Potential relationship between cytomegalovirus and immunosenescence: Evidence from observational studies.

Immunosenescence (IS) occurs as a natural outcome of ageing and may be described as a decline in immune system flexibility and adaptability to sufficiently respond to new, foreign antigens. Potential factors that may precipitate IS include persistent herpesvirus infections, such as cytomegalovirus (CMV). Here, we conducted a review of the literature evaluating the potential association between CMV and IS. Twenty-seven epidemiologic studies that included direct comparisons between CMV-seropositive and CMV-seronegative immunocompetent individuals were analysed. The majority of these studies (n = 20) were conducted in European populations. The strength of evidence supporting a relationship between CMV, and various IS-associated immunologic endpoints was assessed. T-cell population restructuring was the most prominently studied endpoint, described in 21 studies, most of which reported a relationship between CMV and reduced CD4:CD8 T-cell ratio or modified CD8+ T-cell levels. Telomere length (n = 4) and inflammageing (n = 3) were less frequently described in the primary literature, and the association of these endpoints with CMV and IS was less pronounced. An emergent trend from our review is the potential effect modification of the CMV-IS relationship with both sex and age, indicating the importance of considering various effector variables when evaluating associations between CMV and IS. Our analysis revealed plausible mechanisms that may underlie the larger epidemiologic trends seen in the literature that support the indirect effect of CMV on IS. Future studies are needed to clarify CMV-associated and IS-associated immunologic endpoints, as well as in more diverse global and immunocompromised populations.

Incidence of RSV in Adults: A Comprehensive Review of Observational Studies and Critical Gaps in Information.

BACKGROUND: We conducted a global comprehensive literature review of observational studies reporting RSV incidence in adults and determined current evidence gaps. METHODS: PubMed and Embase were searched for English-language publications (2000-2022) and congress abstracts (2019-2021) reporting RSV incidence rates/cumulative incidence. Cross-sectional studies, case series, and other designs estimating only RSV frequency were excluded. The search included all geographic areas; data were extracted by age group and underlying condition where available. RESULTS: 528 potentially relevant records were identified, of which 37 primary studies were relevant to this review. Most evidence was from high-income regions. Approximately two-thirds of the studies reported RSV incidence in the hospital setting. Fifteen studies included or focused exclusively on RSV incidence in adult populations with underlying conditions. Studies varied in their measurement and presentation of incidence. RSV incidence estimates were highly variable within and between geographic regions. Overall, RSV incidence tended to increase with age and was highest in adults with underlying conditions. CONCLUSION: Estimates of RSV incidence are highly variable across populations and geographies. Further population-based studies with well-defined consistent case definitions and surveillance strategies are needed for accurate and comparable estimates of RSV incidence, particularly in the geographic regions identified by the gap analysis.

Clinical outcomes following bone marrow transplantation in patients with sickle cell disease: A cohort study of US Medicaid enrollees.

OBJECTIVES: Bone marrow transplantation (BMT) is currently the only curative therapy available for patients with sickle cell disease (SCD), but clinical outcomes in routine care are not well understood. We describe the rates of vaso-occlusive crises (VOCs), transplant complications, and mortality in SCD patients after BMT. METHODS: A cohort study of SCD patients who underwent BMT was designed using US Medicaid claims data (2000-2013). RESULTS: A total of 204 SCD patients undergoing BMT were identified with a mean (SD) age of 10.6 (7.3) years, with 52.9% male and 67.6% African American. The overall VOC rate was 0.99 per person-year (95% CI: 0.91-1.07) over a median follow-up time of 2.1 years (IQR: 0.8-4.3 years). A total of 138 (67.6%) remained free of VOCs. The mortality rate was 1.7 (95% CI: 0.9-3.1) per 100 person-years, transplant-related complications occurred among 113 (55.4%) patients with an incidence rate of 38.2 (95% CI: 31.7-45.9) per 100 person-years, while 47 (23%) patients had GvHD with an incidence rate of 8.0 (95% CI: 6.0-10.7) per 100 person-years. CONCLUSION: Two thirds of the BMT recipients remained VOC-free over 2 years of follow-up, but transplant-related complications, including GvHD occurred with high frequency. This highlights a continuing unmet need for alternative curative interventions in SCD.

Risk of interstitial lung disease in patients treated for atrial fibrillation with dronedarone versus other antiarrhythmics.

