Use Of H2 Blockers Research Articles

Population pharmacokinetics and exposure-response relationships of maribavir in transplant recipients with cytomegalovirus infection.

Maribavir is approved for management of post-transplant cytomegalovirus (CMV) infections refractory and/or resistant to CMV therapies at a dose of 400mg twice daily (BID). Population pharmacokinetic (PopPK) and exposure-response analyses were conducted to support the appropriateness of 400mg BID dosing. A PopPK model was developed using non-linear mixed-effects modeling with pooled maribavir plasma concentration-time data from phase 1 and 2 studies (from 100mg up to 1200mg as single or repeated doses) and the phase 3 SOLSTICE study (400mg BID). Exposure-response analyses were performed for efficacy, safety, and viral resistance based on data collected in the SOLSTICE study. Maribavir PK after oral administration was adequately described by a two-compartment model with first-order elimination, first-order absorption, and an absorption lag-time. There was no evidence that maribavir PK was affected by age, sex, race, diarrhea, vomiting, disease characteristics, or concomitant use of histamine H2 blockers, or proton pump inhibitors. In the SOLSTICE study, higher maribavir exposure was not associated with increased probability of achieving CMV DNA viremia clearance, nor with reduced probability of treatment-emergent maribavir-resistant CMV mutations. A statistically significant association with maribavir exposure was identified for taste disturbance, fatigue, and treatment-emergent serious adverse events, while transplant type, enrollment region, CMV DNA level at baseline, and/or CMV resistance at baseline were identified as additional risk factors for these safety outcomes. In conclusion, the findings of these PopPK and exposure-response analyses provide further support for the recommended maribavir dose of 400mg BID.

Effect of antibiotic, proton pump inhibitor, H2 blocker, metformin and statin use on outcomes with immune checkpoint inhibitors (ICIs) in patients (pts) with metastatic urothelial carcinoma (mUC) in a real-world setting.

Effect of antibiotic, proton pump inhibitor, H2 blocker, metformin and statin use on outcomes with immune checkpoint inhibitors (ICIs) in patients (pts) with metastatic urothelial carcinoma (mUC) in a real-world setting.

Effectiveness of famotidine on the risk of poor prognosis in patients with COVID-19: A nationwide cohort study in Korea

ObjectiveFamotidine has been proposed as a promising candidate for the treatment of coronavirus disease 2019 (COVID-19). However, there is limited research on the association of famotidine with the poor prognosis of COVID-19. MethodsThe Korean nationwide cohort included 6,556 patients who tested positive on RT-PCR for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The poor COVID-19-related outcomes were defined on the basis of having encountered the composite outcome of high oxygen therapy, intensive care unit admission, administration of mechanical ventilation, or death. In addition, we performed exposure-driven propensity score matching for no H2-blocker use versus current famotidine use, and other H2-blocker use versus current famotidine use. Results4,785 (73.0%) patients did not use a H2-blocker, 393 (6.0%) patients were currently used famotidine, and 1,292 (19.7%) patients currently used H2-blocker other than famotidine. In multivariable analysis after matching (no H2-blocker use versus current famotidine use), there was no significant association between current famotidine use and composite outcomes (adjusted odd ratios [aOR]: 1.30, 95% confidence interval [CI]: 0.55–3.06). On the other hand, another matched cohort (other H2-blocker use versus current famotidine use), demonstrated a positive association between current famotidine use and composite outcomes (aOR: 3.56, 95% CI: 1.03–12.28) ConclusionsOur study results did not support the potential of famotidine as a therapeutic agent for COVID-19. A rather unexpected result could be observed in the comparisons between current famotidine use and other H2-blocker use; it was observed that current famotidine use increased the risk of poor COVID-19 related outcomes. Further studies are needed to clearly prove the causal relationship with several H2-blockers, including famotidine.

