A questionnaire on prescription patterns of proton pump inhibitors for hemodialysis patients in Japan.

BACKGROUND: Proton pump inhibitors (PPIs) are widely used in the general population often without an endpoint. The practice of prescribing PPIs in the hemodialysis (HD) population is unknown. Thus, we aimed to identify the practice pattern related to PPI prescription for HD patients in Japan through a questionnaire survey. METHODS: We conducted a questionnaire survey for physicians engaged in dialysis practice through email. An email was sent to physicians listed in the Japanese Society of Nephrology (JSN) and iHOPE International registry. RESULTS: We received 187 physicians' answers. One-hundred twelve (60%) physicians would prefer to continuously prescribe PPIs after 8 weeks of treatment for peptic ulcer (PU) or gastroesophageal reflux disease (GERD). The main reason for continuous PPI prescription was the concern for recurrence of PU or GERD. Approximately 20% of physicians responded that they were not accustomed to de-prescribing PPIs for PU or GERD. The reason for PPI de-prescription was the concern for side effects or insurance adaptation period. Even in cases wherein PPIs were prescribed for uncertain reasons, 42% physicians would continuously prescribe PPIs. Most physicians (82%) who answered about stopping PPIs regarded HD patients as a high-risk group for PU. CONCLUSIONS: PPI prescription is often continued in HD patients. De-prescription is not a common practice in Japan. It remains unclear whether discontinuation of PPIs should be recommended in hemodialysis patients who have a high risk of gastrointestinal ulcer. Yet, considering the side effects and polypharmacy in the HD population, more discussions on preferable de-prescription of PPIs are needed.

Risk Factors and Incidence of Gastric Cancer After Detection of Helicobacter pylori Infection: A Large Cohort Study.

BACKGROUND & AIMS: Nearly all studies of gastric adenocarcinoma in the United States have relied on national cancer databases, which do not include data on Helicobacter pylori infection, the most well-known risk factor for gastric cancer. We collected data from a large cohort of patients in the United States to calculate the incidence of and risk factors for nonproximal gastric adenocarcinomas after detection of H pylori. Secondary aims included identifying how treatment and eradication affect cancer risk. METHODS: We performed a retrospective cohort study, collecting data from the Veterans Health Administration on 371,813 patients (median age 62 years; 92.3% male) who received a diagnosis of H pylori infection from January 1, 1994, through December 31, 2018. The primary outcome was a diagnosis of distal gastric adenocarcinoma 30 days or more after detection of H pylori infection. We performed a time to event with competing risk analysis (with death before cancer as a competing risk). RESULTS: The cumulative incidence of cancer at 5, 10, and 20 years after detection of H pylori infection was 0.37%, 0.5%, and 0.65%, respectively. Factors associated with cancer included older age at time of detection of H pylori infection (subhazard ratio [SHR], 1.13; 95% confidence interval [CI], 1.11-1.15; P < .001), black/African American race (SHR, 2.00; 95% CI, 1.80-2.22), Asian race (SHR, 2.52; 95% CI, 1.64-3.89) (P < .001 for race), Hispanic or Latino ethnicity (SHR, 1.59; 95% CI, 1.34-1.87; P < .001), and history of smoking (SHR, 1.38; 95% CI, 1.25-1.52; P < .001). Women had decreased risk of gastric adenocarcinoma compared with men (SHR, 0.52; 95% CI, 0.40-0.68; P < .001); patients whose H pylori infection was detected based on serum antibody positivity also had a reduced risk of cancer (SHR 0.74; 95% CI, 0.54-1.04; P = .04). Patients who received treatment for their H pylori infection still had an increased risk of gastric cancer (SHR, 1.16; 95% CI, 0.74-1.83; P = .51) but confirmed H pylori eradication after treatment reduced risk of gastric cancer (SHR, 0.24; 95% CI, 0.15-0.41; P < .001). CONCLUSIONS: In a study of 371,813 veterans with a diagnosis of H pylori infection, we found significantly higher risks of gastric cancer in racial and ethnic minorities and smokers. Treatment of H pylori infection decreased risk only if eradication was successful. Studies are needed on the effects of screening high-risk persons and to identify quality measures for diagnosis, resistance patterns, and treatment efficacy.

Validity and Reliability of the Reflux Sign Assessment.

