuse, malnutrition/weight loss, obesity, smoking-related diseases, previous Staphylococcus aureus infection, laparoscopic approach with acute cholecystitis/obstruction (hazards ratio [HR], 1.58; 95% confidence interval [CI], 1.27-1.96), open approach with (HR, 4.29; 95% CI, 2.45-7.52) or without acute cholecystitis/obstruction (HR, 4.04; 95% CI, 1.96-8.34), conversion to open approach with (HR, 4.71; 95% CI, 2.74-8.10) or without acute cholecystitis/obstruction (HR, 7.11; 95% CI, 3.87-13.08), bile duct exploration, postoperative chronic anemia, and postoperative pneumonia or urinary tract infection. CONCLUSIONS: Acute cholecystitis or obstruction was associated with significantly increased risk of SSI with laparoscopic but not open cholecystectomy. The risk of SSI was similar for planned open and converted procedures. These findings suggest that stratification by operative factors is important when comparing SSI rates between facilities.

Modification of claims-based measures improves identification of comorbidities in non-elderly women undergoing mastectomy for breast cancer: a retrospective cohort study.

BACKGROUND: Accurate identification of underlying health conditions is important to fully adjust for confounders in studies using insurer claims data. Our objective was to evaluate the ability of four modifications to a standard claims-based measure to estimate the prevalence of select comorbid conditions compared with national prevalence estimates. METHODS: In a cohort of 11,973 privately insured women aged 18-64 years with mastectomy from 1/04-12/11 in the HealthCore Integrated Research Database, we identified diabetes, hypertension, deficiency anemia, smoking, and obesity from inpatient and outpatient claims for the year prior to surgery using four different algorithms. The standard comorbidity measure was compared to revised algorithms which included outpatient medications for diabetes, hypertension and smoking; an expanded timeframe encompassing the mastectomy admission; and an adjusted time interval and number of required outpatient claims. A χ2 test of proportions was used to compare prevalence estimates for 5 conditions in the mastectomy population to national health survey datasets (Behavioral Risk Factor Surveillance System and the National Health and Nutrition Examination Survey). Medical record review was conducted for a sample of women to validate the identification of smoking and obesity. RESULTS: Compared to the standard claims algorithm, use of the modified algorithms increased prevalence from 4.79 to 6.79 % for diabetes, 14.75 to 24.87 % for hypertension, 4.23 to 6.65 % for deficiency anemia, 1.78 to 12.87 % for smoking, and 1.14 to 6.31 % for obesity. The revised estimates were more similar, but not statistically equivalent, to nationally reported prevalence estimates. Medical record review revealed low sensitivity (17.86 %) to capture obesity in the claims, moderate negative predictive value (NPV, 71.78 %) and high specificity (99.15 %) and positive predictive value (PPV, 90.91 %); the claims algorithm for current smoking had relatively low sensitivity (62.50 %) and PPV (50.00 %), but high specificity (92.19 %) and NPV (95.16 %). CONCLUSIONS: Modifications to a standard comorbidity measure resulted in prevalence estimates that were closer to expected estimates for non-elderly women than the standard measure. Adjustment of the standard claims algorithm to identify underlying comorbid conditions should be considered depending on the specific conditions and the patient population studied.

Development of a Risk Prediction Model to Individualize Risk Factors for Surgical Site Infection After Mastectomy.

