H2 Blockers Research Articles

The Role of H1 and H2 Blocker in Eradication of Gastrointestinal Malfunctioning

Proton pumps releases acids in GIT which results in increased level of alkaline phosphates. The liver irritation by increased alkaline phosphates results in histamine disbalance. H1 ANDH2 BLOCKER acts as histamine controlling agents. The bacteria use their flagella to stick in stomach mucosal layer. For bacterial growth optimal conditions includes oxygen level b/w 5-15%, approx. CO2 5%, availability of some special amino acids, and 30-37°C temperature. Gastro intestinal Infections involve a spiral-shaped, gram-negative, micro bacterium. It was assumed that earlier no germ might survive in gastric acidic layer, therefore the possibility of microbial colonization of stomach actually was not considered. Thus, the bacterial microenvironment directly surrounds and neutralize the effects of gastric secretions which are corrosive to them and the pathogen escapes.

A Phase IIa, Open-Label, Multicenter Study of Single-Agent Tafasitamab (MOR208), an Fc-Optimized Anti-CD19 Antibody, in Patients with Relapsed or Refractory B-Cell Non-Hodgkin's Lymphoma: Long-Term Follow-up, Final Analysis

A Phase IIa, Open-Label, Multicenter Study of Single-Agent Tafasitamab (MOR208), an Fc-Optimized Anti-CD19 Antibody, in Patients with Relapsed or Refractory B-Cell Non-Hodgkin's Lymphoma: Long-Term Follow-up, Final Analysis

Preoperative Endoscopic Findings in Veterans Undergoing Bariatric Surgery: Prevalence and Predictors of Barrett's Esophagus.

There is no consensus regarding the need for routine esophagogastroduodenoscopy (EGD) in patients before bariatric surgery. The aim of our study is to determine the frequency and predictors of EGD findings in a Veteran population presenting for bariatric surgery. This is a single-center retrospective analysis of Veterans who underwent RYGB or LSG, at a Veterans Affairs hospital between January 2008 and December 2017. All patients received a preoperative EGD. Data abstracted included demographics, comorbidities, preoperative laboratory values, and EGD findings. Univariate and multivariate analyses were performed for common EGD pathologies. Of the 260 Veterans included in our cohort, majority were male (75.0%), Caucasian (73.5%), and aged 54.0 ± 9.0 years old with a BMI of 44.9 ± 7.0 kg/m2. Most had hypertension (78.9%), previously smoked (63.9%), and recently used a proton pump inhibitor (PPI) (53.1%). One third of Veterans had a completely normal preoperative EGD. Common preoperative EGD findings included gastritis (35.8%), hiatal hernia (25.8%), esophagitis (20.8%), duodenitis (10.4%), Barrett's esophagus (7.4%), and Helicobacter pylori infection (4.6%). Preoperative predictors for a normal EGD were female gender, absence of hypertension, and no recent PPI use. Preoperative predictors of Barrett's esophagus included older age, recent PPI use, and recent histamine H2 receptor blocker (H2B) use. Increased age, male gender, and PPI use were associated with a change in surgical and/or medical management. Preoperative factors can be used to identify patients at risk for gastroesophageal pathology. Our data support preoperative EGD especially in older males with a history of PPI or H2B use.

PGI56 EVALUATION OF MORTALITY ASSOCIATED WITH PROTON PUMP INHIBITORS AND H2 BLOCKERS: A REAL WORLD EVIDENCE STUDY

The aim of this analysis was to estimate all-cause mortality among patients taking proton pump inhibitors (PPIs) and histamine H2 antagonists (H2 blockers). Patients identified through a federated network of electronic medical records were required to have taken PPIs or H2 blockers. Among these two cohorts, patients were required to have two records of these treatments recorded in their medical history at least three months apart. Patients treated with PPIs were matched 1-to-1 with patients treated with H2 blockers, using a greedy-nearest-neighbor algorithm. The risk of mortality was measured in the one year, five years, and ten years following the index treatment. All criteria were defined using ICD9/10, CPT, and RxNorm terminology. Kaplan-Meier curves and risk ratios (95% CI) were used to compare groups. The mean age was 54.4 ± 18.8 (N=1,455,638) and 46.6 ± 22.7 (N=496,538) among PPI- and H2 blocker-treated patients. In the matched analysis (N=448,446), H2 blocker patients were 0.089 (0.778,0.841), 0.8 (0.785,0.815), and 0.799 (0.786,0.812) more likely to die than PPI patients in the one year, five years, and ten years following treatment. The survival probability was 0.25%, 1.34%, and 2.35% higher in PPI-treated patients than in H2-treated patients in the one year, five years, and ten years following treatment (all with p<0.05). Taking H2 blockers is associated with a small increased risk of mortality. This burden is observed in patients with and without an indication for PPI or H2 blocker use. PPIs were not associated with an increased risk of death, in contrast to other studies. This difference may be due to a broader and less selective patient population, or use of different controls.