Ventilator Associated Pneunomia in Neonatal Intensive Care Unit: Occurrence and Risk Factors

Objectives: To examine the occurrence of pneumonia linked with a ventilator in the neonatal intensive care unit and to determine the related risk factors. Study design: A cross-sectional study Place and Duration: This study was conducted at Aga Khan University hospital from May 2021 to May 2022 Methodology: This study includes a total of 70 participants admitted in neonatal intensive care unit. All the patients were put under the ventilator for more than 2 days. At the time of admission, the X-ray of the chest was performed, and it was also performed every day. When certain organisms were present on the tracheal aspirate, ventilator-associated pneumonia (VAP) was diagnosed. After 2 days of ventilation, microbial analysis and gram staining were done for tracheal aspirates. They were later examined to determine the occurrence of nosocomial pneumonia and what are the risk factors linked with it. A Chi-square test and t-test were conducted to examine all the data. A confidence level of 0.05 was set. Results: Pneumonia associated with the ventilator occurred in 31.4% of the participants where a large number had developed it between 4-14 days after intubation. There were certain risk factors that were determined in our research. They include the use of H2 blockers, invasive lines, low PaO2/FiO2, and re-intubation. There were two things (use of steroids and enteral feeding through nasogastric) that were not linked with the occurrence of this pneumonia. The patients who were in the group of ventilator-associated pneumonia were having a longer time period of stay and mechanical ventilation. Conclusion: The occurrence of pneumonia associated with ventilators is high. Those patients who were having above mentioned risk factors should require pay special attention towards prevention. Keywords: pneumonia, ventilators, ventilator associated pneumonia, neonatal intensive care unit

Prophylaxis of Invasive Fungal Infection in Neonates: A Narrative Review for Practical Purposes

Candida albicans is the most frequent cause of invasive fungal disease in preterm and/or low birth weight neonates, followed by Candida parapsilosis, whilst infections from other species are rare. Considering the severity of the disease, associated with poor clinical signs and diagnostic difficulties, primary prophylaxis becomes relevant. This paper summarizes the pathogenesis and clinical presentation of invasive candidiasis in neonates, focusing on prophylaxis. For late onset invasive disease, e.g., those occurring after the 3rd (or 7th according to some definitions) day of life possible approaches are the use of fluconazole, recommended in case of weight <1000 g or <1500 g if the local incidence of invasive candidiasis is higher than 2%, or the use of nystatin (for patients < 1500 g). Micafungin must be used in case of colonization by Candida auris, or in centers with a high prevalence of this pathogen. Concurrently, correct management of the central venous catheter and isolation procedures, with special regard to patients colonized by resistant strains, are fundamental. Other approaches such as reduced use of H2 blockers and broad-spectrum antibiotics (e.g., 3rd generation cephalosporins or carbapenems) and promotion of breast feeding proved useful. Reduction of early-onset infections (those occurring in the first 3 days of life) can also be obtained by treating maternal vulvo-vaginal candidiasis, which can represent a fastidious problem during pregnancy. In this case, topic azoles (the only recommendable treatment) can represent a kind of "prophylaxis" of early neonatal candidiasis. However, it must always be remembered that prophylaxis reduces the risk of invasive candidiasis but can not completely eliminate its occurrence, with the parallel risk of selecting for antifungal-resistant strains. Clinicians must maintain a high level of suspicion to start an appropriate therapy and strict epidemiological surveillance to identify the occurrence of clusters and the appearance of strains resistant to prophylaxis.

Ventilator Associated Pneunomia in Neonatal Intensive Care Unit: Occurrence and Risk Factors

Objectives: To examine the occurrence of pneumonia linked with a ventilator in the neonatal intensive care unit and to determine the related risk factors. Purpose of study: To better identify the associated morbidity and mortality, pathophysiology, and recommended measures to avoid this disease, paediatric VAP diagnosis methods must become more standardized and exact. Study design: A cross-sectional study Place and Duration: This study was conducted at Aga Khan University hospital from May 2021 to May 2022 Methodology: This study includes a total of 70 participants admitted in neonatal intensive care unit. All the patients were put under the ventilator for more than 2 days. At the time of admission, the X-ray of the chest was performed, and it was also performed every day. When certain organisms were present on the tracheal aspirate, ventilator-associated pneumonia (VAP) was diagnosed. After 2 days of ventilation, microbial analysis and gram staining were done for tracheal aspirates. They were later examined to determine the occurrence of nosocomial pneumonia and what are the risk factors linked with it. A Chi-square test and t-test were conducted to examine all the data. A confidence level of 0.05 was set. Results: Pneumonia associated with the ventilator occurred in 31.4% of the participants where a large number had developed it between 4-14 days after intubation. There were certain risk factors that were determined in our research. They include the use of H2 blockers, invasive lines, low PaO2/FiO2, and re-intubation. There were two things (use of steroids and enteral feeding through nasogastric) that were not linked with the occurrence of this pneumonia. The patients who were in the group of ventilator-associated pneumonia were having a longer time period of stay and mechanical ventilation. Practical implication: In newborn and paediatric intensive care units, VAP continues to be a significant and unresolved problem. The results of this study will highlight the numerous elements that significantly contribute to ventilator-associated pneumonia. Conclusion: The occurrence of pneumonia associated with ventilators is high. Those patients who were having above mentioned risk factors should require pay special attention towards prevention. Keywords: pneumonia, ventilators, ventilator associated pneumonia, neonatal intensive care unit

