Economic and health impacts of Helicobacter pylori eradication strategy for the treatment of peptic ulcer disease: A cost-effectiveness analysis.

BACKGROUND: Most peptic ulcer cases are associated with Helicobacter pylori (H. pylori) infection or the use of nonsteroidal anti-inflammatory drugs (NSAIDs). H. pylori eradication therapy is recommended for the treatment of H. pylori-positive peptic ulcers. We aimed to assess and validate the cumulative economic and health effects of H. pylori eradication strategy for the treatment of peptic ulcers compared with PPI therapy strategy. MATERIALS AND METHODS: We developed a cohort state-transition model for H. pylori eradication strategy and PPI therapy strategy over a lifetime horizon from a healthcare payer perspective. We targeted two hypothetical cohorts of H. pylori-positive patients with gastric and duodenal ulcers aged 20, 30, 40, 50, 60, 70, and 80. The main outcomes were costs, quality-adjusted life-years (QALYs), life expectancy life-years (LYs), incremental cost-effectiveness ratios, ulcer recurrence cases, and ulcer-associated deaths. One-way and probabilistic sensitivity analyses were conducted to assess the impact of uncertainty. RESULTS: In the base-case analysis, H. pylori eradication strategy was less costly with greater benefits than PPI therapy strategy in all age groups. Cost-effectiveness was not sensitive to any variables in all age groups. Sensitivity analyses showed strong robustness of the results. From 2000 to 2020, H. pylori eradication strategy saved US$14.07 billion over a lifetime, increased 8.65 million QALYs and 1.23 million LYs over a lifetime, and prevented 551,298 ulcer recurrence cases and 59,465 ulcer-associated deaths, compared with PPI therapy strategy. CONCLUSIONS: H. pylori eradication strategy not only has contributed significantly to preventing ulcer recurrence and reducing ulcer-associated deaths but also has resulted in great cost savings. All over the world, H. pylori eradication strategy is likely to have yielded a comparable magnitude of economic and health benefits, depending on the epidemiology of H. pylori-related peptic ulcers and the healthcare environment in each country.

The effects of pantoprazole vs. placebo on 1-year outcomes, resource use and employment status in ICU patients at risk for gastrointestinal bleeding: a secondary analysis of the SUP-ICU trial.

PURPOSE: Patients in intensive care units (ICUs) are at risk of stress-related gastrointestinal (GI) bleeding and stress ulcer prophylaxis (SUP), including proton pump inhibitors, is widely used in the attempt to prevent this. In this secondary analysis of Stress Ulcer Prophylaxis in Intensive Care Unit (SUP-ICU) trial, we assessed 1-year outcomes in the pantoprazole vs. placebo groups. METHODS: In the SUP-ICU trial, 3298 acutely admitted ICU patients at risk of GI bleeding were randomly allocated, stratified for site, to pantoprazole or placebo. In this secondary analysis, we assessed clinically important GI bleedings in ICU and 1-year mortality, health care resource use (e.g. readmission with GI bleeding, use of home care and general practitioner), health care costs, and employment status for the Danish participants using registry data. RESULTS: Among the 2099 Danish participants, 2092 had data in the registries; 1045 allocated to pantoprazole and 1047 to placebo. The number of clinically important GI bleedings in ICU was 1.9 percentage points [95% CI 0.3-3.5] lower in the pantoprazole group vs. the placebo group, but none of the 1-year outcomes differed statistically significantly between groups, including total health care costs (€1954 [- 2992 to 6899]), readmission with GI bleeding (- 0.005 admissions [- 0.016 to 0.005]), 1-year mortality (- 0.013 percentage points [- 0.051 to 0.026]), and employment (- 0.178 weeks [- 0.390 to 0.034]). CONCLUSION: Among ICU patients at risk of GI bleeding, pantoprazole reduced clinically important GI bleeding in ICU, but this did not translate into a reduction in 1-year mortality, health care resource use or improvements in employment status.

Cost-effectiveness and clinical outcomes of intermittent/continuous proton pump inhibitors infusion in high bleeding risk of ulcers: A retrospective observational cohort study.

