Up-Front Endoscopy Maximizes Cost-Effectiveness and Cost-Satisfaction in Uninvestigated Dyspepsia.

BACKGROUND & AIMS: Practice guidelines promote a routine noninvasive, non-endoscopic initial approach to investigating dyspepsia without alarm features in young patients, yet many patients undergo prompt upper endoscopy. We aimed to assess tradeoffs among costs, patient satisfaction, and clinical outcomes to inform discrepancy between guidelines and practice. METHODS: We constructed a decision-analytic model and performed cost-effectiveness/cost-satisfaction analysis over a 1-year time horizon on patients with uninvestigated dyspepsia without alarm features referred to gastroenterology. A RAND/UCLA expert panel informed model design. Four competing diagnostic/management strategies were evaluated: prompt endoscopy, testing for Helicobacter pylori and eradicating if present (test-and-treat), testing for H pylori and performing endoscopy if present (test-and-scope), and empiric acid suppression. Outcomes were derived from systematic reviews of clinical trials. Costs were informed by prospective observational cohort studies and national commercial/federal cost databases. Health gains were represented using quality-adjusted life years. RESULTS: From the patient perspective, costs and outcomes were similar for all strategies (maximum out-of-pocket difference of $30 and <0.01 quality-adjusted life years gained/year regardless of strategy). Prompt endoscopy maximized cost-satisfaction and health system reimbursement. Test-and-scope maximized cost-effectiveness from insurer and patient perspectives. Results remained robust on multiple one-way sensitivity analyses on model inputs and across most willingness-to-pay thresholds. CONCLUSIONS: Noninvasive management strategies appear to result in inferior cost-effectiveness and patient satisfaction outcomes compared with strategies promoting up-front endoscopy. Therefore, additional studies are needed to evaluate the drivers of patient satisfaction to facilitate inclusion in value-based healthcare transformation efforts.

[Four Chinese patent medicines for regulating stomach for functional dyspepsia: a rapid health technology assessment].

This study evaluated and compared the efficacy, safety and economy of four Chinese patent medicines(CPMs) in the treatment of functional dyspepsia(FD) using the method of rapid health technology assessment. It aims to provide decision-makers with rapid decision-making information. The eight Chinese and English databases were comprehensively and systematically searched for the relevant clinical research. Studies were screened and evaluated. A total of 110 studies were identified, including 95 randomized controlled trials(RCTs), 7 controlled clinical trials(CCTs), 7 systematic review/Meta-analysis and 1 economic evaluation, among which 28 were Dalitong Granules, 49 were Zhizhu Kuanzhong Capsules, 3 were Biling Weitong Granules and 30 were Qizhi Weitong Granules(Tablets/Capsules). The quality of the included literature was generally low. The efficacy of four CPMs alone or combined with western medicine in the treatment of FD is different. Dalitong Granules was used to treat motility disorder in FD. Zhizhu Kuanzhong Capsules and Qizhi Weitong Granules(Tablets/Capsules) can treat FD patients with anxiety and depression. Qizhi Weitong Granules(Tablets/Capsules) were mainly used in FD for perimenopausal patients. There were no serious adverse reactions in the clinical study of four CPMs in the treatment of FD. Dalitong Granules has better effects than mosapride in the treatment of FD, but the cost is slightly higher. The cost-effectiveness ratio of Zhizhu Kuanzhong Capsules in the treatment of FD patients with anxiety and depression was lower than that of Domperidone. In terms of average daily price, Qizhi Weitong Tablets has the highest price(27.00 yuan per day), Qizhi Weitong Granules has the lowest price(5.04 yuan per day), Biling Weitong Granules has a relatively high price(15.53 yuan per day), followed by Dalitong Granules(13.03 yuan per day). The evidence of Dalitong Granules covered the efficacy, safety and economy, which is relatively complete compared with the other three drugs. It has effective potential in the treatment of motility disorder in FD. Further research in this field in the future is needed.

[Systematic review and pharmacoeconomic evaluation of Qizhi Weitong Granules in treatment of functional dyspepsia].

