Reliability, validity, and sensitivity of the Japanese version of the University of California Los Angeles scleroderma clinical trial consortium gastrointestinal tract instrument: Application to efficacy assessment of intravenous immunoglobulin administration.

This study aimed to develop and assess the reliability, validity, and sensitivity of the Japanese version of the University of California Los Angeles Scleroderma Clinical Trial Consortium gastrointestinal tract (GIT) Instrument 2.0 (the GIT score), as an evaluation tool for GIT symptoms in systemic sclerosis (SSc). The Japanese version of the GIT score was constructed using the forward-backward method. The reliability and validity of this instrument were evaluated in a cohort of 38 SSc patients. Correlation analysis was conducted to assess the relationship between the GIT score and existing patient-reported outcome measures. Additionally, the sensitivity of the GIT score was examined by comparing GIT scores before and after intravenous immunoglobulin (IVIG) administration in 10 SSc-myositis overlap patients, as IVIG has recently demonstrated effectiveness in alleviating GIT symptoms of SSc. As a result, the Japanese version of the GIT score exhibited internal consistency and a significant association with the Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease. Furthermore, the total GIT score, as well as the reflux and distention/bloating subscales, displayed moderate correlations with the EuroQol 5 dimensions (EQ-5D) pain/discomfort subscale and the Short Form-36 body pain subscale. Notably, following IVIG treatment, there was a statistically significant reduction in the total GIT score and multiple subscales. We first validated the Japanese version of the GIT score in Japanese SSc patients in real-world clinical settings. This instrument holds promise for application in future clinical trials involving this patient population.

Prescribing trends of proton pump inhibitors and histamine blockers among children in the United Kingdom (1998-2019): A population-based assessment.

PURPOSE: To describe the prescribing trends of proton pump inhibitors (PPIs) and H2 receptor antagonists (H2 RAs) among children with gastroesophageal reflux in the United Kingdom between 1998 and 2019. METHODS: We conducted a population-based retrospective cohort study using data from the Clinical Practice Research Datalink that included all children aged ≤18 years with a first ever diagnosis of gastroesophageal reflux between 1998 and 2019. Using negative binomial regression, we estimated crude and adjusted annual prescription rates per 1000 person-years and corresponding 95% confidence intervals (CIs) for PPIs and H2 RAs. We also assessed rate ratios of PPIs and H2 RAs prescription rates to examine changes in prescribing over time. RESULTS: Our cohort included 177 477 children with a first ever diagnosis of gastroesophageal reflux during the study period. The median age was 13 years (IQR: 1, 17) among children prescribed PPIs and 0.2 years (IQR: 0.1, 0.6) among those prescribed H2 RAs. The total prescription rate of all GERD drugs was 1468 prescriptions per 1000 person-years (PYs) (95% CI 1463-1472). Overall, PPIs had a higher prescription rate (815 per 1000 PYs, 95% CI 812-818) than H2 RAs (653 per 1000 PYs 95% CI 650-655). Sex- and age-adjusted rate ratios of 2019 versus 1998 demonstrated a 10% increase and a 76% decrease in the prescription rates of PPIs and H2 RAs, respectively. CONCLUSIONS: Prescription rates for PPIs increased, especially during the first half of the study period, while prescription rates for H2 RA decreased over time.

Cost-effectiveness of alginic acid in combination with proton pump inhibitor for the treatment of gastroesophageal reflux disease in systemic sclerosis patients.