OBJECTIVE: To develop and validate the Reflux Sign Assessment (RSA), a clinical instrument evaluating the physical findings of laryngopharyngeal reflux (LPR). METHODS: A total of 106 patients completed a 3-month treatment based on the association of diet, pantoprazole, alginate, or magaldrate with the LPR characteristics (acid, nonacid, mixed). Forty-two asymptomatic individuals completed the study (control group). The RSA results and reflux finding score (RFS) were documented for the LPR patients at baseline and after treatment. Intrarater reliability was assessed through a test-retest blinded evaluation of signs (7-day intervals). Interrater reliability was assessed by comparing the RSA evaluations of three blinded otolaryngologists through Kendall's W. Responsiveness to change was evaluated through a comparison of the baseline and 3-month posttreatment findings. The RSA cutoffs for determining the presence and absence of LPR were examined by receiver operating characteristic (ROC) analysis. RESULTS: A total of 102 LPR patients completed the study (68 females). The mean age was 53 years. The mean RSA at baseline was 25.95 ± 9.58; it significantly improved to 18.96 ± 7.58 after 3 months of therapy (P < .001). RSA exhibited good intra- (r = 0.813) and interrater (Kendall's W = 0.663) reliabilities (N = 56). There was no significant association between the RSA, gastrointestinal endoscopy findings, and the types of reflux (acid, nonacid, or mixed) according to impedance-pH monitoring. An RSA >14 may be suggestive of LPR. CONCLUSION: The RSA is a complete clinical instrument evaluating both laryngeal and extralaryngeal findings associated with LPR. The RSA demonstrated high intra- and interrater reliabilities and responsiveness to change.

Clinical and Quality of Life Assessment of Patients Undergoing Laparoscopic Hiatal Hernia Repair.

Hiatal hernia repair (HHR) and fundoplication are similarly performed among all hiatal hernia types with similar techniques. This study evaluates the effect of HHR using a standardized technique for cruroplasty with a reinforcing polyglycolic acid and trimethylene carbonate mesh (PGA/TMC) on patient symptoms and outcomes. A retrospective review of patient perioperative characteristics and postoperative outcomes was conducted for cases of laparoscopic hiatal hernia repair (LHHR) using a PGA/TMC mesh performed over 21 months. Gastroesophageal reflux disease symptom questionnaire responses were compared between preoperative and three postoperative time points. Ninety-six patients underwent LHHR with a PGA/TMC mesh. Postoperatively, the number of overall symptoms reported by patients decreased across all postoperative periods (P < 0.001). Patients reported a significant reduction in antacid use long term (P < 0.001). Laryngeal and regurgitation symptoms decreased at all time points (P < 0.05). There was no difference in dysphagia preoperatively and postoperatively at any time point. Individuals undergoing HHR with PGA/TMC mesh experienced improved regurgitation and laryngeal symptoms, and decreased use of antacid medication.

Longitudinal Assessment of Patient-reported Outcome Measures in Systemic Sclerosis Patients with Gastroesophageal Reflux Disease - Scleroderma Clinical Trials Consortium.

OBJECTIVE: Validated gastrointestinal (GI) symptoms scales are used in clinical practice to assess patient-reported GI involvement. We sought to determine whether University of California, Los Angeles (UCLA) GI Tract Questionnaire (GIT) 2.0 Reflux scale, Patient-Reported Outcomes Measurement Information System (PROMIS) Reflux scale, and the Quality of Life in Reflux and Dyspepsia questionnaire (QOLRAD) are sensitive to identifying changes in GI symptoms following therapeutic intervention in participants with systemic sclerosis (SSc) and gastroesophageal reflux disease (GERD). METHODS: Participants with active GERD were recruited during clinical visits at 6 international SSc centers. Patient-reported outcome surveys and the GI self-reported questionnaire were completed at baseline and again at 4 weeks following a single intervention, and patients were classified as "improved" or "not improved." Effect size (ES) was calculated to assess the sensitivity to change. ES was interpreted as 0.50-0.79 as moderate effect and ≥ 0.80 as large effect. RESULTS: There were 116 participants with SSc and active GERD who enrolled. The average age was 53.8 years and mean disease duration was 12.0 years. The UCLA GIT 2.0 Reflux scale and PROMIS Reflux scale had a significant correlation at baseline (0.61, p < 0.0001), and both instruments correlated with the QOLRAD domains (-0.56 to -0.71). In participants who had the UCLA GIT 2.0, PROMIS Reflux scale, and QOLRAD administered over 2 timepoints (n = 57) and were classified as improved, the ES was large for the UCLA GIT 2.0 and PROMIS Reflux scale, and moderate to large across all QOLRAD domains. CONCLUSION: The UCLA GIT 2.0 Reflux scale, PROMIS Reflux scale, and QOLRAD are sensitive to change and can be included in future clinical trials.

