Comparing New-User Cohort Designs: The Example of Proton Pump Inhibitor Effectiveness in Idiopathic Pulmonary Fibrosis.

The prevalent new-user cohort design is useful for assessing the effectiveness of a medication in the absence of an active comparator. Alternative approaches, particularly in the presence of informative censoring, include a variant of this design based on never users of the study drug and the marginal structural Cox model approach. We compared these approaches in assessing the effectiveness of proton pump inhibitors (PPIs) in reducing mortality among patients with idiopathic pulmonary fibrosis (IPF) using a cohort of IPF patients identified in the United Kingdom's Clinical Practice Research Datalink and diagnosed between 2003 and 2016. The cohort included 2,944 IPF patients, 1,916 of whom initiated use of PPIs during follow-up. There were 2,136 deaths (mortality rate = 25.8 per 100 person-years). Using the conventional prevalent new-user design, we found a hazard ratio for death associated with PPI use compared with nonuse of 1.07 (95% confidence interval (CI): 0.94, 1.22). The variant of the prevalent new-user design comparing PPI users with never users found a hazard ratio of 0.82 (95% CI: 0.73, 0.91), while the marginal structural Cox model found a hazard ratio of 1.08 (95% CI: 0.85, 1.38). The marginal structural model and the conventional prevalent new-user design, both accounting for informative censoring, produced similar results. However, the prevalent new-user design variant based on never users introduced selection bias and should be avoided.

The European MultiPartner IPF registry (EMPIRE): validating long-term prognostic factors in idiopathic pulmonary fibrosis.

BACKGROUND: Several registries of idiopathic pulmonary fibrosis (IPF) have been established to better understand its natural history, though their size and duration of follow-up are limited. Here, we describe the large European MultiPartner IPF Registry (EMPIRE) and validate predictors of long-term survival in IPF. METHODS: The multinational prospective EMPIRE registry enrolled IPF patients from 48 sites in 10 Central and Eastern European countries since 2014. Survival from IPF diagnosis until death was estimated, accounting for left-truncation. The Cox proportional hazards regression model was used to estimate adjusted hazard ratios (HR) of death for prognostic factors, using restricted cubic splines to fit continuous factors. RESULTS: The cohort included 1620 patients (mean age at diagnosis 67.6 years, 71% male, 63% smoking history), including 75% enrolled within 6 months of diagnosis. Median survival was 4.5 years, with 45% surviving 5 years post-diagnosis. Compared with GAP stage I, mortality was higher with GAP stages II (HR 2.9; 95% CI: 2.3-3.7) and III (HR 4.0; 95% CI: 2.8-5.7) while, with redefined cut-offs, the corresponding HRs were 2.7 (95% CI: 1.8-4.0) and 5.8 (95% CI: 4.0-8.3) respectively. Mortality was higher with concurrent pulmonary hypertension (HR 2.0; 95% CI: 1.5-2.9) and lung cancer (HR 2.6; 95% CI: 1.3-4.9). CONCLUSIONS: EMPIRE, one of the largest long-term registries of patients with IPF, provides a more accurate confirmation of prognostic factors and co-morbidities on longer term five-year mortality. It also suggests that some fine-tuning of the indices for mortality may provide a more accurate long-term prognostic profile for these patients.

The effect of anti-acid therapy on survival in idiopathic pulmonary fibrosis: a methodological review of observational studies.

International treatment guidelines for idiopathic pulmonary fibrosis (IPF) give a conditional recommendation for anti-acid therapy. As some observational studies reported discrepant findings on the effectiveness of anti-acid therapy on mortality in IPF, we reviewed all studies to evaluate whether immortal time bias explains these discrepancies.We searched the Embase and MEDLINE databases up to July 2017 for observational studies assessing the effectiveness of anti-acid therapy on mortality in IPF. Hazard ratios of mortality with anti-acid therapy were pooled across studies using random-effect models, stratified by the presence of immortal time bias.We identified 10 observational studies. Four of the five studies reporting beneficial effects of anti-acid therapy use on mortality were affected by immortal time bias (pooled hazard ratio 0.46; 95% CI 0.30-0.69), while it was unclear whether the fifth was affected. The five studies that avoided immortal time bias reported no effect of anti-acid therapy on mortality (pooled hazard ratio 0.99; 95% CI 0.81-1.22).The apparent beneficial effects of anti-acid therapy on mortality in patients with IPF result from observational studies affected by immortal time bias. Thus, the effectiveness of anti-acid therapy in IPF remains uncertain and needs to be reassessed with more accurate observational study methods and randomised trials.