BACKGROUND: Systemic sclerosis (SSc) patients often become refractory to proton pump inhibitors (PPI)-a standard treatment for gastroesophageal reflux disease (GERD)-and intolerant to PPI in combination with domperidone. PPI with alginic acid is an alternative treatment option, but alginic acid is costly. OBJECTIVES: We compared the costs and effectiveness of alginic acid plus PPI versus standard treatments (PPI with/without antacids as needed and lifestyle modifications) for GERD in SSc patients unsuitable for, or intolerant to, domperidone. METHODS: An economic evaluation using the Markov model was conducted among SSc patients aged between 40 and 65 years with GERD, having a partial or non-response to 4 weeks of standard-dose omeprazole (40 mg/day) and being unsuitable for or intolerant to domperidone. Using a societal perspective, we computed the incremental cost-effectiveness ratios (ICERs) in terms of Thai baht (THB) per quality-adjusted life-year (QALY) between a combination of alginic acid plus PPI and standard treatment for GERD. The lifetime time horizon was used. RESULTS: The ICER for alginic acid plus PPI versus standard treatments was 377 101 THB/QALY. According to the one-way sensitivity analysis, the cost of alginic acid was the most impactful parameter. If the market prices of alginic acid plus PPI were reduced by 61%, this treatment option would become cost-effective at the willingness-to-pay threshold of 160 000 THB/QALY (34.68 THB/USD data on 25 May 2023). Furthermore, if alginic acid were included in the public health insurance program, the national budget would be increased by 66 313 THB per patient, resulting in an overall budget increase of 5 106 101 to 8 885 942 THB compared with the standard treatment. CONCLUSIONS: Alginic acid plus PPI does not represent good value for money compared with the standard treatment among such SSc patients in Thailand unless its price is reduced significantly.

Cost-effectiveness of a novel, non-active implantable device as a treatment for refractory gastro-esophageal reflux disease.

AIMS: Gastro-esophageal reflux disease (GERD) is a common, chronic gastrointestinal condition characterized by heartburn, chest pain, regurgitation, and bloating. The current standard of care includes chronic treatment with proton pump inhibitors (PPIs) or, in selected patients, laparoscopic anti-reflux surgery. RefluxStop is a novel implantable device indicated for GERD patients eligible for laparoscopic surgical treatment. The aim of this analysis was to assess the cost-effectiveness of RefluxStop against available treatment options for GERD. MATERIAL AND METHODS: A Markov model was developed to assess the cost-effectiveness of RefluxStop compared with PPI-based medical management (MM) and two surgical management options, LNF and magnetic sphincter augmentation (MSA, LINX system), in people with GERD. Clinical outcomes and costs were estimated over a lifetime horizon from the UK National Health Service perspective and an annual discount rate of 3.5% was applied. RESULTS: RefluxStop showed favorable surgical outcomes compared with both LNF and MSA. The base case incremental cost-effectiveness ratios compared with MM, LNF, and MSA were £4,156, £6,517, and £249 per QALY gained, respectively. At the UK cost-effectiveness threshold of £20,000 per QALY gained, the probability that RefluxStop was cost-effective against MM, LNF, and MSA was 100%, 93%, and 100%, respectively. LIMITATIONS: The model presented the results of a comparison, with evidence for RefluxStop derived from its single-arm CE mark trial and that for comparators from the literature. The varied clinical care pathway of individual GERD patients was necessarily simplified for modeling purposes, and necessary assumptions were made; however, the model results proved robust to sensitivity analyses. CONCLUSIONS: Introduction of RefluxStop was estimated to extend life expectancy and improve quality-of-life of GERD patients when compared with MM, LNF, and MSA. The results of the cost-effectiveness analysis demonstrated that RefluxStop is highly likely to be a cost-effective treatment option within NHS England.

Health Care Cost Analysis of PPI or P-CAB-First Treatment in Patients With Gastroesophageal Reflux Disease.

GOALS: The aim was to examine actual health care cost in patients with gastroesophageal reflux disease (GERD) who were initiated on proton pump inhibitor (PPI) or potassium-competitive acid blocker (P-CAB) as first-line therapy in Japanese real-world clinical settings. BACKGROUND: To date, cost-utility evaluation of acid-suppressants treatment in Japan has only been conducted by model analysis. STUDY: A cost utilization analysis was performed using a Japanese nationwide hospital-based claim database by extracting patients with GERD initiated on either PPI or P-CAB (242,102 pairs) and esomeprazole (EPZ) or P-CAB (241,825 pairs). Health care costs were compared in each comparison cohort with propensity-score matched pairs. The switching rates of initial acid-suppressants were also examined. RESULTS: Baseline characteristics were well-balanced after matching. The 3-year mean cumulative GERD-related and hospitalization costs per patient were ¥142,620 and ¥122,444 in PPI-first and P-CAB-first treatment groups, and ¥105,263 and ¥121,958 in EPZ-first and P-CAB-first treatment groups, respectively. Most hospitalization costs were non-GERD related in all the groups. The switching rates of PPI to P-CAB and P-CAB to PPI in 12 months were 7.5% and 20.2%, respectively. CONCLUSIONS: In this propensity-score matched analysis, health care cost was higher in patients with GERD initiated on PPI than in those initiated on P-CAB mainly owing to non-GERD-related hospitalization cost, whereas it was lower in those initiated on EPZ than in those initiated on P-CAB. When considering health care costs except hospitalization costs, PPI-first treatment was less expensive than P-CAB-first treatment. Low switching rate from PPI to P-CAB in the real-world practice may partially explain the discrepancy.

