PURPOSE:Golimumab (GLM), an anti-tumour necrosis factor alpha (anti-TNFα) agent, is indicated for moderate to severe ulcerative colitis (UC). This post-authorisation safety study evaluated the risk of colectomy due to intractable disease and advanced colonic neoplasia (high-grade dysplasia and/or colorectal cancer) under real-world conditions of GLM use. METHODS:This bidirectional cohort study using Spanish ENEIDA registry data (2013-2022) included adults with UC who initiated GLM, other anti-TNFα agents, or thiopurines (TPs). Crude risk analyses-and, when feasible, multivariable models-in cohort and nested case-control designs were performed. For colectomy, we evaluated exposure to GLM only, other anti-TNFα agents, and both (i.e., overlapping exposure). For ACN, we evaluated exposure to GLM, other anti-TNFα agents, and TPs. RESULTS:Sixty-four colectomy cases and 10 ACN cases were identified among patients exposed to GLM (N = 474), other anti-TNFα agents (N = 1737), or TPs (N = 1380). Incidence rates per 1000 person-years and 95% confidence intervals were reported for colectomy (GLM-only [4.4, 1.2-11.2] and other anti-TNFα agents only [12.4, 9.1-16.5]) and ACN (GLM [1.5, 0.2-5.4], other anti-TNFα agents [1.3, 0.5-2.8], and TPs [1.0, 0.3-2.6]). In comparisons excluding overlapping exposure, GLM was not associated with an increased risk of colectomy versus other anti-TNFα agents. GLM was also not associated with an increased risk of ACN versus either comparator. Observed events, especially for ACN, were limited for all exposures. CONCLUSIONS:Findings do not indicate an increased risk of colectomy due to intractable disease or ACN with GLM use versus other therapies for similar disease severity in routine UC care (EUPAS15752).

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.

To evaluate the impact of bullous pemphigoid (BP) on healthcare resource utilization (HCRU) and costs in a retrospective analysis of 2015–2019 US administrative health insurance claims data (MarketScan).

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-naive 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.

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. The aim was to study the association between DL exposure and incidence of first seizure. 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. 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). 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.

Chronic cough (CC) is a condition resulting in negative physical, emotional and social outcomes. Objective measures to quantify frequency of cough are necessary in clinical trials to examine treatment efficacy; however, the degree of cough reduction required to be considered a minimal clinically important difference (MCID) has not been defined. The objective was to define the MCID for objective cough counts (OCCs). Pooled data from a Phase 2 RCT of an investigational treatment for CC were analyzed. Enrollees were non-smokers, had refractory/unexplained CC for ≥1yr, and baseline cough severity VAS ≥40mm. The 24-hour OCC (VitaloJAK™, Vitalograph, Buckingham, UK; Baseline, Week4) and Patient Global Impression of Change (PGIC; Week4) data were analyzed. MCIDs were defined using distribution-based (MCID-D; ½ standard deviation and standard error of measurement) and anchor-based (MCID-A; receiver operating characteristic curves [ROC] and PGIC) analyses. Analyses from n=253 participants (mean age 60.2; 76% female) resulted in MCID-D estimates of 11.3% to 19.7% for OCC. MCID-A/ROC analyses indicated that mean OCC reduction at Week4 of 38% had the best sensitivity/specificity for predicting PGIC responses of "somewhat improved," "improved," or "very much improved". Among those reporting themselves as "somewhat improved" and "improved" vs. "very much improved," the corresponding %reductions in OCC were 29.7% and 57.5%, respectively. Taken together, these results provide guidance on the degree of change in OCC that can be considered clinically meaningful to help guide treatment decisions and drug development. Specifically, clinicians may consider OCC reductions in the range of 20-30% as the MCID.

Background: Clinical trials of antitussive therapies increasingly use sound recording devices to assess cough frequency as an objective measure of efficacy. The VitaloJAK™ (Vitalograph, Buckingham, UK) comprises a digital sound recorder and a computer algorithm to filter out silence and most non-cough sounds from 24-h ambulatory recordings. Trained human cough analysts (CAs) listen to and inspect audio waveforms in the filtered recordings, tagging individual coughs which are tallied automatically. Recordings unsuitable for filtering are analyzed for the full 24 h. The reliability of Vitalograph CAs has not been previously documented. Objective: To describe the intra- and inter-rater reliability of cough frequency measurements assessed by Vitalograph CAs from filtered 24-h cough recordings. Methods: The recordings came from Phase 2 trials of gefipixant in patients with chronic cough. For intra-rater reliability, 13 CAs reviewed 1 randomly-selected recording two times, at least 1 month apart. For inter-rater reliability, 11 recordings were randomly selected and each was reviewed by 5 randomly-selected CAs. Intra-class correlations (ICC) to assess for absolute agreement were used to gauge reliability. Results: Across the 81 recording assessments, the median 24-h cough count was 356 (IQR: 167, 656). ICCs for both intra- and inter-rater reliability were found to be outstanding [0.999 (95% CI: 0.996, 1.000 and 0.999 (95% CI:0.997, 1.000), respectively]. Conclusions: The cough frequencies assessed by Vitalograph CAs were highly reliable. These results support the use of the VitaloJAK cough monitoring system to assess cough frequency in clinical trials.

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.

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.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.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.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.

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.

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 χ 2 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. Infect Control Hosp Epidemiol 2015;36(8):907–914

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Abstract Background: We developed and validated an algorithm to evaluate pure red cell aplasia (PRCA) incidence in chronic hepatitis C (CHC) patients in a large observational database. Methods:

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. Birth Defects Research (Part A) 103:269–275, 2015. © 2015 Wiley Periodicals, Inc.