S1558 Risk of Clostridioides difficile Infection in Patients With Celiac Disease: Insight From a U.S.-Based Population Study

Introduction: Little is known about the association between Clostridioides difficile infection (CDI) and celiac disease. The aim of the study is to describe the risk of CDI in patients with celiac disease and to describe the clinical outcomes in patients with celiac and CDI. Methods: We queried a commercial database (Explorys IncTM, Cleveland, OH, United States), and obtained an aggregate of electronic health record data from 26 major integrated United States healthcare systems comprising 360 hospitals in the United States from 2017 to 2022. Diagnoses were organized into the Systematized Nomenclature of Medicine Clinical Terms (SNOMED–CT) hierarchy. We compared the incidence of new CDI among patients with celiac disease versus those without celiac disease (controls). Univariate and multivariate analyses were performed on the data, and associations were reported as adjusted odds ratios (aOR) with 95% confidence intervals (CI). Results: We identified 90,060 patients with celiac disease and 25,807,720 controls. The incidence of new CDI was 1.31% (1,180) in celiac disease patients, and 0.35% (92,330) in controls, yielding an odds ratio (OR) of 3.69 (95% CI 3.49-3.91; P< 0.0001). Treatment and clinical outcomes were not significantly different. After controlling for common CDI risk factors, the multivariate analysis model uncovered that celiac patients were more likely to develop CDI OR: 1.34 (95% CI: 1.2-1.4, P < 0.0001) compared to controls (Table). Conclusion: In a large US population-based study, patients with celiac disease had a significantly higher incidence of CDI than controls. Clinical outcomes were similar between the groups. Clinicians should be vigilant and consider CDI in celiac patients with new or recurrent diarrhea. Table 1. - Demographics Celiac Patients (n=90,060) Control Patients (n=25,807,720) Age 18-65 years (%) 65,220 (72.4%) 18,331,970 (71%) Age >65 years (%) 24,840 (27.6%) 7,475,750 (29%) Female (%) 66,800 (74.2%) 13,219,060 (51.2%) Race: White (%) 73540 (81.7%) 14,072,590 (54.5%) Smoker (%) 15,120 (16.8%) 2,327,950 (9%) Alcohol abuse (%) 2,530 (2.8%) 552,010 (2.1%) Hypertension (%) 42,250 (46.9%) 8,063,140 (31.2%) Diabetes (%) 25,560 (28.4%) 3,446,990 (13.4%) Obesity (%) 26,170 (29.1%) 3,535,170 (13.7%) Clostridioides difficile infection management and clinical outcomes Developed Clostridioides difficile infection* 1,180 (1.31%) 92,330 (0.35%) Treated with metronidazole 820 (69%) 56,490 (61.1%) Treated with vancomycin 770 (65.2%) 55,270 (59%) Treated with fidaxomicin 70 (5.9%) 4,370 (4.7%) Colectomy** 10 (0.84%) 970 (1.05%) Multivariable model with Clostridioides difficile infection being the outcome Risk Factors Odds Ratio 95% CI; P-value Age ≥65 yr vs < 65yr 2.988 2.962-3.014; < 0.0001 Gender (female vs male) 1.194 1.184-1.204; < 0.0001 Race (White vs rest) 1.483 1.467-1.498; < 0.0001 Antibiotics 3.657 3.6-3.7; < 0.0001 Acid suppressive therapy*** 4.268 4.224-4.313; < 0.0001 Inflammatory bowel disease 6.031 5.93-6.13; < 0.0001 Celiac disease 1.342 1.284-1.403; < 0.0001 *1st occurrence of CDI after celiac diagnosis.**Colectomy performed within 60 days of CDI diagnosis (excluded patients with a history of IBD, ischemic colitis, and neoplasia of the colon).***Acid suppressive therapy includes prior use of proton pump inhibitors or H2 blockers

S432 Fifty Percent Increase in Low-Grade Dysplasia Detection Using Probe-Based Confocal Endomicroscopy in a Metropolitan Veteran Cohort Undergoing Short Segment Barrett’s Esophagus Surveillance