Long-term comparative effectiveness of gastric bypass and sleeve gastrectomy on use of antireflux medication: a difference-in-differences analysis.

BACKGROUND: Gastroesophageal reflux (GERD) is common among patients with obesity who undergo bariatric surgery. Although gastric bypass and sleeve gastrectomy are the most common bariatric operations performed in the United States, their long-term comparative effectiveness on GERD medication use is unknown. OBJECTIVE: To compare the long-term effectiveness of gastric bypass and sleeve gastrectomy on use of antireflux medication. SETTING: National cohort undergoing inpatient bariatric surgery. METHODS: This is a retrospective study of Medicare beneficiaries undergoing gastric bypass and sleeve gastrectomy between January 1, 2012, and December 31, 2017. A difference-in-differences analysis was conducted to evaluate the differential change in antireflux medication use between groups before and after surgery. RESULTS: A total of 16,640 patients underwent gastric bypass, and 26,724 patients underwent sleeve gastrectomy. Before surgery, GERD medication use was higher among patients who underwent gastric bypass (62.4%; 95% confidence interval [CI]: 62.0%-63.7%) compared with patients who underwent sleeve gastrectomy (60.1%; 95% CI: 59.3%-60.9%). Five years after surgery, GERD medication use was lower in patients who underwent gastric bypass (47.8%; 95% CI: 46.3%-49.3%) compared with patients who underwent sleeve gastrectomy (53.7%; 95% CI: 50.5%-56.9%). The differential decrease from baseline GERD medication use was greater for patients who underwent gastric bypass at 2 years (-4.1 percentage points [pp]; 95% CI: -1.7 to -6.5 pp), 3 years (-4.3 pp; 95% CI: -1.6 to -7.0 pp), 4 years (-6.9 pp; 95% CI: -4.1 to -9.6 pp), and 5 years (-8.3 pp; 95% CI: -3.7 to 12.8 pp) after surgery. CONCLUSION: Though use of antireflux medication decreased following both procedures, gastric bypass was associated with a greater reduction in antireflux medication use 5 years after surgery compared with sleeve gastrectomy. Understanding the long-term comparative effectiveness of these common bariatric operations may better inform treatment decisions among patients and surgeons.

Cost Avoidance Analysis of Medication Conversions on the Treatment of Gastroesophageal Reflux Disease in a Medication Therapy Management Call Center: A Budgetary Perspective.

BACKGROUND: The burden of prescription drug prices affects patients and health system, creating a need for pharmacists to use their medication expertise to recommend the most cost-effective treatment for patients. OBJECTIVE: The study aimed to analyze the cost avoidance for medication conversions related to GERD from an integrated medication therapy management call center. METHODS: A quasi-experimental study was conducted at a call center during a 12-month intervention. Adult patients aged ≥18 years who received highercost PPIs were included. The pharmacists provided MTM services to patients telephonically to review all aspects of the patients' medication regimen as well as conversion recommendation to lower-cost PPIs. The cost avoidance analysis and sensitivity analysis were conducted. RESULTS: Of 40 eligible patients, 9 patients accepted the medication conversion, resulting in a 22.5% acceptance rate. The total cost avoidance from medication conversions was $19,937.1 per year, which equated to $2,215.2 per patient. The adjusted cost avoidance of medication conversion was estimated by assuming the patients who accepted the conversion continued taking the medication for 365 days and resulted in a total savings of $40,370.7 per year, which equated to $4,485.6 per patient. There were no significant association between the acceptance of medication conversions and patient's age(P = 0.15), gender(P = 0.73), and insurance status(P = 0.96). CONCLUSION: The study results showed that the call-center MTM with medicationconversion interventions successfully demonstrated an economically advantageous impact from a budgetary perspective. Further studies should explore methods to increase acceptance of MTM services and promote awareness of the profound effect on public health and well-being.