ABSTRACT: The purpose of this study was to evaluate the clinical outcomes, including patient prognosis and medication expense, of proton pump inhibitors administered by high-dose continuous infusion (HDC, 80 mg loading dose, then 8 mg/h for 72 hours) or non-high-dose intermittent infusion (NHDI, 40 mg qd or 40 mg q12 h, for 3 days) regimens in high-risk patients with bleeding peptic ulcers.In this retrospective cohort study, patients with peptic ulcers and endoscopic hemostasis between January, 2013 and December, 2015 were included. The primary endpoints were rebleeding and mortality rates within 7 days. The secondary endpoints were length of stay (LOS), transfusion units of packed red blood cells (PRBCs), and the number needed to treat.A total of 335 patients met the inclusion criteria during the 3-year follow-up period. The cumulative incidence of rebleeding within 7 days was 20.4% and 11.2% in the HDC and NHDI groups, respectively, with a significant difference (P = .021). The mortality rate was 12.1% and 7.3% in the HDC and NHDI groups, respectively, with no significant difference (P = .136). Univariate Cox proportional hazards model analysis showed that the risk of rebleeding within 7 days in the HDC group was higher than that in the NHDI group. The hazard ratio for HDC vs. NHDI was 1.93 (P = .021). There were significant differences in LOS (P = .034) and PRBC units (P = .005) for risk of rebleeding within 7 days, as well as in transfusion units of PRBCs for mortality rate analysis (p < 0.001), between the HDC and NHDI groups. The results showed that the NHDI regimen could reduce the risk of rebleeding within 7 days in 1 of 11 patients (number needed to treat = 11) and could reduce medication cost by US$ 400 to 800.The NHDI regimen showed a lower risk of rebleeding within 7 days, shorter LOS, and fewer PRBC units than that of the HDC regimen. Receiving NHDI has better cost-effective outcomes than that of HDC for patients with high-risk bleeding peptic ulcers.

Clinical and economic impact of "triple therapy" for Helicobacter pylori eradication on peptic ulcer disease in Australia.

BACKGROUND: Helicobacter pylori infection has had a major impact on the global health of billions of people. Triple therapy was extensively used in Australia by 1986 for H pylori eradication after its discovery in 1984 and was critical in reducing the morbidity and mortality associated with this infection. AIMS: This study analyzed hospital admission, mortality, and therapeutic data to determine the economic and clinical impact that antibiotic triple therapy had on peptic ulcer disease (PUD) in Australia. METHODS: An analysis of indirect and direct cost-savings in Australia between 1990 and 2015 associated with triple therapy and the impact on PUD mortality and hospital admissions. RESULTS: The direct and indirect impacts of PUD treated by triple therapy between 1990 and 2015 suggest that triple therapy is likely to have prevented 18 665 deaths, and saved 258 887 life years and 33 776 productive life years. The total savings, over the 26-year period, including direct and indirect costs, are calculated to be $10.03 billion, equating to an average annual saving of $393.419 million. CONCLUSIONS: This study highlights the enormous benefits to Australia's health care of the discovery of triple therapy, a relatively low-cost antibiotic regimen which brought considerable savings via the reduction in morbidity (hospital admissions) and mortality related to PUD. It is likely that benefits of similar scale occurred internationally.

Proton pump inhibitor use and risk of hip fracture in patients with type 2 diabetes.

Type 2 diabetes mellitus (T2DM) is associated with a high rate of comorbidity, including osteoporosis and peptic ulcers. Proton pump inhibitors (PPIs) are a group of acid-suppressing drugs commonly used for treating peptic ulcers. However, observational studies have reported an association between PPI therapy and osteoporotic fractures. This study investigated the association between PPI use and hip fracture (HFx) among patients with T2DM. We conducted this population-based propensity-matched retrospective cohort study using the National Health Insurance Research Database in Taiwan. Patients newly diagnosed with T2DM between 2000 and 2008 were identified. After excluding those who previously used PPIs or suffered HFx, 398,885 patients were recruited (44,341 PPI users; 354,544 non-users). HFx risk data from 2000 to 2013 were collected to calculate the cumulative rate of HFx in these two groups. Sensitivity analyses were conducted to evaluate the effects of PPI dose. After propensity score matching of 1:4, 44,431 and 177,364 patients were assigned to the PPI user and non-user groups, respectively. PPI user group showed an increased risk of HFx with an adjusted hazard ratio of 1.41 (95% CI 1.29-1.54) without dose-response relationship. Thus, there is an increased risk of HFx in patients with T2DM receiving long-term PPI treatment.