Proton Pump Inhibitors, H2 Blocker Use, and Risk of Inflammatory Bowel Disease in Children.

Evidence suggests use of proton pump inhibitors (PPIs) and H2 blockers may provoke disease flares in individuals with established inflammatory bowel disease (IBD); however, there are no studies investigating the relationship of these medications with risk of developing pediatric IBD. The hypothesis was that use of acid suppression therapy in children might be associated with development of pediatric IBD. This was a nested case-control study of 285 Kaiser Permanente Northern California members, age ≤21 years diagnosed with IBD from 1996 to 2016. Four controls without IBD were matched to each case on age, race, and membership status at the case's index date. Disease risk scores (DRS) were computed for each subject. Odds ratios and 95% confidence intervals were calculated by using conditional logistic regression models adjusted for DRS. The children's mean age was 15.1 ± 2.6 years and 49.5% were female. Six cases (n = 3 Crohn's disease [CD], n = 3 ulcerative colitis [UC]) and 6 controls were prescribed PPIs and 10 cases (n = 7 CD, n = 3 UC) and 28 controls were prescribed H2 blockers. The OR for the association of at least 1 PPI or H2 blocker prescription with subsequent IBD was 3.6 (95% CI, 1.1-11.7) for PPIs and 1.6 (95% CI, 0.7-3.7) for H2 blockers. Early-life PPI use appears to be associated with subsequent IBD risk. These findings have implications for clinical treatment of children with gastrointestinal symptoms and warrant further investigation in a larger cohort.

Healthcare facility-onset, healthcare facility-associated Clostridioides difficile infection in Veterans with spinal cord injury and disorder

Objective: To describe the burden and risk of healthcare facility-onset, healthcare facility-associated (HO-HCFA) Clostridioides difficile infection (CDI) in Veterans with spinal cord injury and disorder (SCI/D). Design: Retrospective, longitudinal cohort study from October 1, 2001–September 30, 2010. Setting: Ninety-four acute care Veterans Affairs facilities. Participants: Patients with SCI/D. Outcomes: Incidence rate of HO-HCFA CDI. Methods: Rates of CDI were determined, and crude unadjusted incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were calculated. Multivariable Poisson random-effects regression analyses were used to assess factors independently associated with the rate of CDI. Results: 1,409 cases of HO-HCFA CDI were identified. CDI rates in 2002 were 13.9/10,000 person-days and decreased to 5.5/10,000 person-days by 2010. Multivariable regression analyses found that antibiotic (IRR = 18.79, 95% CI 14.09-25.07) and proton-pump inhibitor (PPI) or H2 blocker use (IRR = 7.71, 95% CI 5.47-10.86) were both independently associated with HO-HCFA CDI. Exposure to both medications demonstrated a synergistic risk (IRR = 37.55, 95% CI 28.39-49.67). Older age, Northeast region, and invasive respiratory procedure in the prior 30 days were also independent risk factors, while longer SCI duration and care at a SCI center were protective. Conclusion: Although decreasing, CDI rates in patients with SCI/D remain high. Targeted antimicrobial stewardship and pharmacy interventions that reduce antibiotic and PPI/H2 blocker use could have profound benefits in decreasing HO-HCFA CDI in this high-risk population.