Evaluation of the efficacy and safety of the hybrid scheme for eradication therapy of Helicobacter pylori infection.

AIM: The aim is to conduct a comprehensive comparative study of the efficacy and safety of the hybrid scheme of eradication therapy (ET) in patients with peptic ulcer of the stomach or duodenum associated with Helicobacter pylori. MATERIALS AND METHODS: Materials and methods. In a prospective, randomized comparative study, 180 patients were divided into three equal groups of 60 people, depending on the prescribed 10-day ET regimen. Group 1 - the standard triple scheme (omeprazole, amoxicillin and clarithromycin); group 2 - four-component therapy with preparations of bismuth (omeprazole, tetracycline, metronidazole, bismuth tricalium dicitrate); group 3 - hybrid scheme (first 5 days: omeprazole and amoxicillin, the next 5 days: omeprazole, amoxicillin, clarithromycin, metronidazole). The effectiveness of ET was determined with the help of a breath test a month after the end of therapy. Adverse events were recorded by patients in specially developed diaries. Pharmacoeconomic analysis was carried out using the "cost-effectiveness" method with calculation of the CER coefficient. RESULTS: Results and discussion. The effectiveness of standard triple therapy was 73.3% (ITT), 75.9% (PP); four-component therapy with bismuth preparations - 78.3% (ITT), 82.4% (PP); hybrid scheme - 85% (ITT), 91% (PP). Hybrid therapy proved to be significantly more effective than standard triple therapy with a odds ratio (OR) of 3.25; 95% confidence interval (CI) 1.08-9.73 (p=0.043, χ2=4.75, p-level=0.029298). The incidence of adverse events with the use of triple, four-component and hybrid ET regimens was 15; 18.3 and 28.3% respectively. The OR of at least one adverse event in patients receiving a hybrid ET regimen compared with triple therapy was 2.24 (95% CI 0.91-5.53, p=0.0823, χ2=3.14, p-level=0.076394), and compared with the four-component therapy - 1.76 (95% CI 0.74-4.17, p=0.2804, χ2=1.68, p-level=0.194924). According to the results of the pharmacoeconomic analysis, the most profitable from an economic point of view was a hybrid ET scheme with a CER of 20.1. CONCLUSION: The conclusion. Hybrid therapy showed the greatest effectiveness in comparison with the triple and four-component ET regimens, however, the incidence of side effects in patients receiving the hybrid ET scheme was higher, although it remained within the acceptable level for use in clinical practice. Pharmacoeconomic analysis also showed the advisability of designating a hybrid ET scheme. The obtained data allow to draw a conclusion about the necessity of further study of the efficiency and safety of the hybrid ET scheme.

Management of Gastroesophageal Reflux Disease.

Management of gastroesophageal reflux disease (GERD) commonly starts with an empiric trial of proton pump inhibitor (PPI) therapy and complementary lifestyle measures, for patients without alarm symptoms. Optimization of therapy (improving compliance and timing of PPI doses), or increasing PPI dosage to twice daily in select circumstances, can reduce persistent symptoms. Patients with continued symptoms can be evaluated with endoscopy and tests of esophageal physiology, to better determine their disease phenotype and optimize treatment. Laparoscopic fundoplication, magnetic sphincter augmentation, and endoscopic therapies can benefit patients with well-characterized GERD. Patients with functional diseases that overlap with or mimic GERD can also be treated with neuromodulators (primarily antidepressants), or psychological interventions (psychotherapy, hypnotherapy, cognitive and behavioral therapy). Future approaches to treatment of GERD include potassium-competitive acid blockers, reflux-reducing agents, bile acid binders, injection of inert substances into the esophagogastric junction, and electrical stimulation of the lower esophageal sphincter.

Health-related Quality of Life and Functional Outcomes in 5-year Survivors After Pancreaticoduodenectomy.