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.

A Comprehensive Review on the Screening Models for the Pharmacological Assessment of Antiulcer Drugs.

BACKGROUND: Due to inappropriate diet, smoking, alcohol consumption, regular use of drugs like NSAIDs and sedentary lifestyle, one may feel upper abdominal pain which may be the predictor of the gastrointestinal disorder called Peptic Ulcer. When an imbalance occurs between the defensive factor and aggressive factor of the stomach, ulcer formation in the esophageal lining, stomach, or duodenum takes place. This leads to the formation of small sores that cause pain. Another condition that synergizes the abdominal pain is vomiting materials which look like coffee grounds, blood in the stool, black or tarry stools. This pain may increase after lunch or dinner. This problem persists, that often leads to the gastroenterologist's consultation. OBJECTIVE: There are many antiulcer screening models present for the determination of antiulcer activity of the drug molecule. The main objective of this study is to find which model is best for the determination of antiulcer activity. METHODS: A literature search was conducted on the databases namely Science direct and PubMed with the help of different keywords such as "Anti-ulcer", "In-vitro models" and "In-vivo models". The search was customized by applying the appropriate filters so as to get the most relevant articles to meet the objective of this review article. RESULT: There are different research and review papers based on the antiulcer screening models for the determination of antiulcer activity of new drug molecules. CONCLUSION: On the basis of our study, we found some useful models for the antiulcer activity of drugs and suggested that, if we use in-vitro and in-vivo methods together, then we may obtain the most relevant result in our research area.

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.

Safety assessment of omeprazole use: a review

ABSTRACT BACKGROUND: Risks regarding hospital admission due to adverse drug reactions and drug interactions from use of omeprazole have been reported. The question guiding the present review was "Which adverse events occur in patients using omeprazole in a Food and Drug Administration-approved and/or off-label manner?" It was also proposed to evaluate the safety of use of omeprazole. DESIGN AND SETTING: Qualitative narrative review with critical evaluation, in a public university. METHODS: The PubMed, SCOPUS, LILACS, SciELO, EMBASE and EBSCO databases were searched on July 31, 2018. Studies evaluating adverse events were screened. RESULTS: 72 articles were included, among which 58 reported on adverse drug events (47, adverse drug reactions; 5, drug interactions; and 6, situations of ineffectiveness). 28 adverse drug reactions not described in compendia and drug leaflets were described in these studies: myocardial infarction (6); stroke (2); spontaneous abortion (1); proliferative changes (1); chills (1); heart failure (1); thrombosis (2); and dementia (1), among others. Severe adverse reactions, for instance cardiac problems, Steven-Johnson syndrome and proliferative changes, were identified. The antiplatelet effects of drugs such as clopidogrel, in patients who underwent heart-related surgery, increased the risk of developing cardiac problems, such as cardiovascular death, myocardial infarction and stroke. In newly transplanted patients, decreased absorption of mycophenolate mofetil occurred, thus leading to rejection of transplanted organs. CONCLUSION: Use of omeprazole should be monitored primarily in patients with heart disorders using antiplatelet agents concomitantly, and in newly transplanted patients using mycophenolic acid, in order to avoid serious adverse reactions.

Do recent reports about the adverse effects of proton pump inhibitors change providers' prescription practice?

