Spirulina Platensis Attenuates Rebound Dyspeptic Symptoms After Proton Pump Inhibitors' Discontinuation: Phase 2 Placebo-controlled Trial.

Context: Rebound acid hypersecretion after cessation of proton pump inhibitors (PPIs) can provoke dyspeptic symptoms. The search for alternatives to minimize the dyspeptic rebound symptoms after PPI discontinuation is warranted. Spirulina platensis, a dietary supplement made from blue-green algae, might be an alternative. Objective: The study intended to assess whether Spirulina platensis, through its anti-inflammatory and analgesic properties, can minimize rebound symptoms after PPI withdrawal. Design: The research team performed a randomized, phase 2, double-blinded, placebo-controlled clinical trial. Setting: The study took place at São Vicente de Paulo Hospital (trial registry number NCT04988347) in Passo Fundo, Brazil. Participants: Participants were 45 Brazilian patients in the clinical practice of two of the research team's member between November 2010 and February 2012, who were using PPIs regularly. Interventions: Participants underwent clinical and endoscopic evaluations after a 28-day run-in phase of 40 mg/day of pantoprazole. In the absence of a large hiatal hernia, peptic ulcer, or severe reflux esophagitis, participants stopped using PPIs, and the research team randomly assigned them to receive either 1.6g/day of spirulina or of a placebo for two months, followed by clinical and endoscopic reevaluations. Outcome measures: Using an intention-to-treat analysis, the primary outcomes postintervention were dyspepsia and typical reflux symptoms, either the appearance or maintenance of symptoms of >50% from baseline. Results: The median time of continuous PPI use was 32 months. The research team excluded two participants due to large hiatal hernias. Among the remaining 43 participants, 18 received spirulina (42%), and 25 used a placebo (58%). Two months later, 12 participants who had received spirulina (67%) and 18 who had received the placebo (72%) completed the study (P = .968). Rebound dyspepsia occurred in 10 out of 18 patients treated with spirulina (55.56%) and in 22 out of 25 patients treated with placebo (88%), with relative risk=0.63, CI95% (0.41-0.98), and P = .039. Reflux symptoms postintervention occurred in 72% and 76%, with the relative risk=0.95, CI95% (0.66-1.36), and P > .05, respectively. No significant side effects occurred in either group. The findings from endoscopy and gastric histology didn't differ between groups. Conclusions: A two-month course of Spirulina platensis was able to attenuate rebound dyspepsia but not reflux symptoms after PPI discontinuation. Considering its good safety profile, spirulina might be useful to relieve dyspeptic symptoms after PPI discontinuation.

Pantoprazole and Vonoprazan Performed Well in Preventing Peptic Ulcer Recurrence in Low-Dose Aspirin Users.

BACKGROUND: Low-dose aspirin (LDA) administration is associated with an elevated risk of recurring peptic ulcer (PU) and gastrointestinal (GI) hemorrhage. AIMS: This systematic review and Bayesian network meta-analysis aimed to comprehensively assess the effectiveness of diverse medications in preventing the recurrence of PU and GI hemorrhage in patients with a history of PU receiving long-term LDA therapy. METHODS: This systematic review and network meta-analysis followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and was registered on PROSPERO (CRD42023406550). We searched relevant studies in main databases from inception to March 2023. All statistical analyses were performed using R (version 4.1.3), with the "Gemtc" (version 1.0-1) package. The pooled risk ratio (RR), corresponding 95% credible interval (95% CrI), and the surface under the cumulative ranking curve (SUCRA) were calculated. RESULTS: 11 Randomized clinical trials (RCTs) were included. The analysis underscored pantoprazole was the most efficacious for reducing the risk of PU recurrence (RR [95% CrI] = 0.02 [0, 0.28]; SUCRA: 90.76%), followed by vonoprazan (RR [95% CrI] = 0.03 [0, 0.19]; SUCRA: 86.47%), comparing with the placebo group. Pantoprazole also performed well in preventing GI hemorrhage (RR [95% CrI] = 0.01[0, 0.42]; SUCRA: 87.12%) compared with Teprenone. CONCLUSIONS: For patients with a history of PU receiving LDA, pantoprazole and vonoprazan might be the optimal choices to prevent PU recurrence and GI hemorrhage.

Safety of Intravenous Pantoprazole Sodium in Pediatric Patients Aged 1 Month to < 1 Year: A Real-World Retrospective Cohort Study.

