Brain metastases in adult patients with melanoma of unknown primary in the Netherlands (2011-2020).

BACKGROUND: Although patients with melanoma of unknown primary (MUP) have a better prognosis than similar-staged melanoma patients with known primary, the occurrence of brain metastases (BM) entails a serious complication. This study provides an overview of the incidence, treatment patterns, and overall survival (OS) of adult patients with BM-MUP in the Netherlands. METHODS: BM-MUP cases were retrieved from the Netherlands Cancer Registry. Patient, disease and treatment-related characteristics were summarised using descriptive statistics. Overall survival (OS) was calculated by the Kaplan-Meier method, and the impact of prognostic factors on OS was assessed using Cox proportional hazard regression analyses. RESULTS: Among 1779 MUP patients, 450 were identified as BM-MUP (25.3%). Of these patients, 381 (84.7%) presented with BM along with other metastases, while 69 (15.3%) had BM only. BM-MUP patients were predominantly male (68.2%), and had a median age of 64 years at diagnosis (interquartile range 54-71 years). Over time, the proportion of BM along other metastatic sites increased, and the occurrence of BM decreased (p = 0.01). 1-Year OS improved for the total population, from 30.0% (95% confidence interval (CI): 19.8-40.9%) in 2011-2012 to 43.6% (95%CI: 34.5-52.3%) in 2019-2020, and median OS more than doubled from 4.2 months (95%CI: 3.3-6.2 months) to 9.8 months (95%CI: 7.0-13.2 months). Patient's age, localisation of BM, presence of synchronous liver metastasis and treatment were identified as independent predictors of OS. CONCLUSION: Notwithstanding the progress made in OS for patients with BM-MUP in the past decade, their overall prognosis remains poor, and further efforts are needed to improve outcomes.

Prognostic factors among patients with brain metastases from cancer of unknown primary site.

PURPOSE: Cancers of an unknown primary site (CUPs) have a dismal prognosis, and the situation is even worse for CUPs patients with brain metastases (BM-CUPs). This study aims to give better insight into the occurrence and survival of BM-CUPs patients. METHODS: Cases were selected from the Netherlands Cancer Registry (1,430 BM-CUPs/17,140 CUPs). Baseline characteristics between CUPs patients with and without BM were tested using chi-square tests and Mann-Whitney U tests. Patients' overall survival (OS) times were estimated by the Kaplan-Meier method and prognostic factors on OS was assessed using Cox proportional hazards regression analyses. RESULTS: The proportion of BM-CUPs patients among CUPs increased from 8% in 2009-2010 to 10% in 2017-2018 (p < 0.001). Most patients presented with multiple brain lesions (53%). Survival of BM-CUPs improved over time: one-year OS increased from 10% for patients diagnosed in 2009-2010 to 17% (2017- 2018) (p < 0.01), and median survival times increased from 1.8 months to 2.2 months. Independent predictors of poor survival were multiple (HR 1.25; p < 0.01) or unknown (HR 1.48; p < 0.01) locations of BM, unknown/poorly/undifferentiated carcinoma histology (HR 1.53; p < 0.01), or clinical symptoms of BM (HR 1.74; p < 0.01), accompanying liver metastasis (HR 1.43; p < 0.01) and more than one metastatic site outside the brain compared to none (HR 1.52; p < 0.01). CONCLUSION: The incidence of patients with BM-CUPs is steadily increasing over time and overall prognosis remains dismal. Our results, however, show distinct patient subgroups that exhibit comparatively better outcomes, and more predictors may likely still be identified.

Meta-analysis: oral or enteral nutritional supplementation in cirrhosis.