OBJECTIVE: Our aim was to assess quality of life (QOL) and functionality in a large cohort of patients ≥5-years after pancreaticoduodenectomy (PD). BACKGROUND: Long-term QOL outcomes after PD for benign or malignant disease are largely undocumented. METHODS: We administered the EORTC QLQ-C30 questionnaire to patients who underwent PD for neoplasms from 1998 to 2011 and compared their scores with an age- and sex-matched normal population. Clinical relevance (CR) of differences was scored as small (5-10), moderate (10-20), or large (>20) based on validated interpretation of clinically important differences. RESULTS: Of 305 PD survivors, 245 (80.3%) responded, of whom 157 (64.1%) underwent PD for nonmalignant lesions. Median follow-up was 9.1 years (range 5.1 -21.2 yrs). New-onset diabetes developed in 10.6%; 50.4% reported taking pancreatic enzymes; 54.6% reported needing antacids. Compared with the age- and sex-adjusted controls, PD survivors demonstrated higher global QOL (78.7 vs 69.7, CR small, P < 0.001), physical (86.7 vs 77.9, CR small, P < 0.001) and role-functioning scores (86.3 vs 74.1, CR medium, P < 0.001). Using linear regression and adjusting for socioeconomic variables, there were no differences in QOL or functional scores in the benign versus malignant subgroups. Older age at operation was associated with worse physical-functioning (-0.4/yr, P = 0.008). Taking pancrelipase (-6.8, P = 0.035) or antacids (-6.3, P = 0.044) were both associated with lower social-functioning scores. CONCLUSIONS: Patients who had a PD demonstrated better global QOL, physical- and role-functioning scores at 5-years when compared with age- and sex-matched controls. Approximately half of the patients required pancreatic enzyme replacement, while only 11% developed new-onset diabetes.

Incremental cost-utility of sevelamer relative to calcium carbonate for treatment of hyperphosphatemia among pre-dialysis chronic kidney disease patients.

BACKGROUND: Sevelamer is an alternative to calcium carbonate for the treatment of hyperphosphatemia among non-dialysis dependent patients with chronic kidney disease (CKD). Although some studies show that it may reduce mortality and delay the onset of dialysis when compared to calcium carbonate, it is also significantly more expensive. Prior studies looking at the incremental cost-effectiveness of sevelamer versus calcium carbonate in pre-dialysis patients are based on data from a single clinical trial. The goal of our study is to use a wider range of clinical data to achieve a more contemporary and robust cost-effectiveness analysis. METHODS: We used a Markov model to estimate the lifetime costs and quality-adjusted life years (QALYs) gained for treatment with sevelamer versus calcium carbonate. The model simulated transitions among three health states (CKD not requiring dialysis, end-stage renal disease, and death). Data on transition probabilities and utilities were obtained from the published literature. Costs were calculated from a third party payer perspective and included medication, hospitalization, and dialysis. Sensitivity analyses were also run to encompass a wide range of assumptions about the dose, costs, and effectiveness of sevelamer. RESULTS: Over a lifetime, the average cost per patient treated with sevelamer is S$180,724. The estimated cost for patients treated with calcium carbonate is S$152,988. A patient treated with sevelamer gains, on average, 6.34 QALYs relative to no treatment, whereas a patient taking calcium carbonate gains 5.81 QALYs. Therefore, sevelamer produces an incremental cost-effectiveness ratio (ICER) of S$51,756 per QALY gained relative to calcium carbonate. CONCLUSION: Based on established benchmarks for cost-effectiveness, sevelamer is cost effective relative to calcium carbonate for the treatment of hyperphosphatemia among patients with chronic kidney disease initially not on dialysis.

[Pharmacoeconomic evaluation of treatment in patients with Helicobacter pylori-associated diseases].