Burden of Hidradenitis Suppurativa: A Systematic Literature Review of Patient Reported Outcomes.

INTRODUCTION: Hidradenitis suppurativa (HS) has a profound negative impact on patients' health-related quality of life (HRQoL). Here we summarize the evidence on HRQoL and Patient Reported Outcomes (PROs) in patients with HS in real-world settings by conducting a systematic literature review (SLR) of observational studies. METHODS: Data sources included MEDLINE, Embase & PsycINFO between January 1, 2010 and August 29, 2021, and conference proceedings between 2019 and 2021. Identified abstracts were reviewed and screened independently by two reviewers. Eligibility criteria included patients with HS of any severity, sample size ≥ 100, reporting PROs including HRQoL measures. Included studies were critically appraised. RESULTS: Fifty-eight observational studies matched inclusion criteria. Dermatology Life Quality Index (DLQI) was the most commonly utilized instrument: 57% of included studies reported mean baseline DLQI scores, ranging between 8.4 and 16.9, indicating a very large impact on the patients' HRQoL. Higher scores were reported with increasing disease severity and among female patients. Pain was assessed mostly by an 11-point (0-10) numeric rating scale (NRS) with a mean baseline score ranging from 3.6 to 7.7 indicating moderate to high pain levels. There was a negative impact of HS on patients' psychological well-being, based on PRO scores related to depression and anxiety. A high proportion of sexual dysfunction was reported, with a larger impact on women than men. Work productivity and leisure activity were consistently found to be impaired in patients with HS. CONCLUSIONS: All included studies reported a negative impact of HS on patients' lives. A diverse set of disease- and non-disease-specific PRO instruments were utilized highlighting the need for more consistent use of HS-specific validated PRO instruments to assess the impact of HS on the different aspects of patients' HRQoL to allow for data to be more meaningfully interpreted and compared in real-world settings. Patients with HS need better disease management approaches that address the observed low quality of life.

Hidradenitis suppurativa (HS) is a skin disease, which mainly involves the hair follicles, and may greatly affect the health of those with the illness. HS often causes painful or itchy bumps or swelling of the skin, especially in the intimate areas. These occasionally drain and have an odor. When they heal, sometimes they leave dark spots or scars. People with HS can feel depressed, anxious, or embarrassed, among other things. In this study, we looked at how existing studies measured the impact of HS on the physical, mental, and social quality of people's lives. When searching the Internet, we found 58 publications on studies around this topic. Across all of the studies, HS had a large negative effect on patients' quality of life. We found that the groups of people which were impacted more by HS had worse cases of the disease. Patients with more severe HS felt higher levels of pain. Women were also affected more than men. Many studies showed that patients with HS often felt depressed and anxious. Three studies showed that HS greatly affected women's sexual health. Many patients said that HS made it hard to work and do things for fun. More and better treatments are needed since HS can have such a big impact on people's lives.

Real-World Findings on the Characteristics and Treatment Exposures of Patients with Hidradenitis Suppurativa from US Claims Data.

INTRODUCTION: Hidradenitis suppurativa (HS) is a chronic, debilitating, and painful inflammatory skin disease that significantly and negatively impacts patients' quality of life. The prevalence of HS in the USA is estimated to be 0.10%, with worldwide reports suggesting a prevalence closer to 1%. There is limited real-world evidence available on the care of patients with HS. We aimed to evaluate the trends in clinical care and treatment in the patient population with HS in the USA in a real-world setting. METHODS: A cohort study was conducted using claims data from IBM MarketScan Databases, including the US Commercial Claims and Encounters with Medicare Supplemental and Coordination of Benefits (CCAE+MDCR) database and IBM US Medicaid database. RESULTS: The annual prevalence of HS increased from 0.06% (2008) to 0.14% (2017), and from 0.17% (2008) to 0.31% (2017) among CCAE+MDCR and Medicaid patients, respectively. Dermatologist visits increased from 31.9% (2008) to 47.8% (2019) in CCAE+MDCR patients, and decreased from 10.9% (2008) to 8.5% (2018) in Medicaid patients. Opioid use decreased from 45.4% (2008) to 25.5% (2019) among CCAE+MDCR patients, and from 71.3% (2008) to 48.1% (2018) among Medicaid patients. Only 8.4% of CCAE+MDCR patients and 5.8% of Medicaid patients were exposed to any biologic in 2018. CONCLUSIONS: Improved care and treatment of HS over the last decade, including the emergence of new treatments, have been accompanied by an increase in awareness and reported prevalence of the disease. However, there are still gaps in access to dermatologic care and low utilization of biologic therapies among patients with HS. INFOGRAPHIC.