BACKGROUND: Malnutrition is a common and clinically significant problem in patients with cirrhosis. The impact of nutritional therapy remains unclear. AIM: To provide an up-to-date systematic review and meta-analysis of RCTs of oral or enteral nutritional supplementation (ONS or ENS) on nutritional and clinical outcomes in adult patients with cirrhosis. METHODS: The primary outcome measure was survival. Included: full-text English language RCTs investigating ONS or ENS vs. a standard nonsupplemented diet in patients with cirrhosis. Excluded: parenteral or branched chain amino acids intervention; treatment duration ≤7 days, exclusive evaluation of posttransplant, postsurgical or quality of life outcomes. RESULTS: Six trials (4 ONS/2 ENS) and 470 patients were included with 71% males and median age 53 years. When all studies were combined, there was no reduction in mortality [Relative risk (RR): 0.75 (0.42, 1.32), P = 0.31]. Subgroup analysis of 3 of the 4 ONS studies did demonstrate a mortality reduction [RR: 0.40 (0.18, 0.90), P = 0.03]. Of the 2 ENS studies, one included the sickest patients in the meta-analysis (82% Child Pugh C) and the other had the shortest mean intervention duration (8.6 days), possibly impacting the potential for benefit. Study quality was suboptimal (median Jadad = 2). CONCLUSIONS: Although there is insufficient evidence to definitively state that oro-enteral nutritional supplementation impacts clinical outcomes, on the basis of this analysis, one can be cautiously optimistic that there is the potential for benefit without an increase in adverse events. Adequately powered, Child Pugh stratified studies of at least 1 month in duration are needed to clarify the impact on relevant clinical outcomes.

Partial symptom-response to proton pump inhibitors in patients with non-erosive reflux disease or reflux oesophagitis - a post hoc analysis of 5796 patients.

BACKGROUND: Although most patients with gastro-oesophageal reflux disease (GERD) benefit from proton pump inhibitor (PPI) therapy, some experience only partial symptom relief. AIM: To determine the prevalence of partial heartburn response to PPIs and its impact on health-related quality of life. METHODS: Four randomised, double-blind studies in adults with reflux disease compared esomeprazole 40 mg/day or 20 mg/day with omeprazole 20 mg/day, or esomeprazole 40 mg/day with pantoprazole 40 mg/day. Patients with heartburn on ≥4 days during the 1-week recall period at baseline were included. Partial response was defined as heartburn on ≥3 days during the last treatment week and reduced heartburn frequency after 4 weeks of treatment compared with baseline. RESULTS: The analysis included 2645 patients with non-erosive reflux disease (mean age: 48.8 years; 54.4% women) and 3151 patients with reflux oesophagitis (mean age: 50.6 years; 37.1% women). At baseline, most patients reported heartburn on 5-7 days (non-erosive reflux disease: 82.2%; reflux oesophagitis: 86.8%). Partial heartburn response occurred in 19.9% of patients with non-erosive reflux disease and 14.0% with reflux oesophagitis. Defining partial response as heartburn on ≥2 days increased these rates to 26.2% and 19.3%, respectively; defining partial response as heartburn of moderate or severe intensity on ≥3 days decreased these rates to 6.4% and 5.3%, respectively. Nonresponse to PPIs was rare (non-erosive reflux disease: 2.4%; reflux oesophagitis: 1.4%). CONCLUSION: Using our conservative definition, partial heartburn response to proton pump inhibitor therapy occurred in 14-20% of gastro-oesophageal reflux disease patients, more commonly in non-erosive reflux disease than in reflux oesophagitis.

Systematic review: faecal transplantation for the treatment of Clostridium difficile-associated disease.

BACKGROUND: Management of recurrent Clostridium difficile-associated disease (CDAD), particularly in elderly patients, remains clinically challenging. Faecal transplantation (FT) may restore normal microbiota and break the cycle of recurrent CDAD. AIM: To critically appraise the clinical research evidence on the safety and effectiveness of FT compared with standard care in the treatment of patients with CDAD. METHODS: A comprehensive literature search was conducted by a research librarian to identify relevant studies published between 2000 and 2011. The Cochrane Library, PubMed, EMBASE, CINAHL, Biological Abstracts, BIOSIS Previews and Web of Science were searched using the following Medical Subject Headings (MeSH) terms and keywords, alone or in combination: Clostridium infections/Clostridium difficile/pseudomembranous/colitis/faeces/rectal/colon flora/gastrointestinal/nasogastric tube/enema/donor/transplant/infusion/bacteriotherapy/human probiotic infusion. Methodological quality of the included case series studies was assessed in terms of patient selection criteria, consecutive recruitment, prospective data collection, reporting of lost to follow-up, and follow-up rates. RESULTS: No controlled studies were found. Based on the weak evidence from seven full-text case series studies of 124 patients with recurrent/refractory CDAD, FT appears to be a safe and effective procedure. In most cases (83%) symptoms improved immediately after the first FT procedure, and some patients stayed diarrhoea free for several months or years. CONCLUSIONS: Although these results appear to be promising, the treatment effects of faecal transplantation cannot be determined definitively in the absence of a control group. Results from randomised controlled trials that compare faecal transplantation to oral vancomycin without or with a taper regimen will help to better define the role of faecal transplantation in the management of recurrent CDAD.