Proton pump inhibitors (PPI) are utilized for a variety of indications, including treatment of gastroesophageal reflux disease, peptic ulcer disease, and prevention of gastrointestinal (GI) bleeding. Several studies have documented an increasing prevalence of inappropriate PPI use. Furthermore, recent media reports have highlighted new research data suggesting a possible association between chronic PPI use and several adverse medical outcomes, leading to frequent patient inquiries about these associations. Thus, providers face the challenge of counseling patients about the balance of risks and benefits related to PPI use. We aimed to explore providers' knowledge and attitudes toward reported adverse effects of PPI use and compare providers' prescription practices. A comprehensive, non-incentivized electronic survey was sent to all providers (residents, fellows, advanced practice providers, and consultants across 8 internal medicine specialties) at our tertiary academic medical center. The survey contained 21 questions covering provider demographics and responses to challenging clinical scenarios dealing with PPI use. Chi-square was used to compare responses from providers. The survey was distributed to 254 providers, of which 94 (24 GI and 70 non-GI) completed the survey (37% response rate). Among those 94 providers, 48 were consultants, 17 were advanced practice providers, and 29 were trainees. Non-GI providers included cardiology, pulmonary, endocrinology, family medicine, general internal medicine, hematology/oncology, and nephrology. Over half of the providers (51 [54%]) described their practice as outpatient setting, 29 (31%) providers defined their practice as a mixed setting (inpatient and outpatient), while 14 (15%) designated it as inpatient only. Nineteen (80%) GI providers and 48 (69%) non-GI providers discussed the risks and benefits with patients (P = 0.64). Fifteen (63%) GI providers and 33 (47%) non-GI providers indicated that recent reports changed their practice (P = 0.49). More GI providers (5 [21%]) lowered the dose of PPI compared with non-GI (1[1%]) (P = 0.004); 18 (26%) of non-GI and 3 (13%) of GI providers discontinued PPI and substituted it with a histamine 2 (H2) blocker (P = 0.29). A larger but nonsignificant percentage of trainees (8 [28%]) switched PPI to H2 blockers compared with consultants (8 [17%]; P = 0.39). Six (25%) of GI providers and 14 (20%) of non-GI providers were concerned about Clostridium difficile infection (P = 0.58). Twenty-four (34%) of the non-GI were worried about kidney diseases compared with 3 (13%) of the GI providers (P = 0.1). Ten (21%) consultants were concerned about risk of osteoporosis compared with 3 (10%) trainees (P = 0.38), while 8 (28%) trainees were worried about the risk of C. difficile infection compared with 10 (21%) consultants (P = 0.69). Most providers (85 [90%]) agreed that educational activities would be helpful to address these challenges. More GI providers lowered the dose of PPI compared with non-GI; non-GI providers were more likely to discontinue PPI and substitute it with an H2 blocker. Educating patients and providers about potential adverse effects of PPI is imperative.

Benefit of an electronic medical record-based alarm in the optimization of stress ulcer prophylaxis.

BACKGROUND: The use of stress ulcer prophylaxis (SUP) has risen in recent years, even in patients without a clear indication for therapy. AIM: To evaluate the efficacy of an electronic medical record (EMR)-based alarm to improve appropriate SUP use in hospitalized patients. METHODS: We conducted an uncontrolled before-after study comparing SUP prescription in intensive care unit (ICU) patients and non-ICU patients, before and after the implementation of an EMR-based alarm that provided the correct indications for SUP. RESULTS: 1627 patients in the pre-intervention and 1513 patients in the post-intervention cohorts were included. The EMR-based alarm improved appropriate (49.6% vs. 66.6%, p<0.001) and reduced inappropriate SUP use (50.4% vs. 33.3%, p<0.001) in ICU patients only. These differences were related to the optimization of SUP in low risk patients. There was no difference in overt gastrointestinal bleeding between the two cohorts. Unjustified costs related to SUP were reduced by a third after EMR-based alarm use. CONCLUSIONS: The use of an EMR-based alarm improved appropriate and reduced inappropriate use of SUP in ICU patients. This benefit was limited to optimization in low risk patients and associated with a decrease in SUP costs.

The appropriate use of proton-pump inhibitors.

