Prognostic Factors of COVID-19: An Umbrella Review Endorsed by the International Society for Pharmacoepidemiology.

During the coronavirus disease 2019 (COVID-19) pandemic, the urgency for updated evidence to inform public health and clinical care placed systematic literature reviews (SLRs) at the cornerstone of research. We aimed to summarize evidence on prognostic factors for COVID-19 outcomes through published SLRs and to critically assess quality elements in the findings' interpretation. An umbrella review was conducted via electronic databases from January 2020 to April 2022. All SLRs (and meta-analyses) in English were considered. Data screening and extraction were conducted by two independent reviewers. AMSTAR 2 tool was used to assess SLR quality. The study was registered with PROSPERO (CRD4202232576). Out of 4,564 publications, 171 SLRs were included of which 3 were umbrella reviews. Our primary analysis included 35 SLRs published in 2022, which incorporated studies since the beginning of the pandemic. Consistent findings showed that, for adults, older age, obesity, heart disease, diabetes, and cancer were more strongly predictive of risk of hospitalization, intensive care unit admission, and mortality due to COVID-19. Male sex was associated with higher risk of short-term adverse outcomes, but female sex was associated with higher risk of long COVID. For children, socioeconomic determinants that may unravel COVID-19 disparities were rarely reported. This review highlights key prognostic factors of COVID-19, which can help clinicians and health officers identify high-risk groups for optimal care. Findings can also help optimize confounding adjustment and patient phenotyping in comparative effectiveness research. A living SLR approach may facilitate dissemination of new findings. This paper is endorsed by the International Society for Pharmacoepidemiology.

Malignancy rates in Crohn's disease patients with perianal fistula: A German retrospective cohort study.

BACKGROUND: Patients with inflammatory bowel disease are at increased risk of colorectal and extra-intestinal cancer. However, the overall cancer risk in patients with Crohn's disease (CD) with perianal fistulas (PF) (CPF) and those with CD without PF (non-PF CD) is unclear. OBJECTIVE: To describe the prevalence and incidence of cancer in patients with CPF and non-PF CD, and to estimate incidence rate ratio (IRR) of cancer between CPF and non-PF CD groups. METHODS: A retrospective cohort study was conducted using the German InGef (Institute for Applied Health Research Berlin) research database. Patients with a CD record and PF from 1 January 2013 to 31 December 2014 were identified and followed up from 1 January 2015 until the first occurrence of cancer, end of health insurance contributing data, death, or end of study period (31 December 2020). Prevalence of any type of cancer including patients with CD diagnosed with cancer in the selection period and incidence of cancer excluding patients with CD diagnosed with cancer in the selection period were calculated. RESULTS: In total, 10,208 patients with CD were identified. Of 824 patients with CPF (8.1%), 67 had had a malignancy (6-year period crude malignancy prevalence 8.13% [95% confidence interval (CI) 6.36%-10.21%]), which was lower than patients with non-PF CD (19.8% [95% CI 19%-20.6%]). Incidence (per 100,000 person-years) in patients with CPF was 1184 (95% CI 879-1561) and in non-PF CD was 2365 (95% CI 2219-2519). There was no significant difference in the adjusted IRR of cancer for the CPF group compared with the non-PF CD group (0.83 [95% CI 0.62-1.10]; p = 0.219). CONCLUSION: There was no significant difference in the incidence of any cancer in patients with CPF compared with non-PF CD. However, patients with CPF had a higher numerical risk of cancer than the general German population.

A Systematic Review of Epidemiology and Outcomes Associated with Local Surgical and Intersphincteric Ligation Procedures for Complex Cryptoglandular Fistulas.