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.

Systematic literature review and pooled analyses of risk factors for finding adenomas at surveillance colonoscopy.

BACKGROUND AND STUDY AIM: Colorectal cancer (CRC) screening guidelines recommend surveillance after polypectomy. There is variation in the surveillance intervals that are being advised. This variation also affects adherence. Surveillance intervals need to be based on risk factors at index. We therefore aimed to systematically review risk factors of adenoma findings at surveillance colonoscopy. METHODS: A systematic literature search was performed up to September 2009. Studies that reported on follow-up colonoscopy findings with stratification for index characteristics were included. Pooled relative risks (RR) were calculated using random effects models, and heterogeneity was determined by means of the I2-statistic. RESULTS: A total of 27 studies met the inclusion criteria. The most important risk factors for adenoma findings were the presence on index colonoscopy of the following: advanced adenomas (RR: 1.81), ≥ 3 adenomas (RR: 1.64), size ≥ 10 mm (RR: 1.66), and age ≥ 60 years (RR: 1.65). The presence of villous adenomas, high grade dysplasia, proximal adenomas, and male gender were associated with less profound increases in RR. Marked variation in study design and substantial heterogeneity between studies was observed. CONCLUSIONS: Convincing evidence exists that patients with advanced adenomas, ≥ 3 adenomas, adenomas ≥ 10 mm, or age ≥ 60 years have an increased risk of adenoma recurrence. The evidence for other baseline findings for an increased risk of adenoma recurrence is inconclusive. Marked variation and consistently lower RRs in studies of medium or low quality emphasize the necessity for well performed and well reported studies. Given the high impact of surveillance on patients and service providers, there is need for further assessment of the risk(s) of adenoma recurrence.

Risk of colorectal carcinoma in post-liver transplant patients: a systematic review and meta-analysis.

Liver transplant patients (LTx) have an increased risk for developing de novo malignancies, but for colorectal cancer (CRC) this risk is less clear. We aimed to determine whether the CRC risk post-LTx was increased. A systematic search was performed in MEDLINE and Cochrane databases to identify studies published between 1986 and 2008 reporting on the risk of CRC post-LTx. The outcomes were (1) CRC incidence rate (IR per 100,000 person-years (PY)) compared to a weighted age-matched control population using SEER and (2) relative risk (RR) for CRC compared to the general population. If no RR data were available, the RR was estimated using SEER. Twenty-nine studies were included. The overall post-LTx IR was 119 (95% CI 88-161) per 100,000 PY. The overall RR was 2.6 (95% CI 1.7-4.1). The non-primary sclerosing cholangitis (PSC) IR was 129 per 100,000 PY (95% CI 81-207). Compared to SEER (71 per 100,000 PY), the non-PSC RR was 1.8 (95% CI 1.1-2.9). In conclusion, the overall transplants and the subgroup non-PSC transplants have an increased CRC risk compared to the general population. However, in contrast to PSC, non-PSC transplants do not need an intensified screening strategy compared to the general population until a prospective study further defines recommendations.

Cost-utility analysis of proton pump inhibitors and other gastro-protective agents for prevention of gastrointestinal complications in elderly patients taking nonselective nonsteroidal anti-inflammatory agents.