PURPOSE: To compare risks of interstitial lung disease (ILD) between patients treated with dronedarone versus other antiarrhythmics. METHODS: Parallel retrospective cohort studies were conducted in the United States Department of Defense Military Health System database (DoD) and the HealthCore Integrated Research Database (HIRD). Study patients were treated for atrial fibrillation (AF) with dronedarone, amiodarone, sotalol, or flecainide. Propensity score matching was employed to create analysis cohorts balanced on baseline variables considered potential confounders of treatment decisions. The study period of July 20, 2008 through September 30, 2014 included a 1-year baseline and minimum 6 months of follow-up, for patients with drugs dispensed between July 20, 2009 and March 31, 2014. Suspect ILD outcomes were reviewed by independent adjudicators. Cox proportional hazards regression compared risk of confirmed ILD between dronedarone and each comparator cohort. A sensitivity analysis examined the effect of broadening the outcome definition. RESULTS: A total 72 ILD cases (52 DoD; 20 HIRD) were confirmed among 27 892 patients. ILD risk was significantly higher among amiodarone than dronedarone initiators in DoD (HR = 2.5; 95% CI = 1.1-5.3, p = 0.02). No difference was detected in HIRD (HR = 1.0; 95% CI = 0.4-2.4). Corresponding risks in sotalol and flecainide exposure groups did not differ significantly from dronedarone in either database. CONCLUSIONS: ILD risk among AF patients initiated on dronedarone therapy was comparable to or lower than that of amiodarone initiators, and similar to that of new sotalol or flecainide users. This finding suggests that elevated ILD risk associated with amiodarone does not necessarily extend to dronedarone or other antiarrhythmic drugs.

Clinical outcomes and healthcare utilization in patients with sickle cell disease: a nationwide cohort study of Medicaid beneficiaries.

To add to the limited existing evidence on clinical outcomes and healthcare use in sickle cell disease (SCD) among beneficiaries of the US Medicaid program, we conducted a cohort study using nationwide Medicaid claims data (2000-2013). Patients were included based on HbSS SCD diagnosis and followed until Medicaid disenrollment, death, bone marrow transplant, or end of data availability to assess vasoocclusive crises (VOC), emergency room (ER) visits, hospitalizations, outpatient visits, and blood transfusions. Annualized event rates (with 95% confidence intervals [CI]) were reported. The impact of VOCs on the risk of mortality was analyzed using a multivariable Cox model with VOC modeled as time-varying and updated annually. In a total of 44,033 SCD patients included with a mean (SD) age of 15.7 (13.6) years, the VOC rate (95% CI) was 3.71 (3.70-3.72) per person-year, with highest rate among patients 19-35 years who had ≥ 5 VOCs at baseline (13.20 [13.15-13.26]). Event rates (95% CI) per person per year for other outcomes were 2.97 (2.97-2.98) ER visits, 2.39 (2.38-2.40) hospitalizations, 5.80 (5.79-5.81) outpatient visits, and 0.91 (0.90-0.91) blood transfusions. A higher VOC burden in the preceding year was associated with an increased risk of mortality, with a hazard ratio (95% CI) of 1.26 (1.14-1.40) for 2-4 VOC vs. < 2 and 1.57 (1.41-1.74) for ≥ 5 VOC vs < 2. In conclusion, we documented a substantial burden of SCD in US Medicaid enrollees, especially during early adulthood and noted that ongoing burden of VOC is associated with mortality in these patients.

Incidence and prevalence of axial spondyloarthritis: methodologic challenges and gaps in the literature.

OBJECTIVES: The incidence and prevalence of axial spondyloarthritis (axSpA), including ankylosing spondylitis (AS) and non-radiographic (nr-)axSpA, have been investigated in multiple populations, though there is a paucity of population-level data. Here, we identify population-based studies in AS and nr-axSpA, and describe the methodologic challenges in conducting these, outlining potential reasons for disparate incidence and prevalence estimates. METHODS: PubMed and Embase were searched for population-based studies providing incidence and prevalence rates, published in English from 1 Jan 2000-30 Jun 2015. Extracted information included incidence/prevalence rates, geographical population, study design, data source, case definition, age/gender, and classification criteria used. RESULTS: Of 2,148 articles identified, 19, from 15 countries, fulfilled eligibility criteria. Incidence rates per 100,000 patient-years were reported in 4 AS studies and varied from 0.4 (Iceland) to 15.0 (Canada). Reported AS prevalence rates per 100,000 persons also showed considerable variation (16 studies: 6.5 [Japan] to 540.0 [Turkey]). Only 3 axSpA and no nr-axSpA prevalence rates were reported. Considerable variation was seen in the methodology used to estimate incidence and prevalence rates, e.g. screening method, study design, and classification criteria. Although the prevalence of AS is known to vary by HLA-B27 status, only 4 studies reported this genetic marker. CONCLUSIONS: There is an unmet need for future studies to use consistent methodology, capture all relevant information (including HLA-B27 positivity), and investigate under-reported populations (e.g. nr-axSpA; southern hemisphere countries) to estimate the population burden of axSpA. Future studies should aim to address data gaps to provide accurate incidence/prevalence estimates for the global axSpA population.

