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Introduction: The rates of serious cardiac, neurologic, and pulmonary events attributable to colonoscopy are poorly characterized, and background event rates are usually not accounted for., Methods: We performed a multistate population-based study using changepoint analysis to determine the rates and timing of serious gastrointestinal and nongastrointestinal adverse events associated with screening/surveillance colonoscopy, including analyses by age (45 to <55, 55 to <65, 65 to <75, and ≥75 years). Among 4.5 million persons in the Ambulatory Surgery and Services Databases of California, Florida, and New York who underwent screening/surveillance colonoscopy in 2005-2015, we ascertained serious postcolonoscopy events in excess of background rates in Emergency Department (SEDD) and Inpatient Databases (SID)., Results: Most serious nongastrointestinal postcolonoscopy events were expected based on the background rate and not associated with colonoscopy itself. However, associated nongastrointestinal events predominated over gastrointestinal events at ages ≥65 years, including more myocardial infarctions plus ischemic strokes than perforations at ages ≥75 years (361 [95% confidence intervals {CI} 312-419] plus 1,279 [95% CI 1,182-1,384] vs 912 [95% CI 831-1,002] per million). At all ages, the observed-to-expected ratios for days 0-7, 0-30, and 0-60 after colonoscopy were substantially >1 for gastrointestinal bleeding and perforation, but minimally >1 for most nongastrointestinal complications. Risk periods ranged from 1 to 125 days depending on complication type and age. No excess postcolonoscopy in-hospital deaths were observed., Discussion: Although crude counts substantially overestimate nongastrointestinal events associated with colonoscopy, nongastrointestinal complications exceed bleeding and perforation risk in older persons. The inability to ascertain modifications to antiplatelet therapy was a study limitation. Our results can inform benefit-to-risk determinations for preventive colonoscopy., (Copyright © 2021 by The American College of Gastroenterology.)

Background & Aims: Colorectal cancer (CRC) incidence at ages younger than 50 years is increasing, leading to proposals to lower the CRC screening initiation age to 45 years. Data on the effectiveness of CRC screening at ages 45-49 years are lacking., Methods: We studied the association between undergoing colonoscopy at ages 45-49 or 50-54 years and CRC incidence in a retrospective population-based cohort study using Florida's linked Healthcare Cost and Utilization Project databases with mandated reporting from 2005 to 2017 and Cox models extended for time-varying exposure., Results: Among 195,600 persons with and 2.6 million without exposure to colonoscopy at ages 45-49 years, 276 and 4844 developed CRC, resulting in CRC incidence rates of 20.8 (95% CI, 18.5-23.4) and 30.6 (95% CI, 29.8-31.5) per 100,000 person-years, respectively. Among 660,248 persons with and 2.4 million without exposure to colonoscopy at ages 50-54 years, 798 and 6757 developed CRC, resulting in CRC incidence rates of 19.0 (95% CI, 17.7-20.4) and 51.9 (95% CI, 50.7-53.1) per 100,000 person-years, respectively. The adjusted hazard ratios for incident CRC after undergoing compared with not undergoing colonoscopy were 0.50 (95% CI, 0.44-0.56) at ages 45-49 years and 0.32 (95% CI, 0.29-0.34) at ages 50-54 years. The results were similar for women and men (hazard ratio, 0.48; 95% CI, 0.40-0.57 and hazard ratio, 0.52; 95% CI, 0.43-0.62 at ages 45-49 years, and hazard ratio, 0.35; 95% CI, 0.31-0.39 and hazard ratio, 0.29; 95% CI, 0.26-0.32 at ages 50-54 years, respectively)., Conclusions: Colonoscopy at ages 45-49 or 50-54 years was associated with substantial decreases in subsequent CRC incidence. These findings can inform screening guidelines., (Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background & Aims: The Hospital Readmissions Reduction Program (HRRP), which was instituted in 2012, may have affected readmission rates for non-target conditions, including colorectal cancer (CRC). We aimed to analyze the nationwide all-cause 30-day readmission rate following CRC surgery in a US nationwide database., Methods: We queried the 2010-2015 Nationwide Readmissions Database to estimate readmission rates. All results were weighted for national estimates., Results: Among 616,348 index cases, the overall 2010-2015 30-day readmission rate was 14.7% (95% confidence interval, 14.5%-14.9% [n = 90,555]), with a decreasing trend from 15.5% in 2010 and 2011 to 13.5% in 2015 (p-trend<0.001). Rectal resection, longer length of stay, non-invasive cancer, surgery at a metropolitan teaching hospital, non-routine discharge, elective admission, and higher Elixhauser comorbidity score were associated with subsequent readmission., Conclusions: In the US, 30-day readmission rates after CRC surgery showed a decreasing trend during 2010-2015, which could represent a spillover effect of the HRRP., Competing Interests: Declaration of competing interest The authors disclose no conflicts., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: The Childhood Health Assessment Questionnaire (CHAQ) is one of the most widely used self- report questionnaires to measure functional status in Juvenile idiopathic arthritis (JIA). The Japanese version of the CHAQ (JCHAQ) has been revised to meet requirements of clinical international trials which need the same number of questions in each functional area of the CHAQ. Methods: The original JCHAQ consisted of 36 items, measuring eight functional areas. This was changed to 30 items of questionnaire so that each functional area has same number of questions as the original US English version. The revised version was professionally translated from English to Japanese, reviewed, and validated with Japanese JIA patients. Results: A total of 42 JIA patients were enrolled in the validation: seven systemic, 30 polyarticular/oligoarticular and five enthesis related. Most patients were well controlled and the median disability index (DI) scores was 0.0 [0-0.03]; however, significant correlation was seen with visual analog scale (VAS) of pain, VAS overall well-being, physician VAS, DAS (Disease Activity Score) 28-ESR, and JADAS (Juvenile Arthritis Disease Activity Score)-27. In comparison of two groups of disease activity, remission or inactive/low disease activity vs. moderate/high disease activity, both DAS28-ESR and JADAS-27 showed significant correlation with DI. Conclusion: The updated JCHAQ was a reliable and valid tool for the functional assessment of children with JIA. It is more suitable for international and transitional comparison.

Background: The Affordable Care Act (ACA) with Medicaid expansion implemented in 2014, extended health insurance to >20-million previously uninsured individuals. However, it is unclear whether enhanced primary care access with Medicaid expansion decreased emergency department (ED) visits and hospitalizations for gastrointestinal (GI)/pancreatic/liver diseases., Methods: We evaluated trends in GI/pancreatic/liver diagnosis-specific ED/hospital utilization over a 5-year period leading up to Medicaid expansion and a year following expansion, in California (a state that implemented Medicaid expansion) and compare these with Florida (a state that did not)., Results: From 2009 to 2013, GI/pancreatic/liver disease ED visits increased by 15.0% in California and 20.2% in Florida and hospitalizations for these conditions decreased by 2.6% in California and increased by 7.9% in Florida. Following Medicaid expansion, a shift from self-pay/uninsured to Medicaid insurance was seen California; in addition, a new decrease in ED visits for nausea/vomiting and GI infections, was evident, without associated change in overall ED/hospital utilization trends. Total hospitalization charges for abdominal pain, nausea/vomiting, constipation, and GI infection diagnoses decreased in California following Medicaid expansion, but increased over the same time-period in Florida., Conclusions: We observed a striking payer shift for GI/pancreatic/liver disease ED visits/hospitalizations after Medicaid expansion in California, indicating a shift in the reimbursement burden in self-pay/uninsured patients, from patients and hospitals to the government. ED visits and hospitalization charges decreased for some primary care-treatable GI diagnoses in California, but not for Florida, suggesting a trend toward lower cost of gastroenterology care, perhaps because of decreased hospital utilization for conditions amenable to outpatient management.

