Including Proton Pump Inhibitors Research Articles

Frequency of Peptic Ulcer Disease in Patients with Chronic Liver Disease Presenting with Upper Gastrointestinal Bleeding

Background: Peptic ulcer disease (PUD) is a significant cause of morbidity and mortality worldwide, particularly in patients with chronic liver disease (CLD). The occurrence of upper gastrointestinal bleeding (UGIB) in CLD patients presents a serious complication, often requiring urgent medical intervention. Objective: The main objective of this study was to determine the frequency of peptic ulcer disease in patients with chronic liver disease presenting with upper gastrointestinal bleeding. Methods: This retrospective observational study was conducted at Ayub Teaching Hospital, Abbottabad, from 2021 to 2023. Data were collected from 105 patients diagnosed with chronic liver disease who presented with symptoms of upper gastrointestinal bleeding. The diagnosis of CLD was confirmed through clinical evaluation, biochemical tests, imaging studies, and/or liver biopsy. Patients included were aged 18 years and above and presented with UGIB evidenced by hematemesis, melena, or both. Exclusion criteria were individuals with bleeding disorders unrelated to CLD and those who did not undergo endoscopic evaluation. Data collection involved demographic information, clinical history, duration and etiology of CLD, comorbid conditions, and UGIB presentation. Upper gastrointestinal endoscopy was performed on all patients to identify the source of bleeding. Statistical analysis was performed using SPSS version 25, with a p-value of less than 0.05 considered statistically significant. Results: The study included 105 patients, with a mean age of 55.3±3.27 years; 65 (61.9%) were male, and 40 (38.1%) were female. The etiologies of CLD were viral hepatitis (42.9%), alcoholic liver disease (28.6%), non-alcoholic fatty liver disease (19.0%), and other causes (9.5%). Clinical presentations of UGIB included hematemesis (66.7%), melena (23.8%), and both (9.5%). Endoscopic findings revealed that 35 patients (33.3%) had peptic ulcer disease, with 20 (57.1%) having duodenal ulcers and 15 (42.9%) having gastric ulcers. Other sources of UGIB included esophageal varices (38.1%), gastric varices (14.3%), erosive gastritis (9.5%), and malignancies (4.8%). Associated risk factors for PUD included NSAID use (42.9%), smoking (28.6%), and coexisting portal hypertension (71.4%). The mean size of ulcers was 10.2 mm. Endoscopic therapy was utilized in 71.4% of cases, with pharmacological treatment primarily including proton pump inhibitors (85.7%). Complications included rebleeding within 7 days (14.3%) and the need for surgical intervention (5.7%). The mean hospital stay was 7.8 days, and in-hospital mortality was observed in 8.6% of patients. Conclusion: Peptic ulcer disease represents a substantial yet manageable complication in patients with chronic liver disease presenting with upper gastrointestinal bleeding. Prompt recognition and targeted therapeutic interventions are crucial for optimizing outcomes in this high-risk population.

Functional Abdominal Pain in Children

Background: Functional abdominal pain (FAP), often affecting girls and those with mental health issues, is a prevalent pediatric disorder characterized by persistent symptoms without a clear identifiable organic pathology. The Rome IV Criteria classify it into subtypes, which have distinct symptoms and required tailored management approaches. Discussion: Subtypes classified by the Rome IV Criteria include irritable bowel syndrome (IBS), functional dyspepsia, abdominal migraine, and FAP - not otherwise specified (NOS). The pathophysiology involves gut hypersensitivity, hyperalgesia, genetic predispositions, and psychosocial triggers. Diagnosis relies on medical history, physical examination, the presence of alarm signs, and the characteristic of pain. Treatment strategies encompass dietary modifications, psychological interventions, pharmacology treatment including proton pump inhibitors, prokinetics, and antidepressants like amitriptyline. Conclusion: Recognizing the specific subtypes, as defined by the Rome IV Criteria, allows healthcare professionals to implement individualized care strategies for optimal outcomes.