Poor adherence to and persistence with biologics in generalized pustular psoriasis: A claim-based study using real-world data from two large US databases.

Background: Generalized pustular psoriasis (GPP) is a rare skin disease characterized by episodes of widespread sterile pustules. Methods: A retrospective cohort study using data from the US IBM MarketScan Commercial and Optum Clinformatics Data Mart databases between October 1, 2015 and March 31, 2020 was performed to describe adherence and persistence to biologics in patients with GPP. Patients were aged ≥18 years with newly diagnosed GPP (International Classification of Diseases code L40.1) and had ≥1 inpatient or ≥2 outpatient claims. Results: Biologics were dispensed to 110 of 502 (22%) and 73 of 528 (14%) patients from MarketScan and Optum databases, respectively. The mean proportion of days covered (PDC) (range) was similar in both databases (MarketScan, 65% [8%-100%]; Optum, 59% [8%-99%]), and good adherence (≥80% PDC) was uncommon (MarketScan, 36%; Optum, 24%). Mean (standard deviation) persistence was similar in both databases (MarketScan, 287 [122] days; Optum, 261 [134] days). In Optum, the mean PDC was similar between age categories; good adherence was more common in patients aged 18 to 64 years (28%) versus ≥65 years (13%). Mean persistence was longer in patients aged 18 to 64 years (267 days) versus ≥65 years (242 days). Conclusions: Overall, adherence and persistence were generally poor and varied according to the biologic class, database, and age. Improving adherence may help improve GPP treatment outcomes.

Economic burden related to fistulas or strictures among commercially insured patients with Crohn's disease in the United States.

BACKGROUND: Crohn's disease (CD) is a chronic, progressive, immune-mediated gastrointestinal condition that can lead to fistulizing or stricturing complications. OBJECTIVE: To quantify the burden of illness related to fistulas and/or strictures in patients with CD. METHODS: Using the Optum Research Database from October 2015 to December 2019, patients with CD were classified according to 1 of 3 condition cohorts: CD with fistula (CD-F), CD with stricture (CD-S), or CD with fistula and stricture (CD-FS). Each cohort was matched to a nonfistula, nonstricture CD cohort. Postdiagnosis per patient per year (PPPY) costs and health care resource utilization were assessed, accounting for variable lengths of follow-up periods. Multivariable generalized linear models were used to estimate the adjusted mean costs in each cohort. RESULTS: The CD-F, CD-S, and CD-FS cohorts included 1,317; 4,650; and 894 patients, respectively. The mean age of patients within the CD-S and their comparator cohorts was higher than in the CD-F or CD-FS cohorts (59.9 vs 49.5 vs 49.6 years). At baseline, cardiovascular disease was the most common comorbidity across all condition and comparator cohorts. Condition cohorts had 2-4 times more inpatient visits, 5-8 times more surgical visits, and 2-3 times more endoscopies PPPY than comparator cohorts. Compared with their respective comparator cohort, patients in the 3 condition cohorts had higher medication, medical, and total health care costs. CONCLUSIONS: This study demonstrates a significant economic burden related to fistulas and/or strictures among patients with CD, highlighting the importance of prevention, early recognition, and appropriate management of CD-related complications. DISCLOSURES: Yanni Fan, Ling Zhang, Jennifer S Thompson, and Kimberly G Brodovicz are employees of Boehringer Ingelheim. Rhonda L Bohn, Monik C Jiménez, and Stephani Gray (Bohn Epidemiology, LLC) are paid consultants to Boehringer Ingelheim. Gil Y Melmed reports receiving grants from Pfizer; consulting fees from Boehringer Ingelheim, AbbVie, Arena, BMS, Celgene, Entasis, Ferring Lilly, Fresenius Kabi, Medtronic, Samsung Bioepis, Janssen, Takeda, Pfizer, Prometheus Labs, and TechLab. We conducted a retrospective study using administrative claims data from the Optum Research Database, a database of a commercially insured population in the United States. All patient data were anonymized and deidentified; therefore, informed consent was not necessary. Restrictions apply to the availability of these data because of a contract between Optum and Boehringer Ingelheim, and data are thus unavailable to the public. For enquiries on the dataset analyzed in this study, please contact Optum (https://www.optum.com).

