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.

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.

Perceptions of patients with inflammatory bowel diseases on biobanking.

BACKGROUND: Little is known about beliefs, understanding, and perceptions of biobanking among patients with inflammatory bowel diseases. We aimed to further understand perceptions of biobanking in the inflammatory bowel disease community. METHODS: Subjects were recruited to participate in a 1:1 telephone interview on their perceptions of the risks and benefits of contributing specimens for research. These interviews informed a survey instrument evaluating perceptions of biobanking within Crohn's and Colitis Foundation of America Partners cohort. We used descriptive statistics to summarize participant responses, and bivariate statistics to compare willingness to participate in biobanking by disease and demographic factors. RESULTS: A total of 26 interviews were conducted. Various themes emerged from the interviews and aided in the development of the survey instrument. Concerns focused on storage, loss of confidentiality, outside uses, and life insurance discrimination. A total of 1007 individuals completed the survey. Overall, 397 (39.4%) reported that they would definitely donate samples, 568 (56.4%) would probably donate, 36 (3.6%) probably not, and 6 (0.6%) would definitely not donate. No significant differences in willingness to donate samples were seen for Crohn's disease versus ulcerative colitis (P = 0.25) or for remission versus active disease (P = 0.14). For sample-type preference, 956 (89.6%) would donate blood, 997 (93.5%) saliva, and 822 (77.1%) stool. CONCLUSIONS: Majorities of patients with inflammatory bowel disease demonstrated willingness to donate specimens for biobanking, albeit with concerns. Addressing these concerns will enhance participation and engagement and create greater alignment between the desires of research participants and the governance structure and operating policies of biobanks.

Validation of an internet-based cohort of inflammatory bowel disease (CCFA partners).

BACKGROUND: As traditional methods have become increasingly difficult, the Internet offers a mechanism for conducting survey research quickly and efficiently. However, the validity of this research depends on the ability of respondents to accurately report health status. We used a large Internet-based inflammatory bowel disease (IBD) cohort to validate self-reported IBD against physician reports. METHODS: Between June 22, 2012, and April 01, 2013, all participants of CCFA Partners (n = 6681) were invited to participate, and 450 were selected by random stratified sampling. We sent physicians a survey to confirm IBD diagnosis and characteristics. We used descriptive statistics to compare data. RESULTS: A total of 4423 participants (66%) indicated interest. Of 450 selected, 261 (58%) consented, and physician reports were obtained for 184 (71%). Physicians confirmed IBD status in 178 (97%) and type in 171 (97% of confirmed). The matching between patient and physician reports for Crohn's disease (CD) was 82% for disease location, 89% for the presence of perianal disease, and 46% for disease behavior. For ulcerative colitis (UC), disease location matched 54% of the time. Physician reports confirmed the status of ever having bowel surgery for 97% of CD and 94% for UC and confirmed current pouch or ostomy in 84% of CD and 81% of UC. CONCLUSIONS: Self-reported IBD in CCFA Partners is highly accurate, and participants are willing to release medical records for research. Self-reported phenotypic characteristics were less valid. The validity of IBD diagnoses among the participants of CCFA Partners supports the use of this cohort for patient-centered outcome research.

Patterns of 6-mercaptopurine and azathioprine maintenance therapy among a cohort of commercially insured individuals diagnosed with Crohn's disease in the United States.

BACKGROUND AND AIMS: Thiopurines, including 6-mercaptopurine (6-MP) and azathioprine (AZA), are the mainstay of maintenance therapy for Crohn's disease (CD). However, studies examining their effectiveness in routine practice among diverse patient populations are lacking. Among a cohort of new users of 6MP/AZA, we described treatment patterns and changes in subsequent therapy. METHODS: Using the Truven Health Analytics databases, we identified all individuals diagnosed with CD and initiating 6-MP/AZA monotherapy from 2001-2008 (n=3,657). We estimated the proportion of CD patients remaining on 6-MP/AZA monotherapy, using Kaplan-Meier methods, and identified predictors of treatment noncontinuation, using multivariable Cox regression. Among the "noncontinuers," we described subsequent patterns of maintenance therapy and summarized the diagnosis and procedure codes and prescription drug claims preceding treatment discontinuation. RESULTS: The 1-year 6-MP/AZA treatment continuation rate was 42%. Children (age ≤18 years) and individuals with no prior anti-tumor necrosis factor (TNF) use were more likely to continue 6-MP/AZA, while those dispensed more (>4) outpatient prescriptions for any drug before initiation of 6-MP/AZA were less likely to continue maintenance treatment. Overall, 1,128 (39%) and 105 (4%) individuals experienced a clinical event potentially indicating active disease or 6-MP/AZA-intolerance prior to discontinuation, respectively. Most patients discontinued therapy; among the remaining patients who failed to continue 6-MP/AZA, most augmented with an anti-TNF. CONCLUSION: Most patients initiating 6-MP/AZA monotherapy did not continue beyond 1 year. In contrast to trial evidence showing 1-year remission rates of 40%-80%, this study observed a lower effectiveness of 6-MP/AZA treatment, possibly due to differences in disease severity, patient demographics, comorbidity, adherence, and health care utilization.