BACKGROUND: Little data are available regarding individual patients' risk of surgical site infection (SSI) following mastectomy with or without immediate reconstruction. Our objective was to develop a risk prediction model for mastectomy-related SSI. METHODS: Using commercial claims data, we established a cohort of women <65 years of age who underwent a mastectomy from 1 January 2004-31 December 2011. International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes were used to identify SSI within 180 days after surgery. SSI risk factors were determined with multivariable logistic regression using derivation data from 2004-2008 and validated with 2009-2011 data using discrimination and calibration measures. RESULTS: In the derivation cohort, 595 SSIs were identified in 7607 (7.8 %) women, and 396 SSIs were coded in 4366 (9.1 %) women in the validation cohort. Independent risk factors for SSIs included rural residence, rheumatologic disease, depression, diabetes, hypertension, liver disease, obesity, pre-existing pneumonia or urinary tract infection, tobacco use disorder, smoking-related diseases, bilateral mastectomy, and immediate reconstruction. Receipt of home healthcare was associated with lower risk. The model performed equally in the validation cohort per discrimination (C-statistics 0.657 and 0.649) and calibration (Hosmer-Lemeshow p = 0.091 and 0.462 for derivation and validation, respectively). Three risk strata were created based on predicted SSI risk, which demonstrated good correlation with the proportion of observed infections in the strata. CONCLUSIONS: We developed and internally validated an SSI risk prediction model that can be used to counsel women with regard to their individual risk of SSI post-mastectomy. Immediate reconstruction, diabetes, and smoking-related diseases were important risk factors for SSI in this non-elderly population of women undergoing mastectomy.

Incidence of Surgical Site Infection Following Mastectomy With and Without Immediate Reconstruction Using Private Insurer Claims Data.

OBJECTIVE: The National Healthcare Safety Network classifies breast operations as clean procedures with an expected 1%-2% surgical site infection (SSI) incidence. We assessed differences in SSI incidence following mastectomy with and without immediate reconstruction in a large, geographically diverse population. DESIGN: Retrospective cohort study. PATIENTS: Commercially insured women aged 18-64 years with ICD-9-CM procedure or CPT-4 codes for mastectomy from January 1, 2004 through December 31, 2011 METHODS: Incident SSIs within 180 days after surgery were identified by ICD-9-CM diagnosis codes. The incidences of SSI after mastectomy with and without immediate reconstruction were compared using the χ2 test. RESULTS: From 2004 to 2011, 18,696 mastectomy procedures among 18,085 women were identified, with immediate reconstruction in 10,836 procedures (58%). The incidence of SSI within 180 days following mastectomy with or without reconstruction was 8.1% (1,520 of 18,696). In total, 49% of SSIs were identified within 30 days post-mastectomy, 24.5% were identified 31-60 days post-mastectomy, 10.5% were identified 61-90 days post-mastectomy, and 15.7% were identified 91-180 days post-mastectomy. The incidences of SSI were 5.0% (395 of 7,860) after mastectomy only, 10.3% (848 of 8,217) after mastectomy plus implant, 10.7% (207 of 1,942) after mastectomy plus flap, and 10.3% (70 of 677) after mastectomy plus flap and implant (P<.001). The SSI risk was higher after bilateral compared with unilateral mastectomy with immediate reconstruction (11.4% vs 9.4%, P=.001) than without (6.1% vs 4.7%, P=.021) immediate reconstruction. CONCLUSIONS: SSI incidence was twice that after mastectomy with immediate reconstruction than after mastectomy alone. Only 49% of SSIs were coded within 30 days after operation. Our results suggest that stratification by procedure type facilitates comparison of SSI rates after breast operations between facilities.

Topiramate use during pregnancy and major congenital malformations in multiple populations.

BACKGROUND: We measured birth prevalence of major congenital malformations (MCMs) after topiramate use during pregnancy to screen for a possible signal of increased risk. METHODS: Using four healthcare databases, we identified three cohorts of pregnant women: cohort 1, used topiramate during the first trimester; cohort 2, used topiramate or another antiepileptic drug previously but not during pregnancy; and cohort 3, were pregnant and did not use topiramate but had indications for use individually matched to those of users. Cohort 1 was compared with cohorts 2 and 3. MCMs were a code for any major congenital malformation dated within 30 days of the delivery date on the mother's claims or within 365 days after infant birth date, excluding a genetic or syndromic basis, and with procedure or healthcare usage consistent with the MCM diagnosis code in the 365 days after infant birth. RESULTS: Of the 10 specific common MCMs evaluated, 1 (conotruncal heart defects) had a prevalence ratio greater than 1.5 for both primary comparisons, and 4 (ventricular septal defect, atrial septal defect, hypospadias, coarctation of the aorta) had a prevalence ratio greater than 1.5 for one of the two comparisons. Following screening of organ systems with elevated MCMs, the prevalence ratio was greater than 1.5 for patent ductus arteriosus in both comparisons and for obstructive genitourinary defects in one comparison. CONCLUSION: To evaluate a large number of MCMs across many pregnancies, we used crude methods for detecting potential signals. Therefore, these results should be seen as potential signals, not causal.

