Effectiveness of management strategies for uninvestigated dyspepsia: systematic review and network meta-analysis

Objective To determine the effectiveness of management strategies for uninvestigated dyspepsia. Design Systematic review and network meta-analysis. Data sources Medline, Embase, Embase Classic, the Cochrane Central Register of Controlled Trials, and clinicaltrials.gov from inception to September 2019, with no language restrictions. Conference proceedings between 2001 and 2019. Eligibility criteria for selecting studies Randomised controlled trials that assessed the effectiveness of management strategies for uninvestigated dyspepsia in adult participants (age ≥18 years). Strategies of interest were prompt endoscopy; test for Helicobacter pylori and perform endoscopy in participants who test positive; test for H pylori and eradication treatment in those who test positive (“test and treat”); empirical acid suppression; or symptom based management. Trials reported dichotomous assessment of symptom status at final follow-up (≥12 months). Results The review identified 15 eligible randomised controlled trials that comprised 6162 adult participants. Data were pooled using a random effects model. Strategies were ranked according to P score, which is the mean extent of certainty that one management strategy is better than another, averaged over all competing strategies. “Test and treat” ranked first (relative risk of remaining symptomatic 0.89, 95% confidence interval 0.78 to 1.02, P score 0.79) and prompt endoscopy ranked second, but performed similarly (0.90, 0.80 to 1.02, P score 0.71). However, no strategy was significantly less effective than “test and treat.” Participants assigned to “test and treat” were significantly less likely to receive endoscopy (relative risk v prompt endoscopy 0.23, 95% confidence interval 0.17 to 0.31, P score 0.98) than all other strategies, except symptom based management (relative risk v symptom based management 0.60, 0.30 to 1.18). Dissatisfaction with management was significantly lower with prompt endoscopy (P score 0.95) than with “test and treat” (relative risk v “test and treat” 0.67, 0.46 to 0.98), and empirical acid suppression (relative risk v empirical acid suppression 0.58, 0.37 to 0.91). Upper gastrointestinal cancer rates were low in all trials. Results remained stable in sensitivity analyses, with minimal inconsistencies between direct and indirect results. Risk of bias of individual trials was high; blinding was not possible because of the pragmatic trial design. Conclusions “Test and treat” was ranked first, although it performed similarly to prompt endoscopy and was not superior to any of the other strategies. “Test and treat” led to fewer endoscopies than all other approaches, except symptom based management. However, participants showed a preference for prompt endoscopy as a management strategy for their symptoms. Systematic review registration PROSPERO registration number CRD42019132528

Latent class analysis does not support the existence of Rome IV functional bowel disorders as discrete entities

Background Previously, we used latent class analysis (LCA) to identify novel subgroups in people with irritable bowel syndrome (IBS). There are four other functional bowel disorders that, although characterized as discrete disorders, overlap considerably with, and fluctuate to, IBS. These might instead be conceptualized as a milder form of IBS. We explored this hypothesis using LCA in a cohort of people with non-IBS functional bowel disorders. Methods We collected demographic, symptom, and psychological health data from 1375 adults in the community who self-identified as having IBS and identified individuals meeting Rome IV criteria for any non-IBS functional bowel disorder. We performed LCA to identify specific subgroups (clusters). We followed participants up at 12 months to reassess gastrointestinal and psychological heath and also gather data about healthcare utilization and impact of symptoms. Key results 811 people met Rome IV criteria for IBS and 558 Rome IV criteria for another functional bowel disorder (76 (5.5%) functional constipation; 198 (14.5%) functional diarrhea; 129 (9.5%) functional abdominal bloating or distension; and 155 (11.4%) unspecified functional bowel disorder). LCA in these 558 people identified five clusters defined by a combination of gastrointestinal symptoms and the extent of psychological co-morbidity. However, correlation between these clusters and the Rome IV functional bowel disorder diagnoses was poor and 75% of people were classified as having mild IBS using our previous IBS-derived model. By 12 months, one-third of people had fluctuated and met criteria for IBS. Clusters with high psychological burden had a poorer prognosis, with higher rates of medical consultation, medication use, and greater impact of symptoms on daily life. Conclusions and inferences The functional bowel disorders may be better characterized as a spectrum of IBS rather than separate disorders. Adopting this pragmatic stance may help to simply diagnosis, treatment, and recruitment of patients to research trials