OBJECTIVE: To estimate the incidence rates (IR) of prespecified outcomes of interest in pediatric patients (1 month to < 1 year) treated with intravenous (IV) pantoprazole using Optum's longitudinal electronic health records database (Optum Market Clarity) from the United States (US). METHODS: This real-world, non-interventional, retrospective cohort study was conducted from 01 January 2007 to 31 December 2020 in patients who received IV pantoprazole. Premature patients and those weighing < 2.36 kg were excluded. Patients were categorized based on diagnosis of gastroesophageal reflux disease (GERD) and erosive esophagitis (EE) into: Subgroup 1 (GERD and EE), Subgroup 2 (GERD and no EE), and Subgroup 3 (absence of GERD and EE). Overall IRs (per 1000 person-years [PY]) and 95% confidence intervals (CI) of outcomes were estimated (overall and subgroups) and stratified by duration of IV pantoprazole treatment (< 4 days versus ≥ 4 days). RESULTS: Of 1879 eligible patients, none were identified in Subgroup 1; 851 (45.3%) and 1028 (54.7%) patients were identified in Subgroups 2 and 3, respectively. IRs of outcomes of interest ranged from 0.0 to 742.8 per 1000 PY. IRs were highest for vomiting (742.80), diarrhea (377.77), abdominal distension (214.31), hyponatremia (204.99), and hypokalemia (203.49). IRs were comparable between Subgroups 2 and 3. For most outcomes, IRs were higher among patients treated with IV pantoprazole for ≥ 4 days versus those treated for < 4 days. CONCLUSION: These results are consistent with the known safety profile of pantoprazole and emphasize the utility of using real-world data from pediatric populations for assessment of safety outcomes.

Repurposing pantoprazole in combination with systemic therapy in advanced head and neck squamous cell carcinoma: a phase I/II randomized study.

Pantoprazole decreases the acidity of the tumor microenvironment by inhibiting proton pumps on the cancer cell. This possibly leads to increased sensitivity to cytotoxic therapy. We conducted a phase I/II randomized controlled trial in adult patients with head and neck squamous cell carcinoma (HNSCC) planned for first-line palliative chemotherapy. Patients were randomized to chemotherapy + / - intravenous (IV) pantoprazole. The primary endpoint in phase I was to determine the maximum safe dose of intravenous pantoprazole, whereas it was progression-free survival (PFS) in phase II. The dose of IV pantoprazole established in phase I was 240 mg. Between Nov'18 and Oct'20, we recruited 120 patients in phase II, 59 on pantoprazole and 61 on the standard arm. Median age was 51 years (IQR 43-60), 80% were men. Systemic therapy was IV cisplatin in 22% and oral-metronomic-chemotherapy (OMC) in 78%. Addition of pantoprazole did not prolong PFS, which was 2.2 months (95% CI 2.07-3.19) in the pantoprazole arm and 2.5 months (95% CI 2.04-3.81, HR, 1.14; 95% CI 0.78-1.66; P = 0.48) in the standard arm. Response rates were similar; pantoprazole arm 8.5%, standard arm 6.6%; P = 0.175. Overall survival was also similar; 5.6 months (95% CI 4.47-8.51) in the pantoprazole arm and 5.4 months (95% CI 3.48-8.54, HR 1.06; 95% CI 0.72-1.57; P = 0.75) in the standard arm. Grade ≥ 3 toxicities were similar. Thus, pantoprazole 240 mg IV added to systemic therapy does not improve outcomes in patients with advanced HNSCC.

EFFICACY AND SAFETY OF GEMIFLOXACIN CONTAINING TREATMENT REGIMEN IN FIRST-LINE TREATMENT OF HELICOBACTER PYLORI.