Stratification of surgical site infection by operative factors and comparison of infection rates after hernia repair.

OBJECTIVE: To investigate whether operative factors are associated with risk of surgical site infection (SSI) after hernia repair. DESIGN: Retrospective cohort study. Patients Commercially insured enrollees aged 6 months-64 years with International Classification of Diseases, Ninth Revision, Clinical Modification procedure or Current Procedural Terminology, fourth edition, codes for inguinal/femoral, umbilical, and incisional/ventral hernia repair procedures from January 1, 2004, through December 31, 2010. METHODS: SSIs within 90 days after hernia repair were identified by diagnosis codes. The χ2 and Fisher exact tests were used to compare SSI incidence by operative factors. RESULTS: A total of 119,973 hernia repair procedures were analyzed. The incidence of SSI differed significantly by anatomic site, with rates of 0.45% (352/77,666) for inguinal/femoral, 1.16% (288/24,917) for umbilical, and 4.11% (715/17,390) for incisional/ventral hernia repair. Within anatomic sites, the incidence of SSI was significantly higher for open versus laparoscopic inguinal/femoral (0.48% [295/61,142] vs 0.34% [57/16,524], P=.020) and incisional/ventral (4.20% [701/16,699] vs 2.03% [14/691], P=.005) hernia repairs. The rate of SSI was higher following procedures with bowel obstruction/necrosis than procedures without obstruction/necrosis for open inguinal/femoral (0.89% [48/5,422] vs 0.44% [247/55,720], P<.001) and umbilical (1.57% [131/8,355] vs 0.95% [157/16,562], P<.001), but not incisional/ventral hernia repair (4.01% [224/5,585] vs 4.16% [491/11,805], P=.645). CONCLUSIONS: The incidence of SSI was highest after open procedures, incisional/ventral repairs, and hernia repairs with bowel obstruction/necrosis. Stratification of hernia repair SSI rates by some operative factors may facilitate accurate comparison of SSI rates between facilities.

Increased Risk of Surgical Site Infection Among Breast-Conserving Surgery Re-excisions.

PURPOSE: The aim of this study was to determine the risk of surgical site infection (SSI) after primary breast-conserving surgery (BCS) versus re-excision among women with carcinoma in situ or invasive breast cancer. METHODS: We established a retrospective cohort of women aged 18-64 years with International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) procedure or Current Procedural Terminology, 4th edition (CPT-4) codes for BCS from 29 June 2004 to 31 December 2010. Prior insurance plan enrollment of at least 180 days was required to establish the index BCS; subsequent re-excisions within 180 days were identified. SSIs occurring 2-90 days after BCS were identified by ICD-9-CM diagnosis codes. The attributable surgery was defined based on SSI onset compared with the BCS date(s). A χ (2) test and generalized estimating equations model were used to compare the incidence of SSI after index and re-excision BCS procedures. RESULTS: Overall, 23,001 women with 28,827 BCSs were identified; 23.2 % of women had more than one BCS. The incidence of SSI was 1.82 % (418/23,001) for the index BCS and 2.44 % (142/5,826) for re-excision BCS (p = 0.002). The risk of SSI after re-excision remained significantly higher after accounting for multiple procedures within a woman (odds ratio 1.34, 95 % confidence interval 1.07-1.68). CONCLUSIONS: Surgeons need to be aware of the increased risk of SSI after re-excision BCS compared with the initial procedure. Our results suggest that risk adjustment of SSI rates for re-excision would allow for better comparison of BCS SSI rates between institutions.