Objectives: Several recent observations have suggested that the prevalence of gout may be increasing worldwide, but there are no recent data from the USA. We analysed the prevalence of hyperuricaemia and gout in the US population from 2007-08 to 2015-16., Methods: We studied adults ⩾20 years of age from the National Health and Nutrition Examination Survey from 2007-08 to 2015-16. Persons with gout were identified from the home interview question 'Has a doctor or other health professional ever told you that you had gout?' Hyperuricaemia was defined as a serum urate level >0.40 mmol/l (6.8 mg/dl) (supersaturation levels at physiological temperatures and pH)., Results: In 2015-16, the overall prevalence of gout among US adults was 3.9%, corresponding to a total affected population of 9.2 million. Hyperuricaemia (>0.40 mmol/l or 6.8 mg/dl) was seen in 14.6% of the US population (estimated 32.5 million individuals). No significant trends were identified in the age-adjusted prevalence of gout and hyperuricaemia. Statistical comparisons between 2007-08 and 2015-16 age-adjusted rates were not significant., Conclusion: While the age-adjusted prevalence of gout and hyperuricaemia has remained unchanged in the most recent decade from 2007-08 to 2015-16, the estimated total number of persons with self-reported gout has increased from 8.3 million to 9.2 million. The age-adjusted prevalence of hyperuricaemia has declined slightly, but the total number of affected individuals is virtually identical (32.5 million in 2015-16 compared with 32.1 million in 2007-08)., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: The full spectrum of serious non-gastrointestinal post-colonoscopy complications has not been well characterized. We analyzed rates of and factors associated with adverse post-colonoscopy gastrointestinal (GI) and non-gastrointestinal events (cardiovascular, pulmonary, or infectious) attributable to screening or surveillance colonoscopy (S-colo) and non-screening or non-surveillance colonoscopy (NS-colo)., Methods: We performed a population-based study of colonoscopy complications using databases from California hospital-owned and nonhospital-owned ambulatory facilities, emergency departments, and hospitals from January 1, 2005 through December 31, 2011. We identified patients who underwent S-colo (1.58 million), NS-colo (1.22 million), or low-risk comparator procedures (joint injection, aspiration, lithotripsy; arthroscopy, carpal tunnel; or cataract; 2.02 million) in California's Ambulatory Services Databases. We identified patients who developed adverse events within 30 days, and factors associated with these events, through patient-level linkage to California's Emergency Department and Inpatient Databases., Results: After S-colo, the numbers of lower GI bleeding, perforation, myocardial infarction, and ischemic stroke per 10,000-persons were 5.3 (95% confidence interval [CI], 4.8-5.9), 2.9 (95% CI, 2.5-3.3), 2.5 (95% CI, 2.1-2.9), and 4.7 (95% CI, 4.1-5.2) without biopsy or intervention; with biopsy or intervention, numbers per 10,000-persons were 36.4 (95% CI, 35.1-37.6), 6.3 (95% CI, 5.8-6.8), 4.2 (95% CI, 3.8-4.7), and 9.1 (95% CI, 8.5-9.7). Rates of dysrhythmia were higher. After NS-colo, event rates were substantially higher. Most serious complications led to hospitalization, and most GI complications occurred within 14 days of colonoscopy. Ranges of adjusted odds ratios for serious GI complications, myocardial infarction, ischemic stroke, and serious pulmonary events after S-colo vs comparator procedures were 2.18 (95% CI, 2.02-2.36) to 5.13 (95% CI, 4.81-5.47), 0.67 (95% CI, 0.56-0.81) to 0.99 (95% CI, 0.83-1.19), 0.66 (95% CI, 0.59-0.75) to 1.13 (95% CI, 0.99-1.29), and 0.64 (95% CI, 0.61-0.68) to 1.05 (95% CI, 0.98-1.11). Biopsy or intervention, comorbidity, black race, low income, public insurance, and NS-colo were associated with post-colonoscopy adverse events., Conclusions: In a population-based study in California, we found that following S-colo, rates of serious GI adverse events were low but clinically relevant, and that rates of myocardial infarction, stroke, and serious pulmonary events were no higher than after low-risk comparator procedures. Rates of myocardial infarction are similar to, but rates of stroke are higher than, those reported for the general population., (Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Importance: The Affordable Care Act (ACA) has expanded access to health insurance for millions of Americans, but the impact of Medicaid expansion on healthcare delivery and utilization remains uncertain., Objective: To determine the early impact of the Medicaid expansion component of ACA on hospital and ED utilization in California, a state that implemented the Medicaid expansion component of ACA and Florida, a state that did not., Design: Analyze all ED encounters and hospitalizations in California and Florida from 2009 to 2014 and evaluate trends by payer and diagnostic category. Data were collected from State Inpatient Databases, State Emergency Department Databases and the California Office of Statewide Health Planning and Development., Setting: Hospital and ED encounters., Participants: Population-based study of California and Florida state residents., Exposure: Implementation of Medicaid expansion component of ACA in California in 2014., Main Outcomes or Measures: Changes in ED visits and hospitalizations by payer, percentage of patients hospitalized after an ED encounter, top diagnostic categories for ED and hospital encounters., Results: In California, Medicaid ED visits increased 33% after Medicaid expansion implementation and self-pay visits decreased by 25% compared with a 5.7% increase in the rate of Medicaid patient ED visits and a 5.1% decrease in rate of self-pay patient visits in Florida. In addition, California experienced a 15.4% increase in Medicaid inpatient stays and a 25% decrease in self pay stays. Trends in the percentage of patients admitted to the hospital from the ED were notable; a 5.4% decrease in hospital admissions originating from the ED in California, and a 2.1% decrease in Florida from 2013 to 2014., Conclusions and Relevance: We observed a significant shift in payer for ED visits and hospitalizations after Medicaid expansion in California without a significant change in top diagnoses or overall rate of these ED visits and hospitalizations. There appears to be a shift in reimbursement burden from patients and hospitals to the government without a dramatic shift in patterns of ED or hospital utilization.