Anxiety‐related factors associated with symptom severity in irritable bowel syndrome

Background Gastrointestinal symptom‐specific anxiety and somatization have both been associated with higher symptom severity in patients with irritable bowel syndrome (IBS); however, this relationship has not been explored fully. Moreover, the performance of the visceral sensitivity index (VSI) for measuring gastrointestinal symptom‐specific anxiety has not been examined in a UK population. We conducted a cross‐sectional survey to examine these issues. Methods Gastrointestinal symptom‐specific anxiety was measured using the VSI, and somatization was measured via the patient health questionnaire‐12 (PHQ‐12) in adults from the UK community with Rome IV‐defined IBS. Exploratory factor analysis was performed on the VSI, prior to subsequent analyses, to establish its factor structure. Multiple regression analysis was used to determine the relationship between demographic features, different factors of the VSI, somatization, and IBS symptom severity. Key Results A total of 811 individuals with IBS provided complete data. Factor analysis of the VSI revealed a three‐factor structure, accounting for 47% of the variance. The first of these VSI factors and the PHQ‐12 were both strongly and independently associated with IBS symptom severity, for the group as a whole and for all four IBS subtypes. Most VSI items concerned with overt gastrointestinal symptom‐specific anxiety loaded onto the other two VSI factors that were not associated with symptom severity. Conclusions and Inferences The factor structure of the VSI requires further investigation. Our findings cast doubt on the central role of gastrointestinal symptom‐specific anxiety as a driver for symptom severity in IBS. Awareness of both gastrointestinal and extra‐intestinal symptoms, however, is strongly associated with symptom severity

Direct healthcare costs of Rome IV or Rome III-defined irritable bowel syndrome in the United Kingdom

Background Previous studies have demonstrated a substantial economic impact of irritable bowel syndrome (IBS). Aims To provide contemporaneous estimates of direct healthcare costs of IBS in the United Kingdom. Methods We collected demographic, gastrointestinal and psychological symptoms, quality of life and healthcare usage data from adults with Rome IV or Rome III IBS in the United Kingdom. We calculated the mean annual direct healthcare costs of IBS per person and used contemporaneous IBS prevalence data, together with census data, to estimate annual direct costs of IBS. We also examined predictors of higher costs. Results The mean annual direct cost of IBS per person among 752 individuals with Rome IV IBS was £556.65 (SD £1023.92) and £474.16 (SD £897.86) for 995 individuals with Rome III IBS. We estimate the annual direct healthcare cost of IBS in the United Kingdom is £1.27 billion if the Rome IV criteria are used to define IBS, and £2.07 billion using Rome III. Among individuals with Rome IV IBS, mean annual costs were higher in those with opiate use (£907.90 vs £470.58, p 5 years £501.60, p = 0.002), lower quality of life (p < 0.001 for trend), and higher depression, somatisation and gastrointestinal symptom-specific anxiety scores (P < 0.001 for trend for all). Conclusion We estimate annual direct healthcare costs of IBS of between £1.3 and £2 billion in the United Kingdom

Systematic review with network meta-analysis: Risk of Herpes zoster with biological therapies and small molecules in inflammatory bowel disease.