The introduction of proton-pump inhibitors (PPIs) into clinical practice since about thirty years has greatly improved our therapeutic approach to acid-related diseases for their well recognized efficacy and safety. Accordingly, the role of surgery has been enormously reduced in this field. The main indications for PPI use are universally acknowledged by many scientific societies and are the following: treatment of gastroesophageal reflux disease in its various forms and complications, eradication of H. pylori infection in combination with two or more antibiotics, therapy of H. pylori-negative peptic ulcers, healing and prevention of NSAID-associated gastric ulcers, co-therapy with endoscopic procedures to control upper digestive bleeding and medical treatment of Zollinger-Ellison Syndrome. Despite the above well-defined indications, however, the use of PPIs continues to grow every year in both Western and Eastern countries and this phenomenon poses serious queries about the appropriate prescription of these drugs worldwide. In fact, the endless expansion of PPI market has created important problems for many regulatory authorities for two relevant features: the progressive and irreversible increase of the costs of therapy with this class of drugs and the greater potential harms for the patients. So, there is the need for a reappraisal of PPI correct indications for both general practitioners and various specialists in order to re-establish a correct use of these effective drugs in daily clinical practice, according to the best evidence-based guidelines.

Stress ulcer prophylaxis in intensive care unit patients receiving enteral nutrition: a systematic review and meta-analysis.

BACKGROUND: Pharmacologic stress ulcer prophylaxis (SUP) is recommended in critically ill patients with high risk of stress-related gastrointestinal (GI) bleeding. However, as to patients receiving enteral feeding, the preventive effect of SUP is not well-known. Therefore, we performed a meta-analysis of randomized controlled trials (RCTs) to evaluate the effect of pharmacologic SUP in enterally fed patients on stress-related GI bleeding and other clinical outcomes. METHODS: We searched PubMed, Embase, and the Cochrane database from inception through 30 Sep 2017. Eligible trials were RCTs comparing pharmacologic SUP to either placebo or no prophylaxis in enterally fed patients in the ICU. Results were expressed as risk ratio (RR) and mean difference (MD) with accompanying 95% confidence interval (CI). Heterogeneity, subgroup analysis, sensitivity analysis and publication bias were explored. RESULTS: Seven studies (n = 889 patients) were included. There was no statistically significant difference in GI bleeding (RR 0.80; 95% CI, 0.49 to 1.31, p = 0.37) between groups. This finding was confirmed by further subgroup analyses and sensitivity analysis. In addition, SUP had no effect on overall mortality (RR 1.21; 95% CI, 0.94 to 1.56, p = 0.14), Clostridium difficile infection (RR 0.89; 95% CI, 0.25 to 3.19, p = 0.86), length of stay in the ICU (MD 0.04 days; 95% CI, -0.79 to 0.87, p = 0.92), duration of mechanical ventilation (MD -0.38 days; 95% CI, -1.48 to 0.72, p = 0.50), but was associated with an increased risk of hospital-acquired pneumonia (RR 1.53; 95% CI, 1.04 to 2.27; p = 0.03). CONCLUSIONS: Our results suggested that in patients receiving enteral feeding, pharmacologic SUP is not beneficial and combined interventions may even increase the risk of nosocomial pneumonia.

Safety assessment of omeprazole use: a review.

BACKGROUND: Risks regarding hospital admission due to adverse drug reactions and drug interactions from use of omeprazole have been reported. The question guiding the present review was "Which adverse events occur in patients using omeprazole in a Food and Drug Administration-approved and/or off-label manner?" It was also proposed to evaluate the safety of use of omeprazole. DESIGN AND SETTING: Qualitative narrative review with critical evaluation, in a public university. METHODS: The PubMed, SCOPUS, LILACS, SciELO, EMBASE and EBSCO databases were searched on July 31, 2018. Studies evaluating adverse events were screened. RESULTS: 72 articles were included, among which 58 reported on adverse drug events (47, adverse drug reactions; 5, drug interactions; and 6, situations of ineffectiveness). 28 adverse drug reactions not described in compendia and drug leaflets were described in these studies: myocardial infarction (6); stroke (2); spontaneous abortion (1); proliferative changes (1); chills (1); heart failure (1); thrombosis (2); and dementia (1), among others. Severe adverse reactions, for instance cardiac problems, Steven-Johnson syndrome and proliferative changes, were identified. The antiplatelet effects of drugs such as clopidogrel, in patients who underwent heart-related surgery, increased the risk of developing cardiac problems, such as cardiovascular death, myocardial infarction and stroke. In newly transplanted patients, decreased absorption of mycophenolate mofetil occurred, thus leading to rejection of transplanted organs. CONCLUSION: Use of omeprazole should be monitored primarily in patients with heart disorders using antiplatelet agents concomitantly, and in newly transplanted patients using mycophenolic acid, in order to avoid serious adverse reactions.