INTRODUCTION: This systematic literature review (SLR) assessed incidence/prevalence of cryptoglandular fistulas (CCF) and outcomes associated with local surgical and intersphincteric ligation procedures for CCFs. METHODS: Two trained reviewers searched PubMed and Embase for observational studies evaluating the incidence/prevalence of cryptoglandular fistula and clinical outcomes of treatments for CCF after local surgical and intersphincteric ligation procedures for CCF. RESULTS: In total 148 studies met a priori eligibility criteria for all cryptoglandular fistulas and all intervention types. Of those, two assessed incidence/prevalence of cryptoglandular fistulas. Eighteen reported clinical outcomes of surgeries of interest in CCF and were published in the past 5 years. Prevalence was reported as 1.35/10,000 non-Crohn's patients, and 52.6% of non-IBD patients were found to progress from anorectal abscess to fistula over 12 months. Primary healing rates ranged from 57.1% to 100%; recurrence occurred in a range of 4.9-60.7% and failure in 2.8-18.0% of patients. Limited published evidence suggests postoperative fecal incontinence and long-term postoperative pain were rare. Several of the studies were limited by single-center design with small sample sizes and short follow-up durations. DISCUSSION: This SLR summarizes outcomes from specific surgical procedures for the treatment of CCF. Healing rates vary according to procedure and clinical factors. Differences in study design, outcome definition, and length of follow-up prevent direct comparison. Overall, published studies offer a wide range of findings with respect to recurrence. Postsurgical incontinence and long-term postoperative pain were rare in the included studies, but more research is needed to confirm rates of these conditions following CCF treatments. CONCLUSION: Published studies on the epidemiology of CCF are rare and limited. Outcomes of local surgical and intersphincteric ligation procedures show differing success and failure rates, and more research is needed to compare outcomes across various procedures. (PROSPERO; registration number CRD42020177732).

A systematic review of epidemiology and outcomes of Crohn's disease-related enterocutaneous fistulas.

BACKGROUND: Enterocutaneous fistulas (ECF) are rare sequelae of Crohn's disease (CD) that occur either postoperatively or spontaneously. ECFs are associated with high morbidity and mortality. This systematic literature review assesses the disease burden of CD-related ECF and identifies knowledge gaps around incidence/prevalence, treatment patterns, clinical outcomes, healthcare resource utilization (HCRU), and patient-reported outcomes (PROs). METHODS: English language articles published in PubMed and Embase in the past 10 years that provided data and insight into the disease burden of CD-related ECF (PROSPERO Registration number: CRD42020177732) were identified. Prespecified search and eligibility criteria guided the identification of studies by two reviewers who also assessed risk of bias. RESULTS: In total, 582 records were identified; 316 full-text articles were assessed. Of those, eight studies met a priori eligibility criteria and underwent synthesis for this review. Limited epidemiologic data estimated a prevalence of 3265 persons with ECF in the USA in 2017. Clinical response to interventions varied, with closure of ECF achieved in 10% to 62.5% of patients and recurrence reported in 0% to 50% of patients. Very little information on HCRU is available, and no studies of PROs in this specific population were identified. CONCLUSION: The frequency, natural history, and outcomes of ECF are poorly described in the literature. The limited number of studies included in this review suggest a high treatment burden and risk of substantial complications. More robust, population-based research is needed to better understand the epidemiology, natural history, and overall disease burden of this rare and debilitating complication of CD.

Mesenchymal Stem Cell Therapy Awareness, Knowledge, and Use for the Treatment of Fistulizing Crohn's Disease: An International Survey Among Gastroenterologists and Colorectal Surgeons.

INTRODUCTION: Mesenchymal stem (or stromal) cells are a promising therapy for the treatment of various inflammatory and autoimmune diseases. This study aimed to understand awareness, knowledge, and perception of mesenchymal stem cells among gastroenterologists and colorectal surgeons, with particular focus on the perianal fistulizing Crohn's disease indication. METHODS: A web-based questionnaire was distributed to currently practicing and registered gastroenterologists and colorectal surgeons across 15 countries in North America, Europe, and Asia Pacific. RESULTS: Of 146 clinicians, 115 (79%) were aware of mesenchymal stem cells. The majority were moderately to largely interested in this therapy (87%), willing to use it in patients with perianal fistulizing Crohn's disease (82%), and believed it addresses unmet needs for these patients (93%). However, most responders reported having limited or no knowledge of this therapy (64%) or its efficacy (51%), safety (53%), and mechanism of action (65%) in perianal fistulizing Crohn's disease. Many clinicians (46%) also expressed concerns about using this therapy in these patients. Attending discussions and presentations on mesenchymal stem cells and seeing more patients with Crohn's disease were associated with increased awareness (both P < 0.001). CONCLUSIONS: Many clinicians demonstrated an interest in mesenchymal stem cells in general and a willingness to use them to treat perianal fistulizing Crohn's disease, but this survey showed suboptimal knowledge of what mesenchymal stem cells are and how they work in this indication. This may explain clinicians' concerns about use of this therapy and calls out for education activities.