AIM: To estimate the pharmacoeconomic parameters of treatment in patients with Helicobacter pylori-associated diseases when using 6 eradication therapy (ET) regimens. SUBJECTS AND METHODS: The investigation enrolled a total of 231 patients who received anti-Helicobacter pylori therapy according to the intention-to-treat (ITT) principle, including 229 patients who met the protocol requirements, i.e. who completed the prescribed per-protocol (PP) treatment: 106 patients with duodenal bulb ulcer disease, 2 with gastric ulcer, 90 with erosive gastritis, and 31 patients with non-atrophic gastritis. In an outpatient setting, the patients received one of the 6 ET regimens: OAC, RBMA, RBCA, EBCA, sequential OACM therapy, and modified sequential OACMB therapy (O--omeprazole; A--amoxicillin; C--clarithromycin; B--bismuth tripotassium dicitrate, R--rabeprazole; M--metronidazole; E--esomeprazole). Treatment costs were calculated only from direct drug expenditures. The effective cost coefficient (K(eff)) was determined from the cost/ treatment efficiency ratio: K(eff) = cos/eff, where the cost was the average total costs; the eff was efficiency (%). RESULTS: The modified sequential OACMB therapy has proven to be more cost-efficient than the other regimens as it has a lower K(eff), (14). The RBMA regimens can overcome an 80% ET barrier (82.4%); however, in this case the K(eff) is 21.5. the sequential OACM therapy can also overcome an 80% ET barrier (84.8%); the K(eff) being 10.8. Incorporation of the bismuth preparation can achieve a more noticeable therapeutic effect up to 95.4%. The EBCA regimen has turned out to be most expensive with the highest K(eff) of 36.9. The RBCA regimen is most effective with the least K(eff) of 29; the therapeutic effect is 96.7%. CONCLUSION: The clinical cost-efficiency of ET is enhanced by the incorporation of the bismuth preparation for the treatment of patients with H. pylori-associated diseases. The modified sequential OACMB therapy can overcome resistance to clarithromycin and metronidazole with a good cost-efficiency.

Use of antacids, alginates and proton pump inhibitors: a survey of the general Danish population using an internet panel.

OBJECTIVE: Both over-the-counter medicine, such as antacids or alginates, and proton pump inhibitors (PPI) are used for treating acid-related disorders. We sought to describe what characterizes users of these different medicines, including long-term PPI users within the general population. METHOD: A cross-sectional survey was conducted in an internet panel representative of the Danish adult population in 2012. Data queried included antacid/alginate and PPI use, reason for therapy, co-medication, and presence of upper gastrointestinal symptoms. Long-term PPI use was defined as using PPI ≥1/3 of the last year (∼120 days). Risk of long-term PPI use was estimated by logistic regression. RESULTS: A total of 18,223 people received the questionnaire, of which 52% (9390) responded. Antacid/alginate use was reported by 23%; 16% reported use of only antacid/alginate. PPI use was reported by 13.6%; 6.2% were defined as long-term PPI users. Antacid/alginate users were younger, used less co-medication, had most often started on therapy because of reflux symptoms, and had less often ongoing symptoms. Risk of long-term PPI use appeared to be increased in male gender, by renewing PPI prescription by phone/e-mail, using co-medication, and having started on PPI for several reasons. Combination of antacid/alginate and PPI was reported by approximately 50% of those on therapy with weekly or daily symptoms. CONCLUSION: 23% of Danish adults were using antacids or alginates and 14% were using PPI, of which one-half were on long-term therapy. Prescription renewal by phone or e-mail and use of other prescription medication were associated with long-term PPI use, indicating a behavioral pattern, in which unnecessary PPI therapy may be maintained.

The efficacy, safety and cost-effectiveness of hydrotalcite versus esomeprazole in on-demand therapy of NERD: A multicenter, randomized, open-label study in China.

OBJECTIVE: The aim of the study was to investigate whether hydrotalcite was comparable to esomeprazole, a proton pump inhibitor, in on-demand therapy for non-erosive reflux disease (NERD). METHODS: This was a multicenter, randomized, open-label clinical trial with initial and on-demand therapy. Patients who had complete symptom relief in the initial therapy were randomized to either hydrotalcite or esomeprazole in the on-demand therapy. The percentage of patients who quit on-demand therapy in the two groups and the cost-effectiveness of the treatment were evaluated as primary end points. The rate of symptom relief and the improvement of symptom score for initial therapy and the weekly average symptom score and weekly average number of days on treatment for on-demand therapy were evaluated as secondary end points. RESULTS: In total, 398 patients were recruited in the initial therapy group, among whom 253 were included in on-demand therapy, with 127 patients in the hydrotalcite group and the remaining 126 in the esomeprazole group. 14 (11.0%) patients in the hydrotalcite group and six (4.8%) in the esomeprazole group quit the on-demand therapy due to unsatisfactory symptom control (P = 0.065). Cost-effectiveness calculated as the ratio of the cost of hydrotalcite to that of esomeprazole (per person/day) was 35.3% in the on-demand therapy. Similar number of patients achieved symptom relief in both groups. CONCLUSION: Hydrotalcite is a good option of on-demand therapy for NERD patients due to its cost-effectiveness and speed of action.