•In eradication treatment of H. pylori gemifloxacin containing triple treatment regimen was as effective as bismuth containing quadruple treatment. •Drug adverse effects were fewer and milder in the gemifloxacin group. •Since treatment period was shorter and pills to be taken were fewer compared to quadruple treatment, patient compliance was significantly higher in the gemifloxacin group. Background - After eradication of Helicobacter pylori (H. pylori) chronic gastritis will resolve, complications due to H. pylori infection and recurrence of infection will be prevented. Objective - To determine efficacy and safety of gemifloxacin containing treatment regimen in first line treatment of H. pylori with comparison to bismuth containing quadruple therapy. Methods - This retrospective study was conducted in a tertiary care university hospital between January 2018 and January 2021 with 410 participants who were diagnosed to have H. pylori infection with biopsies obtained during upper gastrointestinal system endoscopy. Patients were distributed into two groups according to their first-line treatment regimens. First group patients were treated with amoxicillin, gemifloxacin and pantoprazole and second group patients were treated with amoxicillin, metronidazole, bismuth subcitrate and pantoprazole for seven days. Results - Intention to treat and per protocol ratios for gemifloxacin containing regimen were 90.0% and 91.2%, while quadruple treatment has these ratios as 91.7% and 93.8% respectively. Treatment success rate in both regimens were similar. But adverse effects were lower and patient compliance were better in patients who had gemifloxacin containing treatment (P<0.001). Conclusion - Gemifloxacin containing treatment regimen is as effective as bismuth containing quadruple treatment regimen for H. pylori infection and patient compliance is better in this group. Gemifloxacin containing treatment regimens may be novel and effective alternatives for eradication of H. pylori infection.

Characteristics and Patterns of Proton Pump Inhibitors Prescribing at the Primary Health Care.

Background and objectives: the aim of this study was to analyse the utilisation of proton pump inhibitors (PPIs) during a 12-year period and to show the characteristics and patterns of their prescribing. Materials and methods: firstly, in the pharmacoepidemiological analyses the ATC/DDD methodology was used to assess the utilisation of PPIs in the Republic of Srpska. The annual PPI utilisation was expressed as a number of DDD/1000 inhabitants/year. Secondly, the cross-sectional surveys were used to reveal the characteristics of PPIs prescribing and medicines use, namely the dose, duration and indication, and possible adverse reactions. For the purposes of the surveys, the adapted version of questionnaires related to physicians' and patients' perspectives of medicines prescribing and use were performed. Results: the utilisation of medicines for alimentary tract and metabolism (group A/ATC classification) increased by almost threefold in a 12-year period, which was consistent with the total medicine utilisation. Pantoprazole was the most prescribed medicine among the PPIs. With the exclusion of PPIs in the therapy of Helicobacter pylori eradication, more than half of family physicians prescribed PPIs with antibiotics, and only 53/239 physicians, noticed some adverse reactions of PPIs in their patients. Most of the patients knew how to use PPIs and were taking these medicines in recommended daily doses, but approximately 45% of them were using PPIs for a long period of time (>6 months). Conclusions: the overuse of PPIs is a major concern due to potential serious adverse reactions, especially in elderly patients and in a case of prolonged exposure.

[Esophagoprotective therapy in patients with erosive esophagitis].

AIM: To evaluate the advantages of using combined therapy of proton-pump inhibitors (PPIs) and esophagoprotector in comparison with basic therapy of PPIs for 4 weeks based on the results of changes in the endoscopic picture.To compare the effectiveness of 4-week PPI therapy and 4-week combination therapy with PPI and esophagoprotector Alfasoxx (sodium hyaluronate, chondroitin sulfate, poloxomer 407) in patients with erosive esophagitis (EE) of any degree according to the Los Angeles Endoscopic Classification. MATERIALS AND METHODS: 81 patients with EE AC according to the Los Angeles endoscopic classification (1994) was enrolled in the study on the basis of the clinic of Peter the Great, Mechnikov North-Western State Medical University. By computer randomization, patients were divided into the control group 40 patients (pantoprazole 40 mg 1 time per day) and the intervention group 41 patients (pantoprazole 40 mg 1 time per day + Alfasoxx 1 sachet qid). The therapy was carried out for 4 weeks. In all patients before and after therapy, the frequency and severity of the main symptoms of gastroesophageal reflux disease (GERD) were assessed, esophagogastroduodenoscopy was performed. RESULTS: The advantage of combination therapy over standard PPI monotherapy in patients with EE was revealed. According to the results of the control endoscopy, healing of erosions of the esophageal mucosa was observed in 39 out of 41 (95.1%) patients in the intervention group and 32 out of 39 (82.1%) in the control group. The proportion of patients who showed an improvement in the endoscopic picture before and after treatment for 4 weeks by at least 1 level according to the Los Angeles classification was significantly higher in the comparison group 41 patients (100%), while in the control group 33 patients (85%); p0.009. After treatment, the combination therapy group had a lower incidence (p0.01) and severity of heartburn (p0.01). The same results are demonstrated by combination therapy regarding the symptom belching of air: in the study group after treatment, this symptom occurred less frequently (p=0.014), its severity was significantly less than in the control group (p0.01). There was a statistically significant decrease in the need for on-demand antacid therapy in the study group. CONCLUSION: In this study involving 81 patients with erosive GERD, the benefits of combination therapy were demonstrated. The addition of Alfasoxx medical device to PPI therapy increases the clinical and endoscopic efficacy of therapy. This positive effect is associated with the esophagoprotective properties of the drug, based on unique pharmacodynamic characteristics. Combination therapy for GERD is preferred in patients with EE. Studies have shown the expediency of using Alfasoxx in case of insufficient effectiveness of classical acid-suppressive therapy for GERD.