Patients With Stricturing or Penetrating Crohn's Disease Phenotypes Report High Disease Burden and Treatment Needs.

BACKGROUND: Crohn's disease (CD) is a chronic autoimmune disease in which inflammation can progress to complications of stricturing and/or penetrating disease. Real-world data on burden of complicated CD phenotypes are limited. METHODS: We analyzed cross-sectional data from the SPARC IBD (Study of a Prospective Adult Research Cohort with Inflammatory Bowel Disease) registry from 2016 to 2020. Four mutually exclusive phenotype cohorts were created: inflammatory CD (CD-I), complicated CD (stricturing CD, penetrating CD, and stricturing and penetrating CD [CD-SP]). Statistical analyses were performed using CD-I as the reference. RESULTS: A total of 1557 patients were identified: CD-I (n = 674, 43.3%), stricturing CD (n = 457, 29.4%), penetrating CD (n = 166, 10.7%), and CD-SP (n = 260, 16.7%). Patients with complicated phenotypes reported significantly greater use of tumor necrosis factor inhibitors (84.2%-86.7% vs 66.0%; P < .001) and corticosteroids (75.3%-82.7% vs 68.0%; P < .001). Patients with CD-SP reported significantly more aphthous ulcer (15.4% vs 10.5%; P < .05), erythema nodosum (6.5% vs 3.6%; P < .05), inflammatory bowel disease-related arthropathy (25.8% vs 17.2%; P < .01), liquid stools (24.2% vs 9.3%; P < .001), nocturnal fecal incontinence (10.8% vs 2.5%; P < .001), and CD-related surgery (77.7% vs 12.2%; P < .001). CONCLUSIONS: Patients with complicated CD phenotypes reported higher rates of active CD-related luminal and extraintestinal manifestations, and underwent more surgeries, despite being more likely to have received biologics than those with CD-I. The potential for early recognition and management of CD-I to prevent progression to complicated phenotypes should be explored in longitudinal studies.

Patients with complicated (stricturing and/or penetrating) Crohn's disease (CD) phenotypes have a higher disease burden, despite greater use of biologics, than patients with inflammatory CD. Early recognition and optimized management of CD may prevent progression to complicated phenotypes.

Health care utilization of patients diagnosed with idiopathic thrombotic thrombocytopenic purpura in a commercially insured population in the United States.

BACKGROUND: Incident idiopathic thrombotic thrombocytopenic purpura (TTP) is an uncommon, potentially fatal blood disorder for which there are little or no data on health care costs. STUDY DESIGN AND METHODS: Patients satisfying a validated claims-based algorithm including an inpatient diagnosis of TTP and plasma exchange (PE) procedure during the period January 1, 2001 to May 31, 2008 were identified in the HealthCore Integrated Research Database. To characterize patterns of treatment and payments, a quantitative evaluation of comorbidities and treatments, health care utilization, and payments among this population of patients was conducted. All patients were followed until death, end of health plan enrollment, or 365 days after the TTP hospitalization, whichever occurred first. RESULTS: One hundred fifty-one patients met the claims coding algorithm. Mean total health care payments for the TTP hospitalization were $56,347 (standard deviation [SD] $80,230). Ten patients (6.6%) died during the hospitalization for TTP. Mean payments for PE services in the month following discharge were $9127 (SD $20,840). Several patients required prolonged PE during the acute TTP phase (up to 116 separate exchanges over a period of 365 days), prolonging required treatment and skewing payments and resource utilization during the 365-day period following discharge from the index TTP hospitalization. CONCLUSION: These data document the health care resource utilization by patients with idiopathic TTP, demonstrating that management of these patients is not only expensive but also skewed, with some patients requiring prolonged treatment. These data can contribute to cost-effectiveness models when new treatments for TTP become available.