Post-prandial reflux suppression by a raft-forming alginate (Gaviscon Advance) compared to a simple antacid documented by magnetic resonance imaging and pH-impedance monitoring: mechanistic assessment in healthy volunteers and randomised, controlled, double-blind study in reflux patients.

BACKGROUND: Alginates form a raft above the gastric contents, which may suppress gastro-oesophageal reflux; however, inconsistent effects have been reported in mechanistic and clinical studies. AIMS: To visualise reflux suppression by an alginate-antacid [Gaviscon Advance (GA), Reckitt Benckiser, UK] compared with a nonraft-forming antacid using magnetic resonance imaging (MRI), and to determine the feasibility of pH-impedance monitoring for assessment of reflux suppression by alginates. METHODS: Two studies were performed: (i) GA and antacid (Alucol, Wander Ltd, Switzerland) were visualised in the stomach after ingestion in 12 healthy volunteers over 30 min after a meal by MRI, with reflux events documented by manometry. (ii) A randomised controlled, double-blind cross-over trial of post-prandial reflux suppression documented by pH-impedance in 20 patients randomised to GA or antacid (Milk of Magnesia; Boots, UK) after two meals taken 24 h apart. RESULTS: MRI visualized a "mass" of GA form at the oesophago-gastric junction (OGJ); simple antacid sank to the distal stomach. The number of post-prandial common cavity reflux events was less with GA than antacid [median 2 (0-5) vs. 5 (1-11); P < 0.035]. Distal reflux events and acid exposure measured by pH-impedance were similar after GA and antacid. There was a trend to reduced proximal reflux events with GA compared with antacid [10.5 (8.9) vs. 13.9 (8.3); P = 0.070]. CONCLUSIONS: Gaviscon Advance forms a 'mass' close to the OGJ and significantly suppresses reflux compared with a nonraft-forming antacid. Standard pH-impedance monitoring is suitable for clinical studies of GA in gastro-oesophageal reflux disease patients where proximal reflux is the primary outcome.

Effect of the Medicare Part D coverage gap on medication use among patients with hypertension and hyperlipidemia.

BACKGROUND: Prior studies of the Medicare Part D coverage gap are limited in generalizability and scope. OBJECTIVE: To determine the effect of the coverage gap on drugs used for asymptomatic (antihypertensive and lipid-lowering drugs) and symptomatic (pain relievers, acid suppressants, and antidepressants) conditions in elderly patients with hypertension and hyperlipidemia. DESIGN: Quasi-experimental study using pre-post design and contemporaneous control group. SETTING: Medicare claims files from 2005 and 2006 for 5% random sample of Medicare beneficiaries. PATIENTS: Part D plan enrollees with hypertension or hyperlipidemia aged 65 years or older who had no coverage, generic-only coverage, or both brand-name and generic coverage during the gap in 2006. Patients who were fully eligible for the low-income subsidy served as the control group. MEASUREMENTS: Monthly 30-day supply prescriptions available, medication adherence, and continuous medication gaps of 30 days or more for antihypertensive or lipid-lowering drugs; monthly 30-day supply prescriptions available for pain relievers, acid suppressants, or antidepressants before and after coverage gap entry. RESULTS: Patients with no gap coverage had a decrease in monthly antihypertensive and lipid-lowering drug prescriptions during the coverage gap. Nonadherence also increased in this group (antihypertensives: odds ratio [OR], 1.60 [95% CI, 1.50 to 1.71]; lipid-lowering drugs: OR, 1.59 [CI, 1.50 to 1.68]). The proportion of patients with no gap coverage who had continuous medication gaps in lipid-lowering medication use and antihypertensive use increased by an absolute 7.3% (OR, 1.38 [CI, 1.29 to 1.46]) and 3.2% (OR, 1.35 [CI, 1.25 to 1.45]), respectively, because of the coverage gap. Decreases in use were smaller for pain relievers and antidepressants and larger for acid suppressants in patients with no gap coverage. Patients with generic-only coverage had decreased use of cardiovascular medications but no change in use of drugs for symptomatic conditions. No measures changed in the brand-name and generic coverage groups. Results of sensitivity analyses were consistent with the main findings. LIMITATION: Because this study was nonrandomized, unobserved differences may still exist between study groups. CONCLUSION: The Part D coverage gap was associated with decreased use of medications for hypertension and hyperlipidemia in patients with no gap coverage and generic-only gap coverage. The proposed phasing out of the gap by 2020 will benefit such patients; however, use of low-value medications may also increase. PRIMARY FUNDING SOURCE: Penn-Pfizer Alliance and American Heart Association.

