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Chronic idiopathic constipation (CIC) is a prevalent functional gastrointestinal disorder diagnosed based on patient-reported symptoms and the absence of structural gastrointestinal abnormalities. Individuals with CIC typically institute dietary changes and use stool softeners or over-the-counter (OTC) laxatives, possibly at the direction of a healthcare provider, before prescription medications for CIC are initiated. Although highly prevalent, there is limited information regarding CIC patient experiences with OTC medications. This post-hoc analysis used patient-reported data from a questionnaire administered during patient screening for a prospective linaclotide Phase 3b clinical trial in patients with CIC (N = 1482 screened). The questionnaire asked patients to report their experiences with OTC CIC medications over the preceding 6 months. Among patients with screening responses (N = 1423), most were female (85%) and white (66%), with a mean age of 48.9 years. A high proportion of patients had used one or more OTC medications (70% had ≥1 OTC; 19% had ≥3 OTCs), with the majority being bisacodyl (33%) and polyethylene glycol (30%). The most commonly cited reason for stopping an OTC medication was insufficient symptom relief (17-40%). The majority of patients taking OTC medications reported no or little satisfaction with the medication's effect on their constipation (62%) and CIC-specific abdominal symptoms (78%). Many patients had little to no confidence in bowel movement (BM) frequency after taking OTC medications and their confidence in their ability to predict BM timing was also low (49-81% not at all confident). Treatment effects on individual CIC symptoms, predictability of bowel habits, and satisfaction with treatment are all important factors for healthcare providers and patients to consider when establishing an effective treatment regimen for CIC. NCT01642914.

Background : Mathematical models are commonly used to predict future benefits of new therapies or interventions in the healthcare setting. The reliability of model results is greatly dependent on accuracy of model inputs but on occasion, data sources may not provide all the required inputs. Therefore, calibration of model inputs to epidemiological endpoints informed by existing data can be a useful tool to ensure credibility of the results. Objective : To compare different computational methods of calibrating a Markov model to US data. Methods : We developed a Markov model that simulates the natural history of human papillomavirus (HPV) infection and subsequent cervical disease in the US. Because the model consists of numerous transition probabilities that cannot be directly estimated from data, calibration to multiple disease endpoints was required to ensure its predictive validity. Goodness of fit was measured as the mean percentage deviation of model-predicted endpoints from target estimates. During the calibration process we used the manual, random and Nelder-Mead calibration methods. Results : The Nelder-Mead and manual calibration methods achieved the best fit, with mean deviations of 7% and 10%, respectively. Nelder-Mead accomplished this result with substantially less analyst time than the manual method, but required more intensive computing capability. The random search method achieved a mean deviation of 39%, which we considered unacceptable despite the ease of implementation of that method. Conclusions : The Nelder-Mead and manual techniques may be preferable calibration methods based on both performance and efficiency, provided that sufficient resources are available.

Background : A recent study found fewer hospitalizations for congestive heart failure (CHF) patients receiving high-dose versus low-dose statin therapy. Objective : To examine the cost effectiveness of high-dose versus low-dose statin therapy in CHF patients. Methods : Two scenarios (literature-based [base-case scenario] vs trial-based post-event mortality [alternative scenario]) assessed the cost effectiveness of atorvastatin 80mg/day (A80) versus atorvastatin 10 mg/day (A10) in patients with both CHF and coronary heart disease (CHD) [CHF/CHD], using a lifetime Markov model. The model predicts treatment-specific probabilities of major and minor cardiovascular events and death, based on clinical trial data. The quality of life and costs were literature based. Measures included costs per life-year saved (LYS) and QALY gained. Health consequences and costs were discounted at 3.0% annually. Analyses were conducted from the payer perspective and valued in $US, year 2006–7 values. Results : Literature-based mortality estimates (base case) increased life-years and QALYs for A80 compared with A10 (incremental cost-effectiveness ratios [ICERs]: $US9600 per LYS; $US13 600 per QALY). At a willingness to pay of $US100 000 per QALY, A80 was cost effective in 80% of simulations. A10 dominated A80 when using trial-based mortality estimates (alternative scenario). At a willingness to pay of $US100 000 per QALY, A80 was cost effective in 48% of simulations. Conclusions : Intensive A80 treatment may be cost effective versus A10 in cardiovascular prevention in CHF/CHD patients in the US, due to projected gains in life expectancy and health-related quality of life. However, the results are highly sensitive to assumptions about the mortality rate in the model. When using the mortality rate observed in the trial, A10 dominates A80.