The burden of comedication among patients with inflammatory bowel disease.

BACKGROUND: Polypharmacy is of growing concern in the chronically ill, including individuals with inflammatory bowel disease (IBD). The authors aimed to describe the prevalence and predictors of non-IBD medication use and to compare drug use among individuals with and without IBD. METHODS: This cross-sectional study included members of health plans included in the Thomson Reuters MarketScan databases with continuous enrollment during 2009 and 2010. Patients with IBD were identified through diagnosis codes and IBD medication dispensings and matched to 5 individuals without IBD. The prevalences of dispensed prescriptions for analgesics (narcotics, nonnarcotics), psychiatric medications (anxiolytics/sedatives/hypnotics, antidepressants), and broad drug classes defined by the Anatomic Therapeutic Classification system were estimated. Predictors of non-IBD medication use and comparisons of drug use by IBD status were evaluated using logistic regression. RESULTS: The prevalence of medication use was higher among patients with IBD than matched members of the general population for nearly every drug class examined, including narcotic analgesics (48.1% versus 34.1%), nonnarcotic analgesics (12.8% versus 8.1%), anxiolytics/sedatives/hypnotics (25.8% versus 16.7%), and antidepressants (28.3% versus 19.4%). Medicaid insurance, middle age, gastrointestinal surgery, Crohn's disease, and increasing number of inpatient, and outpatient, and prescription events were significantly associated with analgesic and psychiatric medication use among patients with IBD. Psychiatric drug dispensings were more common among female IBD patients than male patients. CONCLUSIONS: Patients with IBD have increased medication use, particularly of analgesic and psychiatric drugs. IBD care providers should be aware of polypharmacy and its potential for drug interactions.

International variation in medication prescription rates among elderly patients with inflammatory bowel disease.

BACKGROUND AND AIMS: The elderly represent a growing demographic of patients with IBD. No study has previously described variations in care or medication prescriptions in senior patients with IBD. We compared prescription rates among elderly patients with IBD in four countries using health administrative data. METHODS: Databases from the United States (US), United Kingdom (UK), Denmark and Canada were queried. Variation in prescription rates between countries was assessed in patients ≥65y with prevalent IBD who had ≥1 prescription for an IBD-related medication in a given quarter between 2004 and 2009. Patients were identified using previously-reported, validated algorithms. Country-specific rates were compared in each quarter using Fisher's exact test. RESULTS: In patients with Crohn's disease, Canada and US had higher prescription rates for oral 5-ASA (P<0.0001 in all quarters) and infliximab (P<0.05 in 22/24 quarters), while the US had higher rates of thiopurine usage (P<0.05 in 23/24 quarters). Canada had greater rates of methotrexate prescriptions (P<0.05 in 21/24 quarters analyzed). In patients with ulcerative colitis (UC), rates of oral steroid usage was lowest in the US (P<0.05 in 22/24 quarters) and oral 5-ASA use was highest in the US and Canada (P<0.0001 in all quarters). Canada and Denmark used more rectal therapy than the US. Infliximab usage in UC was significantly higher in the US and Canada after 2006. CONCLUSIONS: Significant variation in medication prescription rates exists among countries. Future research should assess whether these differences were associated with disparities in outcomes and health care costs.

Recent trends in the prevalence of Crohn's disease and ulcerative colitis in a commercially insured US population.