This study aims to investigate the efficacy, safety, and cost-effecctiveness of Qizhi Weitong Granules in the treatment of functional dyspepsia. Specifically, two commonly used clinical protocols for the treatment of functional dyspepsia were selected: Qizhi Weitong Granules+Mosapride vs Mosapride alone(control). Meta-analysis of previous clinical studies was performed to examine the efficacy and safety, and pharmacoeconomic evaluation was carried out according to the results of the Meta-analysis. The cost-effectiveness analysis was carried out to elucidated the incremental cost-effectiveness ratio(ICER), and the sensitivity was analyzed with tornado dia-gram and Monte Carlo simulation. The willingness-to-pay threshold of patients for functional dyspepsia was investigated and compared with the ICER to evaluate whether Qizhi Weitong Granules was cost-effective. The result showed that the effective rate of Qizhi Weitong Granules combined with Mosapride in the treatment of functional dyspepsia was 95.49%, which was higher than that of Mosapride alone(73.30%)(OR=8.52, 95%CI[4.36, 16.64])(P<0.000 1). The two groups showed no significant difference in safety. The price of Qizhi Weitong Granules+Mosapride was higher than that of Mosapride alone. The ICER was 640.29 CNY, 1 506.67 CNY lower than the willingness-to-pay threshold. The sensitivity analysis showed that the analysis results were relatively stable. Thus, Qizhi Weitong Granules+Mosapride is safe, effective, and economical in the treatment of functional dyspepsia, which should be further promoted in clinical settings.

Helicobacter pylori "Test-and-Treat" strategy with urea breath test: A cost-effective strategy for the management of dyspepsia and the prevention of ulcer and gastric cancer in Spain-Results of the Hp-Breath initiative.

BACKGROUND: Data from clinical trials comparing Helicobacter pylori (H. pylori) management strategies in patients with dyspepsia are limited. Cost-effectiveness simulation models might help to identify the optimal strategy. OBJECTIVE: To assess the cost-effectiveness of the H. pylori "Test and Treat" (T&T) strategy including the use of urea breath test (UBT) vs symptomatic treatment (ST) and vs upper gastrointestinal endoscopy (UGE) as a first procedure in patients with dyspepsia. METHODS: Three main strategies: "T&T" strategy including the use of UBT, "UGE" and "ST" have been compared using cost-effectiveness models developed in accordance with the Spanish medical practice. For the model simulations, a time horizon of 4 weeks was considered for the endpoint "Dyspepsia symptoms relief" and 10 years when using "Peptic ulcer avoided" and "Gastric cancer avoided" endpoints. RESULTS: For the endpoint "Dyspepsia symptoms relief", T&T strategy appears to be the most cost-effective (883€/success) compared to UGE strategy and to ST strategy (respectively 1628€ and 990€/success). For the endpoint "Probability of peptic ulcer", the T&T strategy appears to be the most cost-effective (421€/peptic ulcer avoided/y) compared to UGE strategy and ST strategy (respectively 728€ and 632€/peptic ulcer avoided/y). For the endpoint "Gastric cancer avoided", the T&T strategy appears to be the most cost-effective (524€/gastric cancer avoided/y) compared to UGE strategy and "ST" strategy (respectively 716€ and 696€/gastric cancer avoided/y). CONCLUSIONS: T&T strategy including the use of UBT is the most cost-effective medical approach for management of dyspepsia and for the prevention of ulcer and gastric cancer.

Is administration of proton pump inhibitors in functional dyspepsia worth the risk of developing gastric cancer: a Markov model to bridge the gap between scientific evidence and clinical practice.