Incidence of osteonecrosis of the jaw among users of bisphosphonates with selected cancers or osteoporosis.

PURPOSE: To quantify the incidence of osteonecrosis of the jaw (ONJ) by bisphosphonate exposure among two cohorts of patients. METHODS: In a retrospective cohort study, we identified cohort members via health insurance claim diagnosis codes and identified potential cases of ONJ that were confirmed with medical record review. One cohort included patients aged ≥40 years with breast or prostate cancer or multiple myeloma; the other cohort included men aged ≥60 years and women ≥50 years with osteoporosis. For each cohort, we calculated sex- and age-standardized incidence of ONJ by exposure to oral bisphosphonates and intravenous bisphosphonates. RESULTS: In the cancer cohort (n = 46 542), sex- and age-standardized incidence of ONJ (n = 26 probable or possible cases) adjusted for abstraction proportion was 0.29 per 1000 person-years (95% confidence interval [CI], 0.07-0.52) among those unexposed to bisphosphonates and 5.3 (95%CI, 1.9-8.7) after intravenous bisphosphonate use. Controlling for covariates, the rate ratio for intravenous use versus no use was 8.8 (95%CI, 2.0-38). Patients with multiple myeloma had a rate 4.5 times that of patients with breast cancer. In the osteoporosis cohort (n = 31 244), sex- and age-standardized ONJ (n = 11 probable or possible cases) incidence was 0.26 per 1000 person-years (95%CI, 0.06-0.47) among those unexposed to bisphosphonate and 0.15 (95%CI, 0.00-0.36) after oral bisphosphonate use. CONCLUSION: Among patients with selected cancers, incidence of ONJ was higher among those with multiple myeloma and users of intravenous bisphosphonates.

Validation of a claims-based diagnostic code for Stevens-Johnson syndrome in a commercially insured population.

PURPOSE: To validate the administrative claims identification of a diagnosis of Stevens-Johnson syndrome (SJS) using medical records as the "gold standard" in a large, commercially insured US population. METHODS: Patients with >1 medical claim with the International Classification of Diseases, Ninth Revision, Clinical Modification code 695.1x between 1 July 2000 and 31 May 2007 were queried in the HealthCore Integrated Research Database(SM) , which contains administrative claims data for 14 commercial health insurance plans. Trained nurses and pharmacists abstracted pertinent information from the identified patients' medical records, which were then reviewed by two independent dermatologists to identify criteria to determine SJS diagnosis. Positive predictive values (PPVs) based on the claims and chart data were computed for all the cases. RESULTS: Medical charts for 200 claims-identified cases, with the International Classification of Diseases, Ninth Revision, Clinical Modification code 695.1x, were abstracted and reviewed by the dermatologists. A total of five cases (PPV = 2.50%, 95%CI = 0.8%-5.7%) were determined to be SJS with clinical certainty. PPVs varied with data stratification: PPV for inpatient claims only (PPV = 2.00%, 95%CI = 0.24%-7.04%), inpatient claims with 695.1x in first diagnosis field (PPV = 4.11%, 95%CI = 0.86%-11.54%), and final decisions of either clinical certainty or probable cases of SJS (PPV = 6.00%, 95%CI = 3.14%-10.25%). CONCLUSION: These findings demonstrate the difficulties associated with identifying rare disorders, which lack specific diagnostic criteria, within administrative claims databases. They underscore the challenges of using claims data to monitor ill-defined clinical conditions as well as the need to validate claims-identified cases with information from other sources, such as medical charts. Copyright © 2012 John Wiley & Sons, Ltd.

Risk of Guillain-Barré syndrome after meningococcal conjugate vaccination.

PURPOSE: A new meningococcal conjugate vaccine (MCV4) was introduced in 2005. Shortly after, case reports of Guillain-Barré syndrome (GBS), a serious demyelinating disease, began to be reported to the Vaccine Adverse Event Reporting System. In 2006, the Centers for Disease Control and Prevention and the Food and Drug Administration requested the evaluation of GBS risk after MCV4 vaccination. We conducted a study to assess the risk of GBS after MCV4 vaccination using health plan administrative and claims data together with the review of primary medical records of potential cases. METHODS: Retrospective cohort study among 12.6 million 11- to 21-year-old members of five US health plans with a total membership of 50 million. Automated enrollment and medical claims data from March 2005 through August 2008 were used to identify the population, the vaccinations administered, and the medical services associated with possible GBS. Medical records were reviewed and adjudicated by a neurologist panel to confirm cases of GBS. The study used distributed data analysis methods that minimized sharing of protected health information. RESULTS: We confirmed 99 GBS cases during 18,322,800 person-years (5.4/1,000,000 person-years). More than 1.4 million MCV4 vaccinations were observed. No confirmed cases of GBS occurred within 6 weeks after vaccination. The upper 95% CI for the attributable risk of GBS associated with MCV4 is estimated as 1.5 cases per 1,000,000 doses. CONCLUSIONS: Among members of five US health plans, MCV4 vaccination was not associated with increased GBS risk.