A systematic review of the patient burden of Crohn's disease-related rectovaginal and anovaginal fistulas.

BACKGROUND: Crohn's disease (CD)-related rectovaginal fistulas (RVFs) and anovaginal fistulas (AVFs) are rare, debilitating conditions that present a substantial disease and treatment burden for women. This systematic literature review (SLR) assessed the burden of Crohn's-related RVF and AVF, summarizing evidence from observational studies and highlighting knowledge gaps. METHODS: This SLR identified articles in PubMed and Embase that provide data and insight into the patient experience and disease burden of Crohn's-related RVF and AVF. Two trained reviewers used pre-specified eligibility criteria to identify studies for inclusion and evaluate risk of bias using the Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) tool for observational studies. RESULTS: Of the 582 records identified, 316 full-text articles were assessed, and 16 studies met a priori eligibility criteria and were included. Few epidemiology studies were identified, with one study estimating the prevalence of RVF to be 2.3% in females with Crohn's disease. Seven of 12 treatment pattern studies reported that patients had or required additional procedures before and/or after the intervention of interest, demonstrating a substantial treatment burden. Seven of 11 studies assessing clinical outcomes reported fistula healing rates between 50 and 75%, with varying estimates based on population and intervention. CONCLUSIONS: This SLR reports the high disease and treatment burden of Crohn's-related RVF and AVF and identifies multiple evidence gaps in this field. The literature lacks robust, generalizable data, and demonstrates a compelling need for substantial, novel research into these rare and debilitating sequelae of CD. Registration The PROSPERO registration number for the protocol for this systematic literature review is CRD42020177732.

Prevalence of Inflammatory Bowel Disease in Pediatric and Adult Populations: Recent Estimates From Large National Databases in the United States, 2007-2016.

BACKGROUND: The latest estimate of the prevalence of inflammatory bowel disease (IBD) in the United States was based on 2009 data, which indicates a need for an up-to-date re-estimation. The objectives of this study were to investigate the prevalence of all forms of IBD including ulcerative colitis (UC), Crohn's disease (CD), and IBD unspecified (IBDU). METHODS: Pediatric (age 2-17) and adult (age ≥18) IBD patients were identified from 2 large claims databases. For each year between 2007 and 2016, prevalence was calculated per 100,000 population and standardized based on the 2016 national Census. A fixed-effects meta-analytical model was used for overall prevalence. RESULTS: The pediatric prevalence of IBD overall increased by 133%, from 33.0/100,000 in 2007 to 77.0/100,000 in 2016. Among children, CD was twice as prevalent as UC (45.9 vs 21.6). Prevalence was higher in boys than girls for all forms of IBD, in contrast to the adult population where the prevalence was higher in women than men. We also found that the 10-17 age subgroup was the major contributor to the rising pediatric IBD prevalence. For adults, the prevalence of IBD overall increased by 123%, from 214.9 in 2007 to 478.4 in 2016. The prevalence rates of UC and CD were similar (181.1 vs 197.7) in 2016. CONCLUSIONS: Inflammatory bowel disease continues to affect a substantial proportion of the US population. In 2016, 1 in 209 adults and 1 in 1299 children aged 2-17 were affected by IBD. Prevalence of IBD has been increasing compared with previously published 2009 data.

Identifying Patients With Inflammatory Bowel Diseases in an Administrative Health Claims Database: Do Algorithms Generate Similar Findings?