PURPOSE: Most US inflammatory bowel disease (IBD) epidemiology studies conducted to date have sampled small, geographically restricted populations and have not examined time trends. The aim of our study was to determine the prevalence of Crohn's disease (CD) and ulcerative colitis (UC) in a commercially insured US population and compare prevalences across sociodemographic characteristics and time. METHODS: Using claims data from approximately 12 million Americans, we performed three consecutive 2-year cross-sectional studies. Cases of CD and UC were identified using a previously described algorithm. Prevalence was estimated by dividing cases by individuals in the source population. Logistic regression was used to compare prevalences by region, age, and sex. RESULTS: In 2009, the prevalences of CD and UC in children were 58 [95 % confidence interval (CI) 55-60] and 34 (95 % CI 32-36), respectively. In adults, the respective prevalences were 241 (95 % CI 238-245) and 263 (95 % CI 260-266). Data analysis revealed that IBD prevalences have slightly increased over time. Based on census data, an estimated 1,171,000 Americans have IBD (565,000 CD and 593,000 UC). CONCLUSIONS: Analysis of the epidemiological data revealed an increasing burden of IBD in recent years, which may be used to inform policy.

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.

Risk factors for colon ischemia.

BACKGROUND: To identify predictors of colon ischemia, we examined demographic and clinical characteristics of patients, as well as their prior health care utilization. METHODS: Using insurance data, we identified 700 persons at least 20-yr old with presumed colon ischemia between 1995 and 1999, and 6,440 controls. Case identification was based on diagnosis and procedure codes in insurance claims for which we used a previously reported, validated algorithm. We ascertained preceding medical diagnoses and the use of drugs and health services from the insurance claims files. RESULTS: Patients with colon ischemia were nearly three times as likely to have IBS than controls. A history of nonspecific colitis, lower gastrointestinal tract hemorrhage, systemic rheumatologic disorders, and ischemic heart disease in the preceding 6 months, and abdominal surgery in the past month were also much more common in colon ischemia cases than controls. Use of a drug to treat diarrhea was strongly associated with risk. The most prevalent risk factor for colon ischemia was the use of drugs with a side effect of constipation, found in one-third of cases and one in nine controls. Cases had seen physicians, particularly gastroenterologists, much more commonly in the preceding 6 months than had controls. CONCLUSIONS: Clinically evident colon ischemia arises preferentially in persons with prior abdominal complaints, many of whom carry a diagnosis of IBS. Drugs that reduce bowel motility may constitute a widespread and potentially avoidable risk factor. The frequency of preceding doctor visits, without a specific diagnosis, suggests that colon ischemia may have a prolonged subacute presentation.

Incidence of colonic ischemia, hospitalized complications of constipation, and bowel surgery in relation to use of alosetron hydrochloride.

OBJECTIVE: Alosetron hydrochloride (Lotronex), a potent selective 5-hydroxytryptamine(3) receptor antagonist, was approved in February, 2000 in the United States for the treatment of diarrhea-predominant irritable bowel syndrome (IBS) in women. Marketing was suspended in November, 2000, after reports of colonic ischemia and serious complications of constipation. We sought to compare the incidence of colonic ischemia, hospitalized complications of constipation, and bowel surgery among alosetron users and a cohort of patients with IBS who did not use alosetron. METHODS: We sought outcomes of colonic ischemia, hospitalized complications of constipation, and bowel surgery in 3,631 Lotronex users and 2,480 comparison IBS subjects using diagnoses, procedures, and drugs recorded in the UnitedHealthcare insurance claims database, and validated these by chart review. The initial assessment was to last for 3 yr beginning with the start of alosetron treatment and was to include 10,000 Lotronex users; however, the observation period ended by December 31, 2000, after suspension of marketing. RESULTS: There were 3631 alosetron users among members of UnitedHealthcare from March through December, 2000, and we identified 2480 comparison IBS-only patients; follow-up time averaged about 5 months in both groups. There were no instances of colonic ischemia in either cohort. Thirty instances of bowel surgery occurred, giving rates of 10.2/1000 person-yr in the alosetron cohort and 11.8/1000 person-yr in the IBS/no alosetron cohort. There were three cases of hospitalized complications of constipation. The incidence rates were essentially the same in alosetron users (1.24/1000 person-yr) and in IBS patients with no alosetron use (0.92/1000 person-yr). CONCLUSIONS: Alosetron users did not differ from IBS patients not using alosetron in the incidence of bowel surgery or hospitalized complications of constipation; there were no cases of colonic ischemia. The statistical upper limit of colonic ischemia rates in alosetron users was 2.28/1000 person-yr. Because of the market withdrawal, the size of the cohort and the duration of follow-up were smaller than originally planned; consequently, the statements about the safety of alosetron were necessarily limited. On June 7, 2002, the Food and Drug Administration approved alosetron for reintroduction in the U.S. market for women with severe diarrhea-related IBS.

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.