Hypomagnesemia may be related to frailty, gait and balance problems, and basic activities of daily living in older adults

ABSTRACT Objectives The study aims to investigate the relationship between hypomagnesemia, preclinical hypomagnesemia, and normomagnesemia as along with geriatric syndrome and comprehensive geriatric parameters(CGA). Methods 217 patients who applied to the geriatric clinic between November 2022 and December 2023 were included in the study. All patients underwent CGA. Patients were categorized into three groups: Magnesium (Mg) level ≤ 1.5 mg/dL, Mg level 1.5–1.8 mg/dL, and Mg level > 1.8 mg/dL. These three groups were compared in terms of demographic characteristics, comorbidities, CGA parameters, and geriatric syndromes. Regression analyses was conducted for significant parameters, adjusting for confounders. Results 74.9% of all participants were female, with an average age of 76.5 ± 6.6 years. The frequency of hypomagnesemia was 14.2%. Demographic characteristics and medication use, including proton pump inhibitors and diuretics, were similar in these three groups. While the FRIED frailty scale and the duration of the timed-up-and-go test were higher in the hypomagnesemia group, the Basic Activities Daily of Living (ADLs) and the Tinetti-POMA(performance-oriented mobility assessment) scores were lower in the hypomagnesemia group. When normomagnesemia was accepted as the reference category, FRIED frailty scale, Basic ADLs, and POMA score were more significant in the hypomagnesemia group (p = 0.025, p = 0.013 and p = 0.011,respectively), but there was no significance in the preclinical hypomagnesemia group regardless of the covariates. Conclusion Hypomagnesemia, particularly serum Mg levels below 1.5 mg/dL, may be associated with frailty, basic ADLs, gait, and balance tests. In geriatric practice, patients with hypomagnesemia should be evaluated in terms of the risk of the mentioned disorders.

The Impact of reference pricing on prescribing patterns, costs, and health services utilization of proton pump inhibitors: A quasi-experimental study in British Columbia, Canada

IntroductionThe Reference Drug Program (RDP) was established to steer patients toward equally safe and cost-effective medication under British Columbia's public drug coverage. Each RDP class covers at least one reference drug, and non-reference drugs are reimbursed up to the cost of the reference drug. In 2016, the RDP updated to include proton pump inhibitors (PPIs). This study evaluated the impact on drug expenditures, prescription patterns, and health services utilization. MethodsWe identified a cohort of individuals covered by Fair Pharmacare who used PPIs, and a control group of H2 Blockers users. We used interrupted time series analysis on administrative data from June 2014 to December 2019 on the following outcomes: new users, day supply, expenditures, drug costs, reference drug use, and physician visits and costs. ResultsThe RDP had little impact on overall PPI use patterns. We did not observe any changes in reference drug uptake, new users, physician visits, cost-savings, or significant changes to days supplied post-policy. Cost expenditure results were likely biased due to co-occurring changes to drug prices. ConclusionInclusion of PPIs to the RDP saw no cost-savings for the provincial drug program and had little impact on prescribing patterns. Overall, our findings are consistent with existing evidence that the RDP is safe for similar therapeutic alternatives, but the impact on PPI costs remains unclear.

Current Status of Anti-Reflux Surgery as a Treatment for GERD.

Anti-reflux surgery (ARS) is an efficient treatment option for gastroesophageal reflux disease (GERD). Despite growing evidence of the efficacy and safety of ARS, medications including proton pump inhibitors (PPIs) remain the most commonly administered treatments for GERD. Meanwhile, ARS can be an effective treatment option for patients who need medications continuously or for those who are refractory to PPI treatment, if proper candidates are selected. However, in practice, ARS is often regarded as a last resort for patients who are unresponsive to PPIs. Accumulating ARS-related studies indicate that surgery is equivalent to or better than medical treatment for controlling typical and atypical GERD symptoms. Furthermore, because of overall reduced medication expenses, ARS may be more cost-effective than PPI. Patients are selected for ARS based on endoscopic findings, esophageal acid exposure time, and PPI responsiveness. Although there is limited evidence, ARS may be expanded to include patients with normal acid exposure, such as those with reflux hypersensitivity. Additionally, other factors such as age, body mass index, and comorbidities are known to affect ARS outcomes; and such factors should be considered. Nissen fundoplication or partial fundoplication including Dor fundoplication and Toupet fundoplication can be chosen, depending on whether the patient prioritizes symptom improvement or minimizing postoperative symptoms such as dysphagia. Furthermore, efforts to reduce and manage postoperative complications and create awareness of the long-term efficacy and safety of the ARS are recommended, as well as adequate training programs for new surgeons.

