Gastrointestinal symptom severity in irritable bowel syndrome, inflammatory bowel disease and the general population.

BACKGROUND: Irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) patients report similar gastrointestinal (GI) symptoms, yet comparisons of symptom severity between groups and with the general population (GP) are lacking. METHODS: We compared Patient-Reported Outcomes Measurement Information System (PROMIS® ) GI symptom scales measuring gastro-esophageal reflux (GER), disrupted swallowing, diarrhea, bowel incontinence, nausea/vomiting, constipation, belly pain, and gas/bloating in: (i) USA GP sample, (ii) IBS patients, and (iii) IBD patients from tertiary care and community populations. Symptom severity scores were based on T-score metric with mean 50±10 (standard deviation) relative to the GP. KEY RESULTS: Of 1643 patients enrolled, there were 253 IBS patients (68% F, mean age 45±15 years), 213 IBD patients (46% F, mean age 41±14 years), and 1177 GP subjects (57% F, mean age 46±16 years). IBS patients reported greater severity of GER, disrupted swallowing, nausea/vomiting, belly pain, gas/bloating, and constipation symptoms than their IBD counterparts (all P<.05). Compared to the GP, IBD patients had worse belly pain, gas/bloating, diarrhea, and bowel incontinence, but less severe GER and disrupted swallowing (all P<.05), and IBS patients had more severe nausea/vomiting, belly pain, gas/bloating, and constipation (all P<.05). Women had more severe belly pain and gas/bloating than men, whereas men had more severe bowel incontinence (all P<.05). CONCLUSION & INFERENCES: IBS and IBD are associated with more severe GI symptoms compared to the GP excluding esophageal symptoms. Unlike IBD, IBS is not characterized by observable GI inflammation but patients report more severe upper and lower GI symptoms.

Clinical and demographic characteristics predictive of treatment outcomes for certolizumab pegol in moderate to severe Crohn's disease: analyses from the 7-year PRECiSE 3 study.

BACKGROUND: Clinical factors were previously identified as predictors of short-term treatment efficacy in Crohn's disease (CD). The PRECiSE 3 (P3) 7-year trial provides an opportunity to study predictors of short- and long-term clinical remission among CD patients treated with certolizumab pegol (CZP). AIM: To identify factors that influence long-term remission of CD with CZP treatment. METHODS: Patients who had completed placebo-controlled studies (PRECiSE 1/PRECiSE 2, P1/P2) enrolled in P3 and received open-label CZP 400 mg every 4 weeks up to 7 years. Baseline predictors included, but were not limited to, smoking status, disease duration, prior inflammatory bowel disease (IBD) surgery, Harvey-Bradshaw Index (HBI), albumin, haematocrit and CZP exposure; association with time to initial remission (HBI ≤4) was tested for patients who received CZP in P1/P2; time to loss of remission/frequency of maintenance of remission was also tested. Univariate analyses and multivariate Cox or logistic regression models were used. RESULTS: Predictors for initial remission (N = 377) included age, haematocrit, prior IBD surgery and entry HBI (P < 0.05 for all). Predictors for loss of remission (N = 437) included HBI, serum albumin concentration, haematocrit, smoking status and exposure. Predictors of maintenance of remission (N = 437) included haematocrit, IBD surgery, HBI, disease duration, serum albumin concentration and exposure. Significant predictors were confirmed with stepwise multivariate regression models. CONCLUSIONS: These analyses identified several influential parameters for short-and long-term remission of Crohn's disease with certolizumab pegol treatment. The data yield valuable hypotheses regarding factors that influence certolizumab pegol treatment. More investigation is needed. (ClinicalTrials.gov identifier NCT00552058).

Setting priorities for comparative effectiveness research in inflammatory bowel disease: results of an international provider survey, expert RAND panel, and patient focus groups.

BACKGROUND: Comparative effectiveness research (CER) is an emerging field that compares the relative effectiveness of alternative strategies to prevent, diagnose, or treat patients who are typical of day-to-day practice. We developed a priority list of CER topics for inflammatory bowel disease (IBD). METHODS: Following the Institute of Medicine's approach, we developed and administered a survey to gastroenterologists asking for important CER topics in IBD. Two patient focus groups were convened to solicit additional CER studies. CER topics were presented to the expert panel using the RAND/UCLA methodology. Following initial ratings, the panel met to discuss and re-rate priorities. The top 10 CER topics were identified using a point-allocation system. RESULTS: Responses were collated into 234 CER topics across 21 categories, of which 87 were prioritized for discussion and re-rated. Disagreement regarding priorities was observed in 5 of 87 studies. We utilized a point-allocation system to prioritize the top-10 CER topics. These related to comparing the effectiveness of: biomarkers in IBD; withdrawal of anti-tumor necrosis factor (TNF) or immunomodulators for Crohn's disease in remission; mucosal healing as an endpoint of treatment; infliximab levels versus standard infliximab dosing; anti-TNF monotherapy versus combination therapy in patients failing thiopurines; safety of long-term treatment options; anti-TNF versus thiopurines for prevention of postoperative recurrence; and treatment options for steroid-refractory UC. CONCLUSIONS: We systematically developed a list of high-priority IBD topics for CER based on a survey of gastroenterologists, expert review, and patient input. This list may guide IBD research toward the most important CER studies.

Consequences of frequent nocturnal gastro-oesophageal reflux disease among employed adults: symptom severity, quality of life and work productivity.