Effect of a Postoperative Multimodal Opioid-Sparing Protocol vs Standard Opioid Prescribing on Postoperative Opioid Consumption After Knee or Shoulder Arthroscopy: A Randomized Clinical Trial.

Importance: In arthroscopic knee and shoulder surgery, there is growing evidence that opioid-sparing protocols may reduce postoperative opioid consumption while adequately addressing patients' pain. However, there are a lack of prospective, comparative trials evaluating their effectiveness. Objective: To evaluate the effect of a multimodal, opioid-sparing approach to postoperative pain management compared with the current standard of care in patients undergoing arthroscopic shoulder or knee surgery. Design, Setting, and Participants: This randomized clinical trial was performed at 3 clinical sites in Ontario, Canada, and enrolled 200 patients from March 2021 to March 2022 with final follow-up completed in April 2022. Adult patients undergoing outpatient arthroscopic shoulder or knee surgery were followed up for 6 weeks postoperatively. Interventions: The opioid-sparing group (100 participants randomized) received a prescription of naproxen, acetaminophen (paracetamol), and pantoprazole; a limited rescue prescription of hydromorphone; and a patient educational infographic. The control group (100 participants randomized) received the current standard of care determined by the treating surgeon, which consisted of an opioid analgesic. Main Outcomes and Measures: The primary outcome was postoperative oral morphine equivalent (OME) consumption at 6 weeks after surgery. There were 5 secondary outcomes, including pain, patient satisfaction, opioid refills, quantity of OMEs prescribed at the time of hospital discharge, and adverse events at 6 weeks all reported at 6 weeks after surgery. Results: Among the 200 patients who were randomized (mean age, 43 years; 73 women [38%]), 193 patients (97%) completed the trial; 98 of whom were randomized to receive standard care and 95 the opioid-sparing protocol. Patients in the opioid-sparing protocol consumed significantly fewer opioids (median, 0 mg; IQR, 0-8.0 mg) than patients in the control group (median, 40.0 mg; IQR, 7.5-105.0; z = -6.55; P < .001). Of the 5 prespecified secondary end points, 4 showed no significant difference. The mean amount of OMEs prescribed was 341.2 mg (95% CI, 310.2-372.2) in the standard care group and 40.4 mg (95% CI, 39.6-41.2) in the opioid-sparing group (mean difference, 300.8 mg; 95% CI, 269.4-332.3; P < .001). There was no significant difference in adverse events at 6 weeks (2 events [2.1%] in the standard care group vs 3 events [3.2%] in the opioid-sparing group), but more patients reported medication-related adverse effects in the standard care group (32% vs 19%, P = .048). Conclusions and Relevance: Among patients who underwent arthroscopic knee or shoulder surgery, a multimodal opioid-sparing postoperative pain management protocol, compared with standard opioid prescribing, significantly reduced postoperative opioid consumption over 6 weeks. Trial Registration: ClinicalTrials.gov Identifier: NCT04566250.

Impact of insufficient doses of medications on Helicobacter pylori eradication: a retrospective observational study.