OBJECTIVE: To formulate a decision analysis model based on recently published data that addresses the dilemma, whether improvement in quality of life rationalises continued proton pump inhibitors (PPI) use despite the risk of gastric cancer (GC) in patients with functional dyspepsia (FD). DESIGN: A Markov model consisting of an initial decision regarding treatment with PPI (denoting it by PPI strategy) or any other treatment without PPI (denoting it by placebo strategy) was designed. DATA SOURCES: Data from prospective cross-sectional studies indicating risk stratification for GC after the use of PPI, combined with a Markov model that comprised the following states: Live, GC stages 1-4, Death. OUTCOME MEASURES: The primary outputs included quality-adjusted life years (QALYs) and life expectancy (LE). The improvement in utility in FD without PPI as compared with PPI use was tested (PPI vs placebo strategies). Sensitivity analyses were performed to evaluate the robustness of the model and address uncertainty in the estimation of model parameters. SETTING: We considered only patients whose symptoms were relieved with PPIs and thus, had a better quality of life compared with patients who did not receive PPIs. RESULTS: The base case model showed that PPIs compared with placebo decreased LE by 58.4 days with a gain of 2.1 QALY. If utility (quality of life of patients with FD using PPI compared with patients with FD without PPI) improved by more than 0.8%, PPI use is considered better than placebo. Older patients benefited less from PPI treatment than did younger patients. CONCLUSION: To bridge the gap between evidence and decision making, we found that even a small improvement in the QALY justified continuing PPI treatment.

Consumption of medicines used for gastric acid-related disorders in Australia and South Korea: a cross-country comparison.

PURPOSE: The study's aim was to compare the use of proton pump inhibitors (PPIs), histamine 2-receptor antagonists (H2RAs) and mucoprotective medicines (MPs) used for gastric acid-related disorders (GARD) in Australia and South Korea (Korea) from 2004 to 2017. METHODS: Prescription data for PPIs, H2RAs and MPs for Australian outpatients were extracted from the Australian Statistics on Medicines annual reports, with dose-specific and expenditure data obtained from Medicare. Similar data were obtained from Korean National Health Insurance Service claims data. We analysed the volume and expenditure of medicines use annually using the defined daily dose per 1,000 population per day. We calculated which medicines accounted for 90% of use and estimated the proportions of use for low- and high-dose PPIs. RESULTS: While total utilisation for GARD medicines increased over time in both countries, patterns of use differed. Overall, use was somewhat higher in Australia but increased more rapidly in Korea. PPIs were used more extensively in Australia, while more MPs and H2RAs were used in Korea. Expenditure and use of low-dose PPIs is escalating in Korea. CONCLUSION: There were substantial differences in the use of GARD medicines in Australia and Korea over 14 years. Both countries face similar challenges to promote rational medicines use and contain medical care costs. The discrepant prescribing patterns can be attributed to differences in healthcare systems, pharmaceutical policies and demographics. This study provides a baseline to influence more rational use of these medicines. It provides insight into medicines policies for other countries that face similar challenges.

Economic Impact and Prognostic Factors of Functional Dyspepsia in Children.

OBJECTIVES: Functional dyspepsia (FD) is a functional abdominal pain disorder. There is paucity of data on the economic impact of FD in children. Primary aim of our study was to estimate annual evaluation cost ("diagnosis and visit" cost) and secondary aim was to identify potential prognostic factors of FD in children. METHODS: Out of the 136 patients 86 met inclusion criteria and were divided into 2 clinical groups: Complete Improvement Group (CIG-30 patients) and Partial/No Improvement Group (PIG/NIG-56 patients). Medications used were noted descriptively. Annual evaluation cost was calculated using 2017 Medicare reimbursement rates. RESULTS: Annual evaluation cost in all patients was $724.874 ±â€Š$180.075 ($544.799 ±â€Š$87.995 in CIG and $904.949 ±â€Š79.083 in PIG/NIG). An extrapolated annual cost of evaluation in children with FD would be approximately $5.79 billion. Average number of clinic visits (3.1 ±â€Š1.2 in CIG vs 4.40 ±â€Š3.1 in PIG/NIG), duration of follow-up in months (9.2 ±â€Š6.6 in CIG vs 17.1 ±â€Š13.6 in PIG/NIG), use of imaging studies (7 patients in CIG [23.3%] vs 29 in PIG/NIG [51.8%]) and endoscopic procedures (17 in CIG [56.7%] vs 46 in PIG/NIG [82.1%]) were significantly higher in PIG/NIG (P < 0.005). PIG/NIG required multiple medications for control of symptoms compared to CIG (4 patients in CIG [13.5%] vs 30 in PIG [53.6%], P value <0.001]. For every $500.00 decrease in total evaluation cost the odds of having a complete response was 0.998 (P = 0.027). No prognostic factors were identified in children with FD. CONCLUSIONS: FD in children has a significant economic impact on health care expenditure. Patients with FD who have partial/no response to treatment incur greater financial cost potentially adding to health care expenditure.