Introduction: Seattle protocol (SP) is the standard method to biopsy Barrett’s esophagus. However, SP may miss dysplasia in all types of BE. Few studies have focused on pCLE in the diagnosis of dysplasia in short segment Barrett’s esophagus (SSBE). The primary aim of our study was to determine if pCLE was more effective in diagnosing dysplastic mucosa in patients undergoing surveillance endoscopy in SSBE. Methods: Patients undergoing surveillance endoscopy and diagnosed with SSBE between January 1, 2018 and January 1, 2021 at the VA Loma Linda Healthcare System (VALLHCS) were included. Patients who underwent pCLE were compared to those undergoing SP. Esophagogastroduodenoscopy (EGD) was performed using a high definition diagnostic upper endoscope (Olympus, Center Valley PA). All patients in both pCLE and SP group underwent high-definition white light examination (HD-WLE). All pCLE examinations were performed by two gastroenterologists (C.S.J.and N.S.) using GastroFlex UHD Confocal Miniprobe (Cellvizio, Mauna Kea Technologies). Age, sex, number of EGDs prior to a diagnosis of dysplasia, hiatal hernia length and pCLE findings were assessed. SSBE was defined using Prague criteria, circumference (C) ≤ 2cm and maximal length of Barrett's segment (M) ≤ 3cm. Two pathologists reviewed all biopsies with a diagnosis of dysplasia. Continuous variables were compared using a Fisher’s exact test with p≤0.05 as statistically significant. This study was approved by the institutional review board for VALLHCS. Results: Sixty-seven patients were identified as having SSBE. Sixteen patients underwent pCLE-targeted biopsies while 51 underwent SP. The mean age of the pCLE group was 64 years and 65.9 years for those who underwent SP. There was no difference in age, BMI, smoking status, statin, H2 blocker or PPI use in patients who underwent pCLE-targeted biopsies versus those who underwent SP. Low-grade dysplasia was detected in 17 patients (25.3%). Of these 17 patients, 11 were detected with pCLE, and 6 were detected with SP. The use of pCLE was significantly associated with detection of low-grade dysplasia (11/16, 68.7%) compared to (6/51, 11.7%) with a p-value of < 0.001. Conclusion: In a primarily male metropolitan veteran population, pCLE may be helpful in identifying low grade dysplasia in patients with SSBE. SP biopsy techniques may miss LGD during SSBE surveillance.

Risk factors for candidemia: A case–control study

Background:Candida bloodstream infections (candidemia) have significant mortality and morbidity rates, as well as healthcare cost implications. Emerging multidrug-resistant Candida spp such as Candida auris, as well as increasing resistance among non–albicans species, which are becoming more prevalent, also raise concern. Understanding the epidemiology of this infection could enhance prevention and management efforts. We studied risk factors for candidemia. Methods: This matched case–control study was conducted at a university hospital from December 2019 through May 2021. Cases of candidemia were identified using positive blood-culture results. Controls were matched 5:1 to cases by age, sex, and month and year of admission. Risk factors of interest included total parenteral nutrition (TPN), central venous access (CVA), neutropenia, Clostridium difficile, pancreatic disease, Candida in urine culture, cancer, invasive procedures, H2 blockers, chemotherapy, antibiotic use, immunosuppression, and antifungal use. Bivariate conditional logistic regression models were used to study the association of individual factors with candidemia. Multivariable conditional logistic regression models were performed using factors with a P Results: Overall, 101 patients with candidemia and 505 matched controls were included. In the bivariate analysis, associations were detected between candidemia and TPN, CVA, pancreatic disease, invasive procedures, H2 blocker use, antibiotic use, and antifungal use (all Ps Conclusions: Associations of candidemia with recent antifungal use and pancreatic disease were relatively novel findings. Neutropenia was not an independent risk factor for candidemia in this study. Future directions include further evaluations of previous antifungal use in patients with candidemia to identify opportunities for possible intervention and antifungal stewardship.Funding: NoneDisclosures: None

A Risk Scoring System Utilizing Machine Learning Methods for Hepatotoxicity Prediction One Year After the Initiation of Tyrosine Kinase Inhibitors.