BACKGROUND AND AIMS: The doses of medications may influence the success of Helicobacter pylori (H. pylori) eradication. This real-world observational study aimed to explore the impact of insufficient doses of medications prescribed for the bismuth-containing quadruple therapy (BQT) regimen on successful H. pylori eradication. METHODS: We retrospectively screened the patients who were diagnosed with H. pylori infection and received BQT regimens for H. pylori eradication at our department between January 2017 and July 2020. The rate of successful H. pylori eradication was compared according to the doses of medications prescribed. Standard doses were defined according to the clinical guidelines. RESULTS: Overall, 1054 patients were included. The rate of successful H. pylori eradication was 78.2% (824/1054). Among them, proton pump inhibitors (PPIs) and antibiotics were prescribed at insufficient doses in 37.0% (390/1054) and 6.7% (71/1054) of patients, respectively. Furthermore, pantoprazole (98.7% [385/390]) was the most common type of PPIs prescribed at insufficient doses, and nitroimidazoles (85.9% [61/71]) were the most common type of antibiotics prescribed at insufficient doses. Among the patients receiving colloidal bismuth pectin (CBP) (200 mg tid) and standard-dose antibiotics, the rate of successful H. pylori eradication was lower in insufficient-dose PPIs group than standard-dose PPIs group (78.1% [271/347] versus 82.6% [438/530], P = 0.095). Among the patients receiving CBP (200 mg tid) and standard-dose PPIs, the rate of successful H. pylori eradication was significantly lower in insufficient-dose antibiotics group than standard-dose antibiotics group (37.8% [14/37] versus 82.6% [438/530], P < 0.0001). Among the patients receiving CBP 200 mg tid, the rate of successful H. pylori eradication was significantly lower in patients receiving both PPIs and antibiotics at insufficient doses than those at standard doses (46.4% [13/28] versus 82.6% [438/530], P < 0.0001). CONCLUSION: Among the BQT regimens, PPIs and/or antibiotics, especially pantoprazole and metronidazole, are often prescribed at insufficient doses, compromising the success of H. pylori eradication. ABBREVIATIONS: H. pylori, Helicobacter pylori; UBT, urea breath test; DPM, disintegrations per minute; BQT, bismuth-containing quadruple therapy; PPI, proton pump inhibitor; CBP, colloidal bismuth pectin; qd, once daily; bid, twice daily; tid, three times daily; qid, four times daily.

Gastrointestinal prophylaxis for COVID-19: an illustration of severe bias arising from inappropriate comparators in observational studies.

OBJECTIVES: We aimed to use setting-appropriate comparisons to estimate the effects of different gastrointestinal (GI) prophylaxis pharmacotherapies for patients hospitalized with COVID-19 and setting-inappropriate comparisons to illustrate how improper design choices could result in biased results. STUDY DESIGN AND SETTING: We identified 3,804 hospitalized patients aged ≥ 18 years with COVID-19 from March to November 2020. We compared the effects of different gastroprotective agents on clinical improvement of COVID-19, as measured by a published severity scale. We used propensity score-based fine-stratification for confounding adjustment. Based on guidelines, we prespecified comparisons between agents with clinical equipoise and inappropriate comparisons of users vs. nonusers of GI prophylaxis in the intensive care unit (ICU). RESULTS: No benefit was detected when comparing oral famotidine to omeprazole in patients treated in the general ward or ICUs. We also found no associations when comparing intravenous famotidine to intravenous pantoprazole. For inappropriate comparisons of users vs. nonusers in the ICU, the probability of improvement was reduced by 32%-45% in famotidine users and 21%-48% in omeprazole or pantoprazole users. CONCLUSION: We found no evidence that GI prophylaxis improved outcomes for patients hospitalized with COVID-19 in setting-appropriate comparisons. An improper comparator choice can lead to spurious associations in critically ill patients.

Patient journey in erosive oesophagitis: real-world perspectives from US physicians and patients.

OBJECTIVE: Management of erosive oesophagitis (EE) remains suboptimal, with many patients experiencing incomplete healing, ongoing symptoms, and relapse despite proton pump inhibitor (PPI) treatment. The Study of Acid-Related Disorders investigated patient burden of individuals with EE in a real-world setting. DESIGN: US gastroenterologists (GIs) or family physicians (FPs)/general practitioners (GPs) treating patients with EE completed a physician survey and enrolled up to four patients with EE for a patient survey, with prespecified data extracted from medical records. RESULTS: 102 GIs and 149 FPs/GPs completed the survey; data were available for 73 patients (mean age at diagnosis, 45.4 years). Omeprazole was healthcare professional (HCP)-preferred first-line treatment (60.8% GIs; 56.4% FPs/GPs), and pantoprazole preferred second line (29.4% and 32.9%, respectively). Price and insurance coverage (both 55.5% HCPs) and familiarity (47.9%) key drivers for omeprazole; insurance coverage (52.0%), price (50.0%), familiarity (48.0%), initial symptom relief (46.0%), and safety (44.0%) key drivers for pantoprazole. Only 49.3% patients took medication as instructed all the time; 56.8% independently increased medication frequency some of the time. Despite treatment, 57.5% patients experienced heartburn and 30.1% regurgitation; heartburn was the most bothersome symptom. 58.9% patients believed that their symptoms could be better controlled; only 28.3% HCPs were very satisfied with current treatment options. 83.6% patients wanted long-lasting treatment options. Fast symptom relief for patients was a top priority for 66.1% HCPs, while 56.6% would welcome alternatives to PPIs. CONCLUSION: This real-world multicentre study highlights the need for new, rapidly acting treatments in EE that reduce symptom burden, offer durable healing and provide symptom control.

