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.

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.

Ticagrelor Removal by CytoSorb® in Patients Requiring Emergent or Urgent Cardiac Surgery: A UK-Based Cost-Utility Analysis.

BACKGROUND: Acute coronary syndrome patients receiving dual antiplatelet therapy who need emergent or urgent cardiac surgery are at high risk of major bleeding, which can impair postoperative outcomes. CytoSorb®, a blood purification technology based on adsorbent polymer, has been demonstrated to remove ticagrelor from blood during on-pump cardiac surgery. OBJECTIVE: The aim of this study was to evaluate the cost utility of intraoperative removal of ticagrelor using CytoSorb versus usual care among patients requiring emergent or urgent cardiac surgery in the UK. METHODS: A de novo decision analytic model, based on current treatment pathways, was developed to estimate the short- and long-term costs and outcomes. Results from randomised clinical trials and national standard sources such as National Health Service (NHS) reference costs were used to inform the model. Costs were estimated from the NHS and Personal Social Services perspective. Deterministic and probabilistic sensitivity analyses (PSAs) explored the uncertainty surrounding the input parameters. RESULTS: In emergent cardiac surgery, intraoperative removal of ticagrelor using CytoSorb was less costly (£12,933 vs. £16,874) and more effective (0.06201vs. 0.06091 quality-adjusted life-years) than cardiac surgery without physiologic clearance of ticagrelor over a 30-day time horizon. For urgent cardiac surgery, the use of CytoSorb was less costly than any of the three comparators-delaying surgery for natural washout without adjunctive therapy, adjunctive therapy with short-acting antiplatelet agents, or adjunctive therapy with low-molecular-weight heparin. Results from the PSAs showed that CytoSorb has a high probability of being cost saving (99% in emergent cardiac surgery and 53-77% in urgent cardiac surgery, depending on the comparators). Cost savings derive from fewer transfusions of blood products and re-thoracotomies, and shorter stay in the hospital/intensive care unit. CONCLUSIONS: The implementation of CytoSorb as an intraoperative intervention for patients receiving ticagrelor undergoing emergent or urgent cardiac surgery is a cost-saving strategy, yielding improvement in perioperative and postoperative outcomes and decreased health resource use.

Enrollment factors and bias of disease prevalence estimates in administrative claims data.

PURPOSE: Considerations for using administrative claims data in research have not been well-described. To increase awareness of how enrollment factors and insurance benefit use may contribute to prevalence estimates, we evaluated how differences in operational definitions of the cohort impact observed estimates. METHODS: We conducted a cross-sectional study estimating the prevalence of five gastrointestinal conditions using MarketScan claims data for 73.1 million enrollees. We extracted data obtained from 2009 to 2012 to identify cohorts meeting various enrollment, prescription drug benefit, or health care utilization characteristics. Next, we identified patients meeting the case definition for each of the diseases of interest. We compared the estimates obtained to evaluate the influence of enrollment period, drug benefit, and insurance usage. RESULTS: As the criteria for inclusion in the cohort became increasingly restrictive the estimated prevalence increased, as much as 45% to 77% depending on the disease condition and the definition for inclusion. Requiring use of the insurance benefit and a longer period of enrollment had the greatest influence on the estimates observed. CONCLUSIONS: Individuals meeting case definition were more likely to meet the more stringent definition for inclusion in the study cohort. This may be considered a form of selection bias, where overly restrictive inclusion criteria definitions may result in selection of a source population that may no longer represent the population from which cases arose.

Burden of gastrointestinal disease in the United States: 2012 update.

BACKGROUND & AIMS: Gastrointestinal (GI) diseases account for substantial morbidity, mortality, and cost. Statistical analyses of the most recent data are necessary to guide GI research, education, and clinical practice. We estimate the burden of GI disease in the United States. METHODS: We collected information on the epidemiology of GI diseases (including cancers) and symptoms, along with data on resource utilization, quality of life, impairments to work and activity, morbidity, and mortality. These data were obtained from the National Ambulatory Medical Care Survey; National Health and Wellness Survey; Nationwide Inpatient Sample; Surveillance, Epidemiology, and End Results Program; National Vital Statistics System; Thompson Reuters MarketScan; Medicare; Medicaid; and the Clinical Outcomes Research Initiative's National Endoscopic Database. We estimated endoscopic use and costs and examined trends in endoscopic procedure. RESULTS: Abdominal pain was the most common GI symptom that prompted a clinic visit (15.9 million visits). Gastroesophageal reflux was the most common GI diagnosis (8.9 million visits). Hospitalizations and mortality from Clostridium difficile infection have doubled in the last 10 years. Acute pancreatitis was the most common reason for hospitalization (274,119 discharges). Colorectal cancer accounted for more than half of all GI cancers and was the leading cause of GI-related mortality (52,394 deaths). There were 6.9 million upper, 11.5 million lower, and 228,000 biliary endoscopies performed in 2009. The total cost for outpatient GI endoscopy examinations was $32.4 billion. CONCLUSIONS: GI diseases are a source of substantial morbidity, mortality, and cost in the United States.