The Nepean Dyspepsia Index is a valid instrument for measuring quality-of-life in functional dyspepsia.

BACKGROUND: The Nepean Dyspepsia Index (NDI) has been in widespread use since its publication in 1999 and the addition of a short form in 2001. The NDI was one of the first disease-specific quality-of-life instruments created for functional dyspepsia (FD). However, its psychometric properties have never been validated in an independent sample. AIM: This study aimed to evaluate the validity and reliability of the NDI in an a-priori driven approach in an independent population. PATIENTS AND METHODS: In 289 individuals who fulfilled the Rome criteria for FD enrolled in a randomized placebo-controlled trial (FD treatment trial), we examined construct validity, convergent validity, and internal consistency. RESULTS: Construct validity was supported in its 25-item unweighted and weighted forms as well as the 10-item short form. All items in the 25-item form yielded considerable (>0.5) standardized loadings on their respective latent variables and all reached statistical significance (P<0.0001), supporting their relationships with the hypothesized domains. Convergent validity was strongly supported, with every domain being correlated with multiple external instruments; the majority of correlations were in the range 0.3-0.5 (in absolute values). The items comprising each domain showed good internal consistency, with the lowest value of Chronbach α at 0.80. Scores based on the short form (10-item) version of the NDI correlated strongly with the full 25-item form (tension ρ=0.88, interference ρ=0.94, eat/drink ρ=0.95, knowledge ρ=0.84 and work/study ρ=0.97; all P<0.0001). CONCLUSION: The NDI is a valid instrument that can be used to measure the disease-specific impact of FD on quality of life.

[Evaluation of the prescription of proton pump inhibitors in persons aged 75years and older in a geriatric acute-care unit]. / Évaluation de la prescription des inhibiteurs de la pompe à protons chez la personne âgée de 75 ans et plus dans un service de gériatrie aiguë.

INTRODUCTION AND OBJECTIVES: Proton pump inhibitors (PPI) are widely prescribed in France and could be responsible for adverse drug reactions especially in elderly persons (EP). In order to reduce the misuse of PPI and the excess cost to the Social Security Agency, the French health authorities (Haute Autorité de santé [HAS]) have published strict guidelines for their prescription. We conducted a study in EP to determine the proportion of PPI prescriptions outside HAS guidelines. METHOD: This was a prospective, single-centre observational study in persons aged≥75 years admitted to a geriatric acute-care unit over a period of 6months. The prevalence of prescriptions for PPI and the proportion of prescriptions outside the guidelines were calculated. The sociodemographic and medical characteristics of EP treated with PPI were studied as were the reasons for the prescription of PPI. RESULTS: Among the 818 patients hospitalized during the study period, 270 were taking PPI on admission (33%). Among these prescriptions, 60% were outside the HAS guidelines. Gastro-oesophageal reflux was the leading indication for PPI (30%), followed by dyspepsia (19%). CONCLUSION: This study confirms the high prevalence of prescriptions for PPI and their misuse. As these drugs are apparently well tolerated, prescriptions are often renewed with no medical re-evaluation.

Value of the "Test & Treat" Strategy for Uninvestigated Dyspepsia at Low Prevalence Rates of Helicobacter pylori in the Population.