Hepatitis C viral clearance with coadministration of crushed sofosbuvir/velpatasvir and high-dose pantoprazole after liver transplantation.

PURPOSE: Direct-acting antivirals (DAAs) allow for successful transplantation of livers from hepatitis C nucleic acid test (NAT)-positive donors to negative recipients. However, limited data exist to support crushing DAAs in patients with multiple absorption concerns or significant drug interactions. SUMMARY: Crushed sofosbuvir/velpatasvir has been successfully used in nontransplant patients with dysphagia, but data in transplant patients with absorption concerns are limited. A 31-year-old hepatitis C-negative female underwent liver transplantation from a hepatitis C NAT-positive donor. Her postoperative course was complicated by a mucormycosis infection, gastrointestinal bleed, and necrotizing pancreatitis requiring treatment with liposomal amphotericin B and pantoprazole 80 mg twice daily. Surgical interventions included an above-the-knee amputation and ileostomy. Hepatitis C treatment was initially delayed because of concern for reduced absorption with crushed DAA administration through the nasogastric (NG) tube, high ileostomy output, gastrointestinal bleed, pancreatitis, and a known drug interaction with pantoprazole. One month after transplantation, the patient's bilirubin level remained elevated and hepatitis C treatment was initiated with sofosbuvir/velpatasvir. Crushed sofosbuvir/velpatasvir was mixed with 30 mL of water and administered through the NG tube daily. Hepatitis C viral loads were obtained weekly during treatment to monitor efficacy. Although the patient died before evaluation of sustained virological response at 12 weeks, hepatitis C viral clearance was observed within 4 weeks of initiating treatment. CONCLUSION: A liver transplant patient exhibited viral clearance of hepatitis C following administration of crushed sofosbuvir/velpatasvir in the setting of multiple absorption concerns.

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.

Proton pump inhibitor therapy and risk of knee replacement surgery: a general population-based cohort study.

OBJECTIVE: Proton pump inhibitors (PPIs) are among the most commonly used medications for patients with osteoarthritis (OA). Various types of PPIs have different impacts on lowering serum magnesium level that may affect knee OA progression. We aimed to compare the risk of clinically relevant endpoint of knee replacement (KR) among initiators of five different PPIs with that among histamine-2 receptor antagonist (H2RA) initiators. DESIGN: Among patients with knee OA (≥50 years) in The Health Improvement Network database in the UK we conducted five sequential propensity-score matched cohort studies to compare the risk of KR over 5-year among patients who initiated omeprazole (n = 2,672), pantoprazole (n = 664), lansoprazole (n = 3,747), rabeprazole (n = 751), or esomeprazole (n = 827) with those who initiated H2RA. RESULTS: The prevalence of PPI prescriptions among participants with knee OA increased from 12.7% in 2000-44.0% in 2017. Two-hundred-and-seventy-four KRs (30.8/1,000 person-years) occurred in omeprazole initiators and 230 KRs (25.4/1,000 person-years) in H2RA initiators. Compared with H2RA initiators, the risk of KR was 21% higher in omeprazole initiators (hazard ratio [HR] = 1.21,95% confidence interval [CI]:1.01-1.44). Similar results were observed when pantoprazole use was compared with H2RA use (HR = 1.38,95%CI:1.00-1.90). No such an increased risk of KR was observed among lansoprazole (HR = 1.06,95%CI:0.92-1.23), rabeprazole (HR = 0.97,95%CI:0.73-1.30), or esomeprazole (HR = 0.83,95%CI:0.60-1.15) initiators compared with that among H2RA initiators. CONCLUSIONS: In this population-based cohort study, initiation of omeprazole or pantoprazole use was associated with a higher risk of KR than initiation of H2RA use. This study raises concern regarding an unexpected risk of omeprazole and pantoprazole on accelerating OA progression.

