Relative environmental and social disadvantage in patients with idiopathic pulmonary fibrosis.

BACKGROUND: Air pollution exposure is associated with disease severity, progression and mortality in patients with idiopathic pulmonary fibrosis (IPF). Combined impacts of environmental and socioeconomic factors on outcomes in patients with IPF are unknown. The objectives of this study were to characterise the relationships between relative environmental and social disadvantage with clinical outcomes in patients with IPF. METHODS: Patients with IPF were identified from a longitudinal database at University of California, San Francisco. Residential addresses were geocoded and linked to the CalEnviroScreen 3.0 (CES), a tool that quantifies environmental burden in California communities, combining population, environmental and pollution vulnerability into individual and composite scores (higher scores indicating greater disadvantage). Unadjusted and adjusted linear and logistic regression and Fine and Gray proportional hazards models were used. RESULTS: 603 patients were included. Higher CES was associated with lower baseline forced vital capacity ( ß =-0.073, 95% CI -0.13 to -0.02; p=0.006) and diffusion capacity of the lung for carbon monoxide ( ß =-0.11, 95% CI -0.16 to -0.06; p<0.001). Patients in the highest population vulnerability quartile were less likely to be on antifibrotic therapy (OR=0.33; 95% CI 0.18 to 0.60; p=0.001) at time of enrolment, compared with those in the lowest quartile. An association between CES and mortality was suggested, but sensitivity analyses demonstrated inconsistent results. Relative disadvantage of the study cohort appeared lower compared with the general population. CONCLUSIONS: Higher environmental exposures and vulnerability were associated with lower baseline lung function and lower antifibrotic use, suggesting that relative socioenvironmental disadvantage has meaningful impacts on patients with IPF.

Association between antiseizure medications and quality of life in epilepsy: A mediation analysis.

OBJECTIVE: The relationship between antiseizure medications (ASMs), which improve health outcomes by controlling seizures, and health-related quality of life (HRQOL) is poorly understood and may involve intermediate variables. We evaluated the potential mediators of the association between ASMs and HRQOL. METHODS: Data are from an outpatient registry of adult patients with epilepsy seen at the Foothills Medical Center, Calgary, Alberta, Canada. Quality of life was measured using the 10-item Quality of Life in Epilepsy, and depression was measured using the Neurological Disorders Depression Inventory for Epilepsy. Propensity score matching was used to adjust for covariate imbalance between patients who received a single ASM (monotherapy) and those who received two or more ASMs (polytherapy) due to confounding. Mediation analysis was used to estimate the mediating effects of depression and ASM side effects on the association between patients' ASM polytherapy and HRQOL. RESULTS: Of 778 patients included in this analysis, 274 (35.2%) were on two or more ASMs. Patient-reported depression and ASM side effects jointly mediated the association between ASMs and HRQOL; these mediators accounted for 42% of the total average effect of ASM polytherapy ( ß  = -13.6, 95% confidence interval = -18.2 to -8.6) on HRQOL. SIGNIFICANCE: These findings highlight the importance of managing depression and ASM side effects for improving health outcomes of patients requiring treatment with ASMs. Intervention programs aimed at improving HRQOL of patients with epilepsy need to target these potential mediators.

Association of Enzyme-Inducing Antiseizure Drug Use With Long-term Cardiovascular Disease.

Importance: Enzyme-inducing antiseizure medications (eiASMs) have been hypothesized to be associated with long-term risks of cardiovascular disease. Objective: To quantify and model the putative hazard of cardiovascular disease secondary to eiASM use. Design, Setting, and Participants: This cohort study covered January 1990 to March 2019 (median [IQR] follow-up, 9 [4-15], years). The study linked primary care and hospital electronic health records at National Health Service hospitals in England. People aged 18 years or older diagnosed as having epilepsy after January 1, 1990, were included. All eligible patients were included with a waiver of consent. No patients were approached who withdrew consent. Analysis began January 2021 and ended August 2021. Exposures: Receipt of 4 consecutive eiASMs (carbamazepine, eslicarbazepine, oxcarbazepine, phenobarbital, phenytoin, primidone, rufinamide, or topiramate) following an adult-onset (age ≥18 years) epilepsy diagnosis or repeated exposure in a weighted cumulative exposure model. Main Outcomes and Measures: Three cohorts were isolated, 1 of which comprised all adults meeting a case definition for epilepsy diagnosed after 1990, 1 comprised incident cases diagnosed after 1998 (hospital linkage date), and 1 was limited to adults diagnosed with epilepsy at 65 years or older. Outcome was incident cardiovascular disease (ischemic heart disease or ischemic or hemorrhagic stroke). Hazard of incident cardiovascular disease was evaluated using adjusted propensity-matched survival analyses and weighted cumulative exposure models. Results: Of 10 916 166 adults, 50 888 (0.6%) were identified as having period-prevalent cases (median [IQR] age, 32 [19-50] years; 16 584 [53%] female), of whom 31 479 (62%) were diagnosed on or after 1990 and were free of cardiovascular disease at baseline. In a propensity-matched Cox proportional hazards model adjusted for age, sex, baseline socioeconomic status, and cardiovascular risk factors, the hazard ratio for incident cardiovascular disease was 1.21 (95% CI, 1.06-1.39) for those receiving eiASMs. The absolute difference in cumulative hazard diverges by more than 1% and greater after 10 years. For those with persistent exposure beyond 4 prescriptions, the median hazard ratio increased from amedian (IQR) of 1.54 (1.28-1.79) when taking a relative defined daily dose of an eiASM of 1 to 2.38 (1.52-3.56) with a relative defined daily dose of 2 throughout a maximum of 25 years' follow-up compared with those not receiving an eiASM. The hazard was elevated but attenuated when restricting analyses to incident cases or those diagnosed when older than 65 years. Conclusions and Relevance: The hazard of incident cardiovascular disease is higher in those receiving eiASMs. The association is dose dependent and the absolute difference in hazard seems to reach clinical significance by approximately 10 years from first exposure.