BACKGROUND AND AIM: In populations with a low prevalence rate of Helicobacter pylori (H. pylori) infection from Western countries, guidelines for the management of uninvestigated dyspepsia generally recommend that the "test and treat" strategy should be avoided in favor of empiric proton-pump inhibitor therapy in younger patients (on average < 50 years of age) without alarm symptoms and signs. The prevalence of H. pylori infection has fallen from about 30% to about 10% in Sweden and other countries. We aimed to explore whether the rationale for test and treat is relevant in contemporary clinical practice. MATERIALS AND METHODS: In settings with an infection rate in the adult population of 30% and 10%, we modeled the positive and negative predictive values for indirect (nonendoscopy) tests on current H. pylori infection with a presumed sensitivity and specificity of 95%. We then calculated the difference in false-negative and false-positive test outcome, and eradication prescription rates in the two scenarios. RESULTS: While the positive predictive value for the test decreased from 0.89 to 0.68 when the prevalence of H. pylori fell from 30% to 10%, there were only 1% more false-negative tests and 1% less false-positive tests. The eradication prescription rate would decrease by 18% with a 10% prevalence rate. CONCLUSION: The recommendation to stop applying "test and treat" at lower prevalence rates of H. pylori should be reconsidered. The test and treat strategy is the preferred approach for most patients who present with dyspepsia.

Yields of dual therapy containing high-dose proton pump inhibitor in eradication of H. pylori positive dyspeptic patients.

UNLABELLED: BACKGROUND/AIMs: H. pylori eradication has been recommended for dyspeptic patients in high prevalance regions. Triple therapies are still prescribed mostly because culture and antibiotic susceptibility tests aren't widely available in the world. Dual therapy with high-dose proton pump inhibitors reported to have higher eradication rates. Our objective was to determine eradication success and cost-effectivity of dual therapy in dyspeptic patients. METHODOLOGY: Patients were treated orally with either dual (n:74,omeprazole 20mg q.i.d and amoxicillin 1g b.i.d) or triple therapy (n:116,omeprazole 20mg b.i.d and amoxicillin 1g b.i.d and clarithromycin 500mg b.i.d) for 14 days. HpSA was requested 3 months later. The results were evaluated statistically, p values ˂0,05 were considered significant. RESULTS: Patients (n:190) were included the study((80 female,110 male, mean age: 35.6±11year(p<0.001)). Alcohol/smoking, endoscopic findings and H. pylori rates with pathological examinations were not significantly different between groups whereas there was a significant difference in HpFast tests(p<0.01). When examined with HpSA tests 3 months after the treatment, eradication rate was 81.1% in the dual therapy group versus 63.8% in the triple therapy group (p:0.011). Dual therapy was economic than triple therapy (144USDvs.107USD,p<0.001). CONCLUSIONS: Dual therapy seems more successful, cost-effective and is less risky in terms of side effects compared to standard triple therapy in patients with dyspepsia.

Assessment of diagnostic and therapeutic approaches of Helicobacter pylori-associated iron deficiency and anemia in children with dyspeptic symptoms.

This study assessed the diagnostic approaches of Helicobacter pylori (IP)-associated iron deficiency (ID) and anemia (IDA) in children with dyspeptic symptoms and evaluated the effect of simultaneous anti-H. pylori (anti-HIP) therapy and oral iron in comparison with each of anti? HP therapy and oral iron therapy alone, on iron status as assessed by serum soluble transferrin receptor (sTfR) level. Two hundreds children with dyspeptic symptoms were subjected to clinical evaluation, stool examination, CBC, biochemical assays for serum iron parameters and measurements of serum IgG antibodies to HP and serum sTfR level by ELISA. Sixty children were found to have HP. associated ID or IDA and were randomly divided into 3 groups (20 children each). GA received 2-week anti-HP therapy plus 90-day oral iron, and GB received 2-week anti-HP therapy alone whereas group C received 90-day oral iron alone. Re-evaluation of the 3 groups was performed after 3 months of treatment initiation by repeat CBC and serum sTfR level. Children (45%) were HP-seropositive. The mean values of serum sTfR were significantly higher in HP-positive group and in HP-positive children with IDA than in HP-negative group and in HP-negative children with IDA although no significant differences were noted in hematologic variables and iron parameters between the corresponding groups and children. As regard treatment groups, there were significant improvements in the mean values of indices of IDA status (HIb, MCH, MCV, sTfR) and ID status (sTtRi) at 3 months of treatment initiation compared with their baseline values after. anti-HP triple therapy either with oral iron or without oral iron whereas the control children who were treated with oral iron alone showed insignificant changes despite oral iron administration. The improvements in these parameters were significantly greater in groups of children who received anti-HP therapy either combined with iron or alone, where compared with those who did not receive anti-HP therapy. Their magnitudes were significantly higher among children receiving anti-HP therapy combined with oral iron when compared with that receiving anti-HP therapy alone.