Subcutaneous pantoprazole in an elderly, palliative care patient.

Proton pump inhibitors (PPIs) have become the agents of choice for acid-related diseases. In some clinical situations, PPI therapy by oral or intravenous route may be difficult especially among elderly and patients in palliative care. Off-label PPI subcutaneous injection could be the last alternative to improve patient relief, despite limited published data. We report a case of linitis plastica, peritoneal carcinomatosis and occlusive syndrome who suffered from painful regurgitations which rapidly improved after subcutaneous pantoprazole. No related adverse effects were observed during PPI therapy. Despite some limitations, this report suggests that off-label subcutaneous pantoprazole could be an interesting alternative route when intravenous infusion may be difficult or harmful for elderly and patients in palliative care. Nevertheless, clinical safety and efficiency data on larger populations are needed to validate this use in such population.

Pantoprazole ameliorates liver fibrosis and suppresses hepatic stellate cell activation in bile duct ligation rats by promoting YAP degradation.

Liver fibrosis is one of the most severe pathologic consequences of chronic liver diseases, and effective therapeutic strategies are urgently needed. Proton pump inhibitors (PPIs) are H+/K+-ATPase inhibitors and currently used to treat acid-related diseases such as gastric ulcers, which have shown other therapeutic effects in addition to inhibiting acid secretion. However, few studies have focused on PPIs from the perspective of inhibiting hepatic fibrosis. In the present study, we investigated the effects of pantoprazole (PPZ), a PPI, against liver fibrosis in a bile duct ligation (BDL) rat model, human hepatic stellate cell (HSC) line LX-2 and mouse primary HSCs (pHSCs), and explored the potential mechanisms underlying the effects of PPZ in vitro and in vivo. In BDL rats, administration of PPZ (150 mg· kg-1· d-1, i.p. for 14 d) significantly attenuated liver histopathological injury, collagen accumulation, and inflammatory responses, and suppressed fibrogenesis-associated gene expression including Col1a1, Acta2, Tgfß1, and Mmp-2. In LX-2 cells and mouse pHSCs, PPZ (100-300 µM) dose-dependently suppressed the levels of fibrogenic markers. We conducted transcriptome analysis and subsequent validation in PPZ-treated LX-2 cells, and revealed that PPZ inhibited the expression of Yes-associated protein (YAP) and its downstream targets such as CTGF, ID1, survivin, CYR61, and GLI2. Using YAP overexpression and silencing, we demonstrated that PPZ downregulated hepatic fibrogenic gene expression via YAP. Furthermore, we showed that PPZ promoted the proteasome-dependent degradation and ubiquitination of YAP, thus inhibiting HSC activation. Additionally, we showed that PPZ destabilized YAP by disrupting the interaction between a deubiquitinating enzyme OTUB2 and YAP, and subsequently blocked the progression of hepatic fibrosis.

Possible protective effect of pantoprazole against cisplatin-induced nephrotoxicity in head and neck cancer patients: a randomized controlled trial.

Cisplatin is used to treat solid malignancies including head and neck cancer. However, nephrotoxicity limits its use. In this study, we looked for a possible protective effect of pantoprazole against cisplatin-induced nephrotoxicity. We used novel biomarkers for early detection of nephrotoxicity. Sixty chemotherapy naïve head and neck cancer patients completed the study. Following complete history taking and thorough clinical examination, patients were randomly divided into three groups: 20 patients in each. Group I (control group) received cisplatin without pantoprazole, groups II and III received pantoprazole 80 mg and 40 mg, respectively, concurrently with cisplatin. Blood and urine samples were collected at baseline, and 48 h after the first and third cycles of cisplatin administration. Assessment of serum creatinine and soluble FasL (sFasL), as well as urinary neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) was performed. Nephrotoxicity was detected in 6 patients in group I, none in group II and 3 patients in group III. Serum creatinine significantly increased at the end of treatment in group I compared to groups II and III. Group I also had significantly higher urinary KIM-1 and NGAL and serum sFasL compared to groups II and III after the first and third cycles. On the contrary, there was no significant difference between groups II and III. Pantoprazole prevented the increase in acute kidney injury biomarkers in cisplatin-treated patients. Therefore, it is a promising agent in reducing cisplatin-induced nephrotoxicity.Trial registration Clinical Trials.gov identifier: NCT04217512, registered in January 2020 " retrospectively registered".