Background and Aims: Bile duct surgery (BDS), percutaneous transhepatic cholangiography (PTC), and ERCP are alternative interventions used to treat biliary disease. Our aim was to describe trends in ERCP, BDS, and PTC on a nationwide level in the United States., Methods: We used the National Inpatient Sample to estimate age-standardized utilization trends of inpatient diagnostic ERCP, therapeutic ERCP, BDS, and PTC between 1998 and 2013. We calculated average case fatality, length of stay, patient demographic profile (age, gender, payer), and hospital characteristics (hospital size and metropolitan status) for these procedures., Results: Total biliary interventions decreased over the study period from 119.8 to 100.1 per 100,000. Diagnostic ERCP utilization decreased by 76%, and therapeutic ERCP utilization increased by 35%. BDS rates decreased by 78% and PTC rates by 24%. ERCP has almost completely supplanted surgery for the management of choledocholithiasis. Fatality from ERCP, BDS, and PTC have all decreased, whereas mean length of stay has remained stable. The proportion of Medicare-insured, Medicaid-insured, and uninsured patients undergoing biliary procedures has increased over time. Most of the increase in therapeutic ERCP and decrease in BDS occurred in large, metropolitan hospitals., Conclusions: Although therapeutic ERCP utilization has increased over time, the total volume of biliary interventions has decreased. BDS utilization has experienced the most dramatic decrease, possibly a consequence of the increased therapeutic capacity and safety of ERCP. ERCPs are now predominantly therapeutic in nature. Large urban hospitals are leading the shift from surgical to endoscopic therapy of the biliary system., (Copyright © 2017 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background: Atherosclerosis is a chronic inflammatory disease, with interleukin 6 (IL-6) as a major player in inflammation cascade. IL-6 blockade may reduce cardiovascular risk, but current treatments to block IL-6 also induce dyslipidemia, a finding with an uncertain prognosis., Methods and Results: We aimed to determine the endothelial function responses to the IL-6-blocking agent tocilizumab, anti-tumor necrosis factor α, and synthetic disease-modifying antirheumatic drug therapies in patients with rheumatoid arthritis in a 16-week prospective study. Sixty consecutive patients with rheumatoid arthritis were enrolled. Tocilizumab and anti-tumor necrosis factor α therapy were started in 18 patients each while 24 patients were treated with synthetic disease-modifying antirheumatic drugs. Forty patients completed the 16-week follow-up period. The main outcome was flow-mediated dilation percentage variation before and after therapy. In the tocilizumab group, flow-mediated dilation percentage variation increased statistically significantly from a pre-treatment mean of (3.43% [95% CI, 1.28-5.58] to 5.96% [95% CI, 3.95-7.97]; P =0.03). Corresponding changes were 4.78% (95% CI, 2.13-7.42) to 6.75% (95% CI, 4.10-9.39) ( P =0.09) and 2.87% (95% CI, -2.17 to 7.91) to 4.84% (95% CI, 2.61-7.07) ( P =0.21) in the anti-tumor necrosis factor α and the synthetic disease-modifying antirheumatic drug groups, respectively (both not statistically significant). Total cholesterol increased significantly in the tocilizumab group from 197.5 (95% CI, 177.59-217.36) to 232.3 (201.62-263.09) ( P =0.003) and in the synthetic disease-modifying antirheumatic drug group from 185.8 (95% CI, 169.76-201.81) to 202.8 (95% CI, 176.81-228.76) ( P =0.04), but not in the anti-tumor necrosis factor α group. High-density lipoprotein did not change significantly in any group., Conclusions: Endothelial function is improved by tocilizumab in a high-risk population, even as it increases total cholesterol and low-density lipoprotein levels., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Background: Obesity and abdominal obesity are associated independently with morbidity and mortality. Physical activity attenuates these risks. We examined trends in obesity, abdominal obesity, physical activity, and caloric intake in US adults from 1988 to 2010., Methods: Univariate and multivariate analyses were performed using National Health and Nutrition Examination Survey data., Results: Average body mass index (BMI) increased by 0.37% (95% confidence interval [CI], 0.30-0.44) per year in both women and men. Average waist circumference increased by 0.37% (95% CI, 0.30-0.43) and 0.27% (95% CI, 0.22-0.32) per year in women and men, respectively. The prevalence of obesity and abdominal obesity increased substantially, as did the prevalence of abdominal obesity among overweight adults. Younger women experienced the greatest increases. The proportion of adults who reported no leisure-time physical activity increased from 19.1% (95% CI, 17.3-21.0) to 51.7% (95% CI, 48.9-54.5) in women, and from 11.4% (95% CI, 10.0-12.8) to 43.5% (95% CI, 40.7-46.3) in men. Average daily caloric intake did not change significantly. BMI and waist circumference trends were associated with physical activity level but not caloric intake. The associated changes in adjusted BMIs were 8.3% (95% CI, 6.9-9.6) higher among women and 1.7% (95% CI, 0.68-2.8) higher among men with no leisure-time physical activity compared with those with an ideal level of leisure-time physical activity., Conclusions: Our analyses highlight important dimensions of the public health problem of obesity, including trends in younger women and in abdominal obesity, and lend support to the emphasis placed on physical activity by the Institute of Medicine., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objectives: Gastrointestinal (GI) emergencies may cause substantial morbidity. Our aims were to characterize the national clinical and economic burden of GI visits to emergency departments (EDs) in the United States., Methods: We performed an observational cross-sectional study using the 2007 Nationwide Emergency Department Sample, the largest US all-payer ED database, to identify the leading causes for ED visits due to GI diseases and their associated charges, stratified by age and sex. Logistic regression was used to analyze predictors of hospitalization after an ED visit., Results: Of the 122 million ED visits in 2007, 15 million (12%) had a primary GI diagnosis. The leading primary GI diagnoses were abdominal pain (4.7 million visits), nausea and vomiting (1.6 million visits), and functional disorders of the digestive system (0.7 million visits). The leading diagnoses differed by age group. The fraction of ED visits resulting in hospitalization was 21.6% for primary GI diagnoses vs. 14.7% for non-GI visits. Women had more ED visits with a primary GI diagnosis than men (58.5 (95% CI 56.0-60.9) vs. 41.6 (95% CI 39.8-43.3) per 1000 persons), but lower rates of subsequent hospitalization (20.0% (95% CI 19.4-20.7%) vs. 24.0% (95% CI 23.3-24.6%)). There were no differences in hospitalization rates between sexes after adjustment by age, primary GI diagnosis, and Charlson Comorbidity Score. The total charges for ED visits with a primary GI diagnosis in 2007 were $27.9 billion., Conclusions: GI illnesses account for substantial clinical and economic burdens on US emergency medical services.

Objectives: Because of the limitations of randomized controlled trials (RCTs) and observational studies, a prospective, randomized, open-label, blinded endpoint (PROBE) study may be an appropriate alternative, as the design allows the assessment of clinical outcomes in clinical practice settings. The Gastrointestinal (GI) Randomized Event and Safety Open-Label Nonsteroidal Anti-inflammatory Drug (NSAID) Study (GI-REASONS) was designed to reflect standard clinical practice while including endpoints rigorously evaluated by a blinded adjudication committee. The objective of this study was to assess if celecoxib is associated with a lower incidence of clinically significant upper and/or lower GI events than nonselective NSAIDs (nsNSAIDs) in standard clinical practice., Methods: This was a PROBE study carried out at 783 centers in the United States, where a total of 8,067 individuals aged ≥ 55 years, requiring daily NSAIDs to treat osteoarthritis, participated. The participants were randomized to celecoxib or nsNSAIDs (1:1) for 6 months and stratified by Helicobacter pylori status. Treatment doses could be adjusted as per the United States prescribing information; patients randomized to nsNSAIDs could switch between nsNSAIDs; crossover between treatment arms was not allowed, and patients requiring aspirin at baseline were excluded. The primary outcome was the incidence of clinically significant upper and/or lower GI events., Results: Significantly more nsNSAID users met the primary endpoint (2.4% (98/4,032) nsNSAID patients and 1.3% (54/4,035) celecoxib patients; odds ratio, 1.82 (95% confidence interval, 1.31-2.55); P = 0.0003). Moderate to severe abdominal symptoms were experienced by 94 (2.3%) celecoxib and 138 (3.4%) nsNSAID patients (P=0.0035). Other non-GI adverse events were similar between treatment groups. One limitation is the open-label design, which presents the possibility of interpretive bias., Conclusions: Celecoxib was associated with a lower risk of clinically significant upper and/or lower GI events than nsNSAIDs. Furthermore, this trial represents a successful execution of a PROBE study, where therapeutic options and management strategies available in clinical practice were incorporated into the rigor of a prospective RCT.

Background & Aims: Screening decreases colorectal cancer (CRC) incidence and mortality. Colonoscopy has become the most common CRC screening test in the United States, but the degree to which it protects against CRC of the proximal colon is unclear. We examined US trends in rates of resection for proximal vs distal CRC, which reflect CRC incidence, in the context of national CRC screening data, before and since Medicare's 2001 decision to pay for screening colonoscopy., Methods: We used the Nationwide Inpatient Sample, the largest US all-payer inpatient database, to estimate age-adjusted rates of resection for distal and proximal CRC, from 1993 to 2009, in adults. Temporal trends were analyzed using Joinpoint regression analysis., Results: The rate of resection for distal CRC decreased from 38.7 per 100,000 persons (95% confidence interval [CI], 35.4-42.0) to 23.2 per 100,000 persons (95% CI, 20.9-25.5) from 1993 to 2009, with annual decreases of 1.2% (95% CI, 0.1%-2.3%) from 1993 to 1999, followed by larger annual decreases of 3.8% (95% CI, 3.3%-4.3%) from 1999 to 2009 (P < .001). In contrast, the rate of resection for proximal CRC decreased from 30.0 per 100,000 persons (95% CI, 27.4-32.5) to 22.7 per 100,000 persons (95% CI, 20.6-24.7) from 1993 to 2009, but significant annual decreases of 3.1% (95% CI, 2.3%-4.0%) occurred only after 2002 (P < .001). Rates of resection for CRC decreased for adults ages 50 years and older, but increased for younger adults., Conclusions: These findings support the hypothesis that population-level decreases in rates of resection for distal CRC are associated with screening, in general, and that implementation of screening colonoscopy, specifically, might be an important factor that contributes to population-level decreases in rates of resection for proximal CRC., (Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.)