BACKGROUND: The use of proton pump inhibitors (PPIs) among elderly patients using nonselective nonsteroidal anti-inflammatory drugs (nsNSAIDs) has increased; the price of PPIs is higher than that of majority of alternative treatment strategies. AIM: To evaluate the cost-effectiveness of nsNSAIDS + PPIs relative to alternative gastroprotective regimens in the prevention of GI complications among elderly patients (aged > or = 65 years). METHODS: An incremental cost-utility analysis, comparing PPIs with alternative gastroprotective regimens was conducted using a decision analytical model. Clinical outcomes, costs and utilities were derived from recently published studies. Probabilistic and deterministic sensitivity analyses were performed to test the robustness of the results to variation in model inputs and assumptions. RESULTS: The incremental cost-utility ratio (ICUR) of PPIs, relative to nsNSAID alone, was $206,315 per QALY gained or were more costly and less effective. Other co-prescribed treatment options had higher costs per QALY gained. In patients with a history of a complicated or uncomplicated ulcer, PPIs had ICURs of $24,277 and $40,876, respectively. CONCLUSIONS: Use of PPIs in all elderly patients taking nsNSAIDs is unlikely to represent an efficient use of finite healthcare resources. Co-prescribing PPIs, however, to elderly patients taking nsNSAIDs who have a history of complicated or uncomplicated ulcers appears to be economically attractive.

Wait times for gastroenterology consultation in Canada: the patients' perspective.

Long wait times for health care have become a significant issue in Canada. As part of the Canadian Association of Gastroenterology's Human Resource initiative, a questionnaire was developed to survey patients regarding wait times for initial gastroenterology consultation and its impact. A total of 916 patients in six cities from across Canada completed the questionnaire at the time of initial consultation. Self-reported wait times varied widely, with 26.8% of respondents reporting waiting less than two weeks, 52.4% less than one month, 77.1% less than three months, 12.5% reported waiting longer than six months and 3.6% longer than one year. One-third of patients believed their wait time was too long, with 9% rating their wait time as 'far too long'; 96.4% believed that maximal wait time should be less than three months, 78.9% believed it should be less than one month and 40.3% believed it should be less than two weeks. Of those working or attending school, 22.6% reported missing at least one day of work or school because of their symptoms in the month before their appointment, and 9.0% reported missing five or more days in the preceding month. A total of 20.2% of respondents reported being very worried about having a serious disease (ie, scored 6 or higher on 7-point Likert scale), and 17.6% and 14.8%, respectively, reported that their symptoms caused major impairment of social functioning and with the activities of daily living. These data suggest that a significant proportion of Canadians with digestive problems are not satisfied with their wait time for gastroenterology consultation. Furthermore, while awaiting consultation, many patients experience an impaired quality of life because of their gastrointestinal symptoms.

Pyrosequencing assay to rapidly detect clarithromycin resistance mutations in Canadian Helicobacter pylori isolates.

BACKGROUND: Mutations at positions 2142 or 2143 in the twocopy 23S ribosomal RNA gene of Helicobacter pylori are highly predictive of in vitro clarithromycin resistance and failure of clarithromycin-containing treatment regimens. OBJECTIVE: To design an assay to rapidly detect these mutations using rapid polymerase chain reaction and pyrosequencing, a novel method of 'sequencing by synthesis', and to test this assay with a collection of Canadian H pylori isolates. METHODS: Forty-two H pylori isolates (24 clarithromycin-resistant, 18 clarithromycin-susceptible) were studied. A target region in the 23S gene was rapidly amplified and sequenced by pyrosequencing. RESULTS: Mutations at one of the two positions studied were present in 20 of the 24 (83%) clarithromycin-resistant isolates; 13 had double- copy A2143G mutations, four had double-copy A2142G mutations and three had single-copy A2143G mutations. There were no mutations in 17 of the 18 (94%) susceptible isolates. A single-copy A2142G mutation was detected in one susceptible isolate. CONCLUSIONS: The pyrosequencing assay developed was able to detect and differentiate mutations at positions 2142 and 2143 in either one or both copies of the H pylori 23S ribosdomal RNA gene. Further study is needed to determine whether this pyrosequencing assay can be used to determine H pylori susceptibility to clarithromycin from clinical specimens such as stools or gastric biopsies.

Systematic review: secondary prevention with band ligation, pharmacotherapy or combination therapy after bleeding from oesophageal varices.