Proton pump inhibitors block iron absorption through direct regulation of hepcidin via the aryl hydrocarbon receptor-mediated pathway

Proton pump inhibitors (PPIs) have been used worldwide to treat gastrointestinal disorders. A recent study showed that long-term use of PPIs caused iron deficiency; however, it is unclear whether PPIs affect iron metabolism directly. We investigated the effect of PPIs on the peptide hepcidin, an important iron regulatory hormone. First, we used the FDA Adverse Event Reporting System database and analyzed the influence of PPIs. We found that PPIs, as well as H2 blockers, increased the odds ratio of iron-deficient anemia. Next, HepG2 cells were used to examine the action of PPIs and H2 blockers on hepcidin. PPIs augmented hepcidin expression, while H2 blockers did not. In fact, the PPI omeprazole increased hepcidin secretion, and omeprazole-induced hepcidin upregulation was inhibited by gene silencing or the pharmacological inhibition of the aryl hydrocarbon receptor. In mouse experiments, omeprazole also increased hepatic hepcidin mRNA expression and blood hepcidin levels. In mice treated with omeprazole, protein levels of duodenal and splenic ferroportin decreased. Taken together, PPIs directly affect iron metabolism by suppressing iron absorption through the inhibition of duodenal ferroportin via hepcidin upregulation. These findings provide a new insight into the molecular mechanism of PPI-induced iron deficiency.

2389. Assessing the Time Course of Proton Pump Inhibitor Use and Clostridioides difficile Infection

BackgroundProton pump inhibitors (PPIs) are a known risk factor for Clostridioides difficile infection (CDI) and recurrence, even in the absence of antibiotic use. No studies have specifically assessed the increased risk for CDI based on PPI duration, given that PPIs are frequently newly prescribed during hospitalizations and infrequently discontinued, even when CDI has occurred. The aim of this project was to assess the time course of PPI utilization and risk of CDI.MethodsWe conducted a retrospective matched case–control study comparing patients who developed CDI (cases) with patients who did not develop CDI (controls, matched on age, gender, date of admission and hospital location) from a cohort of patients with a C.difficile PCR test order from an academic medical center. Patient charts were reviewed for PPI use prior to the date of the positive test and whether the PPI was started in the hospital or as a home medication (>30d, 30–90d, 90–180d, >180d). The primary comparison was odds of PPI use between cases and controls using conditional logistic regression adjusted for antibiotic exposure (SAS 9.4, Cary, NC).ResultsA total of 348 patients were included in the study, 174 cases and 174 matched controls. 65% of patients in the study received a PPI, 85% a PPI or H2 blocker and 95% of patients received antibiotics during their admission. Patients on PPIs as home medications were not at an increased risk of CDI (OR = 1.08 (95% CI 0.60–1.93)) compared with those not on PPIs. Patients whose PPIs were initiated in the hospital were at increased risk of CDI compared with those not on PPIs (OR = 1.4 (95% CI 0.81–2.41)). No significant difference was observed across time periods of PPI use prior to admission and development of CDI.ConclusionPatients who started PPIs during inpatient stays were at a higher risk of developing CDI than patients not exposed to PPIs. However, PPI use was not found to be significantly associated with CDI in this analysis, regardless of the time or duration of PPI prescription. The results may be confounded by the high frequency of PPI use and concomitant antibiotic use in both cases and controls. Further study is needed to evaluate the impact of short-course PPI prescriptions in inpatient settings on CDI.Disclosures All authors: No reported disclosures.

Papillary thyroid cancer patient with hyperthyroidism - a case study

Thyroid carcinoma is the majority widespread endocraine malignancy in that papillary thyroid cancer is a well-differentiated type. Since hyperthyroidism protects from thyroid cancer due to lack of reproduction of thyroid tissue by the thyroid-stimulating hormone. The papillary carcinoma is the fast-growing and metastases to local region rapidly. A 60 years old post menopausal women with a known case of hypertension of past 6 years on treatment and with hyperthyroidism of past 2 months was presented in the outpatient department in the hospital with chief complaints of mass in the neck with dyphagia, cough, breathlessness, sense of fullness and odynophagia of past 2 weeks. On physical and general examination patient found with diffuse thyroid swelling with enlarged right sided lymph node. The patient was diagnosed with papillary thyroid caricinoma with various investigation reports includes CT Scan, Immouno history chemistry reports, Histopathology and Two fine-needle aspiration biopsies. The patient has undergone 6 cycles of chemotherapy with the corticosteroids, anti-cancer drugs which includes Vincristine, Cyclophosphamide, Doxorubicin, anti- emetic drugs and also with H2 receptor blockers. The papillary thyroid cancer is common and occurs predominantly in females than in males and with good prognosis and decreased death rates. The higher level of thyroid function is very rare in case of PTC.