Can additional information be obtained from claims data to support surgical site infection diagnosis codes?

OBJECTIVE: International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis codes are increasingly used to identify healthcare-associated infections, often with insufficient evidence demonstrating validity of the codes used. Absent medical record verification, we sought to confirm a claims algorithm to identify surgical site infections (SSIs) by examining the presence of clinically expected SSI treatment. METHODS: We performed a retrospective cohort study, using private insurer claims data from persons less than 65 years old with ICD-9-CM procedure or Current Procedure Terminology (CPT-4) codes for anterior cruciate ligament (ACL) reconstruction from January 2004 through December 2010. SSIs occurring within 90 days after ACL reconstruction were identified by ICD-9-CM diagnosis codes. Antibiotic utilization, surgical treatment, and microbiology culture claims within 14 days of SSI codes were used as evidence to support the SSI diagnosis. RESULTS: Of 40,702 procedures, 401 (1.0%) were complicated by SSI, 172 (0.4%) of which were specifically identified as septic arthritis. Most SSIs were associated with an inpatient admission (232/401 [58%]), and/or surgical procedure(s) for treatment (250/401 [62%]). Temporally associated antibiotics, surgical treatment procedures, and cultures were present for 84% (338/401), 61% (246/401), and 59% (238/401), respectively. Only 5.7% (23/401) of procedures coded for SSI after the procedure had no antibiotics, surgical treatments, or cultures within 14 days of the SSI claims. CONCLUSIONS: More than 94% of patients identified by our claims algorithm as having an SSI received clinically expected treatment for infection, including antibiotics, surgical treatment, and culture, suggesting that this algorithm has very good positive predictive value. This method may facilitate retrospective SSI surveillance and comparison of SSI rates across facilities and providers.

Provider collaboration: cohesion, constellations, and shared patients.

BACKGROUND: There is a natural assumption that quality and efficiency are optimized when providers consistently work together and share patients. Diversity in composition and recurrence of groups that provide face-to-face care to the same patients has not previously been studied. OBJECTIVE: Claims data enable identification of the constellation of providers caring for a single patient. To indirectly measure teamwork and provider collaboration, we measure recurrence of provider constellations and cohesion among providers. DESIGN: Retrospective analysis of commercial healthcare claims from a single insurer. PARTICIPANTS: Patients with claims for office visits and their outpatient providers. To maximize capture of provider panels, the cohort was drawn from the four regions with the highest plan coverage. Regional outpatient provider networks were constructed with providers as nodes and number of shared patients as links. MAIN MEASURES: Measures of cohesion and stability of provider constellations derived from the networks of providers to quantify patient sharing. RESULTS: For 10,325 providers and their 521,145 patients, there were 2,641,933 collaborative provider pairs sharing at least one patient. Fifty-four percent only shared a single patient, and 19 % shared two. Of 15,449,835 unique collaborative triads, 92 % shared one patient, 5 % shared two, and 0.2 % shared ten or more. Patient constellations had a median of four providers. Any precise constellation recurred rarely-89 % with exactly two providers shared just one patient and only 4 % shared over two; 97 % of constellations with exactly three providers shared just one patient. Four percent of constellations with 2+ providers were not at all cohesive, sharing only the hub patient. In the remaining constellations, a median of 93 % of provider pairs shared at least one additional patient beyond the hub patient. CONCLUSION: Stunning variability in the constellations of providers caring for patients may challenge underlying assumptions about the current state of teamwork in healthcare.

Topiramate use in pregnancy and the birth prevalence of oral clefts.