We investigated the effect of long-term corticosteroid usage in suppressing the progression of functional disability in patients with early rheumatoid arthritis (RA). We studied 3,982 RA patients, who had continuous enrollment for at least 3 years, among 9,132 RA patients enrolled in an observational cohort study, IORRA, in Tokyo, Japan, from 2000 to 2007. The DAS28 and Japanese version of Health Assessment Questionnaire (J-HAQ) scores were collected at 6-month intervals (each phase). Among these patients, those with DAS28 values under 3.2 in all phases and RA disease duration under 2 years at study entry were selected as "early RA patients with well-controlled disease". These patients were further classified into 3 groups based on average months of steroid usage per year: Non-users, Medium-users, and Frequent-users. Multiple linear regression analysis was used to study the relationship between steroid usage and the final J-HAQ scores. Among the 3,982 patients, 109 had DAS28 values under 3.2 in all the phases and were selected as study cohort. The average Final J-HAQ in Non-user (N = 64), in Medium-user (N = 25), in Frequent-user group (N = 20) was 0.04, 0.06, and 0.33, respectively. Multiple linear regression analysis after adjusting for all potential covariates confirmed that frequent steroid usage was the most significant factor associated with higher final J-HAQ scores (P < 0.05). Frequent steroid usage was associated with significantly higher final J-HAQ scores in early RA patients, even though their disease was managed efficiently by maintaining the DAS28 values under 3.2 over a long-term period.

Background: Chronic constipation (CC) is a common condition but its concurrent conditions are not well characterized. We measured the prevalence and risk of developing 15 pre-specified concurrent conditions in patients with CC., Methods: Retrospective cohort study using the Medicaid database of California, utilizing ICD-9 codes for detection of cases (CC), controls (patients with GERD) and concurrent conditions. Study period was 01/01/1995 to 06/30/2005. Index date was the date 3 months before the first physician visit for CC. Pre-index time (12 months) was compared to post-index time (12 months) to assess the association of every concurrent condition within each cohort. To account for ascertainment bias, an adjusted odds ratio was calculated by comparing the odds ratio for every concurrent condition in the CC cohort to that in the GERD cohort., Results: 147,595 patients with CC (mean age 54.2 years; 69.7% women; 36.2% white) and 142,086 patients with GERD (mean age 56.3 years; 65.3% women; 41.6% white) were evaluated. The most prevalent concurrent conditions with CC were hemorrhoids (7.6%), diverticular disease (5.9%), ano-rectal hemorrhage (4.7%), irritable bowel syndrome (3.5%) and fecal impaction (2%). When adjusted for ascertainment bias, the most notable associations with CC were Hirschsprung's disease, fecal impaction and ano-rectal conditions such as fissure, fistula, hemorrhage and ulcers., Conclusion: Chronic constipation is associated with several concurrent conditions of variable risk and prevalence. To reduce the overall burden of CC, these concurrent conditions need to be addressed.

Background & Aims: Irritable bowel syndrome (IBS) imposes significant clinical and economic burdens. We aimed to characterize practice patterns for patients with IBS in a large health maintenance organization, analyzing point of diagnosis, testing, comorbidities, and treatment., Methods: Members of Kaiser Permanente Northern California who were diagnosed with IBS were matched to controls by age, sex, and period of enrollment. We compared rates of testing, comorbidities, and interventions., Results: From 1995-2005, IBS was diagnosed in 141,295 patients (mean age, 46 years; standard deviation, 17 years; 74% female). Internists made 68% of diagnoses, gastroenterologists 13%, and others 19%. Lower endoscopy did not usually precede IBS diagnosis. Patients with IBS were more likely than controls to have blood, stool, endoscopic, and radiologic tests and to undergo abdominal or pelvic operations (odds ratios, 1.5-10.7; all P < .0001). Only 2.7% were tested for celiac disease, and only 1.8% were eventually diagnosed with inflammatory bowel disease. Chronic pain syndromes, anxiety, and depression were more common among IBS patients than among controls (odds ratios, 2.7-4.6; all P < .0001). Many patients with IBS were treated with anxiolytics (61%) and antidepressants (55%). Endoscopic and radiologic testing was most strongly associated with having IBS diagnosed by a gastroenterologist. Psychotropic medication use was most strongly associated with female sex., Conclusions: In a large, managed care cohort, most diagnoses of IBS were made by generalists, often without endoscopic evaluation. Patients with IBS had consistently higher rates of testing, chronic pain syndromes, psychiatric comorbidity, and operations than controls. Most patients with IBS were treated with psychiatric medications., (Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for treating symptoms of rheumatologic diseases, such as osteoarthritis and rheumatoid arthritis. Knowing their side effects and the way to minimize them is a medical responsibility. To reduce NSAID-related risk, clinicians should choose a gastroprotective strategy. This may include coprescribing a traditional NSAID with a proton pump inhibitor or a high-dose histamine 2-receptor antagonist (H 2 RA), or using a cyclo-oxygenase (COX)-2 selective inhibitor or a COX-2 with a proton pump inhibitor. Assessing each patient's risk (cardiovascular and gastrointestinal) is a priority in order to decide the best intervention to minimize toxicity. In this article, we review some of the common interventions for reducing the gastrointestinal side effects of NSAIDs., Competing Interests: The authors report no conflicts of interest in this work.

Background: Studies on mostly veterans found the majority of chronic hepatitis C (CHC) patients were not treated. Little information exists on a broad-based population., Aims: To determine the national trend of ambulatory visits with a diagnosis of hepatitis C and the prescription of antiviral therapy associated with such visits., Methods: Retrospective analysis of national cross-sectional databases, the National Ambulatory Medical Care Survey (NAMCS), and the National Hospital Ambulatory Medical Care Survey (NHAMCS) encompassing all ambulatory visits from 2000 to 2006., Results: During the study period, 16.5 million visits (0.21% of all visits) carried a diagnosis of hepatitis C and the number initially increased. Characteristics of the hepatitis C patients were: 65% male; 71% white, 22% black; 69% >or=45 years old. Overall, 47% had private insurance, 24% had Medicaid, and 12% had Medicare. Only 9.1% of these patients were prescribed antiviral treatment for CHC. There was no significant difference between those who received treatment and those who did not in terms of age, gender, race, and insurance status. HIV infection, mood, substance-use disorders, and anemia were more common in the CHC group., Conclusions: Less than 10% of the ambulatory visits for hepatitis C were associated with a prescription for antiviral therapy, independent of demographic and insurance status. Purposes of the clinic visits were different in the CHC group compared to the general population. The reason for the low treatment rate is not clear but deserves further investigation.

Background and Aim: Intestinal and extra-intestinal complications are associated with inflammatory bowel disease (IBD) but their exact incidence is not well known. In order to improve our understanding of their incidence and impact, we assessed the complications associated with ulcerative colitis (UC) and Crohn's disease (CD) in a population-based study in Medicaid patients., Methods: We utilized a retrospective cohort design and identified cases of UC and CD using Medi-Cal, the Medicaid program for the State of California. The disease cohort was age- and gender-matched to four controls each and the intestinal and extra-intestinal complications of CD and UC (analyzed separately) were studied over a period of 5 years following the initial diagnosis., Results: For UC, the total number of intestinal complications, per 100 cases, was 92 observed compared to 21 expected; the total number of extra-intestinal complications was 42 observed compared to 30 expected. For CD, the number of intestinal complications was 81 observed compared to 20 expected and for extra-intestinal complications, 37 observed compared to 26 expected (all p < 0.001). For both UC and CD, bleeding was the most frequently seen intestinal complication, while the most common extra-intestinal complication was osteoporosis., Conclusions: IBD is associated with several intestinal and extra-intestinal complications of variable incidence and risk. Success of therapeutic regimens should be measured by decreases in incidence, risks, and costs of these complications, in addition to the usual impact on disease activity.