Discussion

Discussion

Association of gastric acid suppression with efficacy of immune checkpoint inhibitors (ICIs) in advanced cancer patients

Abstract Background Recent studies have shown that proton pump inhibitor (PPI) negatively impacts on the clinical benefit from ICIs. Gut microbiome modulated by PPI may contribute to decreased efficacy. It has been also reported that H2 blocker (H2B) or gastrectomy affected gut microbiome. We assessed in this study the association of GAS including PPI, H2B and gastrectomy with clinical outcome from ICI. Methods We retrospectively investigated advanced cancers pts treated with ICIs as the 1st- to the 3rd-line treatment at our institution between July 2014 and September 2018. GAS was defined as using PPI or H2B within 30 days before start of ICI, or having past history of gastrectomy. Response to ICIs was assessed by RECIST v1.1. Performance status (PS), body mass index, antibiotics, steroid, LDH level, albumin level, CPR and neutrophil-lymphocyte ratio (NLR) were compared between the GAS and non-GAS arms. Associations of nominal variables with the response were evaluated. Results Total of 115 pts (lung 69.9%, skin 11.3%, head and neck 7.8%, renal cell 6.9%, stomach 4.2%, and urothelium 2.5%) were evaluated. The types of ICIs were nivolumab of 72.2%, pembrolizumab of 22.6%, and atezolizumab of 5.2%. Sixty of 115 pts recieved GAS (PPI 83.3%, H2B 11.6%, and gastorectomy 5%) before start of ICI. Patients’ characteristics between the GAS and non-GAS arms was almost well balanced. However, pts with lower PS (>2) or high NLR were more frequently observed in the GAS arm (20% vs. 0%, 40% vs. 16%, respectively). The response rate (RR) was almost significantly lower in the GAS arm than the non-GAS arm (12% vs. 25%, P = 0.055). GAS did not remain statistically significant in a multivariate analysis (P = 0.091), while LDH was significant in both uni- and multivariate analyses. Conclusion Pts with GAS and pts without GAS have different patients’ background such as PS and NLR, and the RR in pts with GAS was numerically lower compared to that without GAS in advanced cancer treated with ICI.

1210 Implementation of Stress Ulcer Prophylaxis Appropriate Use Criteria in a Community Hospital

INTRODUCTION: Upper gastrointestinal stress ulcer formation is a potential risk for critically ill hospitalized patients. Due to this, SUP is an important preventative measure for at risk patients. Stress ulcer medications such as PPIs and H2 blockers do come with potential side effects.1,2 A widely accepted guideline was written by the American Society of Health System Pharmacists which along with similar variations continue to be used today.3,4 One such guideline has been implemented within the Ascension Health System (Figure 1). Despite guidelines, inappropriate administration continues to be a common problem. Studies show rates of inappropriate administration anywhere from 20 to 70 percent.5–9 A discrepancy in knowledge from providers leads to inappropriate prescribing of SUP medications. Administration of these laminated cards will improve appropriate administration of the medications. METHODS: Laminated cards were dispersed to fit on ID badges of IM and FP residents which following the Ascension SUP guidelines. Data was collected on all patients admitted under the core faculty of an IM or FP attending between 7/1/18–9/30/18 and 11/1/18–1/31/19. 10/1/19-10/31/19 constituted the run-in period. Patients were excluded if they had active diagnoses of GERD, PUD, H. Pylori. Eligible patients' charts were reviewed at random by using an online number generator. The A&amp;P section of the H&amp;P note was reviewed to determine if SUP was was appropriately administered, appropriately held, inappropriately administered, or inappropriately held. Any discrepancies were reviewed by the principal investigator. A t-test was performed to determine if statistical significance was achieved. RESULTS: There were 124 and 115 patients in the pre and post-intervention period respectively. There was an overall improvement of 5.64% (P = 0.21) after distribution of cards (Figure 1). Inappropriately given SUP use improved by 5.01% (P = 0.22). Inappropriately held SUP use improved by 0.61% (P = 0.78). CONCLUSION: Administration of cards improved appropriate prescribing. The cards provided a resource to aid in enhancing knowledge and on-the-go decision making. The availability of implementing these guidelines or similar such protocols using EMR may be more effective in reaching a wider audience of physicians and provide a consistent effect on prescribing habits.