BACKGROUND: Variable methods are available for secondary prevention after oesophageal variceal bleeding (EVB). AIM: To compare band ligation (BL), pharmacotherapy (PT) and BL+PT for EVB secondary prevention. METHODS: A systematic search of databases, references and meeting abstracts was conducted for randomized trials of BL, PT or BL+PT. The outcomes were mortality, rebleeding and adverse events. A random-effects model was used for meta-analyses. RESULTS: Twelve trials were included (6 BL vs. PT, 4 BL+PT vs. BL, 2 BL+PT vs. PT). All trials used beta-blockers +/- isosorbide mononitrate (ISMN) as PT. Mortality was not significantly different among trials. Rebleeding was not significantly different for BL vs. PT (RR 1.00, 95% CI 0.73-1.37). BL reduced rebleeding compared with PT for trials with mean beta-blocker dose <80 mg/day (RR 0.67, 95% CI 0.49-0.91). There were nonsignificant differences in rebleeding for BL+PT vs. BL (RR 0.57, 95% CI 0.31-1.08) and BL+PT vs. PT (RR 0.76, 95% CI 0.56-1.03). There was no difference in adverse events between BL vs. PT, but was higher with BL+PT vs. BL. CONCLUSION: Band ligation and PT alone are comparable for secondary prevention of rebleeding after EVB. Further trials with adequate PT dosing are required to determine the efficacy of combination BL+PT therapy.

Diagnostic utility of alarm features for colorectal cancer: systematic review and meta-analysis.

OBJECTIVE: Colorectal cancer is the second most common cause of cancer death in Europe and North America. Alarm features are used to prioritize access to urgent investigation, but there is little information concerning their utility in the diagnosis of colorectal cancer. METHODS: A systematic review and meta-analysis of the published literature was carried out to assess the diagnostic accuracy of alarm features in predicting colorectal cancer. Primary or secondary care-based studies in unselected cohorts of adult patients with lower gastrointestinal symptoms were identified by searching MEDLINE, EMBASE and CINAHL (up to October 2007). The main outcome measures were accuracy of alarm features or statistical models in predicting the presence of colorectal cancer after investigation. Data were pooled to estimate sensitivity, specificity, and positive and negative likelihood ratios. The quality of the included studies was assessed according to predefined criteria. RESULTS: Of 11 169 studies identified, 205 were retrieved for evaluation. Fifteen studies were eligible for inclusion, evaluating 19 443 patients, with a pooled prevalence of colorectal carcinoma of 6% (95% CI 5% to 8%). Pooled sensitivity of alarm features was poor (5% to 64%) but specificity was >95% for dark red rectal bleeding and abdominal mass, suggesting that the presence of either rules the diagnosis of colorectal cancer in. Statistical models had a sensitivity of 90%, but poor specificity. CONCLUSIONS: Most alarm features had poor sensitivity and specificity for the diagnosis of colorectal carcinoma, whilst statistical models performed better in terms of sensitivity. Future studies should examine the utility of dark red rectal bleeding and abdominal mass, and concentrate on maximising specificity when validating statistical models.

Clinical trial design in adult reflux disease: a methodological workshop.

BACKGROUND: The development of well-tolerated acid suppressant drugs has stimulated substantial growth in the number of trials assessing therapy options for gastro-oesophageal reflux disease (GERD). AIM: To develop consensus statements to inform clinical trial design in adult patients with GERD. METHODS: Draft statements were developed employing a systematic literature review. A modified Delphi process including three rounds of voting was used to reach consensus. Between voting, statements were revised based on feedback from the Working Group and additional literature reviews. The final vote was at a face-to-face meeting that included discussion time. Voting was conducted using a six-point scale. RESULTS: At the last vote, 93% of the final 102 statements achieved consensus (defined a priori as being supported by >or=75% of the votes). The Working Group strongly supported the development of validated patient-reported outcome instruments. Symptom assessments carried out by the investigator were considered unacceptable. There was agreement that exclusion from clinical trials should be minimized to improve generalizability, that prospective evaluation ideally requires electronic timed/dated methods and that endoscopists should be blinded to patient symptom status. CONCLUSIONS: Implementation of the consensus statements will improve the quality and comparability of trials, and make them compatible with regulatory requirements.