Estimate of Refractory Reflux Disease in the United States: Economic Burden and Associated Clinical Characteristics.

GOALS: To update the estimate of the prevalence of refractory gastroesophageal reflux disease (GERD) in the United States, and to assess the clinical and economic differences between patients with and without refractory GERD. BACKGROUND: GERD affects 18% to 28% of the US population, with nearly 40% of GERD patients presenting with refractory symptoms despite ongoing therapy. STUDY: Retrospective analysis of the IBM MarketScan databases between January 2011 and June 2018. Inclusion criteria were prescription fill and subsequent refill of a proton pump inhibitor or H2-receptor antagonist (earliest claim=index date), diagnosis of GERD 60 days preceding and/or following index, continuous insurance enrolment for 12 months preceding/following index, and absence of prior GERD diagnosis or GERD medication. We derived refractory GERD symptom scores for all patients on the basis of a previously published algorithm. Health care costs and comorbidities were assessed for all patients and compared between those with and without refractory GERD. RESULTS: In total, 399,017 GERD patients qualified for the study; 103,654 (26%) met our definition of having indications of refractory GERD symptoms. Patients with refractory GERD symptoms reported significantly higher rates of hiatal hernia (25.1% vs. 5.9%), esophagitis (37.3% vs. 11.8%), esophageal stricture (11.3% vs. 1.5%), and dysphagia (26.8% vs. 7.1%; P<0.01 for each). The refractory GERD symptoms cohort incurred ~$10,000 greater health care costs per patient per year compared with patients without refractory GERD symptoms ($26,057±$58,948 vs. $15,285±$39,307; P<0.01). CONCLUSIONS: Refractory GERD symptoms were associated with a substantial increase in health care costs. Treatments aimed at improving refractory GERD symptoms may mitigate symptom burden, potentially reducing health care expenditure.

Gastroesophageal reflux and asthma: when, how, and why.

PURPOSE OF REVIEW: Gastro-esophageal reflux is a possible cause of uncontrolled symptoms of asthma and should be actively investigated and treated before severe asthma is diagnosed and biological therapy started. RECENT FINDINGS: Recent investigations on esophageal function and tissue biomarkers in patients with asthma and associated GERD have established a relevant role for esophageal motility and neuronal sensory abnormalities in linking the two diseases. Characterization of the underpinning inflammatory substrate has showed mixed results as both neutrophilic and eosinophilic type 2 inflammatory changes have been described. SUMMARY: New findings regarding inflammatory mechanisms in GERD-associated asthma as well as new diagnostic tools to investigate functional esophageal abnormalities and characterize asthma endotype have identified potential treatable traits that may improve the clinical management and outcome of asthmatic patients with GERD.

[Complex assessment of esophageal acidification and motor function in patients with Barrett's esophagus on antisecretory therapy].

AIM: To determine predictors of insufficient effectiveness of proton pump inhibitors based on the parameters of 24-hours pH-impedance and features of motor function of the esophagus in patients with Barrett's esophagus. MATERIALS AND METHODS: 17 patients with histologically verified Barrett's esophagus undergoing acid-suppressive therapy were examined. All patients underwent 24-hours pH-impedance and high-resolution esophageal manometry. RESULTS: According to daily pH-impedance, group 1 consisted of 11 patients with an adequate response to antisecretory therapy, group 2 6 patients with insufficient effectiveness of antisecretory therapy, 5 of whom had no clinical manifestations. The total number of reflux averaged 52 and 91, respectively, in groups 1 and 2. The average number of acid reflux in group 1 was 4.36, in group 2 40.5. The average number of non-acid reflux prevailed in patients of group 2, averaging 58, compared with group 1, where the average was 47. According to the results of high-resolution esophageal manometry, when assessing the structure and function of the esophageal-gastric junction, violations were detected in 6 out of 17 patients. Disorders of the motor function of the thoracic esophagus were detected in 10 out of 17 patients. The tone of the lower esophageal sphincter in group 1 patients was significantly higher in comparison with patients in group 2. CONCLUSION: A number of patients with Barrett's esophagus have insufficient effectiveness of antisecretory therapy, which may not manifest itself clinically and thereby increase the risk of progression. There was a tendency to more frequent motor disorders in the group with insufficient effectiveness of antisecretory therapy, as well as significantly lower tone of the lower esophageal sphincter, which may be a potential predictor of suboptimal effectiveness of antisecretory therapy.