Objective: To perform a Cochrane systematic review of benefit (American College of Rheumatology 50% improvement criteria; ACR50) and safety (adverse events and withdrawals) of golimumab in patients with rheumatoid arthritis (RA)., Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), OVID Medline, CINAHL, Embase, Science Citation Index (Web of Science), and Current Controlled Trials databases for randomized or controlled clinical trials of golimumab compared to placebo or disease-modifying antirheumatic drug in adults with RA. Two authors independently selected appropriate studies and abstracted study characteristics and safety and efficacy data and performed risk-of-bias assessment. We calculated mean differences for continuous measures, and relative risks for categorical measures., Results: Four randomized controlled trials with 1231 golimumab-treated and 483 placebo-treated patients were included. Of these, 436 were treated with golimumab at 50 mg every 4 weeks [a dosage approved by the US Food and Drug Administration (FDA)]. At an average of 4-6 months, compared to patients treated with placebo and methotrexate (MTX), patients treated with the FDA-approved dosage of golimumab and MTX were 2.6 times more likely to reach ACR50 (p = 0.005, 95% CI 1.3, 4.9; absolute percentage, 38% vs 15%) and 0.5 times as likely to have overall withdrawals (p = 0.005, 95% CI 0.3, 0.8; absolute percentage, 5% vs 10%). Golimumab-treated patients were significantly more likely than those taking placebo to achieve remission (22% vs 4%; p < 0.00001), and to have improvement in functional ability on the Health Assessment questionnaire [0.2 points lower (p < 0.00001, 95% CI 0.25, 0.15); absolute risk difference, -20% (95% CI -25% to -15%); relative percentage difference, -11% (95% CI -14% to -8.3%)]. The studies were too small and short to be powered sufficiently for safety outcomes, but no substantive statistically significant differences were noted between golimumab and placebo regarding adverse events, serious adverse events, infections, serious infections, lung infections, tuberculosis, cancer, withdrawals due to adverse events, and withdrawals due to inefficacy and deaths., Conclusion: At the approved dosage, in patients with active RA taking background MTX, golimumab is significantly more beneficial than placebo. The short-term safety profile is reasonable. Longterm surveillance studies are needed for safety assessment.

Our objective was to describe outpatient medical care costs of patients with rheumatoid arthritis (RA) in the prebiologics period in Japan. The outpatient costs of 6,771 RA patients (17,666 patient years) who were enrolled in an observational cohort study at the Institute of Rheumatology, Rheumatoid Arthritis (IORRA), in Tokyo, Japan, were calculated from the billing records dated from 2000 to 2004. Associations between outpatient costs and variables such as age, RA duration, RA disease activities, and disability levels were assessed. The average outpatient cost gradually increased (+7.7% in 4 years) from 271,498 JPY per year in 2000 to 292,417 JPY per year in 2004. Medications accounted for approximately 50% of total outpatient costs, which increased 29.6% during the 4 years. The outpatient costs increased in association with aging, longer RA duration, higher Disease Activity Score of 28 Joints (DAS28), and higher Japanese version of Health Assessment Questionnaire (J-HAQ) score. Generalized linear regression analysis revealed that both DAS28 and J-HAQ scores were the most significant factors associated with outpatient costs (p < 0.001). Outpatient costs for patients with RA increased year after year over the 4-year period under observation in Japan. Medical costs were higher with increasing RA disease activity and disability levels.

Background: Golimumab is a humanized inhibitor of Tumor necrosis factor-alpha, recently approved by the Food and Drug Administration (FDA) for the treatment of Rheumatoid arthritis (RA)., Objectives: The objective of this systematic review was to compare the efficacy and safety of golimumab (alone or in combination with DMARDs or biologics) to placebo (alone or in combination with DMARDs or biologics) in randomized or quasi-randomized clinical trials in adults with RA., Search Strategy: An expert librarian searched six databases for any clinical trials of golimumab in RA, including the Cochrane Central Register of Controlled Trials (CENTRAL), OVID MEDLINE, CINAHL, EMBASE, Science Citation Index (Web of Science) and Current Controlled Trials databases., Selection Criteria: Studies were included if they used golimumab in adults with RA, were randomized or quasi-randomized and provided clinical outcomes., Data Collection and Analysis: Two review authors (JS, SN) independently reviewed all titles and abstracts, selected appropriate studies for full review and reviewed the full-text articles for the final selection of included studies. For each study, they independently abstracted study characteristics, safety and efficacy data and performed risk of bias assessment. Disagreements were resolved by consensus. For continuous measures, we calculated mean differences or standardized mean differences and for categorical measures, relative risks. 95% confidence intervals were calculated., Main Results: Four RCTs with 1,231 patients treated with golimumab and 483 patients treated with placebo were included. Of these, 436 were treated with the FDA-approved dose of golimumab 50 mg every four weeks. Compared to patients treated with placebo+methotrexate, patients treated with the FDA-approved dose of golimumab+methotrexate were 2.6 times more likely to reach ACR50 (95% confidence interval (CI) 1.3 to 4.9; P=0.005 and NNT= 5, 95% confidence interval 2 to 20), no more likely to have any adverse event (relative risk 1.1, 95% Cl 0.9 to 1.2; P=0.44), and 0.5 times as likely to have overall withdrawals (95% Cl 0.3 to 0.8; P=0.005). Golimumab-treated patients were significantly more likely to achieve remission, low disease activity and improvement in functional ability compared to placebo (all statistically significant). No significant differences were noted between golimumab and placebo regarding serious adverse events, infections, serious infections, lung infections, tuberculosis, cancer, withdrawals due to adverse events and inefficacy and deaths. No radiographic data were reported., Authors' Conclusions: With an overall high grade of evidence, at the FDA-approved dose, golimumab is significantly more efficacious than placebo in treatment of patients with active RA , when used in combination with methotrexate. The short-term safety profile, based on short-term RCTs, is reasonable with no differences in total adverse events, serious infections, cancer, tuberculosis or deaths. Long-term surveillance studies are needed for safety assessment.

Objective: Nonsteroidal antiinflammatory drugs (NSAID) not only cause damage to the upper gastrointestinal (GI) tract but also affect the lower GI tract. To date, there is no endpoint that evaluates serious GI events in the entire GI tract. The objective of this report is to introduce a novel composite endpoint that measures damage to the entire GI tract - clinically significant upper and lower GI events (CSULGIE) - in patients with NSAID-induced GI damage., Methods: We reviewed the data from largescale, multicenter, randomized, clinical trials on lower GI toxicity associated with NSAID use. The rationale for using CSULGIE as a primary endpoint in 2 ongoing trials - the Celecoxib vs Omeprazole and Diclofenac for At-risk Osteoarthritis (OA) and Rheumatoid Arthritis (RA) Patients (CONDOR) trial and the Gastrointestinal Randomized Events and Safety Open-Label NSAID Study (GI-REASONS) - is also discussed., Results: Previous randomized trials focused primarily on damage to the upper GI tract and often neglected the lower GI tract. The CSULGIE endpoint extends the traditional "perforation, obstruction, and bleeding" assessment of upper GI complications by including events in the lower GI tract (small/large bowel) such as perforation, bleeding, and clinically significant anemia., Conclusion: By providing clinicians with a new, descriptive language for adverse events through the entire GI tract, the CSULGIE endpoint has the potential to become a standard tool for evaluating the GI effects of a range of therapies.

Nonsteroidal anti-inflammatory drugs (NSAIDs) and aspirin are among the most commonly used medications worldwide. Their use is associated with significant gastroduodenal adverse effects, including dyspepsia, bleeding, ulcer formation, and perforation. Given their long-term use by millions of patients, there is a substantial impact at the population level of these complications. In this evidence-based review, we have endeavored to answer 12 commonly encountered questions in clinical practice that deal with the following: extent of the problem of NSAID/aspirin-induced gastroduodenal damage and its impact on public health; role of proton pump inhibitors (PPIs) in the primary prevention, healing, and secondary prevention of NSAID/aspirin-induced gastroduodenal ulceration as assessed by using endoscopic end points; role of PPIs in the prevention of adverse clinical outcomes related to NSAID/aspirin use; whether PPIs are effective in NSAID-induced dyspepsia; comparison of PPI co-therapy with selective cyclooxygenase-2 inhibitors for risk reduction of adverse clinical outcomes; role of PPIs in preventing rebleeding from aspirin +/- clopidogrel therapy in high-risk patients; identifying high-risk patients who can benefit from PPI co-therapy; the role of other gastroprotective agents for prevention of NSAID/aspirin-induced gastroduodenal damage; and the cost-effectiveness of and limitations to the use of PPIs for prevention of gastroduodenal damage related to the use of NSAIDs or aspirin. We then summarized our recommendations on the use of PPIs for the clinical management of patients using NSAIDs or aspirin.