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.

Impact of potential inappropriate NSAIDs use in chronic pain.

Pain remains one of the main reasons for medical consultation worldwide: moderate- to severe-intensity pain occurs in 19% of adult Europeans, seriously affecting the quality of their social and working lives. Nonsteroidal anti-inflammatory drugs (NSAIDs) are not recommended for long-term use and a careful surveillance to monitor for toxicity and efficacy is critical. This study aims to assess: 1) the pattern of use of NSAIDs and opioids in a population covered by a cloud-based pharmacovigilance surveillance system; and 2) potential inappropriate use. A retrospective 18-months systematic analysis on patients' pain treatment was performed. The primary endpoint was evaluating the prevalence of NSAIDs and opioids use and the duration of therapy regimen. The secondary endpoint was to investigate the prevalence of NSAIDs taken for >21 consecutive days concomitant with drugs for peptic ulcer and gastroesophageal reflux disease (GORD) or antiplatelet drugs. The yearly cost for individual users of concomitant NSAIDs for more than 21 consecutive days and of GORD medications has been estimated. A total of 3,050 subjects with chronic pain were enrolled; 97% of them took NSAIDs for >21 consecutive days; about one-fourth of these users also received drugs for peptic ulcer and GORD (Anatomical Therapeutic Chemical code A02B). The yearly cost foran individual who uses NSAIDs for >21 consecutive days as well as concomitant GORD medications is 61.23 euros. In total, 238 subjects (8%) using NSAIDs for >21 days also received one antiplatelet agent. About 11% of subjects received opioids at least once and only 2% of them carried on the therapy for more than 90 consecutive days. In evaluating the escalation in dosage as a proxy of dependence risk, this study shows no dosage escalation in our cohort of chronic pain population - that is to say we show no risk of dependence.

[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.

Helicobacter pylori: friend or foe?

Helicobacter pylori (H. pylori) is a Gram-negative spiral bacterium that is present in nearly half the world's population. It is the major cause of peptic ulcer disease and a recognized cause of gastric carcinoma. In addition, it is linked to non-ulcer dyspepsia, vitamin B12 deficiency, iron-deficient anemia and immune thrombocytopenic purpura. These conditions are indications for testing and treatment according to current guidelines. An additional indication according to the guidelines is "anyone with a fear of gastric cancer" which results in nearly every infected person being eligible for eradication treatment. There may be beneficial effects of H. pylori in humans, including protection from gastroesophageal reflux disease and esophageal adenocarcinoma. In addition, universal treatment will be extremely expensive (more than $32 billion in the United States), may expose the patients to adverse effects such as anaphylaxis and Clostridium difficile infection, as well as contributing to antibiotic resistance. There may also be an as yet uncertain effect on the fecal microbiome. There is a need for robust clinical data to assist in decision-making regarding treatment of H. pylori infection.

Gastroprotective and anti-Helicobacter pylori potential of herbal formula HZJW: safety and efficacy assessment.