How Would You Manage This Patient With Nonvariceal Upper Gastrointestinal Bleeding? : Grand Rounds Discussion From Beth Israel Deaconess Medical Center.

Nonvariceal upper gastrointestinal bleeding is common, morbid, and potentially fatal. Cornerstones of inpatient management include fluid resuscitation; blood transfusion; endoscopy; and initiation of proton-pump inhibitor therapy, which continues in an individualized manner based on risk factors for recurrent bleeding in the outpatient setting. The International Consensus Group released guidelines on the management of nonvariceal upper gastrointestinal bleeding in 2019. These guidelines provide a helpful, evidence-based roadmap for management of gastrointestinal bleeding but leave certain management details to the discretion of the treating physician. Here, 2 gastroenterologists consider the care of a patient with nonvariceal upper gastrointestinal bleeding from a peptic ulcer, specifically debating approaches to blood transfusion and endoscopy timing in the hospital, as well as the recommended duration of proton-pump inhibitor therapy after discharge.

Absorption of nonheme iron during gastric acid suppression in patients with hereditary hemochromatosis and healthy controls.

Phlebotomies are performed in hereditary hemochromatosis (HH) to maintain normal iron concentrations. Proton-pump inhibitors (PPIs) can reduce the number of phlebotomies in patients with HH. However, in patients without HH, the iron concentrations do not appear to be compromised when using PPIs. Therefore, we aim to explain the differences in iron absorption between patients with and without HH. In 10 p.cysteine282tyrosine (p.C282Y) homozygous HH patients with normalized iron stores and 10 healthy control subjects (HCs), the iron parameters and hepcidin concentrations were determined before ingestion of a pharmacological dose of 50 mg iron [ferric iron (Fe3+)] polymaltose and hourly for 4 h afterward. This was repeated after 7 days of treatment with pantoprazole 40 mg once daily. Serum iron concentrations and transferrin saturation percentages dropped significantly during PPI use in the patients with HH, whereas no changes were observed in the HCs. Hepcidin concentrations were lower in the patients with HH compared with the HCs both before and during PPI use. In both groups, hepcidin levels did not significantly decrease during the treatment. Seven-day PPI use significantly reduces iron absorption in patients with HH but not in HCs. Changes in hepcidin concentrations could not explain these different PPI effects on iron absorption probably due to a small sample size.NEW & NOTEWORTHY This study confirms that lowering gastric acidity by proton pump inhibitors results in a reduction in iron absorption in patients with hemochromatosis and not in healthy control subjects. The presupposition that a decrease in hepcidin concentration in healthy control subjects in response to lowering gastric acidity can explain the difference in iron absorption between these groups could not be confirmed probably because of a small sample size.

Effectiveness and safety of proton pump inhibitors for treating acute pancreatitis: A protocol for systematic review and meta analysis.

BACKGROUND: Previous studies have showed that anti-acid therapy with proton pump inhibitors (PPIs) can inhibit pancreatic secretion and it may be used in treating acute pancreatitis (AP). But at present, there is no systematic reviews for the evidence and the therapeutic effectiveness and safety of anti-acid therapy with PPIs in AP were not unclear. Therefore, we will undertake a systematic review of the literature to summarize previous evidence regarding this topic, in order to clarify the effectiveness and safety of anti-acid therapy with PPIs in AP. METHODS: We will search the EMBASE, WANFANG DATA, Web of Knowledge, China National Knowledge Infrastructure, PubMed, ClinicalTrials.gov and Cochrane Library from inception to June 30,2021 to retrieve relevant studies using the search strategy: ("Proton pump inhibitors" OR "PPI" OR "PPIs" OR "Omeprazole" OR "Tenatoprazole" OR "Pantoprazole" OR "acid suppression therapy" OR "acid suppression drugs") AND ("pancreatitis" OR "pancreatitides"). Two authors independently judged study eligibility and extracted data. Heterogeneity will be examined by computing the Q statistic and I2 statistic. RESULTS: This study assessed the efficiency and safety of proton pump inhibitors for treating acute pancreatitis. CONCLUSIONS: This study will provide reliable evidence-based evidence for the clinical application of PPIs for treating AP. ETHICS AND DISSEMINATION: Ethical approval is unnecessary as this protocol is only for systematic review and does not involve privacy data. The findings of this study will be disseminated electronically through a peer-review publication or presented at a relevant conference.