BACKGROUND: Effects of frequent nocturnal symptoms of gastro-oesophageal reflux disease (GERD-FNS) on health-related quality of life (HRQOL) and work productivity are not well documented. AIM: To assess symptom severity, production loss, and HRQOL among employed adults with and without GERD-FNS. METHODS: Using several validated outcome measures in a web survey design, GERD was pre-specified as GERD Symptom and Medication Questionnaire score >9, and > or =1 episode of heartburn or acid regurgitation during the preceding week. GERD-FNS patients were those reporting > or =2 symptom-nights during the previous week; their outcomes were compared with those of patients having minimal or no nocturnal symptoms (GERD-NNS) and vs. non-GERD controls. RESULTS: Data were collected from 1002 GERD patients (476 GERD-FNS, 526 GERD-NNS) and 513 controls. Severe symptoms were more common, sleep abnormalities were more frequent (P < 0.0001) and SF-36 scores lower (P < 0.05, all scores) among GERD-FNS patients vs. GERD-NNS patients. GERD-related work loss was greater among those with GERD-FNS vs. GERD-NNS (P < 0.0001). Work loss and functional limitations were more pronounced when comparing GERD-FNS cases vs. non-GERD controls. CONCLUSION: Employed adults with frequent nocturnal GERD report more severe symptoms, and are associated with impaired sleep, HRQOL and work productivity compared with controls and patients with minimal or no nocturnal symptoms.

Guidelines for the appropriate use of non-steroidal anti-inflammatory drugs, cyclo-oxygenase-2-specific inhibitors and proton pump inhibitors in patients requiring chronic anti-inflammatory therapy.

AIM: To rationalize decision making around the use of different non-steroidal anti-inflammatory drug (NSAID) treatment strategies in patients with varying degrees of gastrointestinal and cardiovascular risk. METHODS: The panel comprised nine physicians (three rheumatologists, two internists, two gastroenterologists and two cardiologists) from geographically diverse areas practising in community-based settings (n = 4) and academic institutions (n = 5). A literature review was performed by the authors on the risks, benefits and costs of NSAIDs, cyclo-oxygenase-2-specific inhibitors and proton pump inhibitor co-therapy. The RAND/UCLA Appropriateness Method was used to rate 304 clinical scenarios as 'appropriate', 'uncertain' or 'inappropriate'. RESULTS: In patients with no previous gastrointestinal event and not concurrently on aspirin (low risk), the panel rated the use of an NSAID alone as 'appropriate' for those aged < 65 years, and the use of an NSAID +proton pump inhibitor or cyclo-oxygenase-2-specific inhibitor + proton pump inhibitor as 'inappropriate'. For patients aged > 65 years and at low risk, an NSAID or cyclo-oxygenase-2-specific inhibitor alone was rated as 'uncertain'. For patients with a previous gastrointestinal event or who concurrently received aspirin, an NSAID alone was rated as 'inappropriate', and either a cyclo-oxygenase-2-specific inhibitor or an NSAID +proton pump inhibitor was rated as 'appropriate'. Finally, for patients with a previous gastrointestinal event and on aspirin, an NSAID or cyclo-oxygenase-2-specific inhibitor in conjunction with a proton pump inhibitor was rated as 'appropriate'. CONCLUSIONS: Clinicians and managed care entities need to balance the risks, benefits and costs of NSAIDs, cyclo-oxygenase-2-specific inhibitors and the prophylactic use of proton pump inhibitors. The guidelines given here can assist this process.

Life after radical prostatectomy: a longitudinal study.

PURPOSE: We investigate the longitudinal recovery of quality of life after radical prostatectomy in men with localized prostate cancer. MATERIALS AND METHODS: We assessed the self-reported health related quality of life in 247 men undergoing radical prostatectomy for prostate cancer. Patients were assessed at baseline before surgery and postoperatively every 3 months for 1 year and then every 6 months for up to 48 months (median 30). We measured general and prostate specific health related quality of life with the RAND 36-Item Health Survey 1.0 SF-36 and University of California, Los Angeles Prostate Cancer Index. The Cox proportional hazards regression model was used to determine whether some patients were more likely than others to have a successful return to baseline functioning after treatment. RESULTS: In the SF-36 60% of patients reached baseline in all domains by 3 months. By 12 months, greater than 90% of patients reached baseline in all domains. Mean recovery time for these domains was about 4(1/2) months. The recovery of urinary function to baseline was 21% at 3, 56% at 12 and 63% at 30 months, respectively. About 80% of patients recovered to baseline urinary bother. In the urinary domains patients who recovered did so at an average of 7 to 8 months, and there was little additional recovery after 18 months. By 1 year postoperatively, approximately a third of patients reached baseline sexual function and about half recovered to baseline sexual bother. At 2 years postoperatively, sexual function and bother returned to baseline in 40% and 60% of patients, respectively. Mean recovery time was about 11 months for sexual function and about 9 months for sexual bother. There was little additional recovery in the sexual domains after 18 to 24 months. In the bowel domains more than two thirds of patients returned to baseline by 3 months, and greater than 90% recovered by 12 months, with a mean recovery of 4.8 months. Unmarried men were more likely than those married to regain baseline sexual function (p = 0.03) and urinary function (p = 0.07). Patients who were 65 years and older were more likely than those younger to return to baseline sexual bother (p = 0.03). There were trends that showed patients with higher incomes as well as those who were white were more likely to recover baseline scores for urinary function and the physical component summary. Another trend suggested that men with a higher education were less likely to regain urinary function (p = 0.08). CONCLUSIONS: Most quality of life recovery occurs early after radical prostatectomy, except in several domains, including urinary and sexual, which continue to improve even beyond 2 years postoperatively. Patients should be encouraged that recovery may continue for months or years after surgery.