Therapeutic and cost effectiveness of proton pump inhibitor regimens for idiopathic or drug-induced peptic ulcer complication.

Peptic ulcer (PU) disease has a high rate of occurrence and recurrence in Korean and the selection of drug for treatment is diverse. In this study, the therapeutical effectiveness of regimens including proton pump inhibitors (PPI) was compared with the single PPI therapy. The clinical data were collected from 1,658 patients having idiopathic or drug-induced PU complication from a Medical Center in Daegu, Korea, and analyzed retrospectively based on the results of endoscopic examination, the drug history and the therapeutic cost depending on drugs used. The comparison of complete healing rate and recurrence rate showed no significant differences between the single PPI groups and the combination group with antacids, prokinetic agent or mucosa protectants. However, the combination therapy of PPI with mucosa protectants gave a slightly better therapeutic outcome than single PPI treatment in gastric ulcer patients. Comparatively, the combination of PPI with antacids significantly reduced the therapeutic effectiveness in duodenal ulcer patients. The analysis of cost-based therapeutic effectiveness reveals that any economic benefits in PU treatment were not gained by the combination of other class of ulcer drugs. Even though the rapidity of healing rate was not considered, it can be concluded that the PPI combination therapy might be not desirable in PU treatment. Particularly triplet or quartet combination therapy in PPI regimen was absolutely economically ineffective therapy in spite of the increase of medication costs.

Empiric quadruple vs. triple therapy for primary treatment of Helicobacter pylori infection: Systematic review and meta-analysis of efficacy and tolerability.

OBJECTIVES: Recent treatment guidelines recommend two first-line therapies for Helicobacter pylori infection: proton pump inhibitor (PPI), bismuth, tetracycline, and metronidazole (quadruple therapy) or PPI, clarithromycin, and amoxicillin (triple therapy). We performed a systematic review and meta-analysis to compare the efficacy and tolerability of these regimens as first-line treatment of H. pylori. METHODS: A search of MEDLINE, EMBASE, Google Scholar, the Cochrane Central Register of Controlled Trials, ACP Journal Club, the Database of Abstracts of Reviews of Effectiveness, Cochrane Methodology Register, Health Technology Assessment Database, and abstracts from prominent gastrointestinal scientific meetings was carried out. Randomized controlled trials (RCTs) comparing bismuth quadruple therapy to clarithromycin triple therapy were selected for meta-analysis. Two independent reviewers extracted data, using standardized data forms. Meta-analysis was carried out with the metan command in Stata 10.1. Funnel plots and subgroup analyses were carried out. RESULTS: Nine RCTs (N=1,679) were included. Although dosing regimens of clarithromycin triple therapy were quite consistent between trials, dosing regimens varied considerably for bismuth quadruple therapy. Bismuth quadruple therapy achieved eradication in 78.3% of patients, whereas clarithromycin triple therapy achieved an eradication rate of 77.0% (risk ratio (RR)=1.002, 95% confidence interval (CI): 0.936-1.073). There was moderate heterogeneity and no evidence for significant publication bias. Subgroup analyses by study location, treatment duration, and study population did not account for the heterogeneity. There were no statistically significant differences in side effects yielded by quadruple vs. clarithromycin triple therapy (RR=1.04, 95% CI: 1.04-1.14). CONCLUSIONS: Quadruple and triple therapies yielded similar eradication rates as primary therapy for H. pylori infection. Both therapies yielded suboptimal eradication rates. Patient compliance and side effects are similar for quadruple and triple therapies.

Emerging drugs for gastroesophageal reflux disease.

Proton pump inhibitors (PPIs) are very effective and safe drugs for the treatment of erosive and non-erosive gastroesophageal reflux disease (GERD). Nevertheless, a significant proportion of GERD patients (30 - 40%) continue to suffer from symptoms during PPI treatment, which has stimulated the search for better drugs. Improvement of PPI pharmacokinetics and pharmacodynamics has been the main focus of drug development in the past decade with the ultimate goal of optimizing acid inhibition. New inhibitors of the proton pump with a longer half-life, acting faster and longer, have been developed, including potassium-competitive acid blockers. Recent data, however, suggest that the therapeutic efficacy of acid suppression may have reached its maximum and other mechanisms may have to be targeted to further improve symptom control. Potential drugs interacting with different targets are reflux inhibitors such as GABA(B) receptor agonists and mGluR5 antagonists. These agents reduce the number of transient lower esophageal sphincter relaxation thereby reducing both acid and non-acid reflux. Theoretically, visceral analgesics to modulate visceral perception or even growth factors to enhance mucosal healing may be other emerging drugs to treat GERD.