Application of selective algorithms to administrative health claims databases allows detection of specific patients and disease or treatment outcomes. This study identified and applied different algorithms to a single data set to compare the numbers of patients with different inflammatory bowel disease classifications identified by each algorithm. A literature review was performed to identify algorithms developed to define inflammatory bowel disease patients, including ulcerative colitis, Crohn's disease, and inflammatory bowel disease unspecified in routinely collected administrative claims databases. Based on the study population, validation methods, and results, selected algorithms were applied to the Optum Clinformatics® Data Mart database from June 2000 to March 2017. The patient cohorts identified by each algorithm were compared. Three different algorithms were identified from literature review and selected for comparison (A, B, and C). Each identified different numbers of patients with any form of inflammatory bowel disease (323 833; 246 953, and 171 537 patients, respectively). The proportions of patients with ulcerative colitis, Crohn's disease, and inflammatory bowel disease unspecified were 32.0% to 47.5%, 38.6% to 43.8%, and 8.7% to 26.6% of the total population with inflammatory bowel disease, respectively, depending on the algorithm applied. Only 5.1% of patients with inflammatory bowel disease unspecified were identified by all 3 algorithms. Algorithm C identified the smallest cohort for each disease category except inflammatory bowel disease unspecified. This study is the first to compare numbers of inflammatory bowel disease patients identified by different algorithms from a single database. The differences between results highlight the need for validation of algorithms to accurately identify inflammatory bowel disease patients.

Post-authorisation Safety Study of Pioglitazone Use and Safety Endpoints of Interest in Denmark After Direct Healthcare Professional Communication.

INTRODUCTION: A Direct Healthcare Professional Communication (DHPC) sent in Denmark on 11 August 2011 provided information on new pioglitazone labelling and guidance on monitoring treatment effectiveness. We describe pioglitazone use in Denmark after the DHPC, estimate the incidence of heart failure (HF), quantify pioglitazone cessation following a diagnosis of bladder cancer (BC) or uninvestigated macroscopic haematuria, and describe glycated haemoglobin (HbA1c) values. METHODS: This was a cohort study. From Danish population-based registries, cohorts of type 2 diabetes mellitus incident or prevalent users of pioglitazone or insulin in 2011-2015 were created. Patient characteristics, treatment patterns, laboratory results (available for a regional subset of the population), and incidence rates of HF and BC were estimated. RESULTS: There were 80 pioglitazone and 17,699 insulin incident users, 140 pioglitazone and 13,183 insulin prevalent users. There were no new BC cases among incident pioglitazone users, and < 5 new BC cases among prevalent pioglitazone users. Pioglitazone was rarely the first-line treatment. History of haematuria was documented in < 5 incident and 11 prevalent pioglitazone users. During follow-up, there were < 5 HF cases among 77 incident pioglitazone users and < 5 among 133 prevalent pioglitazone users without a history of HF. Median HbA1c at index date was 7.8% and 8.8% in incident pioglitazone and insulin cohorts, and 7.5% and 7.6% in prevalent pioglitazone and insulin cohorts, respectively. During follow-up of up to 4.4 years, 28.8% incident and 20.7% prevalent pioglitazone users discontinued pioglitazone. CONCLUSIONS: Numbers of pioglitazone users in Denmark were low and decreased over time. Risks of BC or HF were low and risk estimates imprecise.

Pioglitazone use and risk of bladder cancer: a systematic literature review and meta-analysis of observational studies.