Background Biologics and small molecules for inflammatory bowel disease (IBD) may increase infection risk. Herpes zoster causes acute and long-term symptoms, but vaccination is not recommended in patients with IBD, unless >50 years of age. Aims To examine risk of Herpes zoster infection with all licensed biologics and small molecules for IBD using network meta-analysis. Methods We searched the literature to 4th October 2022, for randomised controlled trials of these drugs in luminal Crohn's disease or ulcerative colitis reporting data on occurrence of Herpes zoster infection during follow-up. We used a frequentist approach and a random effects model, pooling data as relative risks (RRs) with 95% confidence intervals (CIs). Results We identified 25 trials (9935 patients). Only tofacitinib 10 mg b.d. (RR = 6.90; 95% CI 1.56–30.63, number needed to harm (NNH) = 97; 95% CI 19–1022) and upadacitinib 45 mg o.d. (RR = 7.89; 95% CI 1.04–59.59, NNH = 83; 95% CI 10–14,305) were significantly more likely to increase risk of Herpes zoster infection. Janus kinase inhibitors were the most likely drug class to increase risk of infection, and risk increased with higher doses (RR with lowest dose = 3.16; 95% CI 1.02–9.84, NNH = 265; 95% CI 65–28,610, RR with higher dose = 5.91; 95% CI 2.21–15.82, NNH = 117; 95% CI 39–473). Conclusions In a network meta-analysis, the janus kinase inhibitor tofacitinib, and all janus kinase inhibitors considered as a class, were most likely to increase risk of Herpes zoster infection. Risk increased with higher doses

Willingness to accept risk with medication in return for cure of symptoms among patients with Rome IV irritable bowel syndrome

Background Some drugs for irritable bowel syndrome (IBS) have serious side effects. Aims To examine the willingness of individuals with IBS to accept risks with medication in return for symptom cure. Methods We collected demographic, gastrointestinal symptoms, psychological health, quality of life and impact on work and daily activities data from 752 adults with Rome IV-defined IBS. We examined median willingness to accept death in return for cure with a hypothetical medication using a standard gamble, according to these variables. Results Participants would accept a median 2.0% (IQR 0.0%-9.0%) risk of death in return for a 98.0% (IQR 91.0%-100.0%) chance of permanent symptom cure. The median accepted risk of death was higher in men (5.0% vs 2.0%, P < 0.001), those with continuous abdominal pain (4.0% vs 1.0%, P < 0.001), more severe symptoms (P = 0.005 for trend), abnormal depression scores (P < 0.001 for trend), higher gastrointestinal symptom-specific anxiety (P < 0.001 for trend), and lower IBS-related quality of life (P < 0.001 for trend). Those willing to accept above median risk of death were more likely to be male (17.1% vs 9.1%, P < 0.001), take higher levels of risks in their daily life (P = 0.008 for trend), and report continuous abdominal pain (53.1% vs 39.4%, P < 0.001), and had higher depression (P = 0.004 for trend) and lower quality of life (P < 0.001 for trend) scores. Conclusion Patients are willing to accept significant risks in return for cure of their IBS symptoms

Willingness to pay for medications among patients with Rome IV Irritable Bowel Syndrome

Background Little is known about willingness to pay for medications among individuals with irritable bowel syndrome (IBS). Methods We collected demographic, gastrointestinal symptom, psychological health, quality of life, and healthcare usage data from 752 adults with Rome IV-defined IBS. We examined willingness to pay for a hypothetical medication in return for improvement in IBS symptoms using a contingent valuation method, according to these variables. Results The median amount of money individuals was willing to pay was £1–£50 (IQR £0–£100) per month for a medication with a 100% chance of improving IBS symptoms. Women, compared with men, (92.7% willing to pay “£0,” 89.8% “£1–£50,” 87.3% “£51–£100,” 78.9% “£101–£200,” and 78.5% “more than £200,” p = 0.008) were less likely to be willing to pay for a pill with a 100% chance of improving IBS symptoms whilst those with an annual income of £30,000 or more (12.2% willing to pay “£0,” 25.2% “£1–£50,” 33.5% “£51–£100,” 40.2% “£101–£200,” and 35.1% “more than £200,” p = 0.002) were more likely. We observed a higher willingness to pay among those with lower IBS-related quality of life (p = 0.002 for trend). Of all 752 individuals, 92.7%, 74.5%, and 58.0% would be willing to pay for a medication that would give them a 100%, 50%, or 30% chance of improving IBS symptoms, respectively. Conclusion Patients with IBS are willing to pay for medications which improve IBS symptoms. Future studies should investigate the relative importance of medication pricing, efficacy, and side effect profile among individuals with IBS