Cohort profile: The Forzani & MacPhail Colon Cancer Screening Centre biorepository, Calgary, Alberta.

PURPOSE: The Colon Cancer Screening Centre (CCSC) biorepository (Calgary, Canada) supports a wide range of research topics related to colorectal cancer (CRC) by collecting, and storing biospecimens (blood, urine, normal colon tissue) from consenting patient participants. Housing unique biospecimens along with detailed participant lifestyle and health history questionnaire data, the CCSC biorepository can support a variety of research related to CRC risk factors, biomarkers, genetic causes and more. PARTICIPANTS: Currently, 2292 average risk CRC patients have consented to participate in the CCSC cohort and have provided stored biospecimens. The collected samples and data provide important high-quality materials for research, discovery and evaluation related to CRC screening and carcinogenesis and is available for access by outside researchers. In addition to biological samples, the CCSC collects detailed patient information on their lifestyle, physical activity and dietary patterns through questionnaires at the time of their enrolment. FINDINGS TO DATE: The majority of participants (75%) are between 50 and 64 years of age. Women make up 46% (1055) of the cohort. Additional characteristics of the cohort included 44% reporting a body mass index of 25-30 kg/m2 (overweight), 53% having never smoked tobacco and 13% having a family member with CRC. FUTURE PLANS: The CCSC cohort plans to include the recruitment of high risk CRC cohorts. High-risk participants would comprise patients with a positive faecal immunochemical test and family history of CRC.

Association Between Endoscopist Annual Procedure Volume and Colonoscopy Quality: Systematic Review and Meta-analysis.

BACKGROUND & AIMS: In addition to monitoring adverse events (AEs) and post-colonoscopy colorectal cancers (PCCRC), indicators for assessing colonoscopy quality include adenoma detection rate (ADR) and cecal intubation rate (CIR). It is unclear whether there is an association between annual colonoscopy volume and ADR, CIR, AEs, or PCCRC. METHODS: We searched publication databases through March 2019 for studies assessing the relationship between annual colonoscopy volume and outcomes, including ADR, CIR, AEs, or PCCRC. Pooled odds ratios (ORs) were calculated using DerSimonian and Laird random effects models. Sensitivity analyses were performed to assess for potential methodological or clinical factors associated with outcomes. RESULTS: We performed a systematic review of 9235 initial citations, generating 27 retained studies comprising 11,276,244 colonoscopies. There was no association between procedural volume and ADR (OR, 1.00; 95% CI, 0.98-1.02 per additional 100 annual procedures). CIR improved with each additional 100 annual procedures (OR, 1.17; 95% CI, 1.08-1.28). There was a non-significant trend toward decreased overall AEs per additional 100 annual procedures (OR, 0.95; 95% CI, 0.90-1.00). There was considerable heterogeneity among most analyses. CONCLUSIONS: In a systematic review and meta-analysis, we found higher annual colonoscopy volumes to correlate with higher CIR, but not with ADR or PCCRC. Trends toward fewer AEs were associated with higher annual colonoscopy volumes. There are few data available from endoscopists who perform fewer than 100 annual colonoscopies. Studies are needed on extremes in performance volumes to more clearly elucidate associations between colonoscopy volumes and outcomes.

Prophylactic Endoscopic Clipping Does Not Prevent Delayed Postpolypectomy Bleeding in Routine Clinical Practice: A Propensity Score-Matched Cohort Study.

INTRODUCTION: Delayed postpolypectomy bleeding (DPPB) is a relatively common adverse event. Evidence is conflicting on the efficacy of prophylactic clipping to prevent DPPB, and real-world effectiveness data are lacking. We aimed to determine the effectiveness of prophylactic clipping in preventing DPPB in a large screening-related cohort. METHODS: We manually reviewed records of patients who underwent polypectomy from 2008 to 2014 at a screening facility. Endoscopist-, patient- and polyp-related data were collected. The primary outcome was DPPB within 30 days. All unplanned healthcare visits were reviewed; DPPB cases were adjudicated by committee using a criterion-based lexicon. Multivariable logistic regression was performed, yielding adjusted odds ratios (AORs) for the association between clipping and DPPB. Secondary analyses were performed on procedures where one polyp was removed, in addition to propensity score-matched and subgroup analyses. RESULTS: In total, 8,366 colonoscopies involving polypectomy were analyzed, yielding 95 DPPB events. Prophylactic clipping was not associated with reduced DPPB (AOR 1.27; 0.83-1.96). These findings were similar in the single-polyp cohort (n = 3,369, AOR 1.07; 0.50-2.31). In patients with one proximal polyp ≥20 mm removed, there was a nonsignificant AOR with clipping of 0.55 (0.10-2.66). Clipping was not associated with a protective benefit in the propensity score-matched or other subgroup analyses. DISCUSSION: In this large cohort study, prophylactic clipping was not associated with lower DPPB rates. Endoscopists should not routinely use prophylactic clipping in most patients. Additional effectiveness and cost-effectiveness studies are required in patients with proximal lesions ≥20 mm, in whom there may be a role for prophylactic clipping.