1765 Delayed Esophageal Clearance Plays an Important Role in Reflux Symptomology in Scleroderma Patient

INTRODUCTION: We present the case of a patient with advanced scleroderma who experienced symptoms of refractory reflux despite maximum acid suppressing therapy. The use of 24-hour ambulatory esophageal pH impedance measurement led to the diagnosis of esophageal stasis, with subsequent management leading to the improvement of symptoms even with decreased proton pump inhibitor (PPI) dose. CASE DESCRIPTION/METHODS: 70-year old female with history of advanced scleroderma presented with severe retrosternal burning which she described as worst at night. She was taking 60mg Dexlansoprazole daily, an aluminum-magnesium-antacid, as well as an H2 blocker. An outside CT of the chest and abdomen showed a fluid-filled dilated esophagus and upper endoscopy was significant for a small hiatal hernia. The patient initially underwent high resolution manometry (HRM) which showed absent peristalsis. Subsequent pH impedance study identified low impedance in the esophagus with good gastric acid control (gastric acid exposure of 36%) but markedly abnormal gastric acid exposure in the distal esophagus: recumbent time acid exposure 94%, upright acid exposure 3%, and total acid exposure time of 40% despite high dose PPI. Recumbent position acid exposure at the distal esophagus was more prolonged than nocturnal gastric acidity, indicating esophageal stasis was a major factor in symptomatology. The patient was instructed to take her PPI and antacids close to bedtime, sleep with head elevation, and avoid late meals. The patient experienced significant symptom improvement and her PPI dose was successfully decreased. DISCUSSION: Scleroderma is a multiorgan connective tissue disorder affecting the gastrointestinal tract. The most commonly affected portion of the GI tract is the esophagus, with destruction of the smooth muscles of the lower esophageal sphincter and distal esophageal body. Abnormal reflux has been identified in patients with scleroderma on 24-hour pH monitoring in as many as 80% of patients. However, these study findings do not account for delayed esophageal clearance from failed or ineffective esophageal contractions. Patients with systemic sclerosis frequently have large dilated esophagi (pseudoachalasia) with subsequent stasis a major contributing factor for their symptoms. Thus, while pH studies are a useful diagnostic tool in patients with advanced scleroderma, therapeutic measures addressing esophageal stasis, such as nighttime head elevation, should be encouraged.

1876 A Rare Case of Giardia Duodenalis on Duodenal Biopsy in a Patient With Chronic Abdominal Pain

INTRODUCTION: Giardia duodenalis is an intestinal flagellated protozoan parasite and is the most common parasitic infection in the GI tract, having been estimated to effect as much as 2-5% of the population in developed countries. Symptoms of giardiasis in children include diarrhea, flatulence, abdominal cramping, nausea, and dehydration; however, in adults the symptoms are often absent or short-lived. Giardiasis is typically diagnosed by identification of cysts or trophozoites with a test for ova and parasites in the stool of infected patients. Here we present a rare care of a patient with chronic abdominal pain who was diagnosed with giardiasis via duodenal biopsy. CASE DESCRIPTION/METHODS: A 65-year-old male with a past medical history of COPD, HTN, and depression was evaluated for abdominal pain that had been ongoing for the last two years. The pain was primarily epigastric with occasional radiation to the upper quadrants, worse after eating, and often occurred at night, awakening him from sleep. He denied any constipation, diarrhea, hematochezia, melana, or weight loss. He did not take any PPIs or H2 blockers. His last colonoscopy was in 2015 and was notable only for a few polyps. Physical exam was notable for mild tenderness in the upper quadrants and epigastric area. Esophagogastroduodenoscopy (EGD) showed mild dilation in the distal esophagus, nodularity in the gastric corpus, patchy erythema and erosions in the antrum of the stomach. Duodenum was notable for diffuse erythema and friability in the bulb. The second portion of the duodenum appeared normal. Pathology was notable for multiple pieces of the duodenal mucosa showing numerous Giardia parasites and focal acute erosive duodenitis (Figure 1). Multiple pieces of gastric mucosa showed chronic gastritis and numerous H. pylori organisms. Moderate esophagitis compatible with reflux was also observed. Presidential Poster AwardThe patient was prescribed triple therapy with omeprazole 20mg BID, amoxicillin 1g TID, and metronidazole 500mg TID for 10 days to cover both H. pylori and Giardia duodenalis and then was instructed to continue on omeprazole 20mg daily. DISCUSSION: For patients in whom Giardia or other infectious etiology is suspected, stool O&amp;P are routinely ordered. However, the sensitivity of examining one stool specimen is only 50-70%. This case demonstrates the utility of EGD as a more sensitive diagnostic tool when there is strong clinical suspicion but stool studies fail to reveal a definitive diagnosis.