Supragastric belching in Japan: lower prevalence and relevance for management of gastroesophageal reflux disease compared to United Kingdom.

BACKGROUND: Supragastric belching (SGB) may play a role in the pathophysiology of proton pump inhibitors (PPIs)-refractoriness in gastroesophageal reflux disease (GERD). SGB may be present in up to 40% of reflux symptoms in PPI-refractory GERD. Most reports on SGB have come from Western countries, and little is known about the prevalence and relevance of SGB in Asian refractory GERD patients. This study aimed at comparing the role of SGB in GERD patients in Japan and the UK. METHODS: We re-analyzed impedance-pH monitoring tracings from patients who were referred to tertiary centers in Japan and the UK due to PPI-refractory reflux symptoms. The prevalence of excessive SGB and the impact of SGB on reflux symptoms were compared between the two countries. RESULTS: Impedance-pH tracings from124 Japanese and 83 British patients were re-analyzed. Japanese patients were significantly younger and had smaller body mass index than the British (P < 0.001). Japanese patients had significantly lower prevalence of excessive SGB (18.5%) than the UK (36.1%) irrespective of reflux phenotype (P = 0.006). Logistic regression analysis showed that the geographical/cultural difference was the only factor associated with the different prevalence of SGB (odds ratio; 2.91, 95% CI 1.09-7.73, P = 0.032). SGB were related to typical reflux symptoms very rarely in Japan [0% (0-4.9)] compared to the UK [35% (0-54.1)] (P = 0.071). CONCLUSIONS: The prevalence of SGB and their impact on reflux symptoms is significantly lower in Japan compared to the UK. The difference is not related to reflux parameters but might come from ethnic/cultural factors to be further characterized.

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.

Assessment and Management of Gastroesophageal Reflux in The Newborn.

Gastroesophageal reflux is the involuntary retrograde passage of gastric contents into the esophagus with or without regurgitation and is considered a normal physiologic process, occurring daily in greater than one-third of all infants. Gastroesophageal reflux disease (GERD) is pathologic reflux associated with poor weight gain, irritability, dysphagia and often requires evaluation and treatment. No gold-standard testing for GERD exists. Measurements made by pH probe or multichannel intraesophageal impedance may provide insight into the quantity and character of reflux. Those events do not correlate well with clinical symptoms. Most cases of GERD can be treated conservatively with alterations in the infant's environment and/or feeding pattern. Proton pump inhibitors remain the mainstay for pharmacotherapy of GERD, although these have been associated with increased rates of infection, especially in the preterm population. Neonatal GERD remains a difficult entity to define and manage, and additional studies to aid in the clinical diagnosis and management are needed. [Pediatr Ann. 2020;49(2):e77-e81.].

Practice patterns of reflux medication prescriptions in otolaryngology compared to other specialties.

OBJECTIVES/HYPOTHESIS: To describe the trends in proton pump inhibitor (PPI) prescription rates and durations and compare them to those of H2-receptor antagonists (H2RAs) between 2013 and 2016 in otolaryngology, gastroenterology, and family practice, following the increasing publications on PPI adverse effects and inappropriate prescribing. STUDY DESIGN: Retrospective review of publicly available Medicare Part D prescribing data. METHODS: PPI and H2RA prescription and beneficiary data were obtained through the Centers for Medicare and Medicaid Services website. For prescription rates, 30-day fill counts were analyzed nationally and regionally per 10,000 Medicare members. Days supply per beneficiary was examined to show average prescription durations. Results were compared between otolaryngology, gastroenterology, and family practice. Medication-related economic burden per year was calculated based on reported drug cost. RESULTS: From 2013 to 2016, PPI 30-day fill counts remained stable, whereas H2RA prescription rates increased by up to 62% per 10,000 Medicare beneficiaries. The South consistently prescribed two to three times as much antireflux medication as the lowest prescribing region over time and across all three specialties. The days supply per beneficiary remained stable and ranged from an average of 128 to 203 days depending on the specialty. Antireflux medication-related healthcare cost decreased steadily. CONCLUSIONS: Despite numerous publications describing a multitude of adverse events and inappropriate prescribing patterns of PPIs in the past decade, prescription rates and durations per beneficiary have remained stable in the fields of otolaryngology, gastroenterology, and family practice. Additionally, H2RA prescriptions have increased from 2013 to 2016. LEVEL OF EVIDENCE: NA Laryngoscope, 130:321-327, 2020.