PURPOSE: First marketed in the USA in 1996, topiramate (TPM) is an antiepileptic drug later approved for migraine prophylaxis, and in 2012 for weight loss in combination with phentermine. Some studies indicate an elevated prevalence of oral cleft (OC) in infants exposed to TPM in utero. We evaluated the association between TPM use in early pregnancy and the risk of OC. METHODS: This retrospective cohort study used 1997-2011 automated data from four sources: HealthCore and OptumInsight (commercial insurance claims), Truven Health (Medicaid claims), and Kaiser Permanente Northern California Region (electronic medical records). We compared the prevalence of OCs in infants of women exposed to TPM in the first trimester (TPM cohort) with the prevalence in infants of women formerly exposed to TPM or other antiepileptic drugs (formerly exposed [FE] cohort) and infants of women with similar medical profiles (SMPs) to the TPM cohort that were not exposed to TPM (SMP cohort). To control for confounding, we used stratification and standardization for individual variables and propensity score deciles. RESULTS: The birth prevalence of OCs was 0.36% (7/1945) in the TPM cohort, 0.14% (20/13 512) in the FE cohort, and 0.07% (9/13 614) in the SMP cohort. Standardized by site, the prevalence ratio (PR) for TPM versus FE was 2.5 (95% CI: 1.0-6.0) and for TPM versus SMP was 5.4 (95% CI: 2.0-14.6). Adjustment for covariates one at a time or by propensity score yielded similar results. CONCLUSION: Consistent with other recent epidemiologic research, first-trimester TPM exposure was associated with an elevated birth prevalence of OC.

Risk of ischemic cerebrovascular and coronary events in adult users of anticonvulsant medications in routine care settings.

BACKGROUND: Older-generation anticonvulsants that highly induce cytochrome P450 enzyme system activity produce metabolic abnormalities that may increase cardiovascular risk. The objective of this study was to evaluate the risk of ischemic cerebrovascular and coronary events in adult new users of anticonvulsants that highly induce cytochrome P450 activity compared with other anticonvulsant agents, as observed in a routine care setting. METHODS AND RESULTS: This was a cohort study of patients 40 to 64 years old from the HealthCore Integrated Research Database who had initiated an anticonvulsant medication between 2001 and 2006 and had no recorded major coronary or cerebrovascular condition in the 6 months before treatment initiation. Propensity score (PS) matching was used to evaluate ischemic cerebrovascular and coronary risk among anticonvulsant new users. High-dimensional propensity score (hdPS)-matched analyses were used to confirm adjusted findings. The study identified 913 events in 166 031 unmatched new treatment episodes with anticonvulsant drugs. In a PS-matched population of 22 864 treatment episodes, the rate ratio (RR) for ischemic coronary or cerebrovascular events associated with highly inducing agents versus other agents was 1.22 (95% CI, 0.90-1.65). The RR moved to 0.99 (95% CI, 0.73-1.33) with adjustment for hdPS matching (RR, 1.47; 95% CI, 0.95-2.28 for cerebrovascular events; RR, 0.70; 95% CI, 0.47-1.05 for coronary events). CONCLUSIONS: In this exploratory analysis, there was no evidence of a consistent and statistically significant effect of initiating anticonvulsants that highly induce cytochrome P450 activity on ischemic coronary or cerebrovascular outcomes compared with other agents, given routine care utilization patterns.

Risk of malignancy in children with juvenile idiopathic arthritis not treated with biologic agents.

OBJECTIVE: To estimate the relative risk of incident cancer diagnosis among patients with juvenile idiopathic arthritis (JIA) compared to patients without JIA. METHODS: A cohort of biologics-naive patients diagnosed with JIA between 1998 and 2007 and a matched cohort of comparators without JIA were assembled from the PharMetrics Patient-Centric Database. The primary outcome was any incident malignancy, excluding nonmelanoma skin cancer and carcinoma in situ. Claims profiles of patients with any cancer-related diagnosis codes were reviewed to determine outcomes. Incidence rates and 95% confidence intervals (95% CIs) of cancer were calculated and compared between cohorts using Cox proportional hazards regression. Standardized incidence ratios (SIRs) for each cohort compared to the general population were calculated using reference rates from the US Surveillance, Epidemiology, and End-Results (SEER) program. RESULTS: The JIA and non-JIA cohorts included 3,605 and 37,689 patients, respectively, with a mean age of 11 years. The incidence rates of cancer were 67.0 (95% CI 1.3-132.5) cases/100,000 person-years (PY) for JIA and 23.2 (95% CI 12.2-34.2) cases/100,000 PY for non-JIA. The risk of cancer associated with biologics-naive JIA was elevated (hazard ratio 2.8, 95% CI 0.9-8.3). The JIA cohort had a significantly elevated SIR of 4.0 (95% CI 2.6-6.0); the non-JIA cohort SIR was not significantly above SEER rates (SIR 1.4, 95% CI 0.6-2.6). CONCLUSION: We found a nearly 3-fold increased risk of cancer in biologics-naive JIA patients, which approached significance despite the small number of outcomes. This finding suggests an elevated underlying risk of cancer in this disease population.