Use of health care services and pharmaceutical agents in coeliac disease: a prospective nationwide study.

BACKGROUND: Approximately 1% of the population suffer from coeliac disease. However, the disease is heavily underdiagnosed. Unexplained symptoms may lead to incremented medical consultations and productivity losses. The aim here was to estimate the possible concealed burden of untreated coeliac disease and the effects of a gluten-free diet. METHODS: A nationwide cohort of 700 newly detected adult coeliac patients were prospectively evaluated. Health care service use and sickness absence from work during the year before diagnosis were compared with those in the general population; the data obtained from an earlier study. Additionally, the effect of one year on dietary treatment on the aforementioned parameters and on consumption of pharmaceutical agents was assessed. RESULTS: Untreated coeliac patients used primary health care services more frequently than the general population. On a gluten-free diet, visits to primary care decreased significantly from a mean 3.6 to 2.3. The consumption of medicines for dyspepsia (from 3.7 to 2.4 pills/month) and painkillers (6.8-5.5 pills/month) and the number of antibiotic courses (0.6-0.5 prescriptions/year) was reduced. There were no changes in hospitalizations, outpatient visits to secondary and tertiary care, use of other medical services, or sickness absence, but the consumption of nutritional supplements increased on treatment. CONCLUSIONS: Coeliac disease was associated with excessive health care service use and consumption of drugs before diagnosis. Dietary treatment resulted in a diminished burden to the health care system and lower use of on-demand medicines and antibiotic treatment. The results support an augmented diagnostic approach to reduce underdiagnosis of coeliac disease. TRIAL REGISTRATION: ClinicalTrials.gov NCT01145287.

Work productivity improvement after acid suppression in patients with uninvestigated dyspepsia.

INTRODUCTION: Lost productivity accounts for a significant part of the costs caused by gastrointestinal symptoms. We aimed to describe selfreported productivity in patients presenting with dyspepsia. MATERIAL AND METHODS: Data were sourced from a randomized, double-blinded study of two weeks of esomeprazole 40 mg or placebo in 805 primary-care patients with uninvestigated dyspepsia. Work productivity was tested using the Work Productivity and Activity Impairment questionnaire. Treatment effect on work productivity loss was tested according to the likelihood of treatment response. RESULTS: A total of 401/805 employed patients were included in the analysis. The average work productivity loss in the past seven days was 10.5 working hours/week. The productivity loss grew with increasing severity of symptoms at baseline. Following two weeks of treatment, the mean improvement in work productivity was significantly higher for both absenteeism (1 hour versus 0.1 hour, p < 0.05) and presenteeism (5.3 hours versus 4.3 hours, p < 0.05) in patients treated with esomeprazole versus placebo. The most substantial improvement was seen in patients who, based on baseline symptoms, were assessed to be likely treatment responders. CONCLUSION: Dyspepsia symptoms represent a significant economic burden in terms of lost productivity. The RESPONSE algorithm is successful in determining which patients will benefit from acid suppression in terms of enhanced productivity.

Proton pump inhibitors prescribing following the introduction of generic drugs.