Unveiling the uncommon: Lichenoid esophagitis secondary to Steven Johnson syndrome

Lichenoid Esophagitis (LE) is a rare pathology characterized by inflammation of the esophagus resembling a lichenoid pattern for which a precise histological diagnosis cannot be established. The diagnosis of LE is often challenging due to its nonspecific clinical presentation and lack of a definitive histological diagnosis. LE can cause various complications, including esophageal strictures, Barrett’s esophagus, dysphagia, esophageal ulcers, and an increased risk of esophageal cancer. Treatment options include proton pump inhibitors, dietary changes, and corticosteroids. In this report, we describe the case of a 47-year-old female who developed lichenoid esophagitis due to SJS as a result of sulfasalazine therapy.

Clinical Utility of Dupilumab for the Treatment of Eosinophilic Esophagitis in Pediatric Patients

Background:Eosinophilic esophagitis (EoE) is a chronic inflammatory disease of the esophagus characterized by symptoms of esophageal dysfunction and 15 or more eosinophils per high-powered field (HPF) on esophageal biopsy. Treatment options for EoE include proton pump inhibitors (PPIs), topical corticosteroids (TCS), dietary elimination, and dupilumab. Dupilumab is monoclonal antibody against IL-4 and IL-13 administered subcutaneously and was granted FDA approval for EoE in adults and adolescents recently in 2022. Outcomes of real-world, clinical use of dupilumab for EoE remains unknown.
 Objectives:To observe outcomes in pediatric patients with EoE treated with dupilumab.
 Methods:A retrospective cohort study of pediatric patients prescribed dupilumab for EoE was conducted. Medical records were reviewed for demographic and clinical information as well as endoscopic and histologic findings before and after dupilumab treatment.
 Results:A total of 28 patients were included (mean age 15y, 71.4% male). Mean baseline maximum eosinophils/HPF was 48 ± 41. 75% of patients were treated with combination therapy of EoE with diet elimination, PPIs, or TCS prior to being prescribed dupilumab. Prior authorization for dupilumab was required in 85.7% of cases. Ten patients had follow-up endoscopy with biopsy after starting dupilumab, and among these patients the mean maximum eosinophils/HPF with dupilumab significantly improved from 44 ± 37 to 13 ± 15 (p=0.027). Among 12 patients who had follow up clinic visits, two patients reported pain or swelling at injection sites, but no otheradverse events were reported
 Conclusions:Dupilumab significantly improves histologic findings of EoE and is well tolerated among pediatric patients. We hope for continued monitoring of these patients to understand the clinical utility of dupilumab for EoE over time.

Esofagitis eosinofílica

Eosinophilic esophagitis is a chronic immune-mediated inflammatory disease of the esophagus. Its incidence has increased in recent years and it is one of the most prevalent esophageal diseases, with a significant impact on physical health and quality of life. Symptoms are variable and it is an increasingly common cause of dysphagia in both children and adults. The gold standard for diagnosis is upper gastrointestinal endoscopy with biopsies of patches demonstrating inflammatory infiltrate with more than 15 eosinophils per high-power field. Various effective treatments are currently available for both induction and maintenance of disease remission, including proton pump inhibitors, swallowed topical corticosteroids, and exclusion diets.

Safety of Proton Pump Inhibitors in Pediatric Population: A Systematic Review.

Objective. Commonly recommended drugs for adults and children include proton pump inhibitors (PPIs), proven effective for treating peptic diseases like stomach ulcers, GERD, and Helicobacter pylori infections in children over 1-year-old. Yet, prolonged PPI use carries higher risks of adverse reactions, prompting this study's analysis. Methods. We have performed a systematic review of 30 articles, which include a total of 762 505 pediatric patients. Results. Adverse effects were encountered in 6.98% of the population. The 5 most common adverse effects were respiratory tract complications, gastrointestinal complications, urinary tract infections, asthma, and ENT infections. Conclusion. Hence, PPIs should be prescribed only when necessary, and physicians should prioritize patient education when considering their use.