BACKGROUND: Studies investigating bladder cancer risk in pioglitazone-treated type 2 diabetes mellitus patients report conflicting results. Previous meta-analyses on this topic utilized publications prior to 2013. More long-term observational studies have been published since then. We reviewed the accumulated evidence and updated findings from previous meta-analyses. METHODS: This meta-analysis was based on a systematic review of peer-reviewed observational studies published prior to September 30, 2016. Eligible studies were identified using a specified MEDLINE search. References from included studies and from previous meta-analyses were screened for additional records. Meta-analysis hazards ratios were derived using a random-effects model. Several sensitivity analyses including hierarchical Bayesian meta-analysis with country-specific effects were conducted. RESULTS: Of 363 identified records, 23 studies were included in this review and 18 in the actual meta-analyses. For bladder cancer outcome, the estimated effect size for ever vs. never use of pioglitazone was 1.16 [95% confidence interval (CI), 1.04-1.28]. In the cumulative dose and duration analyses, highest effect was observed in the highest/longest exposure group, but substantial heterogeneity was present. In the sensitivity analysis, only studies adjusted for lifestyle-related factors were included and the frequentist effect size was 1.18 (95% CI, 1.00-1.40, p = 0.054). However, the risk was not verified in the Bayesian framework with an effect size of 1.17 [95% credible interval (CrI), 0.94-1.54]. CONCLUSIONS: In line with previous meta-analyses, we observed a small but statistically significant association between ever (vs. never) use of pioglitazone and bladder cancer risk; however, causality is not established and alternative explanations cannot be ruled out.

Risk factors for postoperative infection after gastrointestinal surgery among adult patients with inflammatory bowel disease: Findings from a large observational US cohort study.

BACKGROUND AND AIM: Postoperative infection (POI) is a major source of morbidity and prolongation of hospitalization in inflammatory bowel disease (IBD) patients. This large observational study was conducted to further describe risk factors and to quantify the proportion of POIs that are preventable. METHODS: We conducted a retrospective cohort analysis of the Optum US health insurance claims database. The study population included adults with ulcerative colitis (UC) or Crohn's disease (CD) who underwent lower gastrointestinal (GI) surgery of small intestine, colon, rectum, or anus during September 2014 to September 2016. Multiple logistic regression was used to identify and quantify risk factors and determine the proportion of infections that are preventable. RESULTS: A total of 3360 adult IBD patients with lower GI surgery were included in the study. Their mean age was 51 years, 52.5% were women, and 59.5% had CD. The 30-day POI incidence was 15.1% (95% confidence interval: 14.0-16.4%). We identified the following nonmodifiable or procedural risk factors: history of POI, open procedure, red blood cell transfusion within 6 months, preoperative hospital stay of at least 4 days, lower GI ostomy surgery, lower GI resection surgery, and a history of chronic obstructive pulmonary disease. Modifiable risk factors included corticosteroid use and anemia prior to surgery, but few infections were attributable to these modifiable factors. CONCLUSIONS: This large, observational, real-world evidence study from the US found that the majority of the observed risk factors were nonmodifiable or procedure-related. Corticosteroid use and anemia before surgery were identified as modifiable risk factors.

Evaluation of exposure to pioglitazone and risk of prostate cancer: a nested case-control study.

OBJECTIVES: Investigate potential association between pioglitazone exposure and risk of prostate cancer. RESEARCH DESIGN AND METHODS: Nested, matched case-control study. UK primary care data (Clinical Practice Research Datalink (CPRD) GOLD) linked to inpatient (Hospital Episode Statistics (HES)) and cancer registry (National Cancer Information Network (NCIN)) data. English men aged ≥40 years diagnosed with type 2 diabetes mellitus, January 1, 2001 to January 5, 2015. Cases, with prostate cancer diagnosis, matched with up to 4 controls by age, cohort entry date and region. ORs for association of exposure to pioglitazone to incident prostate cancer, adjusted for potential confounders. RESULTS: From a cohort of 47 772 men with 243 923 person-years follow-up, 756 definite cases of prostate cancer were identified. Incidence was 309.9/100 000 person-years (95% CI 288.6 to 332.8). Pioglitazone use was not associated with prostate cancer risk; adjusted OR 0.759, 95% CI 0.502 to 1.148. Analyses showed no difference when possible cases, prostate cancer in CPRD GOLD only, included (adjusted OR 0.726, 95% CI 0.510 to 1.034). No association when adjusted for channeling bias (OR 0.778, 95% CI 0.511 to 1.184) or limited to an index date prior to July 1, 2011 (adjusted OR 0.508, 95% CI 0.294 to 0.879), despite prostate-specific antigen screening occurring more frequently among cases than controls (81.6% of 756 definite cases cf. 24.2% of 2942 controls (p<0.01)). No association with duration of pioglitazone use, increasing pioglitazone dose or increasing time since initiation. CONCLUSIONS: In this real-world, nested matched case-control study, exposure to pioglitazone was not associated with increased risk of prostate cancer.