BackgroundThere is currently no method to predict tyrosine kinase inhibitor (TKI) -induced hepatotoxicity. The purpose of this study was to propose a risk scoring system for hepatotoxicity induced within one year of TKI administration using machine learning methods.MethodsThis retrospective, multi-center study analyzed individual data of patients administered different types of TKIs (crizotinib, erlotinib, gefitinib, imatinib, and lapatinib) selected in five previous studies. The odds ratio and adjusted odds ratio from univariate and multivariate analyses were calculated using a chi-squared test and logistic regression model. Machine learning methods, including five-fold cross-validated multivariate logistic regression, elastic net, and random forest were utilized to predict risk factors for the occurrence of hepatotoxicity. A risk scoring system was developed from the multivariate and machine learning analyses.ResultsData from 703 patients with grade II or higher hepatotoxicity within one year of TKI administration were evaluated. In a multivariable analysis, male and liver metastasis increased the risk of hepatotoxicity by 1.4-fold and 2.1-fold, respectively. The use of anticancer drugs increased the risk of hepatotoxicity by 6.0-fold. Patients administered H2 blockers or PPIs had a 1.5-fold increased risk of hepatotoxicity. The area under the receiver-operating curve (AUROC) values of machine learning methods ranged between 0.73-0.75. Based on multivariate and machine learning analyses, male (1 point), use of H2 blocker or PPI (1 point), presence of liver metastasis (2 points), and use of anticancer drugs (4 points) were integrated into the risk scoring system. From a training set, patients with 0, 1, 2-3, 4-7 point showed approximately 9.8%, 16.6%, 29.0% and 61.5% of risk of hepatotoxicity, respectively. The AUROC of the scoring system was 0.755 (95% CI, 0.706-0.804).ConclusionOur scoring system may be helpful for patient assessment and clinical decisions when administering TKIs included in this study.

S474 Barrett's Esophagus in the United States From 2005-2016: Analysis of Office Visits From the National Ambulatory Medical Care Survey

Introduction: Barrett’s Esophagus (BE) is a premalignant condition by which metastatic columnar mucosa replaces the normal stratified squamous mucosa in the distal esophagus. Most cases occur in older white males with a long-standing history of acid reflux. Our aim was to conduct a cross-sectional study examining trends in demographics and medications use of BE patients in the US from 2005-2016. Methods: The CDC’s National Ambulatory Medical Care Survey (NAMCS) uses weighted sampling methods to generate cross-sectional data representative of ambulatory care visits in the US. Using ICD-9 code 530.85 (BE), we identified patients with BE for the period 2005-2016. For these patients, we identified patients with GERD (ICD-9 530.81 or 530.11) and used visit codes to identify presenting symptoms and drug codes to evaluate PPI and H2 blocker use. Weighting of encounters using SPSS were performed to provide population estimates. Results: There were 6,803,008 unique outpatient visits for BE. Mean age was 61.2 ± 14.7y, 57.9% male, and 95.6% non-Hispanic white. Mean age in males was 58.7±14.5y vs females 64.8 ± 14.3y (p< 0.01). Median BMI was 25.8, 16.6% of patients were obese, and 14.8% had current tobacco use. Overall, 69.6% of visits were to a gastroenterologist (GI), 26.9% to a primary care provider (PCP), and 3.5% to surgery. Mean time spent per visit was 21.8± 11.2m. Among presenting complaints for the visit, 7.4% had abdominal pain, 5.6% had dysphagia, 2.8% with heartburn, and most had no GI complaints. 34.6% of patients had concomitant GERD. Most patients were on PPI therapy (69.4%): 23.4% on esomeprazole, 23.3% omeprazole, 14.1% pantoprazole, and 8.8% lansoprazole. 29.5% were no PPI or H2 blocker, 5.6% were on H2 blocker in addition to PPI, and 5.6 % were on aspirin. PPI use has significantly decreased from 86.3% in 2005-2008 to 62.7% in 2009-2012 to 62.1% in 2013-2016 (p< 0.01). Conclusion: Our nationwide results reaffirm that BE predominantly affects older, obese, white, males. Over one-third of BE patients had GERD, which is 3 times higher than the general population supporting the association. Most BE patients were asymptomatic during their office visit and were primarily seen by a GI specialist. Current guidelines recommend indefinite PPI use for patients with BE; our study showed that though most were on PPI, one-third of patients are not at their office visits when predominantly asymptomatic and PPI use has decreased over time. Continued vigilance in treating patients with BE is needed.

Does chronic use of H2 blockers in adults cause loss of bone density?

Does chronic use of H2 blockers in adults cause loss of bone density?