BACKGROUND: In many countries, the introduction of generic proton pump inhibitors (PPIs) onto the pharmaceutical market increased the phenomenon of therapeutic substitution in acid-related disorders (ARDs). AIM: To investigate the treatment of ARDs in an Italian primary care setting from 2005 to 2008 by verifying: (i) dynamics of PPI prescribing; (ii) predictors of PPI switching; and (iii) healthcare resource consumption costs. METHODS: This was a retrospective cohort study of 102 general practitioners (GPs) who managed an average of 150000 inhabitants in Naples. Multilevel logistic regression was used to assess the potential predictors of both PPI switching and termination. Primary care costs were expressed as the cost of ARD management per PPI user year. RESULTS: The percentage of PPI users with ARD increased from 5·5% (2005) to 7·0% (2008) (P<0·0001), especially for dyspepsia (from 9·5% to 13·7%; P<0·0001) and chronic treatments (from 23·4% to 29·4%; P<0·0001). PPI switching rose from 13·0% to 16·7% during the period observed (P<0·0001). Calendar years, long-term treatments and gastroesophageal reflux disease were positive predictors of PPI switching. Primary care costs relating to PPI switchers increased by 61·14€ compared with nonswitchers (P<0·0001). CONCLUSIONS: The introduction of generic PPIs onto the Italian market was associated with an increasing amount of PPI prescribing related to chronic treatments, unlicensed indications (e.g. dyspespsia) and therapeutic substitutions. Growing overall costs linked to the phenomenon of PPI switching was also found. Our data support the need to assess the effects of the introduction of generic drugs on both clinical outcomes and the cost management of ARDs.

Functional Dyspepsia Treatment Trial (FDTT): a double-blind, randomized, placebo-controlled trial of antidepressants in functional dyspepsia, evaluating symptoms, psychopathology, pathophysiology and pharmacogenetics.

BACKGROUND: Functional dyspepsia (FD) is a common problem affecting up to 10-25% of individuals. FD accounts for significant health care costs and affects quality of life but has no definitive treatment. OBJECTIVES: The Functional Dyspepsia Treatment Trial (FDTT) aims to test whether treatment with an antidepressant (amitriptyline or escitalopram) leads to improvement of symptoms in patients with moderate to severe FD. DESIGN: The FDTT is an international multicenter, parallel group, randomized, double-blind, placebo-controlled trial to evaluate whether 12 weeks of treatment with escitalopram or amitriptyline improves FD symptoms compared to treatment with placebo. Secondly, it is hypothesized that acceleration of solid gastric emptying, reduction of postprandial satiation, and enhanced gastric volume change with a meal will be significant positive predictors of short- and long-term outcomes for those on antidepressants vs. placebo. The third aim is to examine whether polymorphisms of GNß3 and serotonin reuptake transporter influence treatment outcomes in FD patients receiving a tricyclic antidepressant, selective serotonin reuptake inhibitor therapy, or placebo. METHODS: The FDTT enrollment began in 2006 and is scheduled to randomize 400 patients by the end of 2012 to receive an antidepressant or placebo for 12 weeks, with a 6-month post-treatment follow-up. The study incorporates multiple validated questionnaires, physiological testing, and specific genetic evaluations. The protocol was approved by participating centers' Institutional Review Boards and an independent Data Safety Monitoring Board was established for monitoring to ensure patient safety and a single interim review of the data in December 2010 (ClinicalTrials.gov number NCT00248651).

Randomised clinical trial: the burden of illness of uninvestigated dyspepsia before and after treatment with esomeprazole--results from the STARS II study.