The Treating to New Targets (TNT) clinical trial found that intensive 80 mg atorvastatin (A80) treatment reduced cardiovascular events by 22% when compared to 10 mg atorvastatin (A 10) treatment. We evaluated the cost-effectiveness of intensive A80 vs A10 treatment in the United Kingdom (UK), Spain, and Germany. A lifetime Markov model was developed to predict cardiovascular disease-related events, costs, survival, and quality-adjusted life-years (QALYs). Treatment-specific event probabilities were estimated from the TNT clinical trial. Post-event survival, health-related quality of life, and country-specific medical-care costs were estimated using published sources. Intensive treatment with A80 increased both the per-patient QALYs and corresponding costs of care, when compared to the A10 treatment, in all three countries. The incremental cost per QALY gained was € 9,500, € 21,000, and € 15,000 in the UK, Spain, and Germany, respectively. Intensive A80 treatment is estimated to be cost-effective when compared to A10 treatment in secondary cardiovascular prevention.

Objective : The aim of this study was to examine how calibration uncertainty affects the overall uncertainty of a mathematical model and to evaluate potential drivers of calibration uncertainty. Methods : A lifetime Markov model of the natural history of human papillomavirus (HPV) infection and cervical disease was developed to assess the cost effectiveness of a hypothetical HPV vaccine. Published data on cervical cancer incidence and mortality and prevalence of pre-cursor lesions were used as endpoints to calibrate the age- and HPV-type-specific transition probabilities between health states using the Nelder-Mead simplex method of calibration. A conventional probabilistic sensitivity analysis (PSA) was performed to assess uncertainty in vaccine efficacy, cost and utility estimates. To quantify the uncertainty around calibrated transition probabilities, a second PSA (calibration PSA) was performed using 25 distinct combinations of objective functions and starting simplexes. Results : The initial calibration produced an incremental cost-effectiveness ratio (ICER) of $US4300 per QALY for vaccination compared with no vaccination, and the conventional PSA gave a 95% credible interval of dominant to $US9800 around this estimate (2005 values). The 95% credible interval for the ICERs in the calibration PSA ranged from $US1000 to $US37 700. Conclusions : Compared with a conventional PSA, the calibration PSA results reveal a greater level of uncertainty in cost-effectiveness results. Sensitivity analyses around model calibration should be performed to account for uncertainty arising from the calibration process.

INTRODUCTION:GERD is a common disorder often treated with proton pump inhibitors (PPIs). However, many patients experience persistent GERD symptoms despite PPI treatment. The objective of this study was to estimate the prevalence of persistent GERD symptoms despite PPI treatment and to describe the characteristics of these patients in the US adult population.METHODS:The Acumen Health Research Institute survey is a cross-sectional health survey of US adults in which a subgroup of participants self-identified as having GERD (GERD patients). Participants aged ≥ 18 years were recruited in 2018 using sampling framework that ensured a composition representative of the US population. Patients were asked about their GERD history, treatments, and symptoms using the GERD Symptom Assessment Scale. Health-related quality of life (HRQoL) was assessed using the Veterans RAND 12-item (VR-12) physical component summary (PCS), mental component summary (MCS), and health utility (VR-6D). Work productivity and sleep disturbance due to GERD were also assessed. Persistent GERD was defined a priori as the presence of bothersome symptoms on at least 2 days in the preceding week despite taking PPIs for at least 25 days per month. Effectiveness of PPI treatment was rated as “a little” or “a lot.” GERD patients with and without persistent GERD symptoms were compared using descriptive statistics.RESULTS:Of 12,348 survey respondents, 1566 (12.7%) self-identified as GERD patients; 855 (54.6%) reported taking PPIs. Of those, 301 (35.2%) met the definition for persistent GERD. Patients with persistent GERD had decreased HRQoL (36.2 vs. 40.5 PCS, 41.6 vs. 45.7 MCS, and 0.60 vs. 0.66 VR-6D) and greater impairment in work productivity (3.2 vs. 2.1 work hours/week missed due to health) than those without. GERD patients with persistent GERD were more likely to take antacids (50.2%) and H2-receptor antagonists (17.9%) in addition to their PPI than those without (30.9% and 13.4%, respectively). GERD patients with persistent symptoms had more difficulty with sleep than those without. In the preceding week, 38.2% and 14.4%, respectively, reported difficulty falling asleep because of GERD symptoms on > 2 nights, and 29.3% and 10.6%, respectively, woke because of GERD symptoms on > 2 nights.CONCLUSION:Among GERD patients taking PPIs, more than one-third had persistent symptoms. Patients with persistent GERD symptoms had decreased HRQoL, greater impairment of work productivity, and greater sleep disturbance than those without.