Gastrointestinal symptoms and healthcare utilization have increased among patients with functional gastrointestinal and motility disorders during the COVID-19 pandemic.

BackgroundThe coronavirus disease 2019 (COVID‐19) pandemic has led to unprecedented disruptions in healthcare. Functional gastrointestinal and motility disorders (FGIMD) are associated with significant healthcare utilization. The clinical implications of these healthcare disruptions due to the COVID‐19 pandemic on clinical outcomes in patients with FGIMD are unclear.MethodsWe performed a retrospective study of patients with three common FGIMD (irritable bowel syndrome [IBS], gastroparesis, functional dyspepsia [FD]) tested for SARS‐CoV‐2 to describe alterations in gastrointestinal symptoms, medication use, and healthcare utilization during and before the pandemic and factors associated with COVID‐19.Key ResultsThe prevalence of COVID‐19 during the pandemic (03/2020–09/2020) was 3.20% (83/2592) among patients with FGIMD, 3.62% in IBS (57/1574), 3.07% in gastroparesis (23/749), and 2.44% in FD (29/1187) at our institution. Patients with FGIMD had increased abdominal pain, nausea/vomiting, diarrhea, constipation, and weight loss (p < 0.001) along with increased proton pump inhibitor, H2 blocker, and opioid use (p < 0.0001). Both inpatient hospitalizations and outpatient visits (p < 0.0001) and number of diagnostic tests including cross‐sectional imaging (p = 0.002), and upper and lower endoscopies (p < 0.0001) were significantly higher during the pandemic as compared to 6 months prior. Diarrhea‐predominant IBS was positively (OR 2.37, 95% CI 1.34–4.19, p = 0.003) associated with COVID‐19, whereas functional dyspepsia was negatively (OR 0.46, 95% CI 0.27–0.79, p = 0.004) associated.Conclusions & InferencesPatients with common functional gastrointestinal and motility disorders have reported more gastrointestinal symptoms during the COVID‐19 pandemic with concurrent increased medication use and healthcare utilization.

REBOUND PHENOMENON OF PROTON PUMP INHIBITOR THERAPY

Proton pump inhibitors (PPIs) are the most potent drugs for suppressing gastric acid secretion. They are used in the treatment of acid-peptic disorders, including peptic ulcer disease, gastroesophageal reflux disease, Zollinger Ellison syndrome, in the eradication of Helicobacter pylori infection and ulcer prophylaxis. In the pharmacotherapy of these disorders, they have significantly suppressed the use of H2 blockers, like other, older groups of antisecretory drugs. Long-term PPI therapy leads to moderate hypergastrinemia (increased gastrin secretion) in 20-25% of patients. This hypergastrinemia results in rebound acid hypersecretion (RAHS) in 30-40% patients, who abruptly discontinue PPI. Most patients who abruptly discontinue PPI have symptoms of dyspepsia and gastroesophageal reflux, most commonly heartburn and a burning sensation in the esophagus. Therefore, care should be taken to properly discontinue PPI and reduce the dose of the drug before complete discontinuation. A less effective acid blocker (H2 blocker) can be switched, since H2 receptor blockers cause less pronounced hypergastrinemia and hyperplasia of enterochromaffin-like cells (ECL cells) compared to PPI.

Machine Learning Approaches to Predict Hepatotoxicity Risk in Patients Receiving Nilotinib.

Background: Although nilotinib hepatotoxicity can cause severe clinical conditions and may alter treatment plans, risk factors affecting nilotinib-induced hepatotoxicity have not been investigated. This study aimed to elucidate the factors affecting nilotinib-induced hepatotoxicity. Methods: This retrospective cohort study was performed on patients using nilotinib from July of 2015 to June of 2020. We estimated the odds ratio and adjusted odds ratio from univariate and multivariate analyses, respectively. Several machine learning models were developed to predict risk factors of hepatotoxicity occurrence. The area under the curve (AUC) was analyzed to assess clinical performance. Results: Among 353 patients, the rate of patients with grade I or higher hepatotoxicity after nilotinib administration was 40.8%. Male patients and patients who received nilotinib at a dose of ≥300 mg had a 2.3-fold and a 3.5-fold increased risk for hepatotoxicity compared to female patients and compared with those who received <300 mg, respectively. H2 blocker use decreased hepatotoxicity by 11.6-fold. The area under the curve (AUC) values of machine learning methods ranged between 0.61–0.65 in this study. Conclusion: This study suggests that the use of H2 blockers was a reduced risk of nilotinib-induced hepatotoxicity, whereas male gender and a high dose were associated with increased hepatotoxicity.