Background: Previous studies that reported the incidence of perforation from a colonoscopy are limited by small sample sizes, restricted age groups, or single-center data., Objective: To determine the incidence and risk factors of colonic perforation from a colonoscopy in a large population cohort., Design: Retrospective, population-based, cohort study, followed by a nested case-control study., Setting: California Medicaid program claims database., Patients: A total of 277,434 patients (aged 18 years and older) who underwent a colonoscopy during 1995 to 2005, age, sex, and time matched to 4 unique general-population controls., Main Outcome Measurements: Perforation incidence in the 7 days after colonoscopy (or matched index date for controls) with odds ratio (OR); multivariate logistic regression to calculate adjusted ORs for subsequent analysis of risk factors., Results: A total of 228 perforations were diagnosed after 277,434 colonoscopies, which corresponded to a cumulative 7-day incidence of 0.082%. The OR of getting a perforation from a colonoscopy compared with matched controls (n = 1,072,723) who did not undergo a colonoscopy was 27.6 (95% CI, 19.04-39.92), P < .001. On multivariate analysis, when comparing the group that had a perforation after a colonoscopy (n = 216) with those who did not (n = 269,496), increasing age, significant comorbidity, obstruction as an indication for the colonoscopy, and performance of invasive interventions during colonoscopy were significant positive predictors. Performance of biopsy or polypectomy did not affect the perforation risk. The rate of perforation did not change significantly over time., Limitations: Validity of coding and capturing of all perforation diagnoses may possibly be deficient., Conclusion: The risk of perforation from a colonoscopy is low, but, despite increased experience with the procedure, it remains unchanged over time.

Celecoxib is a selective cyclo-oxygenase 2 inhibitor licensed for use in musculoskeletal symptoms as well as in primary dysmenorrhea and acute pain. One advantage celecoxib has over traditional nonsteroidal anti-inflammatory drugs is that of significantly fewer gastrointestinal side-effects associated with its use. Much has been published on the potential cardiovascular and cerebrovascular complications of its administration. This review details the available evidence to allow prescribers to make informed decisions in the light of potentially conflicting evidence. The overall cardiovascular risk is increased with higher doses of celecoxib but is comparable with nonselective nonsteroidal anti-inflammatory use. As with all of these drugs, the potential cardiovascular and gastrointestinal risks of prescription need to be weighed up against possible benefits for each individual patient and discussed with the patients themselves.

Purpose of Review: In the last 2 years, there have been numerous publications on the safety of nonsteroidal anti-inflammatory drugs and cyclo-oxygenase-2 inhibitors. An evaluation of the potential risks and benefits of other analgesics has also followed. In this time of greater analysis of analgesic use, this review seeks to present the most recent evidence., Recent Findings: Concerns of potential hepatotoxicity of therapeutic doses of paracetamol have been highlighted in the last 18 months. The efficacy and risks of long-term opioid use have also been reevaluated. The debate over nonsteroidal anti-inflammatory drug and cyclo-oxygenase-2 inhibitor safety continues., Summary: Recent evidence has prompted a reassessment of the safety of paracetamol in certain groups of patients. Further clarification on the risks of nonsteroidal anti-inflammatory drug and cyclo-oxygenase-2 therapy for individuals is covered. Their use, increased cardiovascular risk and long-term implications need to be evaluated.

Background: The epidemiology of acute alcoholic pancreatitis (AP), chronic alcoholic pancreatitis (CP), acute alcoholic hepatitis (AH), and chronic alcoholic hepatitis with cirrhosis (CH) alone or in combination is not well described. To better understand alcohol-related liver and pancreas effects on and associations with different ethnic groups and sexes, we analyzed the trends of AP, CP, AH, CH, AP plus AH, and CP plus CH in the United States., Methods: We examined discharge records from the Nationwide Inpatient Sample, the largest representative sample of US hospitals. Hospital discharges, case-fatality, and sex and race contributions were calculated from patients with discharge diagnoses of AP, CP, AH, CH, AP plus AH, or CP plus CH between 1988 and 2004., Results: The distribution of overall hospital discharges per 100 000 persons between 1988 and 2004 was as follows: AP, 49.2; CP, 8.1; AH, 4.5; and CH, 13.7. Overall hospital discharges per 100 000 persons for AP plus AH were 1.8; and for CP plus CH, 0.32. There were higher male to female ratios for AH and CH, and less so for AP and CP. A markedly higher frequency of AP (63.5) and CP (11.3) was seen among blacks than among whites (AP, 29.6 and CP, 5.1), Hispanics (AP, 27.1 and CP, 3.7), Asians (AP, 12.8 and CP, 1.4), and American Indians (AP, 15.5 and CP, 2.3). This higher frequency remained stable between 1994 and 2004. Overall case fatality steadily decreased in all categories, but remains highest in CH (13.6%) with similar racial distributions., Conclusions: In the United States, AP is the most common discharge diagnosis among alcohol-related liver or pancreas complications, while CH has the highest case fatality rate and male to female ratio. Blacks have the highest frequency of alcohol-related pancreatic disease.

Patients with rheumatoid arthritis and osteoarthritis have relied upon NSAIDs as a cornerstone of their analgesic regime for decades. The choice of anti-inflammatory agents broadened for this group of patients when the selective inhibitors of cyclooxygenase-2 enzyme were developed. Much has been published in the past few years regarding the superior gastrointestinal safety of this class of drugs when compared with traditional NSAIDs. Their triumphant debut was swiftly followed by the emergence of data detailing their associated increased serious cardiovascular risks. This also led to a reevaluation of data concerning more traditional NSAIDs, and surprisingly, a similar trend was seen. The US Food and Drug Administration has recommended that both classes of drugs carry a black box warning with regard to gastrointestinal and cardiovascular risks.

The aim of our study was the adaptation of the Health Assessment Questionnaire's Disability Index (HAQ-DI) for Estonia along with the assessment of its psychometric properties. The linguistic validation included phases of translation, back translation and testing on patients. Reliability and validity were tested on a sample of 50 rheumatoid arthritis patients by administering the HAQ-DI and the comparator instruments at two visits; disease activity and radiological stage were assessed. The participants were asked to comment on the questionnaires. The HAQ-DI was easily translatable into Estonian. It showed good test-retest reliability, internal consistency, and ability to discriminate between different levels of self-perceived severity. Comparison with the comparators and performed assessments demonstrated expected convergent and divergent validity. Still, the participants' comments revealed issues disregarded during the adaptation process. We recommend the Estonian HAQ-DI for rheumatoid arthritis clinical studies and trials; some aspects of the adaptation process are highlighted for further discussion.

Background & Aims: Constipation is a multisymptom disorder that frequently compromises quality of life and leads patients to seek medical advice. To evaluate the clinical and fiscal effects of constipation, we assessed health care resource use by patients with constipation enrolled in a large state Medicaid program., Methods: We identified 105,130 patients older than age 18 who saw a physician at least once for constipation and were enrolled in the California Medicaid program (Medi-Cal). We then studied health care resource use and costs (reimbursed by Medi-Cal) in 76,854 patients without supplementary insurance. The 15-month analysis period encompassed 3 months before and 12 months after the first visit. The prevalence of comorbid conditions was assessed in the sample of 105,130 patients., Results: During the study period, 106,555 physician visits were for constipation; the total associated cost was $3,016,017 ($39/patient). The total cost for gastrointestinal procedures and laboratory testing was $14,052,503 ($183/patient). There were 41,723 over-the-counter and 1665 prescription drug purchases; the total cost was $388,780 ($5/patient). Approximately 0.6% of patients (n = 479) were admitted to the hospital for constipation; the total cost was $1,433,708 ($2993/admission). The total direct health care costs for patients with constipation in the Medi-Cal system for the 15-month period was $18,891,008 ($246/patient). Within 12 months of the first physician visit for constipation, 5657 of 105,130 patients had hemorrhoids and 2288 had intestinal impaction or obstruction., Conclusions: Adults seeking treatment for constipation account for significant health care resource use and often have comorbid conditions. The clinical and fiscal burden of constipation in US adults cannot be disregarded or trivialized.