Factors associated with lower disease-specific and generic health-related quality of life in Rome IV irritable bowel syndrome

Background Little is known about associations with reduced quality of life in irritable bowel syndrome (IBS) or impact of IBS on quality of life compared with other chronic conditions. Methods We collected demographic, gastrointestinal and psychological symptoms, healthcare usage, direct healthcare costs, impact on work and activities of daily living data from 752 individuals with Rome IV-defined IBS. We used the irritable bowel syndrome quality of life (IBS-QOL) and the EQ-5D-5L questionnaires to examine characteristics associated with lower quality of life. Results The mean IBS-QOL among all 752 individuals with Rome IV IBS was 48.4 (SD 22.3) and the mean EQ-5D score was 0.570 (SD 0.283), the latter being comparable to people with stroke, leg ulcers or chronic obstructive pulmonary disease. Lower levels of both disease-specific and generic quality of life were associated with severe IBS symptom scores, abnormal anxiety or depression scores, and higher somatoform symptom-reporting and gastrointestinal symptom-specific anxiety scores (p < 0.001 for all analyses). Those with lower quality of life had significantly higher healthcare usage and direct healthcare costs and more impairment in work and activities of daily living (p < 0.01 for all analyses). Avoidance of alcohol, lower educational level, abnormal anxiety, depression or somatoform symptom-reporting scores, and impairment in social leisure activities, home management or maintaining close relationships were all independently associated with lower quality of life. Conclusion IBS has a substantial impact on the quality of life of those affected, and worse than observed in some severe chronic organic conditions

Impact of generic alendronate cost on the cost-effectiveness of osteoporosis screening and treatment

Introduction: Since alendronate became available in generic form in the Unites States in 2008, its price has been decreasing. The objective of this study was to investigate the impact of alendronate cost on the cost-effectiveness of osteoporosis screening and treatment in postmenopausal women. Methods: Microsimulation cost-effectiveness model of osteoporosis screening and treatment for U.S. women age 65 and older. We assumed screening initiation at age 65 with central dual-energy x-ray absorptiometry (DXA), and alendronate treatment for individuals with osteoporosis; with a comparator of "no screening" and treatment only after fracture occurrence. We evaluated annual alendronate costs of $20 through$800; outcome measures included fractures; nursing home admission; medication adverse events; death; costs; quality-adjusted life-years (QALYs); and incremental cost-effectiveness ratios (ICERs) in 2010 U.S. dollars per QALY gained. A lifetime time horizon was used, and direct costs were included. Base-case and sensitivity analyses were performed. Results: Base-case analysis results showed that at annual alendronate costs of $200 or less, osteoporosis screening followed by treatment was cost-saving, resulting in lower total costs than no screening as well as more QALYs (10.6 additional quality-adjusted life-days). When assuming alendronate costs of$400 through $800, screening and treatment resulted in greater lifetime costs than no screening but was highly cost-effective, with ICERs ranging from$714 per QALY gained through $13,902 per QALY gained. Probabilistic sensitivity analyses revealed that the cost-effectiveness of osteoporosis screening followed by alendronate treatment was robust to joint input parameter estimate variation at a willingness-to-pay threshold of$50,000/QALY at all alendronate costs evaluated. Conclusions: Osteoporosis screening followed by alendronate treatment is effective and highly cost-effective for postmenopausal women across a range of alendronate costs, and may be cost-saving at annual alendronate costs of $200 or less. © 2012 Nayak et al