Helicobacter pylori infection in Canadian and related Arctic Aboriginal populations.

In 2006, the Canadian Helicobacter Study Group identified Aboriginal communities among Canadian population groups most at risk of Helicobacter pylori-associated disease. The objective of this systematic review was to summarize what is known about the H pylori-associated disease burden in Canadian and related Arctic Aboriginal populations to identify gaps in knowledge. Six health literature databases were systematically searched to identify reports on H pylori prevalence in Canadian population groups, or any topic related to H pylori in Canadian Aboriginals, Alaska Natives or Aboriginals of other Arctic regions. Identified reports were organized by subtopic and summarized in narrative form. Key data from studies of H pylori prevalence in defined populations were summarized in tabular form. A few Arctic Aboriginal communities were represented in the literature: two Canadian Inuit; one Canadian First Nation; two Greenland Inuit; one Russian Chutkotka Native; and several Alaska Native studies. These studies uniformly showed elevated H pylori prevalence; a few studies also showed elevated occurrence of H pylori-related diseases and high rates of treatment failure. Based on the evidence, it would be warranted for clinicians to relax the criteria for investigating H pylori and related diseases in patients from Arctic Aboriginal communities, and to pursue post-therapy confirmation of eradication. Additional community-based research is needed to develop public health policies for reducing H pylori-associated health risks in such communities.

[The Montreal definition and classification of gastroesophageal reflux disease: a global, evidence-based consensus paper]. / Die Montreal-Definition und -Klassifikation der gastroösophagealen Refluxkrankheit: Ein globales evidenzbasiertes Konsensus-Papier.

AIM: A world-wide recognised and accepted definition and classification of gastroesophageal reflux disease (GERD) would be highly desirable for research and clinical practice. The purpose of this project was to develop such a generally accepted definition and classification that could be used equally by patients, physicians, and supervisory bodies. METHODS: In order to ensure a consensus among the participating experts a modified delphi process with a step-wise selection modality was employed. For this the working group of five persons formulated a series of statements on the basis of a systematic search of the literature using three databases (Embase, Cochrane-Study register, Medline). Then these statements were developed further for two years, revised and finally passed as consensus. The consensus group consisted of 44 experts from 18 countries. Each key vote was held on the basis of a six-point scale. A "consensus" was considered to have been reached when two-thirds of the participants voted in favour of the respective statement. RESULTS: The level of agreement between the experts increased in the course of the multistep decision process, in the individual voting steps requiring at least two-thirds of the participants, the results were at first 86%, then 88% through to 94% and finally 100% in favour of the chosen statement. In the final voting, 94% of the final 51 statements were accepted by 90% of the consensus group. 90% of all statements were accepted unanimously or with only minor reservations. GERD was defined as a disease that is associated with troublesome symptoms and/or complications on account of reflux of stomach contents into the esophagus. The complaints are divided into esophageal and extra-esophageal syndromes. Among the novel aspects of this definition are the patient-orientated approach that is independent of endoscopic findings, the classification of the ailment into independent syndromes as well as the consideration of laryngitis, cough, asthma and dental problems as possible GERD syndromes. Furthermore, a new definition of suspected or demonstrated Barrett's esophagus is proposed. CONCLUSION: Irrespective of country-specific differences in terminology, language, prevalence and manifestations of this disease, evidence-based, world-wide valid consensus definitions are possible. A global consensus definition of GERD will simplify disease management, make mutual research possible and help in the design of generally valid studies. This will not only help the patient but also the physician and supervisory bodies.

One-week acid suppression trial in uninvestigated dyspepsia patients with epigastric pain or burning to predict response to 8 weeks' treatment with esomeprazole: a randomized, placebo-controlled study.