Effectiveness of Proton Pump Inhibitors in Idiopathic Pulmonary Fibrosis: A Population-Based Cohort Study.

BACKGROUND: Gastroesophageal reflux disease is a common comorbidity in idiopathic pulmonary fibrosis (IPF) and may contribute to its progression. Anti-acid therapy, such as proton pump inhibitors (PPIs), has been considered as a potential treatment option for IPF. The evidence for this treatment comes from several observational studies affected by time-related bias. RESEARCH QUESTION: Is use of PPIs in patients with IPF associated with a reduction in all-cause mortality, respiratory-related mortality, and respiratory-related hospitalization? STUDY DESIGN AND METHODS: We used the UK Clinical Practice Research Datalink to identify a cohort of patients diagnosed with IPF between 2003 and 2016. The prevalent new-user cohort design was used to match patients initiating PPIs with non-users using time-conditional propensity scores, with follow-up until death or end of observation. Cox models were used to estimate hazard ratios (HR) and 95% CIs of death and of a respiratory-related hospitalization, correcting for informative censoring by inverse probability weighting. RESULTS: There were 1,852 PPI users who were matched to 1,852 non-users identified among the cohort of patients with IPF, with a median survival of 2.8 years (mortality rate, 26.7 per 100 per year). The HR of all-cause mortality with PPI use was 1.07 (95% CI, 0.94-1.22), relative to non-use. For respiratory-related mortality, the HR was 1.10 (95% CI, 0.94-1.28) and 1.00 (95% CI, 0.86-1.16) for respiratory-related hospitalizations. INTERPRETATION: PPI use was not associated with lower mortality or hospitalization incidence in this large study conducted among patients with IPF within a real-world setting of clinical practice and designed to avoid the time-related biases affecting previous studies. PPIs may not be as beneficial in treating IPF as suggested by some studies and conditionally recommended in treatment guidelines.

Risks of Cardiac Valve Regurgitation and Heart Failure Associated with Ergot- and Non-Ergot-Derived Dopamine Agonist Use in Patients with Parkinson's Disease: A Systematic Review of Observational Studies.

BACKGROUND: Dopamine agonists (DAs) are commonly used in the therapy of Parkinson's disease (PD). However, several observational studies have suggested a putative association between DAs and specific cardiac adverse events. OBJECTIVES: The aim of this study was to systematically review and summarize the available epidemiologic evidence on the association between use of ergot- and non-ergot-derived DAs and the risk of valvular heart disease, specifically cardiac valve regurgitation (CVR) and heart failure (HF) in patients with PD. METHODS: The databases MEDLINE/PubMed and EMBASE were searched for all relevant articles published before February 2015. Studies were eligible if they met the following inclusion criteria: exposure to any approved non-ergot- or ergot-derived DA, presentation of original data, inclusion of an unexposed reference group, and valvular heart disease or heart failure as the primary outcome of interest. RESULTS: Thirteen publications for CVR were identified (two nested case-control, one cohort and ten cross-sectional studies). Compared with non-ergot DAs or other anti-parkinsonian drugs, exposure to ergot-derived DAs pergolide and cabergoline was associated with an increased risk of CVR among PD patients. Incidence rate ratios (IRR) in the nested case-control and cohort studies ranged from 2.00 to 7.10 and 4.58 to 4.90, respectively. Longer treatment duration and higher dose of those DAs was also associated with a higher risk of CVR. Risk of HF was estimated in three nested case-control studies and one cohort study. Use of cabergoline (IRR range 1.30-2.39) and the non-ergot-derived DA pramipexole (IRR range 1.40-1.81) was associated with a higher HF risk among patients with PD. Pergolide may also be associated with a higher risk of HF. CONCLUSION: Despite the heterogeneous methodological approaches of the included studies, there is strong evidence that treatment with pergolide and cabergoline is associated with a higher risk of CVR, and moderate evidence that treatment with pramipexole and cabergoline is associated with a higher risk of HF in patients with Parkinson's disease.