BACKGROUND: A traditional Chinese Medicine (TCM) formula, HZJW, has been applied in clinics in China for gastrointestinal disorders. However, the therapeutic mechanism underlying its efficacy and safety remained to be defined. The present investigation was undertaken to evaluate the formula HZJW for its gastroprotective potential, possible effect on Helicobacter pylori along with safety to justify its anti-ulcer action and safe clinical application. METHODS: The gastroduodenal cytoprotective potential was evaluated in rodent experimental models (HCl/Ethanol and NSAID-induced ulcer protocols). The anti-H. pylori property was assessed by agar dilution assay in vitro and analysis in vivo including rapid urease test, immunogold test and histopathology. For toxicity assessment, acute toxicity study was performed according to fixed dose procedure with a single oral administration of HZJW to mice. In the oral chronic toxicity, rats (80 males, 80 females) were administrated HZJW orally in 0, 1000, 2500, or 5000 mg/kg/day doses for 26 weeks (n = 40/group of each sex). Clinical signs, mortality, body weights, feed consumption, ophthalmology, hematology, serum biochemistry, gross findings, organ weights and histopathology were examined at the end of the 13- and 26-week dosing period, as well as after the 4-week recovery period. RESULTS: In the HCl/Ethanol-induced ulcer model, it was observed that oral administration with HZJW (260, 520 and 1040 mg/kg) and ranitidine (250 mg/kg) significantly reduced the ulcerative lesion index (116.70 ± 36.4, 102.20 ± 18.20, 84.10 ± 12.1 and 73.70 ± 16.70) in a dose-dependent manner, respectively, with respect to control group (134.10 ± 31.69). Significant inhibition was also observed in ulcerative index from aspirin-induced ulcer model, with decreases of 35.40 ± 5.93, 31.30 ± 8.08, 26.80 ± 8.27and 20.40 ± 6.93 for the groups treated with HZJW and ranitidine, in parallel to controls (41.60 ± 10.80). On the other hand, treatment with HZJW efficaciously eradicated H. pylori in infected mice in rapid urease test (RUT) and immunogold antibody assay, as further confirmed by reduction of H. pylori presence in histopathological analysis. In the in vitro assay, MICs for HZJW and amoxicillin (positive control) were 125 and 0.12 µg/mL respectively. The LD50 of HZJW was over 18.0 g/kg for mice. No drug-induced abnormalities were found as clinical signs, body weight, food consumption, hematology, blood biochemistry, ophthalmology and histopathology results across three doses. No target organ was identified. The No Observed Adverse Effect Level (NOAEL) of HZJW was determined to be 5,000 mg/kg/day for both sexes, a dose that was equivalent to 50 times of human dose. CONCLUSIONS: These results suggested the efficacy and safety of HZJW in healing peptic ulcer and combating H. pylori, which corroborated their conventional indications and contributed to their antiulcer pharmacological validation, lending more credence to its clinical application for the traditional treatment of stomach complaints symptomatic of peptic ulcer disease (PUD). HZJW might have the potential for further development as a safe and effective alternative/complementary to conventional medication in treating gastrointestinal (GI) disorders.

Cost-effectiveness analysis: stress ulcer bleeding prophylaxis with proton pump inhibitors, H2 receptor antagonists.

OBJECTIVES: Proton pump inhibitors (PPIs) and H2-receptor antagonists (H2RAs) present varying pharmacological efficacy in preventing stress ulcer bleeding (SUB) in intensive care units. The literature also reports disparate rates of ventilator-assisted pneumonia (VAP) as side effects of these treatments. We compared the cost-effectiveness of these two prophylactic pharmacological options. METHODS: We constructed a decision tree with a 60-day time horizon for patients at high risk for developing SUB, receiving either PPIs or H2RAs. For each treatment strategy, patients could be in one of three states of health: SUB, VAP, or no complication. Contemporary, clinically relevant probabilities were obtained from a broad literature search. Costs were estimated by using a representative US countrywide database. A third-party payer perspective was adopted. Cost-effectiveness and univariate and multivariate sensitivity analyses were performed. RESULTS: Probabilities of SUB and VAP were 1.3% and 10.3% for PPIs versus 6.6% and 10.3% for H2RAs, respectively. Lengths of stay and per diem costs were 24 days and US $2764 for SUB, 42 days and US $3310 for VAP, and 14 days and US $2993 for patients without complications. Average costs per no complication were US $58,700 for PPIs and US $63,920 for H2RAs. The H2RA strategy was dominated by PPIs. Sensitivity analysis showed that these findings were sensitive to VAP rates but PPIs remain cost-effective. The acceptability curve shows the stability of the probabilistic results according to varying willingness-to-pay values. CONCLUSION: PPI prophylaxis is the most efficient prophylactic strategy in patients at high risk of developing SUB when compared with using H2RAs.