United Kingdom immune thrombocytopenia registry: retrospective evaluation of bone marrow fibrosis in adult patients with primary immune thrombocytopenia and correlation with clinical findings.

Fibrosis has been reported in some patients with immune thrombocytopenia (ITP) treated with thrombopoietin receptor agonists (TPO-RA). However, fibrosis has also been reported in patients with various stages of ITP, who were TPO-RA treatment-naïve. In our study, we looked for fibrosis in bone marrow trephine biopsies taken at initial diagnosis from 32 adult patients with ITP. Ten of the 32 evaluated samples (31·25%) showed increased reticulin (Grade 1-2 on Bauermeister scale and Grade 0-1 on the European Consensus scale), which showed a positive correlation with ethnicity (0·3%) but did not correlate with disease severity, any clinical features or co-morbidities.

Thrombocytopenia in adult cancer patients receiving cytotoxic chemotherapy: results from a retrospective hospital-based cohort study.

BACKGROUND: Data on the frequency and relative risk (RR) of chemotherapy-induced thrombocytopenia (CIT) in patients with solid tumours receiving chemotherapy in clinical practice are limited. OBJECTIVE: The aim of the study was to estimate the frequency and RR of thrombocytopenia in adult patients with solid tumours receiving chemotherapy treatment. METHODS: For this retrospective, hospital-based study, adult patients with solid tumours who received chemotherapy at the University Medical Center Utrecht in the period 2004-6 were identified from the Utrecht Patient Oriented Database. We examined the frequency of (i) overall thrombocytopenia (defined as platelet count <100 × 109/L) with or without other cytopenias; (ii) isolated thrombocytopenia (i.e. without other cytopenias); and (iii) the frequency and RR of overall thrombocytopenia and isolated thrombocytopenia associated with different cytotoxic agents. RESULTS: A total of 614 patients receiving one of 37 different chemotherapy regimens was included. Overall thrombocytopenia frequency was 21.8% and isolated thrombocytopenia frequency was 6.2%. The highest frequencies of thrombocytopenia were observed in patients receiving carboplatin monotherapy (81.8%) and combination therapies that included carboplatin (58.2%), gemcitabine (64.4%) or paclitaxel (59.3%). The highest RRs of thrombocytopenia, compared with cisplatin-based therapy, were observed for combination therapies of carboplatin/gemcitabine (RR 10.1; 95% CI 5.5, 18.5) and carboplatin/paclitaxel/etoposide (RR 11.8; 95% CI 6.7, 20.8). In 54% of cases, the thrombocytopenia was of grade 2-4, which are considered to be the most clinically relevant grades. The highest frequencies of isolated thrombocytopenia were found with combination therapies that included oxaliplatin (28.6%) or gemcitabine (28.9%). CONCLUSIONS: The results suggest that CIT is a relevant problem in clinical practice. Further research is necessary to investigate the clinical consequences of thrombocytopenia. The observed frequencies of thrombocytopenia were lower than those observed in older studies, but comparable with that observed in a recent US-based study. The observed increased risks for possible immune-mediated thrombocytopenia associated with exposure to oxaliplatin and gemcitabine contribute to the suspicion that these drugs can cause immune-mediated thrombocytopenia, and warrant further investigation. For clinicians, the mechanism has important consequences because in immune-mediated thrombocytopenia the drug must be avoided, while in dose-dependent thrombocytopenia a dose reduction may be sufficient.

Single nucleotide polymorphism (SNP) analysis demonstrates a significant association of tumour necrosis factor-alpha (TNFA) with primary immune thrombocytopenia among Caucasian adults.