Healthcare Resource Utilization and Related Costs in Chronic Fibrosing Interstitial Lung Diseases with a Progressive Phenotype: A US Claims Database Analysis.

INTRODUCTION: We aimed to describe healthcare resource utilization (HCRU) patterns and costs in patients with fibrosing interstitial lung disease (ILD) and those with a progressive phenotype of fibrosing ILD in a US claims database. METHODS: Data from the IBM® MarketScan® databases (1 October 2011-30 September 2015) were used. Diagnosis codes documented on medical claims on two occasions (without any claims during the 12 months prior) identified patients with incident fibrosing ILD. Patients with chronic fibrosing ILD with a progressive phenotype were identified by proxies for progression. Patients aged ≥ 18 years with 365 days of continuous coverage before the index date were eligible for inclusion. Data were analyzed for 12 months prior to identification of fibrosing ILD/progressive phenotype (baseline) and 12 months after (follow-up). Outcomes included treatment patterns, outpatient and inpatient claims, and costs. RESULTS: We identified 23,577 patients with incident fibrosing ILD and 14,722 with the progressive phenotype. Follow-up data were available for 9986 and 5840 patients, respectively. The most frequent ILD-related medications during baseline were corticosteroids (49.4% and 56.6%). Mean (± standard deviation [SD]) annualized number of outpatient claims was 30.0 (± 26.4) and 34.1 (± 27.7) in the baseline period and 36.2 (± 28.6) and 41.9 (± 30.2) in the follow-up in fibrosing ILD and with a progressive phenotype, respectively. Mean (SD) number of all-cause hospitalizations was 0.5 (± 1.1) and 0.7 (± 1.2) during baseline and 0.6 (± 1.1) and 0.7 (± 1.2) during follow-up. Mean (SD) total costs were $40,907 (± 92,496) and $49,561 (± 98,647) during baseline and $46,157 (± 102,858) and $54,215 (± 116,833) during follow-up. Inpatient mortality during follow-up was 53.50 and 77.44 per 1000 patient-years. CONCLUSION: HCRU and costs were high in patients with chronic fibrosing ILD with a progressive phenotype, likely reflecting the disease severity and the need for close monitoring and acute care. Outpatient claims accounted for a substantial proportion of the total costs.

Some patients with lung diseases have inflammation or scarring of the lung tissues (interstitial lung diseases, or ILDs). In some patients with lung scarring, the scarring may become progressive (i.e., it worsens over time). In this study, we looked at these patients identified in US health insurance records. We counted how many times patients visited a doctor, were admitted to hospital, or needed medications or tests. We also looked at the total cost of all this medical care. Overall, we concluded that patients with ILDs with progressive lung scarring had a high number of visits to the doctor, and the total costs of their medical care were high.

Prevalence and Incidence of Chronic Fibrosing Interstitial Lung Diseases with a Progressive Phenotype in the United States Estimated in a Large Claims Database Analysis.