Evaluation of clinical outcomes with alvimopan in clinical practice: a national matched-cohort study in patients undergoing bowel resection.

OBJECTIVE: To evaluate in-hospital clinical outcomes after open and laparoscopic bowel resection (BR) with or without alvimopan treatment. BACKGROUND: Delayed return of gastrointestinal function after BR may be associated with greater postoperative morbidity and increased hospital length of stay (LOS). In clinical trials, alvimopan--a peripherally acting µ-opioid receptor antagonist--accelerated gastrointestinal recovery after open BR. METHODS: A retrospective matched-cohort study (NCT01150760) was conducted using a national inpatient database. Each alvimopan patient was exact matched (surgical procedure, surgeon specialty) and propensity score matched (baseline characteristics) to a nonalvimopan BR patient. Outcomes included gastrointestinal and other morbidity (cardiovascular, pulmonary, infection, cerebrovascular, thromboembolic); mortality; readmission rate; and intensive care unit (ICU) stay (intent-to-treat [ITT] population). Postoperative LOS and estimated cost were also compared (modified ITT population). RESULTS: Each cohort included 3525 ITT patients with similar baseline characteristics. Gastrointestinal (29.8% vs 35.7%) and other morbidity (cardiovascular [19.4% vs 24.0%], pulmonary [7.3% vs 10.5%], infectious [9.6% vs 11.8%], thromboembolic [1.2% vs 2.1%]), mortality (0.4% vs 1.0%), and mean ICU stay (0.3 vs 0.6 days) were lower in the alvimopan group (P ≤ 0.003 for each). Postoperative LOS and estimated direct cost were lower for all alvimopan patients and after laparoscopic and open BR (LOS: -1.1, -0.8, and -1.8 days respectively; cost: -$2345, -$1382, and -$3218, respectively; P ≤ 0.0008 for each). CONCLUSIONS: On average, alvimopan-treated patients had a lower incidence of mortality and most incidents of morbidities. Length of stay, ICU use, and estimated cost were also lower with comparable readmissions. These results in patients outside the clinical trial setting include laparoscopic colectomy and demonstrate a potential association between acceleration of gastrointestinal recovery and improved early postoperative outcomes.

Impact of alvimopan (entereg) on hospital costs after bowel resection: results from a large inpatient database.

PURPOSE: Delayed gastrointestinal (GI) recovery after bowel resection is associated with longer hospital stays and increased health care costs. Alvimopan (Entereg), a peripherally acting mu-opioid receptor antagonist, accelerates GI recovery after bowel-resection surgery. We undertook a study to evaluate the economic impact of alvimopan in clinical practice. METHODS: We conducted a retrospective matched cohort study using data from a large national hospital database and identified adults who had undergone small-bowel or large-bowel resection with primary anastomosis. The patients were discharged between January 1, 2009, and June 30, 2009. The surgery was performed at a hospital where alvimopan was used at least once during the study period. We matched each alvimopan patient ("user") with two controls ("non-users"). The primary outcome of total hospital costs (including the cost of alvimopan) and secondary outcomes of cost components and length of stay were compared between groups. RESULTS: The final study cohort included 480 alvimopan patients and 960 matched controls. The mean total hospital cost was $12,865 for alvimopan patients, compared with $13,905 for controls, for a difference of $1,040 (P = 0.033). There was a non-significant trend toward lower ileus-related costs between groups ($83 for alvimopan vs. $114 for controls, P = 0.086). Pharmacy and diagnostic radiology costs did not differ significantly. The mean length of stay was 5.6 days for alvimopan patients and 6.5 days for controls (P < 0.001). CONCLUSION: Patients receiving alvimopan capsules had significantly lower total hospital costs compared with controls. Along with other initiatives to improve quality and reduce costs of surgical care, alvimopan might be a good choice for use in the perioperative management of patients who undergo segmental bowel resection with primary anastomosis.

Prevalence of opioid dispensings and concurrent gastrointestinal medications in an elderly population from Ontario, Canada.

BACKGROUND: Although opioid analgesics are effective therapeutic agents, gastrointestinal (GI) side effects represent a challenging consequence of treatment. In an elderly population, age-related physiological changes, such as decreased GI functioning and dehydration, may compound the adverse effects of opioids; therefore, appropriate prophylactic treatment, utilizing laxatives and/or acid suppressants, is particularly important in an elderly population. AIM: This study describes the prevalence of outpatient opioid dispensings and the concomitant dispensing of opioids and GI medications in a population 65 years or older enrolled in the Ontario Drug Benefit Program in 2005. METHODS: Using a retrospective cohort design, dispensings of opioids, laxatives, and acid suppressants were identified using claims reimbursement data. Concurrent dispensings were defined as having at least one "GI medication-dispensed day" overlapping an "opioid-dispensed day". RESULTS: More than 18 percent of the elderly, drug plan population was dispensed an opioid in 2005. Women had more opioid dispensings and were dispensed opioids for extended periods of time as compared with men. Approximately half of patients with an opioid dispensing were concomitantly dispensed a GI medication; these medications were dispensed nearly twice as frequently among people with chronic opioid dispensings when compared with people with nonchronic opioid dispensings. CONCLUSIONS: Although laxatives are commonly recommended in patients taking opioids, only half of the older adults in Ontario who were dispensed an opioid also received a concomitant GI medication dispensing. As the elderly are more likely to develop opioid-induced constipation, the prophylactic use of laxatives and/or acid suppressant medications is often necessary to mitigate the side effects associated with their pain management.