Secondary patents: innovator and generic strategies.

The global pharmaceutical industry consists of innovators and generics. Innovators focus on drug discovery, and bring new drugs into the marketplace after filing the new drug applications. In contrast, the generics enter the market by making a bioequivalent product by filing abbreviated new drug applications. In order to maximize their returns on R&D and maintain market share, the innovators introduce a wide range of drug products based on the same 'new molecular entity' and protect them against competition by filing what the industry term as secondary patents. The patents of four innovator viz., AstraZeneca, Takeda, Eisai and Wyeth related to the gastroesophageal reflux disease drugs and how their new molecular entity patents overcame the nonobviousness criteria is analyzed and studied in detail.

Cost-utility analysis of a 'vonoprazan-first' strategy versus 'esomeprazole- or rabeprazole-first' strategy in GERD.

BACKGROUND: Gastroesophageal reflux disease (GERD) can be treated using a vonoprazan-first strategy (first-line treatment with vonoprazan), or esomeprazole-first/rabeprazole-first strategies (first-line treatment with proton-pump inhibitors [PPIs], esomeprazole/rabeprazole, followed by a switch to vonoprazan). This cost-utility analysis used long-term simulation modeling to evaluate the cost-effectiveness of a vonoprazan-first strategy compared with the esomeprazole-first and rabeprazole-first strategies. METHODS: A Markov simulation model was developed to evaluate the cost-effectiveness of vonoprazan-first, esomeprazole-first, and rabeprazole-first strategies, comprising healing and maintenance therapies, over 5 years (4-week cycles). Healing therapy began with the administration of a normal dose of drug per real-world practice. If patients were not healed endoscopically, either a longer duration of healing therapy was provided (vonoprazan), the dose was increased (rabeprazole), or patients were switched to vonoprazan (immediately for esomeprazole, and after dose-escalation for rabeprazole, respectively). Healed patients received maintenance (lower/same dose as healing therapy). Recurrence resulted in re-challenge with healing therapy. Transition probabilities were derived from the results of indirect comparisons (network meta-analysis) and costs calculated from the Japanese payer perspective. Outcomes were defined as quality-adjusted life years (QALYs), with utilities based on published values. RESULTS: Expected costs of the vonoprazan-, esomeprazole-, and rabeprazole-first strategies were ¥36,194, ¥76,719, and ¥41,105, respectively, over 5 years. QALY gains for vonoprazan-first strategy versus the esomeprazole- and rabeprazole-first strategies were 0.014 and 0.003, respectively. Both estimated incremental cost-effectiveness ratios were dominant and robust to two sensitivity analyses. CONCLUSIONS: Vonoprazan-first strategy increased QALYs and appeared to be cost-effective for GERD patients compared with the esomeprazole- or rabeprazole-first strategies.

Vonoprazan versus Lansoprazole for the Initial Treatment of Reflux Esophagitis: A Cost-effectiveness Analysis in Japan.

Objective Gastroesophageal reflux disease (GERD) is a highly prevalent disorder that negatively affects patients' quality of life and reduces their work productivity. The medical expenses associated with the treatment of GERD are the highest among all digestive diseases. Current guidelines recommend the administration of a standard dose of proton pump inhibitor (PPI) for eight weeks as an initial GERD treatment. However, there is growing concern regarding the safety of PPI treatment. Recently, a novel potassium-competitive acid blocker (P-CAB), vonoprazan (VPZ), was approved for the treatment of reflux esophagitis in Japan and may provide clinical benefits in GERD treatment. This study was conducted to evaluate the cost-effectiveness of a P-CAB, VPZ vs. a PPI, lansoprazole (LPZ), for the acute medical treatment of reflux esophagitis. Methods A clinical decision analysis was performed using a Markov chain approach to compare VPZ to LPZ in the acute treatment of reflux esophagitis in Japan. Results The P-CAB strategy was superior to the PPI strategy in terms of cost-effectiveness (direct cost per patient to achieve clinical success) and the number of days for which medication was required. Sensitivity analyses revealed that this superiority was robust within the plausible range of probabilities. This remained true even when the healing rates in cases of mild esophagitis were applied. Conclusion The P-CAB strategy was consistently superior to the conventional PPI strategy using the original LPZ in terms of cost-effectiveness and the number of days for which medication was required. Thus, VPZ appears to be the drug of choice for the acute medical treatment of reflux esophagitis.