Clinical importance of the drug interaction between statins and CYP3A4 inhibitors: a retrospective cohort study in The Health Improvement Network.

OBJECTIVE: To compare the relative hazard of muscle toxicity, renal dysfunction, and hepatic dysfunction associated with the drug interaction between statins and concomitant medications that inhibit the CYP3A4 isoenzyme. BACKGROUND: Although statins provide important clinical benefits related to mitigating the risk of cardiovascular events, this class of medications also has the potential for severe adverse reactions. The risk for adverse events may be potentiated by concomitant use of medications that interfere with statin metabolism. METHODS: Data from The Health Improvement Network (THIN) from 1990 to 2008 were used to conduct a retrospective cohort study. Cohorts were created to evaluate each outcome (muscle toxicity, renal dysfunction, and hepatic dysfunction) independently. Each cohort included new statin initiators and compared the relative hazard of the outcome. The interaction ratio (I*R) was the primary contrast of interest. The I*R represents the relative effect of each statin type (statin 3A4 substrate vs. statin non-3A4 substrate) with a CYP3A4 inhibitor, independent of the effect of the statin type without a CYP3A4 inhibitor. We adjusted for confounding variables using the multinomial propensity score. RESULTS: The median follow-up time per cohort was 1.5 years. There were 7889 muscle toxicity events among 362,809 patients and 792,665 person-years. The adjusted muscle toxicity I*R was 1.22 (95% confidence interval [CI] = 0.90-1.66). There were 1449 renal dysfunction events among 272,099 patients and 574,584 person-years. The adjusted renal dysfunction I*R was 0.91 (95%CI = 0.58-1.44). There were 1434 hepatic dysfunction events among 367,612 patients and 815,945 person-years. The adjusted hepatic dysfunction I*R was 0.78 (95%CI = 0.45-1.31). CONCLUSIONS: Overall, this study found no difference in the relative hazard of muscle toxicity, renal dysfunction, or hepatic dysfunction for patients prescribed a statin 3A4 substrate versus a statin non-3A4 substrate with CYP3A4 inhibitor concomitancy.

Recombinant human bone morphogenetic protein-2 and pancreatic cancer: a retrospective cohort study.

PURPOSE: To assess whether use of recombinant human bone morphogenetic protein-2 (rhBMP-2) during lumbar spinal fusion surgery affects subsequent risk of pancreatic cancer. METHODS: Using US Medicare claims data, we performed a retrospective cohort study of patients who underwent lumbar spinal fusion surgery between October 2003 and December 2005. The study population, all >66 years, was identified from procedure codes for lumbar fusion. Claims for a bone morphogenetic protein (BMP) served as a proxy for rhBMP-2 exposure (another BMP product shared the same code). Pancreatic cancer was identified from claims indicating this diagnosis and cancer-specific therapy. We used Cox proportional hazard regression to estimate hazard ratios (HRs) and 95%CIs. RESULTS: Of the 93,654 patients in the study, the mean age was 75 years, and 16.5% had claims for BMP. During a mean 1.4 years of follow-up, 91 patients were diagnosed with pancreatic cancer (eight in the BMP- and 83 in the non-BMP cohort). Consistent with previous research, pancreatic cancer was associated with older age, male gender, black race, and diabetes mellitus. Compared to those who did not receive BMP, patients exposed to BMP were not at increased risk of pancreatic cancer (adjusted HR=0.70, 95%CI: 0.34-1.45). A chart review substudy validated the exposure measure; 52/55 patients with claims for BMP received rhBMP-2. CONCLUSIONS: In this large study of elderly patients who underwent lumbar fusion surgery, exposure to BMP was not associated with an increased risk of pancreatic cancer.