BACKGROUND: While empiric acid-suppressive therapy for uninvestigated dyspepsia patients with symptoms of epigastric pain or burning is standard practice, it is unknown whether an early response to therapy predicts outcome. AIM: To evaluate whether a 1-w acid suppression trial is effective for predicting 8-w response in such patients. METHODS: Helicobacter pylori-negative patients (aged 18-50 years) in primary care with uninvestigated epigastric pain or burning were randomized to esomeprazole 40 mg q.d.s. or b.d. for 1w, followed by esomeprazole 40 mg q.d.s. or placebo for 7w. Each day, patients rated the severity of their symptoms. RESULTS: Based on the last 3d, 1-w response rates were 39% (231 of 588) and 43% (258 of 596) with esomeprazole 40 mg q.d.s. and b.d., respectively. Based on the last 7d, response rates at 4w were 38% (283 of 738) and 25% (93 of 380) for esomeprazole and placebo, respectively, and 47% (339 of 716) and 34% (124 of 368), respectively, at 8w (both P < 0.001 vs. placebo). The sensitivity and specificity of esomeprazole treatment were 58% and 70%, respectively, at 8w. CONCLUSION: A 1-w acid suppression trial is of limited clinical value for predicting 8-w response in patients with symptoms of epigastric pain or burning. Esomeprazole provides greater symptom control than placebo at 4w and 8w.

Randomized-controlled trial of esomeprazole in functional dyspepsia patients with epigastric pain or burning: does a 1-week trial of acid suppression predict symptom response?

BACKGROUND: Early identification of true responders to acid suppression in functional dyspepsia patients with symptoms of epigastric pain or burning may enable clinicians to optimally tailor treatment. AIM: To evaluate whether a 1-w acid suppression trial is useful for identifying true responders in this population. METHODS: Patients (18-70 years) were randomized to either esomeprazole 40 mg q.d.s., b.d. or placebo for 1w, and then esomeprazole 40 mg q.d.s. or placebo for 7w. Epigastric pain and/or burning were recorded on a 4-point scale (0 = none, 3 = severe). Trial-week response was defined as symptom score sum < or = 1 on last 3d of therapy; response at 8w was symptom score sum < or = 1 over preceding 7d. RESULTS: 1-w response rates were 33% (199 of 597), 29% (188 of 629) and 23% (71 of 315) with esomeprazole q.d.s., esomeprazole b.d. and placebo, respectively (P = 0.002 for esomeprazole groups vs. placebo). At 8w, trial week sensitivity and specificity were 46% and 80%, respectively, for esomeprazole (40 or 80 mg), and 33% and 87%, respectively, for placebo. The positive and negative predictive values for esomeprazole were 60% and 69%. CONCLUSION: Response to a 1-w acid suppression trial is of limited use for predicting symptom response at 8w in patients with unexplained epigastric pain or burning.

Generation of dyspeptic symptoms by direct acid infusion into the stomach of healthy Japanese subjects.

OBJECTIVE: The relationship between acid and dyspeptic symptoms has not been fully understood. AIM: To investigate the type and severity of dyspeptic symptoms induced by direct acid infusion into the stomach of Japanese healthy subjects. METHODS: This was a multi-centre, cross-over, randomized, double-blind study in 27 healthy subjects (mean age 27). Each fasted subject received two tests with 150 mL of 0.1 mol/L hydrochloric acid infusion (15 mL/min for 10 min) and the same volume of pure water infusion. The type and severity of symptoms were assessed by a 10 cm visual analogue scale administered every 2 min up to 30 min. RESULTS: Various symptoms were reported after both acid and water infusions. Most of the symptoms were more severe after acid infusion compared with water infusion (acid vs. water: discomfort 1.8 +/- 0.4 vs. 0.5 +/- 0.1, pain 0.6 +/- 0.3 vs. 0.1 +/- 0.1, reflux 1.0 +/- 0.3 vs. 0.3 +/- 0.1 and satiety 1.1 +/- 0.4 vs. 0.2 +/- 0.1). The area under curve for dysmotility like symptoms (heavy feeling in the stomach, bloating, nausea or feeling sick, and belching) was significantly higher in acid infusion, and symptoms continued after infusion of the acid. CONCLUSION: Acid induced into stomach induced dysmotility-like predominant dyspeptic symptoms in Japanese healthy control subjects, demonstrating the possible importance of acid in symptom generation.