Indian consensus on gastroesophageal reflux disease in adults: A position statement of the Indian Society of Gastroenterology.

The Indian Society of Gastroenterology developed this evidence-based practice guideline for management of gastroesophageal reflux disease (GERD) in adults. A modified Delphi process was used to develop this consensus containing 58 statements, which were generated by electronic voting iteration as well as face-to-face meeting and review of the supporting literature primarily from India. These statements include 10 on epidemiology, 8 on clinical presentation, 10 on investigations, 23 on treatment (including medical, endoscopic, and surgical modalities), and 7 on complications of GERD. When the proportion of those who voted either to accept completely or with minor reservation was 80% or higher, the statement was regarded as accepted. The prevalence of GERD in India ranges from 7.6% to 30%, being < 10% in most population studies, and higher in cohort studies. The dietary factors associated with GERD include use of spices and non-vegetarian food. Helicobacter pylori is thought to have a negative relation with GERD; H. pylori negative patients have higher grade of symptoms of GERD and esophagitis. Less than 10% of GERD patients in India have erosive esophagitis. In patients with occasional or mild symptoms, antacids and histamine H2 receptor blockers (H2RAs) may be used, and proton pump inhibitors (PPI) should be used in patients with frequent or severe symptoms. Prokinetics have limited proven role in management of GERD.

1346 CA 19-9: Elevation in Mycobacterium Avium-Intracellulare Infections

INTRODUCTION: Carbohydrate antigen 19-9 is usually associated with pancreatic malignancy. However, other causes as bronchiectasis can cause lab elevation. Here we present a case of an elevated CA 19-9 with pulmonary mycobacterium avium-intracellulare. CASE DESCRIPTION/METHODS: 66 year old HIV negative female with MAI (Figure 1) on Ethambutol, Rifampin, Azithromycin (started 4/2017, stopped 10/2017, restarted 1/2018) presented to clinic with complaints of epigastric pain with unintentional weight loss. She was started on proton pump inhibitor and H2 blocker therapy and underwent EGD and colonoscopy with biopsies positive for Helicobacter pylori. She received quadruple therapy with eradication on stool antigen. She complained of a mass in her supra-pubic region and given this with her weight loss and normal endoscopies, a CT Abdomen and Pelvis was performed which showed no hepato-biliary abnormalities but significant bladder distention (Figure 2). This resolved on its own prior to her seeing urology or coming in for follow up. A CA 19-9 remained elevated at 105, 94, and 111 during this time frame. DISCUSSION: Mycobacterium is a masquerader causing hydronephrosis to bronchiectasis, both seen in our patient, with the mechanism of CA 19-9 elevation unknown. Shin et al presented a patient with MAI and elevated CA 19-9 levels, which improved with treatment. 1 Studies have shown an elevated CA 19-9 may be from MAI infection or other causes of bronchiectasis, such as Chang et al in 2013. 2 Yamazaki et al compared CA 19-9 in patients with deteriorated (96.9) vs non-deteriorated (19.2) disease. 3 Hong and colleagues in their analysis showed that CA 19-9 could be elevated in patients with MAI and improved with treatment. 4 Here, we highlight the importance of a differential diagnosis of non-pancreatic etiologies for elevated CA 19-9 levels.