A randomised controlled trial of structured nurse-led outpatient clinic follow-up for dyspeptic patients after direct access gastroscopy.

BACKGROUND: Dyspepsia is a common disorder in the community, with many patients referred for diagnostic gastroscopy by their General Practitioner (GP). The National Institute of Clinical Excellence (NICE) recommends follow-up after investigation for cost effective management, including lifestyle advice and drug use. An alternative strategy may be the use of a gastro-intestinal nurse practitioner (GNP) instead of the GP. The objective of this study is to compare the effectiveness and costs of systematic GNP led follow-up to usual care by GPs in dyspeptic patients following gastroscopy. RESULTS: Direct access adult dyspeptic patients referred for gastroscopy; without serious pathology, were followed-up in a structured nurse-led outpatient clinic. Outcome measurement used to compare the two study cohorts (GNP versus GP) included Glasgow dyspepsia severity (Gladys) score, Health Status Short Form 12 (SF12), ulcer healing drug (UHD) use and costs. One hundred and seventy five patients were eligible after gastroscopy, 89 were randomised to GNP follow-up and 86 to GP follow-up. Follow-up at 6 months was 81/89 (91%) in the GNP arm and 79/86 (92%) in the GP arm. On an intention to treat analysis, adjusted mean differences (95%CI) at follow-up between Nurse and GP follow-up were: Gladys score 2.30 (1.4-3.2) p < 0.001, SF12 140.6 (96.5-184.8) p =< 0.001 and UHD costs pound39.60 ( pound24.20- pound55.10) p =< 0.001, all in favour of nurse follow-up. CONCLUSION: A standardised and structured follow-up by one gastrointestinal nurse practitioner was effective and may save drug costs in patients after gastroscopy. These findings need replication in other centres.

Effect and cost-effectiveness of step-up versus step-down treatment with antacids, H2-receptor antagonists, and proton pump inhibitors in patients with new onset dyspepsia (DIAMOND study): a primary-care-based randomised controlled trial.

BACKGROUND: Substantial physician workload and high costs are associated with the treatment of dyspepsia in primary health care. Despite the availability of consensus statements and guidelines, the most cost-effective empirical strategy for initial management of the condition remains to be determined. We compared step-up and step-down treatment strategies for initial management of patients with new onset dyspepsia in primary care. METHODS: Patients aged 18 years and older who consulted with their family doctor for new onset dyspepsia in the Netherlands were eligible for enrolment in this double-blind, randomised controlled trial. Between October, 2003, and January, 2006, 664 patients were randomly assigned to receive stepwise treatment with antacid, H(2)-receptor antagonist, and proton pump inhibitor (step-up; n=341), or these drugs in the reverse order (step-down; n=323), by use of a computer-generated sequence with blocks of six. Each step lasted 4 weeks and treatment only continued with the next step if symptoms persisted or relapsed within 4 weeks. Primary outcomes were symptom relief and cost-effectiveness of initial management at 6 months. Analysis was by intention to treat (ITT); the ITT population consisted of all patients with data for the primary outcome at 6 months. This trial is registered with ClinicalTrials.gov, number NCT00247715. FINDINGS: 332 patients in the step-up, and 313 in the step-down group reached an endpoint with sufficient data for evaluation; the main reason for dropout was loss to follow-up. Treatment success after 6 months was achieved in 238 (72%) patients in the step-up group and 219 (70%) patients in the step-down group (odds ratio 0.92, 95% CI 0.7-1.3). The average medical costs were lower for patients in the step-up group than for those in the step-down group (euro228 vs euro245; p=0.0008), which was mainly because of costs of medication. One or more adverse drug events were reported by 94 (28%) patients in the step-up and 93 (29%) patients in the step-down group. All were minor events, including (other) dyspeptic symptoms, diarrhoea, constipation, and bad/dry taste. INTERPRETATION: Although treatment success with either step-up or step-down treatment is similar, the step-up strategy is more cost effective at 6 months for initial treatment of patients with new onset dyspeptic symptoms in primary care.