Prevalence and characteristics of opioid use in the US adult population.

This report describes the prevalence of opioid use in the US adult population, overall and in subgroups, the characteristics of opioid use, and concomitant medication use among opioid users. Data were obtained from the Slone Survey, a population-based random-digit dialing survey. One household member was randomly selected to answer a series of questions regarding all medications taken during the previous week. There were 19,150 subjects aged > or = 18 interviewed from 1998 to 2006. Opioids were used 'regularly' ( > or = 5 days per week for > or = 4 weeks) by 2.0%; an additional 2.9% used opioids less frequently. Regular opioid use increased with age, decreased with education level, and was more common in females and in non-Hispanic whites. The prevalence of regular opioid use increased over time and was highest in the South Central region. Nearly one-fifth of regular users had been taking opioids for > or = 5 years. Concomitant use of > or = 10 non-opioid medications was reported by 21% of regular opioid users compared to 4.5% of subjects who did not use opioids. Regular opioid users were more likely to use stool softeners/laxatives (9% vs. 2%), proton pump inhibitors (25% vs. 8%), and antidepressants (35% vs. 10%). From this nationally-representative telephone survey, we estimate that over 4.3 million US adults are taking opioids regularly in any given week. Information on the prevalence and characteristics of use is important as opioids are one of the most widely prescribed classes of drugs in the US.

Algorithms to identify colonic ischemia, complications of constipation and irritable bowel syndrome in medical claims data: development and validation.

PURPOSE: A challenge in the use of insurance claims databases for epidemiologic research is accurate identification and verification of medical conditions. This report describes the development and validation of claims-based algorithms to identify colonic ischemia, hospitalized complications of constipation, and irritable bowel syndrome (IBS). METHODS: From the research claims databases of a large healthcare company, we selected at random 120 potential cases of IBS and 59 potential cases each of colonic ischemia and hospitalized complications of constipation. We sought the written medical records and were able to abstract 107, 57, and 51 records, respectively. We established a 'true' case status for each subject by applying standard clinical criteria to the available chart data. Comparing the insurance claims histories to the assigned case status, we iteratively developed, tested, and refined claims-based algorithms that would capture the diagnoses obtained from the medical records. We set goals of high specificity for colonic ischemia and hospitalized complications of constipation, and high sensitivity for IBS. RESULTS: The resulting algorithms substantially improved on the accuracy achievable from a naïve acceptance of the diagnostic codes attached to insurance claims. The specificities for colonic ischemia and serious complications of constipation were 87.2 and 92.7%, respectively, and the sensitivity for IBS was 98.9%. CONCLUSIONS: U.S. commercial insurance claims data appear to be usable for the study of colonic ischemia, IBS, and serious complications of constipation.

Projecting future complications of chronic hepatitis C in the United States.

Chronic hepatitis C virus (HCV) infection is common and often results in slowly progressive liver disease. Although acute hepatitis C is now uncommon, most patients with acute infection have developed chronic hepatitis, and, therefore, the pool of infected patients is large. We used a modification of a previously described natural history model for HCV infection to project the number of cases of HCV infection, cirrhosis, and liver failure over the next 40 years. The model estimated the prevalence of HCV infection in the United States was 3.07 x 10(6) in 1993 (compared with an adjusted National Health and Nutrition Evaluation Survey (NHANES) III estimate of 2.8 to 3.5 x 10(6)). A gradual decline in the prevalence of infection should occur by year 2040 because of aging and natural deaths among the infected pool. However, as the duration of infection increases in the surviving cohort, the proportion with cirrhosis will increase from 16% to 32% by 2020 in an untreated population. Complications of cirrhosis also will increase dramatically over the next 20 years: hepatic decompensation (up 106%), hepatocellular carcinoma (up 81%), and liver-related deaths (up 180%). Although current treatment regimens eradicate HCV in over 50% of cases, many more patients would need to be treated to significantly impact disease progression. Identification and treatment of every case of HCV infection (with or without cirrhosis) would reduce the number of cases of decompensated cirrhosis by almost half after 20 years. Despite the declining incidence of acute HCV infection, chronic hepatitis C is common. The prevalence of cirrhosis and the incidence of its complications will increase over the next 10 to 20 years, because the duration of infection increases among those with chronic hepatitis C. These data emphasize the need for greater access to transplantation by expansion of the donor pool, increasing use of split livers and living donors, and novel options such as xenotransplantation.