T-helper 1 polarization in patients with primary immune thrombocytopenia (ITP) is well documented. However, the genetic contribution to this imbalance remains unclear. To address this question, we selected six candidate single nucleotide polymorphisms within cytokine or cytokine receptor genes for association testing among Caucasian adults. Patients from the United Kingdom Adult ITP Registry were gender-matched (1:3) with healthy controls from the Wellcome Trust Case Control Consortium. Variants IL10 -819 c>t, TNFA -308 g>a, TGFB1 -509 c>t, IL1A -889 c>t, IL10 -592 c>t, and IL4R q576r were measured in cases and retrieved for controls from the European Genome-phenome Archive. Associations were evaluated using logistic regression models. In total, 206 patients with primary ITP were matched with 618 controls. A significant per allele odds ratio of 1·34 (95% confidence interval, 1·03-1·75; P = 0·03) was observed for TNFA -308 g>a, implicating an increased disease susceptibility among Caucasian carriers of the rare allele.

Hepatobiliary laboratory abnormalities among patients with chronic or persistent immune thrombocytopenia (ITP).

Therapies for immune thrombocytopenia (ITP) may be associated with abnormal hepatobiliary laboratory (HBL) values, but the epidemiology of these abnormalities is unknown in the ITP population. The study aim was to provide prevalence and incidence rates, as well as risk factors for abnormal HBL values among a cohort of patients with chronic or persistent primary ITP. Health insurance claims data from 3,244 patients with chronic or persistent ITP was examined to estimate the prevalence of abnormal HBL values: elevated levels of Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), total bilirubin, and Alkaline Phosphatase (ALP). Incidence of abnormal HBL values was estimated in a sub cohort of 2557 (79%) patients without evidence of comorbidities related to secondary thrombocytopenia, liver disease, or abnormal HBL values during the 12-month baseline period. The baseline prevalence of ALT and AST > 3x the upper limit of normal (ULN) was 4.6 and 3.7%, respectively. The baseline prevalence of total bilirubin and ALP >1.5x ULN was 4.2 and 3.2%, respectively. The incidence rate of new HBL abnormalities (HBLA) was 1.24/1,000 person-years (95% CI: 0.52-2.56) for ALT>3x ULN and 0.41/1,000 person-years (95% CI: 0.08-1.32) for AST>3x ULN. HBLAs were significantly associated with male gender, liver disease, diabetes, congestive heart failure, lupus, hematological cancers, and HIV infection. In conclusion, the prevalence of HBLA, specifically ALT>3x ULN, among the ITP population is relatively high compared with atrial fibrillation, though within the confidence interval for that estimate. HBLAs were significantly associated with male gender, liver disease, and several other comorbidities, thus, distinguishing drug-induced liver injury in this population is clinically challenging.

Comorbidities in patients with persistent or chronic immune thrombocytopenia.

There is a paucity of epidemiological data on the risk of comorbidities in adults with persistent or chronic immune thrombocytopenia (ITP). In this study, we compared the rates of cataracts, diabetes, renal failure, vascular events, lymphoma, and leukemia among patients with and without persistent or chronic ITP. Using administrative data, adult patients with medical claims for ITP from January, 2000 through September, 2006 were identified. An age- and gender-matched comparison cohort without evidence of ITP was randomly selected. The incidence rate ratio (IRR) of each comorbidity among ITP patients relative to the comparison group was estimated using Poisson regression, adjusting for baseline covariates. A total of 3,131 patients with persistent or chronic ITP were identified, and 9,392 were selected for the comparison cohort. The adjusted IRRs were as follows: diabetes 1.73 (95% CI 1.36-2.20), renal failure 2.05 (95% CI 1.67-2.51), any vascular event 1.70 (95% CI 1.41-2.05), lymphoma 5.91 (95% CI 2.61-13.37), leukemia 19.83 (95% CI 5.84-67.34), and mortality 4.21 (95% CI 3.06-5.79). There was no increased risk for cataract or myocardial infarction in the ITP cohort. Patients with persistent or chronic ITP are at increased risk for several comorbidities including hematologic malignancies, relative to a matched comparison cohort.