BACKGROUND: Patients with dyspepsia often experience troublesome symptoms. AIM: To assess the burden of uninvestigated dyspepsia (symptoms, health-related quality of life [HRQL] and work productivity) before and after 8 weeks' esomeprazole treatment. METHODS: Patients (n=1250) with uninvestigated dyspepsia (no endoscopy within 6 months and ≤ 2 endoscopies within 10 years) underwent a 1-week esomeprazole acid-suppression test before randomisation to 7 weeks' esomeprazole or placebo. The Reflux Disease Questionnaire (RDQ), Quality of Life in Reflux and Dyspepsia (QOLRAD) and Work Productivity and Activity Impairment (WPAI) questionnaires were completed at baseline (1-week off-treatment) and 8 weeks. WPAI results were further analysed among patients who responded to the acid-suppression test. RESULTS: The highest baseline symptom score was for the RDQ dyspepsia domain, and the highest disease burden was for QOLRAD vitality and food/drink problems. After 8 weeks, significant improvements vs. placebo were observed for all RDQ and QOLRAD domains. The sub-population of acid-suppression test responders, but not the total WPAI population, had a significant work productivity improvement vs. placebo. CONCLUSIONS: Uninvestigated dyspepsia is associated with high symptom load and impacts on HRQL and work productivity. Esomeprazole improves HRQL among such patients, and improves work productivity among 1-week acid-suppression trial responders. ClinicalTrials.gov identifier: NCT00251992.

Emerging drugs for functional dyspepsia.

INTRODUCTION: Functional dyspepsia (FD) is a highly prevalent condition with a major impact on quality of life and high socio-economic and healthcare costs. To date, no treatment of established efficacy in FD is available. AREAS COVERED: This review of the literature summarizes recent progress in drug development for FD. Gastroprokinetics are considered therapeutically relevant in FD, although it has been difficult to prove symptomatic benefit. Recently studied drugs include 5-HT(4) receptor agonists (tegaserod), motilin receptor agonists (GSK962040 and others) and ghrelin receptor agonists (TZP-101, TZP-102). Fundic relaxant drugs are a novel approach to FD therapy. Recently studied drugs include 5-HT(1A) receptor agonists (buspirone, tandospirone, R137696) and acotiamide (or Z-338 or YM443), a first-in-class muscarinic M(1)/M(2) receptor antagonist and cholinesterase inhibitor. Extensive Phase II studies support the potential efficacy of acotiamide, especially for postprandial distress syndrome. In refractory cases, psychotropics are considered and recently studied agents include venlafaxine, which in a large multi-center study did not confirm efficacy, and a combination preparation of flupenthixol/melitracen, which showed potential efficacy in a small study. EXPERT OPINION: While many new prokinetic drugs are in the early stages of evaluation, acotiamide emerges as the drug with a promising efficacy profile. Convincing evidence for the efficacy of psychotropics is lacking.

CUSUM charts for monitoring clinical practice quality using primary care prescribing data: a case study of an initiative to encourage generic prescribing of proton pump inhibitors.

WHAT IS KNOWN AND OBJECTIVE: Expectations on organizations to monitor quality of care are growing. Whilst relevant data are increasingly becoming available it is, in many cases, difficult to distinguish real effects from background variation. Here, the potential usefulness of cumulative sum (CUSUM) charts for monitoring the use of medicines is explored through a case study of an initiative to encourage the prescribing of lowest cost proton pump inhibitors (PPI) in the context of implementation of national guidelines for the management of dyspepsia. METHODS: This was a longitudinal study involving analysis of routinely collected prescribing data, set in all 12 primary care trusts (PCT) in the North East Strategic Health Authority. In it, comparison (by subtraction) of the time-series of the percentage of generic PPI prescription items for Gateshead with the mean of the other 11 PCTs was used to reduce both variation and bias. This was followed by the construction of a CUSUM chart displaying the effect of the Gateshead initiative. RESULTS AND DISCUSSION: The simple process of comparison was very successful both in removing extraneous trends and reducing background variation, and the CUSUM highly effective for displaying the evidence for the hypothesized step-change in prescribing behaviour consequent on the Gateshead initiative. The effectiveness of the CUSUM here is strongly linked to the success of the preliminary comparison step. WHAT IS NEW AND CONCLUSION: CUSUM, a statistical process control technique, has already been tested as a tool for interpreting hospital and general practice mortality rates. Here, its potential for more general applications in quality monitoring is demonstrated using routinely collected prescribing data. Such data contain valuable information about changes in clinical practice and CUSUM charts, when coupled with the idea of removing time trends and extraneous variation by reference to average behaviour, can provide a simple but effective technique for extracting it.