A Randomized Open-Label Study of Two Methods of Proton Pump Inhibitors Discontinuation.

BackgroundProton pump inhibitors (PPIs) are effective in treating gastroesophageal reflux disease (GERD). Unfortunately, they are often inappropriately prescribed and long-term use has potential adverse effects. A single best method for discontinuation of PPIs does not currently exist. The objective of this study was to determine if there is a significant difference in successfully discontinuing PPI use at 12 months between patients discontinuing abruptly or tapering first.MethodologyWe conducted a randomized trial with 38 patients diagnosed with GERD. We collected six weekly and then monthly surveys of symptoms based on the Dyspepsia Symptom Severity Index. Chart review at 12 months determined whether the patient was able to discontinue PPI.ResultsA Kaplan-Meier survival analysis at 12 months did not show a statistically significant difference between the abrupt and taper groups for discontinuation of PPI medication (p = 0.75). Cox regression analysis showed no association of alcohol use, smoking, or caffeine use with failure to discontinue PPI, but H2 blocker use was associated with a 79% reduction in risk of failure to discontinue PPI (p = 0.004). The taper group had significantly less symptoms 14, 18, 22, and 30 weeks after discontinuation.ConclusionsOur study suggests that there is no difference in successful discontinuation of PPIs between abrupt and taper methods at 12 months; however, there are less symptoms in the taper method, and H2 blocker use is associated with success. Further study is needed with larger numbers of participants and randomization of H2 blocker use.

Medication use and microscopic colitis: a multicentre retrospective cohort study.

Medication use has been implicated in the development of microscopic colitis (MC). However, studies have demonstrated inconsistent findings and there exist variations in design. To measure the association between medication use and MC. Patients who underwent a colonoscopy over a 10-year period at two academic medical centres (Columbia University Medical Centre and Mayo Clinic) were identified. Cases were patients with biopsy-proven MC and controls were patients who underwent colonoscopy for evaluation of diarrhoea with biopsies negative for MC. Cases were matched by age, gender and calendar period with up to two controls. Demographics, medication use, smoking history and coeliac disease status were collected. Conditional logistic regression was used with and without adjustment for smoking. A total of 344 patients with MC were matched to 668 controls. After adjusting for smoking, there was an inverse association between MC and use of proton pump inhibitors (PPIs) (OR 0.64; 95% CI 0.47-0.87), H2 blockers (OR 0.46; 95% CI 0.24-0.88) and oral diabetes medications (OR 0.47; 95% CI 0.27-0.81). There was a positive association with nonsteroidal anti-inflammatory drug (NSAID) use and MC (OR 1.63; 95% CI 1.12-2.38). NSAID use was associated with MC, while use of PPIs, H2 blockers and oral diabetes medications were inversely related to MC. Our use of a control group with diarrhoea, as opposed to healthy controls, may have contributed to these inverse associations. Future studies of drug-induced microscopic colitis should include control groups with diarrhoea, and not only healthy controls.

Management of Laryngopharyngeal Reflux Around the World: An International Study.

To investigate worldwide practices of otolaryngologists in the management of laryngopharyngeal reflux (LPR). An online survey was sent on the management of LPR to members of many otolaryngological societies. The following aspects were evaluated: LPR definition, prevalence, clinical presentation, diagnosis, and treatment. A total of 824 otolaryngologists participated, spread over 65 countries. The symptoms most usually attributed to LPR are cough after lying down/meal, throat clearing and globus sensation while LPR-related findings are arytenoid erythema and posterior commissure hypertrophy. Irrespective to geography, otolaryngologists indicate lack of familiarity with impedance pH monitoring, which they attribute to lack of knowledge in result interpretation. The most common therapeutic regimens significantly vary between world regions, with a higher use of H2 blocker in North America and a lower use of alginate in South America. The duration of treatment also significantly varies between different regions, with West Asia/Africa and East Asia/Oceania otolaryngologists prescribing medication for a shorter period than the others. Only 21.1% of respondents are aware about the existence of nonacid LPR. Overall, only 43.2% of otolaryngologists believe themselves sufficiently knowledgeable about LPR. LPR knowledge and management significantly vary across the world. International guidelines on LPR definition, diagnosis, and treatment are needed to improve knowledge and management around the world. N.A. Laryngoscope, 131:E1589-E1597, 2021.