Course of Esophageal Strictures in Eosinophilic Esophagitis Using Structured Esophagram Protocol

A key unknown in eosinophilic esophagitis (EoE) is the long-term course of esophageal stenosis. Our aim was to evaluate the course of esophageal strictures using structured serial esophagrams and determine predictors of diameter improvement in patients with EoE. This was a retrospective study of 78 EoE patients who completed 2 structured esophagrams at an academic tertiary referral center between 2003 and 2021. Maximum and minimum esophageal diameters were measured during esophagram using a standardized protocol to reduce measurement errors. The median age at first esophagram was 36.2 (12.9-64.3) years; 60.3% of patients were male; 41 patients had active EoE; and 9 were inactive. Of the patients, 39.7% had allergic rhinitis, asthma (32.1%), and atopic dermatitis (7.7%). Medical therapies at second esophagram and esophagogastroduodenoscopy included proton pump inhibitors (39.5%), swallowed topical steroids (31.6%), diet elimination (13.2%), biologic therapies (1.3%), and clinical trial medications (1.3%). Median maximum diameter significantly increased by 1.0 mm (Q1:-1.0 mm, Q3: 3.0 mm) (P= .034), independent of dilation (P= .744). Increase was most profound in patients starting in the lowest maximum diameter group (9-15 mm) with median increase of 3.0 mm. For patients in disease remission at the second esophagram, there was a significant increase in maximum diameter per year compared to active disease at 0.8 mm (Q1: 0.0 mm, Q3: 5.3 mm) and 0.0 mm (Q1:-0.4 mm, Q3: 0.6 mm) respectively (P= .019). Long-term improvement in esophageal strictures in patients with EoE may occur but is modest and likely occurs over years. Progression also appears to be minimal. Continuous medical treatment may reduce the rate of stricture recurrence and may improve stricture diameter over time.

Assessment of prescription pattern and impact of statin in lipid profile among ischemic heart disease patients.

Analysis of prescription patterns and lipid profiles can play a crucial role in rational drug use and patient safety. This study aimed to analyze the prescription pattern and impact of statin in lipid profile among ischemic heart disease (IHD) patients. A prospective observational study was conducted for 7 months in the cardiology department. IHD patients above 18 years and undergoing statin therapy for at least 3 months were enrolled. Patients with elevated liver enzymes and unfit for statin therapy, pregnant women, psychiatry patients, and critically ill subjects were excluded. Of the total participants, 214 (71.8%) were males and 84 (28.2%) were females, with a mean age of 62.55 ± 9.56 years. The most common age group diagnosed with IHD was between 60 and 69 years. Hypertension was observed in 64.4% of the patients, while diabetes was present in 55.7% as the most commonly associated comorbidities. The majority of patients (75.8%) received atorvastatin. The prescription pattern for various drug classes included proton pump inhibitors (93%), antiplatelet agents (82.2%), statins (82.2%), nitrates (60.4%), beta-blockers (34.6%), diuretics (16.8%), biguanides (17.4%), and insulin (15.1%). After 3 months of statin therapy, a statistically significant change was observed in the lipid profile (P < 0.001). Statin agents were the most frequently prescribed class of drugs, followed by antiplatelets. Significant improvements were observed in the lipid profile after a 3-month course of statin therapy. Effective therapeutic monitoring can significantly impact a positive health outcome in patients.

Sleep disruption due to nocturnal heartburn: a review of the evidence and clinical implications

Nocturnal heartburn (NHB) is a symptom that affects up to 25% of the general population and has been shown to cause sleep disruption that adversely affects quality of life and psychomotor performance. Few studies have evaluated the association between occasional NHB and sleep disturbances; therefore, this connection may be underappreciated and left untreated by the primary care provider and patient, with potentially significant negative clinical consequences and effects on quality of life. This review sought to describe what is currently known about the interplay between occasional NHB and sleep disruption, and identify whether acid suppression therapy can improve symptoms of occasional NHB and associated sleep disruptions. The pathophysiology of heartburn-induced sleep disruption appears to follow a bidirectional cycle due to the normal physiologic changes that occur in the upper gastrointestinal tract during sleep and due to the potential for heartburn symptoms to cause sleep arousal. The majority of the identified studies suggested that pharmacologic interventions for acid reduction, including proton pump inhibitors or histamine type-2 receptor antagonists (H2RAs), improved objective and/or subjective sleep outcomes among individuals with gastroesophageal reflux disease (GERD) and NHB. Several studies specific to famotidine demonstrated that treatment with 10 mg or 20 mg reduced nighttime awakenings due to NHB. In conclusion, NHB symptoms can cause sleep dysfunction that can have a profound adverse downstream effect on quality of life, next-day functioning, and health-related outcomes. The current approach to managing occasional NHB is similar to that associated with GERD, highlighting the need for studies specific to the occasional heartburn population. Health care providers should investigate NHB as one of the potential causes of sleep complaints, and patients with heartburn should be questioned about sleep quality, recalled arousals, next-day vitality, early fatigue, and next-day functioning.