Drug utility pattern of antiulcer agents used in osteoarthritis patients at tertiary care hospital

Background: Osteoarthritis is the most common form of joint disease and the leading cause of pain in elderly people. Osteoarthritis (OA) is a progressive and painful chronic disease that mainly affects knee, hand and hip joints.Aim of study was to evaluate current trend of antiulcer drugs and to assess the group of antiulcer agents use in osteoarthritis patient.Methods: A prospective observational study was conducted in a tertiary care hospital for period of twelve months in collaboration with department of orthopaedics. Patients data recorded in case report form and analysed to study prescription pattern and related information Results: Total of 630 cases were enrolled in this study. Prescribed antiulcer drugs in OA were ranitidine, omeprazole, pantoprazole, rabeprazole, sucralfate and esomeprazole. Most commonly prescribed drug was Ranitidine i.e. 80.79% followed by omeprazole i.e. 8.42% pantoprazole i.e. 3.97% rabeprazole i.e. 3.81%, sucralfate i.e. 2.53% and esomeprazole i.e. 0.48% respectively. In this study, the commonest group prescribed was H2 blockers i.e. 80.79% followed by proton pump inhibitors i.e. 16.68%, and ulcer healing agent i.e. 2.53% respectively.Conclusions: Most commonly prescribed drug was ranitidine followed by omeprazole, pantoprazole, rabeprazole, sucralfate and esomeprazole respectively. In this study, the commonest group prescribed was H2 blockers followed by proton pump inhibitors, and ulcer healing agent respectively.

A Proposal of Conducting Bioequivalence Trials with Gastric pH Modulators for Two Oral Formulations Demonstrating Different Dissolution Profiles at Elevated pH.

In this paper, a special case for bioequivalence evaluation of oral formulations is discussed. Drug formulations with different forms of active moieties (e.g., free base and salt) may yield different dissolution characteristics and, thus, differ in absorption at elevated gastric pH. However, routine bioequivalence trials using subjects with normal gastric pH (i.e., ~ 1) may fail to identify these differences because dissolution/absorption profiles of the two formulations at normal gastric pH are similar. In the case of palbociclib, it is confirmedthat the free base and salt formulations showed different absorption in patients with different gastric pH. Significant reduction in drug absorption was observed only in patients with elevated gastric pH using free base formulation. The discovery that the free base had significantly reduced absorption hinged on the inclusion of enough patients with elevated gastric pH to detect a difference in a bioequivalence trial. This raises a concern, as demonstrated through simulation, that dissolution/absorption differences in other formulations could be missed in routine bioequivalence trials. Aside from differences in active pharmaceutical ingredients (APIs), other factors, such as changes in excipients or manufacturing methods, may also lead to exposure differences between formulations at elevated gastric pH. For formulations containing different forms of the same active moiety or the same API and showing different dissolution profiles at elevated pH (i.e., pH ~ 4–6.8), evaluation of bioequivalence with gastric pH modulators (e.g., a H2 blocker) in addition to routine bioequivalence assessments may help to ensure therapeutic equivalence in patients with elevated gastric pH.

Risk factors associated with the incidence and time to onset of lapatinib-induced hepatotoxicity.

Although lapatinib-induced hepatotoxicity can cause severe clinical complications in patients, the factors affecting hepatotoxicity have rarely been investigated. The purpose of this study was to investigate risk factors for hepatotoxicity and time to lapatinib-induced hepatotoxicity. This retrospective study was performed on metastatic breast cancer patients treated with lapatinib. Various factors were evaluated for hepatotoxicity and time to hepatotoxicity, including sex, age, body weight, height, body surface area, underlying disease, smoking history, start dose of lapatinib, status of liver metastasis, and concomitant drugs. Among 159 patients, the percentage of patients with hepatotoxicity after lapatinib initiation was 57.9% (n = 92). Multivariate analysis showed that concomitant use of H2 blockers increased the incidence of hepatotoxicity by 2.3-fold. Patients who received CYP3A4 inducers had 3.1 times higher risk of hepatotoxicity incidence; the attributable risks of H2 blockers and CYP3A4 inducers were 56.7% and 68.1%, respectively. Use of H2 blockers increased the hazard of time to hepatotoxicity by 1.8-fold compared to non-use of H2 blockers. Our study demonstrated that concomitant use of H2 blockers and CYP3A4 inducers was associated with lapatinib-induced hepatotoxicity. Close liver function monitoring is recommended, especially in patients receiving H2 blockers or CYP3A4 inducers.

Acute calcific retropharyngeal tendinitis

A 44-year-old man with a 3-day history of limited range of motion of the bilateral shoulders, neck pain, dysphagia and mild fever presented to our emergency department. He had no...