The concomitant use of tyrosine kinase inhibitors and proton pump inhibitors: Prevalence, predictors, and impact on survival and discontinuation of therapy in older adults with cancer.

BACKGROUND: The concomitant use of tyrosine kinase inhibitors (TKIs) and proton pump inhibitors (PPIs) is a significant concern because of potential drug-drug interaction that reduces TKI absorption, thus potentially reducing the effectiveness of TKIs. The objective of this study was to evaluate the prevalence and predictors of concomitant TKI-PPI receipt and its impact on survival and therapy discontinuation in older adults with cancer. METHODS: This retrospective study used linked Surveillance, Epidemiology, and End Results-Medicare data for the years 2007 through 2012. In total, 12,538 patients with lung cancer, renal cell cancer, chronic myelogenous leukemia, liver cancer, or pancreatic cancer were included. The primary exposure variable was concomitant receipt of TKI-PPI, defined as at least 30 days of PPI use in the first 90 days from the start of the TKI (exposure period). The outcomes measured were overall survival and discontinuation of therapy in 90 days and 1 year after the end of the exposure period. Cox proportional-hazards regression with inverse probability of treatment weighting was used to evaluate the association between exposure and outcome. RESULTS: The overall prevalence of TKI-PPI receipt was 22.7%. Predictors that were associated with increased use included polypharmacy and prior PPI receipt. TKI-PPI use decreased survival in 90 days (hazard ratio, 1.16; 95% confidence interval, 1.05-1.28) and in 1 year (hazard ratio, 1.10; 95% confidence interval, 1.04-1.18) but was not associated with discontinuation. CONCLUSIONS: Nearly 1 in 4 older adults with cancer who receive TKIs also receive PPIs concomitantly, and concomitant use is associated with an increased risk of death. Concerted efforts to manage medications are needed to identify and reduce the receipt of PPIs when TKIs are initiated.

Trajectory assessment is useful when day-to-day esophageal acid exposure varies in prolonged wireless pH monitoring.

Acid exposure time commonly varies from day-to-day in prolonged wireless pH monitoring. Thus, diagnosis based on the number of days with abnormal acid burden may be misleading or inconclusive. We hypothesize that assessing longitudinal patterns of acid exposure may be diagnostically useful. Therefore, this study aims to describe acid exposure trajectories and evaluate agreement between identified trajectory patterns and conventional grouping. In this retrospective cohort study, we assessed patients with nonresponse to proton pump inhibitor therapy who underwent wireless pH monitoring (≥72 h) off therapy between August 2010 and September 2016. The primary outcome was esophageal acid exposure time. Subjects were grouped as 0, 1, 2, and 3+ days positive based on number of days with an acid exposure time >5.0%. Latent class group-based mixture model identified distinct longitudinal acid exposure trajectory groups. Of 212 subjects included 44%, 18%, 14%, and 24% had 0, 1, 2, 3+ days positive, respectively. Group-based modeling identified three significantly stable acid exposure trajectories: low (64%), middle (28%), and high (8%). Trajectory grouping and days positive grouping agreed substantially (weighted K 0.69; 95% CI: 0.63-0.76). Trajectory grouping identified 62% of subjects with conventionally inconclusive studies (one or two days positive) into the low trajectory. Agreement between trajectory groups when using three versus four days of monitoring was substantial (K 0.70; CI: 0.61-0.78). In summary, we found that patients with nonresponse to proton pump inhibitors follow three acid exposure trajectories over prolonged pH-monitoring periods: low, middle, and high. Compared to conventional day positive grouping, the trajectory modeling identified the majority of inconclusive days positive into the low trajectory group. Analyzing prolonged wireless pH data according to trajectories may be a complimentary method to conventional grouping, and may increase precision and accuracy in identifying acid burden.