INTRODUCTION: Many fibrosing interstitial lung diseases (ILDs) develop a chronic progressive phenotype. While idiopathic pulmonary fibrosis, which is always progressive, is well characterized with established treatment options, the epidemiology of other chronic fibrosing ILDs with a progressive phenotype has not been widely investigated. Treatment options are limited, with a high unmet need. This claims database study estimates the incidence and prevalence of these diseases in the USA. METHODS: Diagnosis, procedure and resource utilization codes from insurance claims were used to identify patients with fibrosing ILD and those with a chronic progressive phenotype among 37,565,644 adult patients in the IBM® MarketScan® Research Database 2012-2015. Two eligible ILD claims were required for a fibrosing ILD diagnosis. Progression was defined using a novel algorithm constituted by criteria considered proxies for progression. Patients were defined as having incident (new) or existing diagnoses based on claims during a 365-day period before study entry. RESULTS: The estimated age- and sex-adjusted prevalence per 100,000 persons of fibrosing ILD (95% confidence interval) was 117.82 (116.56, 119.08) and of chronic fibrosing ILDs with a progressive phenotype was 70.30 (69.32, 71.27). The estimated adjusted incidence per 100,000 patient-years of fibrosing ILD was 51.56 (50.88, 52.24) and of chronic fibrosing ILDs with a progressive phenotype was 32.55 (32.01, 33.09). Among incident fibrosing ILD patients, 57.3% experienced progression over a median of 117 days (interquartile range 63-224), with largely comparable rates of progression among different diseases. CONCLUSIONS: Chronic fibrosing ILDs with a progressive phenotype comprise a relatively new disease construct requiring varied approaches to obtain reliable estimates of prevalence and incidence. This is the first large claims database study using real-world data to provide estimates of the prevalence and incidence of these diseases among a very large segment of the US population and could form the groundwork for future studies.

Progressive lung fibrosis occurs in idiopathic pulmonary fibrosis; however, interstitial lung fibrosis may occur in other diseases such as rheumatoid arthritis, chronic hypersensitivity pneumonitis and sarcoidosis, and may or may not be progressive in these diseases. Little is known about the frequency of lung fibrosis among patients with these diseases or how often such fibrosis is progressive. This study used information from a large insurance claims database (IBM^® MarketScan^®) to estimate the frequency and progression of lung fibrosis associated with different diseases.

The Annual Diagnostic Prevalence of Ankylosing Spondylitis and Axial Spondyloarthritis in the United States Using Medicare and MarketScan Databases.

OBJECTIVE: The objective of this study was to investigate the diagnostic prevalence of ankylosing spondylitis (AS) and axial spondyloarthritis (axSpA) in the United States and examine treatment patterns for these diseases. METHODS: This retrospective observational cohort study drew from 2006-2014 data in the US Medicare Fee-for-Service and IBM MarketScan databases. AS and axSpA diagnoses were identified through International Classification of Diseases, Ninth Revision [ICD-9] codes. Diagnostic prevalence (per 10,000 patients) was calculated as patients with AS and axSpA with full insurance coverage in each calendar year divided by the total patients with full insurance coverage in the same year. Two diagnosis definitions were used: definition 1 (D1), one or more relevant ICD-9 codes from hospital claims or two or more relevant ICD-9 codes from outpatient claims; definition 2 (D2), one or more codes from hospital/outpatient claims. Primary analyses assessed annual AS and axSpA prevalence (D1); sensitivity analyses assessed annual (D2) and 2-year prevalence. Patterns in prevalence and treatment use were analyzed descriptively; no statistical tests were performed. RESULTS: An increase in AS prevalence (per 10,000 patients) was seen from 2006 to 2014 in primary analyses (Medicare: 2.12-3.60; MarketScan: 0.85-1.42) and sensitivity analyses. A similar trend occurred for axSpA (Medicare: 4.39-6.52; MarketScan: 1.33-2.21). For Medicare, the proportion of patients with AS (D1) using tumor necrosis factor α inhibitors (TNFis), conventional synthetic antirheumatic drugs (csARDs), nonsteroidal antiinflammatory drugs (NSAIDs), opioids, and glucocorticoids remained relatively stable; for MarketScan, TNFi-treated patients increased (51.7% to 65.7%) and NSAID-treated patients decreased (63.5% to 55.7%). CONCLUSION: AS and axSpA prevalence may have increased in the United States between 2006 and 2014. Reasons are unknown, but this may be due to increased disease awareness, among other factors.

Validation of claims-based diagnostic and procedure codes for cardiovascular and gastrointestinal serious adverse events in a commercially-insured population.