We evaluated the effects of the use of nonsteroidal anti-inflammatory drugs (NSAIDs) on endoscopic and histological findings in patients with rheumatoid arthritis (RA) before and after the eradication of Helicobacter pylori infection. Helicobacter pylori (H. pylori) eradication using lansoprazole 30 mg, amoxicillin 750 mg, and clarithromycin 200 mg twice daily for 1 week was conducted in 44 patients (mean age: 56.5 years) with RA. Using the updated Sydney system, endoscopic and histological findings of the greater curvature of the antrum, the greater curvature of the upper corpus, and the lesser curvature of the lower corpus were compared before and after eradication, for a mean follow-up period of 3.5 months. Overall, H. pylori eradication was successful in 32 patients (72.7%). Of these 32 patients, 23 were NSAID users. In the successful eradication group, (1) there was no significant change on endoscopic findings, including gastric erythema and erosion in all three regions irrespective of NSAIDs use; (2) of 17 active ulcers before eradication in NSAIDs users, all healed except for one duodenal ulcer that persisted, where one patient newly developed a gastric ulcer, one developed erosive duodenitis, and two developed reflux esophagitis, all in NSAID users; (3) neutrophil infiltration and chronic inflammation were significantly improved in all three regions after H. pylori eradication irrespective of use of NSAIDs, while atrophic change and intestinal metaplasia did not change. In the eradication failure group; (1) there was no significant change on endoscopic and histological findings in the three regions; (2) two of three ulcers present before eradication on NSAID users persisted even after eradication, and no new cases of gastric ulcer or erosive duodenitis occurred. In conclusion, over a mean follow-up period of 3.5 months, use of NSAIDs in Japanese patients with RA did not impair the healing process of gastric and duodenal ulcers nor did it affect the endoscopic and histological improvements associated with H. pylori eradication.

The objective of this study was to show whether the disease activity of rheumatoid arthritis (RA) patients had improved in Japan, and whether the improvement of disease activity had resulted in a better outcome of patients. In a single-institute-based prospective observational cohort of RA patients (Institute of Rheumatology, Rheumatoid Arthritis, IORRA), a total of 7512 patients were enrolled, and their information was collected biannually. A cross-sectional data set A that included all patients in each phase was analyzed. From October 2000 to April 2006, disease activity score DAS28 significantly improved from 4.15 to 3.63, and the frequency of patients in remission (DAS28 < 2.6) increased from 8.5% to 21.5%. During this period, the frequency of methotrexate users increased from 33.9% to 58.7% and the average dosage of methotrexate also increased from 5.59 mg/week to 6.94 mg/week; on the other hand, there was no increase in any adverse reaction among the methotrexate users. To investigate the relationship between longitudinal disease control and progression of disability, a longitudinal data set B that included 712 patients who completed all phases of the study from 2000 to 2006 was selected and was analyzed. The disability index JHAQ of a poorly controlled group (average DAS > 5.1) increased (+34.8%), that of a moderately controlled group (average DAS 3.2-5.1) also increased (+14.0%), but that of a well-controlled group (average DAS < 3.2) decreased (-13.0%). In conclusion, by using a prospective observational cohort IORRA in Japan, we demonstrate that RA disease activity improved from 2000 to 2006, which correlates with an increased use of methotrexate. The suppression of disease activity resulted in a better outcome for patients.

Objective: Exposure to non-steroidal anti-inflammatory drugs (NSAIDs) is associated with increased risk of serious gastrointestinal (GI) events compared with non-exposure. We investigated whether that risk is sustained over time., Data Sources: Cochrane Controlled Trials Register (to 2002); MEDLINE, EMBASE, Derwent Drug File and Current Contents (1999-2002); manual searching of reviews (1999-2002)., Study Selection: From 479 search results reviewed and 221 articles retrieved, seven studies of patients exposed to prescription non-selective NSAIDs for more than 6 months and reporting time-dependent serious GI event rates were selected for quantitative data synthesis. These were stratified into two groups by study design., Data Extraction: Incidence of GI events and number of patients at specific time points were extracted., Data Synthesis: Meta-regression analyses were performed. Change in risk was evaluated by testing whether the slope of the regression line declined over time. Four randomised controlled trials (RCTs) provided evaluable data from five NSAID arms (aspirin, naproxen, two ibuprofen arms, and diclofenac). When the RCT data were combined, a small significant decline in annualised risk was seen: - 0.005% (95% CI, - 0.008% to - 0.001%) per month. Sensitivity analyses were conducted because there was disparity within the RCT data. The pooled estimate from three cohort studies showed no significant decline in annualised risk over periods up to 2 years: - 0.003% (95% CI, - 0.008% to 0.003%) per month., Conclusions: Small decreases in risk over time were observed; these were of negligible clinical importance. For patients who need long-term (> 6 months) treatment, precautionary measures should be considered to reduce the net probability of serious GI events over the anticipated treatment duration. The effect of intermittent versus regular daily therapy on long-term risk needs further investigation.

Purpose: To evaluate the efficacy and upper gastrointestinal (UGI) safety of celecoxib, compared with nonspecific nonsteroidal anti-inflammatory drugs (NSAIDs), among patients with osteoarthritis., Methods: A total of 13274 osteoarthritis patients from 39 countries were randomly assigned to double-blind treatment with either celecoxib 100 mg twice daily (BID), celecoxib 200 mg BID, or nonselective NSAID therapy (diclofenac 50 mg BID or naproxen 500 mg BID) for 12 weeks. Standard validated measures were used to assess osteoarthritis efficacy. Serious UGI events were evaluated by 2 blinded, independent, gastrointestinal events committees., Results: Results from all primary efficacy assessments showed that both dosages of celecoxib were as effective as NSAIDs in treating osteoarthritis. Significantly more ulcer complications occurred within the nonselective NSAID group (0.8/100 patient-years) compared with the celecoxib group (0.1/100 patient-years) (odds ratio = 7.02; 95% confidence interval [CI], 1.46 to 33.80; P =.008). There were fewer ulcer complications in the celecoxib group compared with the NSAID group, both in patients taking concomitant aspirin and those not taking aspirin, but the difference reached statistical significance only in the latter comparison. The number of cardiovascular thromboembolic events was low and not statistically different between the groups (eg, myocardial infarction rates: celecoxib 10 events [0.55/100 patient-years] vs NSAIDs 1 event [0.11/100 patient-years], (P =.11), but the study was not powered to detect such differences., Conclusions: In the treatment of osteoarthritis, celecoxib is as effective as the nonspecific NSAIDs naproxen and diclofenac, but has significantly fewer serious upper gastrointestinal events.

The use of cyclo-oxygenase 2 selective nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with increased risk of acute myocardial infarction (AMI). The association between the risks of AMI with nonselective NSAIDs is less clear. We reviewed the published evidence and assessed the risk of AMI with nonselective NSAIDs. We performed a meta-analysis of all studies containing data from population databases that compared the risk of AMI in NSAID users with that in non-users or remote NSAID users. The primary outcome was objectively confirmed AMI. Fourteen studies met predefined criteria for inclusion in the meta-analysis. Nonselective NSAIDs as a class was associated with increased AMI risk (relative AMI risk 1.19, 95% confidence interval [CI] 1.08 to 1.31). Similar findings were found with diclofenac (relative AMI risk 1.38, 95% CI 1.22-1.57) and ibuprofen (relative AMI risk 1.11, 95% CI 1.06 to 1.17). However, this effect was not observed with naproxen (relative AMI risk 0.99, 95% CI 0.88-1.11). In conclusion, based on current evidence, there is a general direction of effect, which suggests that at least some nonselective NSAIDs increase AMI risk. Analysis based on the limited data available for individual NSAIDs, including diclofenac and ibuprofen, supported this finding; however, this was not the case for naproxen. Nonselective NSAIDs are frequently prescribed, and so further investigation into the risk of AMI is warranted because the potential for harm can be substantial.