Use of venlafaxine compared with other antidepressants and the risk of sudden cardiac death or near death: a nested case-control study.

OBJECTIVE: To assess whether use of the antidepressant venlafaxine is associated with an increased risk of sudden cardiac death or near death compared with other commonly used antidepressants. DESIGN: Population based observational study. SETTING: We did a nested case-control analysis within a new user cohort formed using the United Kingdom General Practice Research Database. PARTICIPANTS: New users of venlafaxine, fluoxetine, citalopram, or dosulepin on or after 1 January 1995, aged 18 to 89 years, with a diagnosis of depression or anxiety. Participants were followed-up until February 2005, or the occurrence of sudden cardiac death or near death, identified from medical records indicating non-fatal acute ventricular tachyarrhythmia, sudden death due to cardiac causes, or out of hospital deaths from acute ischaemic cardiac events. For each case, 30 controls were selected matched for age, sex, calendar time, and indication. We used conditional logistic regression to calculate the adjusted odds ratio of sudden cardiac death or near death associated with current use of venlafaxine compared with current use of fluoxetine, citalopram or dosulepin. RESULTS: 207 384 participants were followed-up for an average of 3.3 years. There were 568 cases of sudden cardiac death or near death, which were matched to 14 812 controls. The adjusted odds ratio of sudden cardiac death or near death associated with venlafaxine use was 0.66 (95% confidence interval 0.38 to 1.14) relative to fluoxetine use, whereas compared with citalopram it was 0.89 (0.50 to 1.60) and with dosulepin 0.83 (0.46 to 1.52). CONCLUSIONS: In this large, population based study, the use of venlafaxine was not associated with an excess risk of sudden cardiac death or near death compared with fluoxetine, dosulepin, or citalopram, in patients with depression or anxiety.

Untreated hypertension and the emergency department: a chance to intervene?

OBJECTIVES: Untreated hypertension (HTN) is a major public health problem. Screening for untreated HTN in the emergency department (ED) may lead to appropriate treatment of more patients. The authors investigated the accuracy of identifying HTN in the ED, the proportion of ED patients with untreated HTN, patient characteristics predicting untreated HTN, and provider documentation of untreated HTN. METHODS: The authors performed a retrospective cross-sectional study on a random sample of 2,061 adults treated at an urban academic ED. The validity of six candidate definitions of HTN in the ED was assessed in a subsample using outpatient clinic records as the reference standard. "Untreated HTN" was HTN without a HTN medication listed in the ED history. "Documentation of untreated HTN was documentation of HTN as a visit problem, specific referral for HTN, or ED discharge with a HTN" information sheet or a HTN medication. Multivariable logistic regression was used to determine associations. RESULTS: The preferred definition of HTN in the ED had sensitivity of 86% (95% confidence interval [CI] = 80% to 90%), specificity of 78% (95% CI = 69% to 85%), and accuracy of 83% (95% CI = 78% to 87%). Of the 42% (95% CI = 40% to 44%) of ED patients with HTN, 43% (95% CI = 39% to 46%) had untreated HTN. Patients who were younger and male, without primary care physicians, with fewer prior ED visits, and without cardiovascular comorbidities, had higher odds of untreated HTN. Of those with untreated HTN, 8% (95% CI = 5% to 11%) had their untreated HTN documented. CONCLUSIONS: Untreated HTN was common in the ED but rarely documented. Providers can use ED blood pressures along with patient characteristics to identify those with untreated HTN for referral to primary care.