PURPOSE: To validate administrative claims codes with medical chart review for myocardial infarction (MI), ischemic stroke, and severe upper gastrointestinal (UGI) bleed events in a large, commercially-insured US population. METHODS: These validation studies were part of a larger study examining the risk of MI, ischemic stroke, and severe UGI bleeds in patients receiving a new prescription of selective cyclooxygenase (COX)-2 inhibitors (coxibs) and non-over-the-counter (OTC) non-steroidal anti-inflammatory drugs (NSAIDs), between 1 July 2002 and 30 September 2004. Patients from the study cohort and other health plan members from the HealthCore Integrated Research Database(SM) (HIRD) experiencing these events were selected for these studies. The positive predictive value (PPV) of each of the claims code algorithms, using medical chart review as the gold standard, was calculated. RESULTS: Two hundred charts per event were abstracted. The PPV for MI was 88.4% (177/200; 95%CI, 83.2-92.5%); PPV for ischemic stroke was 87.4% (175/200; 95%CI, 82.0-91.7%); PPV for severe UGI bleed was 56.5% (109/193; 95%CI, 49.2-63.6%). Refining the ischemic stroke claims algorithm resulted in a PPV of 95.5% (95%CI, 91.0-98.2%); refining the claims algorithm for severe UGI bleed resulted in a PPV of 87.8% (95%CI, 78.7-94.0%). CONCLUSION: The results suggest that, for certain adverse events, claims data can serve as the basis for pharmacoepidemiology research and drug safety surveillance in the US.

Anticonvulsant medications and the risk of suicide, attempted suicide, or violent death.

CONTEXT: In 2008, the US Food and Drug Administration mandated warning labeling for anticonvulsant medications regarding the increased risk of suicidal thoughts and behaviors. The decision was based on a meta-analysis not sufficiently large to investigate individual drugs. OBJECTIVE: To evaluate the risk of suicidal acts and combined suicidal acts or violent death associated with individual anticonvulsants. DESIGN: A cohort study of the risk of suicidal acts and combined suicidal acts or violent death in patients beginning use of anticonvulsant medications compared with patients initiating a reference anticonvulsant drug. SETTING AND PATIENTS: Patients 15 years and older from the HealthCore Integrated Research Database (HIRD) who began taking an anticonvulsant between July 2001 and December 2006. MAIN OUTCOME MEASURES: Cox proportional hazards models and propensity score-matched analyses were used to evaluate risk of attempted or completed suicide and combined suicidal acts or violent death, controlling for psychiatric comorbidities and other risk factors, among individual anticonvulsants compared with topiramate and secondarily carbamazepine. RESULTS: The study identified 26 completed suicides, 801 attempted suicides, and 41 violent deaths in 297,620 new episodes of treatment with an anticonvulsant (overall median follow-up, 60 days). The incidence of the composite outcomes of completed suicides, attempted suicides, and violent deaths for anticonvulsants used in at least 100 treatment episodes ranged from 6.2 per 1000 person-years for primidone to 34.3 per 1000 person-years for oxcarbazepine. The risk of suicidal acts was increased for gabapentin (hazard ratio [HR], 1.42; 95% confidence interval [CI], 1.11-1.80), lamotrigine (HR, 1.84; 95% CI, 1.43-2.37), oxcarbazepine (HR, 2.07; 95% CI, 1.52-2.80), tiagabine (HR, 2.41; 95% CI, 1.65-3.52), and valproate (HR, 1.65; 95% CI, 1.25-2.19), compared with topiramate. The analyses including violent death produced similar results. Gabapentin users had increased risk in subgroups of younger and older patients, patients with mood disorders, and patients with epilepsy or seizure when compared with carbamazepine. CONCLUSION: This exploratory analysis suggests that the use of gabapentin, lamotrigine, oxcarbazepine, and tiagabine, compared with the use of topiramate, may be associated with an increased risk of suicidal acts or violent deaths.

The clinical, humanistic, and economic burden of palmoplantar pustulosis: a structured review.

Introduction: Palmoplantar pustulosis (PPP) is a chronic, relapsing and refractory disease characterized by sterile pustules appearing on the palms and/or soles, accompanied by erythema, blistering, scales and/or keratinization. The overall burden of PPP in terms of its clinical impact, effect on patients and families, and economic consequences has not previously been investigated in a structured manner.Areas covered: A structured search focused on identification of studies in PPP using specific search terms in PubMed and EMBASE® from 2005 onwards, with additional back-referencing and pragmatic searches. Outcomes of interest included clinical burden, humanistic burden, and economic burden.Expert opinion: In cross-sectional studies, approximately 75% of all PPP patients suffer from active disease, with risk of relapse remaining constant over time. Patients' health-related quality of life is significantly impaired, as expected for a disease affecting hands and feet. Tools have been described that assess the clinical as well as patient-reported burden of PPP; their performance in larger cohorts and/or clinical trials remains to be investigated. The key data limitations identified include inconsistent definitions for characterizing remission/relapse, and limited humanistic and economic burden data; future studies are required to address these evidence gaps.