Objective: To review the methodological insights gained from the CLASS and VIGOR coxib trials and make suggestions for primary safety outcomes in future trials., Study Design and Setting: We reviewed the methodology and findings of recent coxib trials and similar studies that have produced considerable controversy., Results: There were statistical power problems with the primary and unexpected endpoints in both coxib trials. One approach for decreasing sample size requirements is using composite outcomes, wherein different clinically relevant endpoints are combined. By virtue of increasing the event rate fewer patients are required to detect a relative treatment effect of 50%., Conclusions: The recent withdrawal from the market of rofecoxib took years; the approach proposed here could shorten this time. It is important to revisit the comprehensiveness of the ability to detect important outcomes. Composite outcomes can be more varied in content, including mortality and morbidity. The proposed basket would consist of predefined designated endpoints in each organ system that could be associated with the population one is treating, and not just expected to be related to treatment. The goal is to anticipate and have a reasonable chance of detecting the unexpected side effect.

We evaluated the prevalence of Helicobacter pylori infection and the association of H. pylori infection and/or nonsteroidal anti-inflammatory drug (NSAID) use with upper gastrointestinal (UGI) ulcers in a cohort of Japanese patients with rheumatoid arthritis (RA). Using the clinical database of the cohort of RA patients and the serum titers of H. pylori antibody, 1815 patients were analyzed. Clinical data were successfully collected for 1529 patients over 2 years, and the history of NSAID use and the occurrence of newly diagnosed UGI ulcer were ascertained by patient self-reports and confirmed by their medical records. A total of 871 patients (49.3%) were H. pylori antibody-positive. Rates of positivity for H. pylori in patients with and without NSAID use were 47.5% and 54.7%, respectively (odds ratio = 0.75, 95% confidence intervals [CI]: 0.58-0.96). The incidence of newly diagnosed UGI ulcer was 0% in the H. pylori-/NSAID- group, 1.24% in the H. pylori-/NSAID+ group, 1.06% in the H. pylori+/NSAID- group, and 3.46% in the H. pylori+/NSAID+ group. The odds ratios of H. pylori infection and NSAID for the occurrence of new UGI ulcers after adjusting for age and sex were 2.97 (95% CI: 1.19-7.38) and 4.31 (95% CI: 0.57-32.4), respectively. Although the prevalence of H. pylori antibody was low in patients with RA compared with that in healthy Japanese individuals, H. pylori infection was a significant risk factor for UGI ulcer in patients with RA.

Background: Patients with rheumatoid arthritis are at high risk for acute myocardial infarction (AMI). The treatment of rheumatoid arthritis has become more intensive over the past 2 decades, resulting in tighter control of inflammation and lower levels of disability. The impact of this on atherosclerotic cardiovascular diseases is not known., Methods and Results: Death rates from AMI in a cohort of 3862 patients with rheumatoid arthritis followed up from 1980 to 1997 were studied. Time trends in AMI mortality among successive incidence and birth cohorts were examined by use of multivariable Poisson regression models and by comparing standardized mortality ratios. The mean age was 56 years in this predominantly female cohort (76%), and median disease duration was 6.5 years. During the period of observation, the use of methotrexate increased substantially, whereas that of prednisone was relatively stable. Over the 22,209 person-years of observation, there were 157 deaths as a result of AMI, with a death rate of 7.06 per 1000 person-years. Mortality rates were higher in older age groups and in men. After adjustment for age, sex, race, and disease duration, the risk of AMI declined in successive incidence years (relative risk, 0.94; 95% CI, 0.92 to 0.96). Patients with rheumatoid arthritis incident after 1990 did not have excess AMI mortality compared with general population. Declines in mortality trends were observed in successive birth cohorts as well., Conclusions: Mortality as a result of AMI among patients with rheumatoid arthritis has declined over time.

Purpose: To assess the risk of serious gastrointestinal and thromboembolic complications with approved doses of meloxicam., Methods: We pooled data from clinical trials of meloxicam at doses of 7.5 or 15 mg/d. A blinded gastrointestinal adjudication committee used prespecified criteria to identify gastric or duodenal perforation, gastric outlet obstruction, or hemodynamically important upper gastrointestinal bleeding. For analysis of thromboembolic complications, investigator-reported events were analyzed without adjudication., Results: We analyzed data from 24,196 patients from 28 trials, most of whom had been followed for up to 60 days. Of these patients, 13,118 received meloxicam (10,158 received a daily dose of 7.5 mg and 2960 received 15 mg), 5283 were treated with diclofenac 100 mg, 181 received diclofenac 150 mg, 5371 were treated with piroxicam 20 mg, and 243 received naproxen 500 mg twice daily. Patients who received 7.5 mg of meloxicam daily had a 0.03% risk of serious upper gastrointestinal events, which was significantly lower than the risk in those who received diclofenac, naproxen, or piroxicam (P <0.02). With the 15 mg daily dose of meloxicam, this risk was significantly different only when compared with piroxicam (P = 0.03). The risk of thromboembolic events in patients treated with meloxicam at either dose was lower than with diclofenac, but similar to that observed with piroxicam and naproxen., Conclusion: This pooled analysis of 24,196 patients demonstrates that meloxicam has a favorable gastrointestinal and thromboembolic safety profile. However, only a small number of patients were followed for more than 60 days, and meaningful comparisons were not possible in this subgroup.

Objective: Patient dropout (attrition) can bias and threaten validity of databank-based studies. Although there are several databanks of rheumatoid arthritis (RA) in operation, this phenomenon has not been well studied., Methods: We studied the attrition patterns of patients with RA in 11 long-running databanks where patients were followed using semiannual Health Assessment Questionnaires. Attrition rates were calculated as the proportion of living patients who were in active followup at the cutoff date. Mantel-Haenszel methods and Weibull regression were used to model the relationship between attrition and age, sex, race, education, disease duration, functional disability, and other characteristics., Results: Overall, 6346 patients with RA were recruited into the study cohorts and followed for 32,823 person-years with 65,649 observations. The crude attrition rate was 3.8% per cycle. Rates were lowest in community-based databanks. Smaller size of the centers, inner-city location, and university clinic settings were associated with worse attrition. In multivariable analyses, younger age, lower levels of education, and non-Caucasian race predicted attrition. Level of disability and disease duration were not associated with attrition. Conclusion. In terms of person-years of followup and observation-points, this may be the largest study on attrition to date. While it is possible to have very high overall retention rates, certain types of databanks (smaller, inner-city-based, and university-based) are more likely to be biased due to selective retention of older, more educated Caucasian patients.

Nonsteroidal antiinflammatory drugs (NSAIDs) are widely used to treat arthritis but are associated with adverse gastrointestinal events. While the selective COX-2 inhibitors show fewer gastrointestinal complications than NSAIDs, they may not be suitable for all patients and one of them has been associated with serious thrombotic cardiovascular events. Furthermore, many arthritis patients are at high risk of coronary artery disease and take low-dose aspirin, which is also associated with adverse gastrointestinal events. Proton pump inhibitor (PPI) therapy has been shown to be effective in reducing the risk of gastrointestinal complications in this patient population. Recent randomized clinical trials have also shown that pantoprazole therapy is effective in the healing of NSAID-induced gastrointestinal damage. Several studies have also demonstrated that pantoprazole is effective in preventing the development of gastrointestinal lesions in patients with continuous NSAID intake. The use of PPIs in combination with nonselective NSAIDs has also been found to be beneficial in patients at high risk for rebleeding and reduces the incidence of dyspepsia. Finally, the combination of a COX-2 inhibitor with a PPI has shown promise in patients with previous NSAID-related gastrointestinal complications who are at high risk for reinjury., ((c) 2004 Prous Science)