The clinical impact of delirium in the patients with acute decompensated heart failure

Abstract Background Delirium is frequent in-hospital complication in patients with illness. However, the clinical impact of delirium on cardiovascular mortality has not been fully addressed in patients with acute decompensated heart failure (ADHF). Methods Between April 2016 and May 2019, 474 consecutive patients with ADHF admitted to our institution were enrolled and followed for 6 months after discharge. Delirium was defined according to the Intensive Care Delirium Checklist. To compare the clinical outcome, we divided study patients into 3 groups according to the presence or absence of delirium: non-delirium (ND) (n=349), improved-delirium during hospitalization (ID) (n=68), and prolonged delirium (PD) (n=57). Results One hundred twenty-five (26.4%) patients developed delirium. During hospitalization, PD had higher incidence of all-cause death, cardiovascular death, and worsening heart failure compared with ND and ID (20.0% vs. 3.7% and 2.9%, 10.9% vs. 2.5% and 1.4%, 21.8% vs. 2.5% and 4.3%, p&amp;lt;0.001, respectively). Multivariable analysis identified the presence of frailty (OR: 8.56, 95% CI: 3.46–23.7) and dementia (OR: 7.34, 95% CI: 3.52–15.9), use of H2-blocker (OR: 3.41, 95% CI: 1.08–10.9) and plasma level of CRP (OR: 1.30, 95% CI: 1.06–1.61) as significant independent determinants of delirium. Also, in multivariable analysis, the development of frailty (OR: 5.51, 95% CI: 2.80–11.5), delirium (OR: 4.59, 95% CI: 2.23–9.66) and age (OR: 1.06, 95% CI: 1.03–1.11) were the independent determinants of composite endpoint with in-hospital death and discharge to other than home. Early treatment of delirium performed significantly higher in ID than PD (55.7% vs. 29.1%, p=0.003). Conclusion This study suggested that PD contributed to increasing in-hospital events in the patients with ADHF and significance of early screening and treatment for delirium. Figure 1. Outcomes during hospitalization Funding Acknowledgement Type of funding source: None

S3306 H2-Blocker Use Is Associated With Acute Kidney Injury Among COVID-19 Patients

INTRODUCTION: The Coronavirus Disease 2019 (COVID-19) has infected over 6.5 million people worldwide, claiming nearly 400,000 lives as of June 2020. Among those hospitalized, acute kidney injury (AKI) occurs in approximately 20–40% of patients. Proton pump inhibitors (PPIs) and H2-blockers (H2Bs) are commonly used medications and have been linked to acute and chronic interstitial nephritis. We assessed the association between PPI or H2B use prior to admission and AKI among patients admitted with COVID-19 infections. METHODS: This was a single center retrospective cohort study. Adult patients with confirmed COVID-19 infection admitted from March to April 2020 were identified. Patients with end-stage renal disease were excluded. Charts were reviewed for patient demographics, outpatient medication list, creatinine at baseline and upon admission, and hospital course. The primary outcome was any association between PPI or H2B use with development of AKI. RESULTS: We reviewed 100 consecutive patients admitted with COVID-19 and 93 patients were included. The mean age of this cohort was 58.9 years and 36.5% were female (Table 1). Sixteen patients were prescribed a PPI prior to admission and 6 patients were on H2B. Of the 93 patients, 84 did not have known chronic kidney disease (CKD). Among patients without CKD, PPI use was not associated with AKI (P = 0.857) but patients taking H2Bs were more likely to develop AKI on admission (P = 0.032) (Figure 1). There were no differences in average BUN-to-creatinine ratios (P = 0.172) or rates of systemic inflammatory response syndrome (P = 0.904) between those who were on H2Bs versus those who were not. CONCLUSION: Among non-CKD patients who were admitted for COVID-19 infection, H2B use was associated with development of AKI whereas PPI use was not. In vitro studies have shown cimetidine to raise serum creatinine theoretically by competitive tubular secretion for creatinine. In the setting of COVID-19 infection and systemic inflammation, reduced renal blood flow adds insult to the kidneys and may synergistically raise serum creatinine with famotidine use. Increased awareness of the relationship between medications and COVID-19 infection may be helpful in providing comprehensive care for critically ill patients.Table 1.: Demographics and clinical characteristicsFigure 1.: Incidence of acute kidney injury (AKI) on admission among patients without chronic kidney disease (CKD).