ВСТРЕЧАЕМОСТЬ АЛЛЕЛЕЙ И ГЕНОТИПОВ ПО АЛЛЕЛЬНЫМ ВАРИАНТАМ CYP2С9*2 И CYP2С9*3 СРЕДИ БОЛЬНЫХ С БОЛЕВЫМ СИНДРОМОМ, ПРИНИМАВШИХ НЕСТЕРОИДНЫЕ ПРОТИВОВОСПАЛИТЕЛЬНЫЕ СРЕДСТВА

Abstract. Introduction. The most clinically significant polymorphic markers of the CYP2C9 gene are the amino acid substitutions of CYP2C9*2. One of the human cytochrome P450 types, i.e., cytochrome CYP2C19, is essential to the metabolism of some drugs, including proton pump inhibitors. Genetic polymorphism of СУР2С19 has some pronounced interindividual differences. Significance of genetic polymorphism is detected where the occurrence of variant alleles exceeds 1% in the population. Aim of the study was to improve the principles of pharmacotherapy with nonsteroidal anti-inflammatory drugs, as related to the frequency of alleles and genotypes on the allelic variants of CYP2С9*2 and CYP2С9*3 in pain syndrome patients taking nonsteroidal anti-inflammatory drugs. Materials and Methods. The study included 69 patients with pain syndrome. Association between being the carrier of genotypes on the CYP2С9*2 and CYP2С9*3 alleles and developing gastropathies as reactions to administering anti-inflammatory drugs was investigated by conducting a prospective case-control study. Molecular genetic testing was performed based on the Laboratory of Medical Genetics of the Research Institute of Hematology and Blood Transfusion at the Ministry of Health of the Republic of Uzbekistan. Results and Discussion. No statistically significant differences were found in the frequencies of the CYP2C9 and CYP2C19 alleles between the groups of patients with and without adverse gastrointestinal reactions to administering nonsteroidal anti-inflammatory drugs or proton pump inhibitors. Conclusions. Our findings allow us to suggest that being a carrier of the allelic CYP2C9*2 and CYP2C9*3 variants should be considered as a gastropathy risk factor of using nonsteroidal anti-inflammatory drugs. It can be assumed that, to reduce the risk of adverse reactions developed in the patients of this category to nonsteroidal anti-inflammatory drugs, the latter ones need a concomitant administration with proton pump inhibitors. It is necessary to continue studying the frequencies of the alleles and genotypes on allelic CYP2С9*2 and CYP2С9*3 variant sin pain syndrome patients taking nonsteroidal anti-inflammatory drugs.

IBC-Oxford University2023_BJSOral_24Comparison of postoperative GERD after LSG with omentopexy versus LSG without omentopexy, incidence of peri-operative GERD LSG in East Asia.

Abstract Background Gastroesophageal Reflux Disease (GERD) is known as the most common long-term complication after laparoscopic sleeve gastrectomy (LSG). The pathophysiology is assumed that the sleeved stomach after LSG is prone to be herniated through the hiatus with high intra- abdominal pressure in obese patients. The omentopexy is thought to make the remnant stomach fixed in abdominal cavity to decrease GERD symptom. Objectives This study aims to compare postoperative GERD after LSG with omentopexy versus LSG without omentopexy as well as to report incidence of peri-operative GERD LSG in East Asia with obesity. Methods This was a single-center retrospective comparative study. Patients with severe obesity (BMI &amp;gt; 35 or &amp;gt; 30 with second metabolic disease) who underwent LSG between January 2019 and June 2021 in Seoul National University Bundang Hospital were enrolled. Patient data were collected preoperatively and at postoperative 1 year. At each time point, body weight, laboratory tests and esophagogastroduodenoscopy were assessed. The patients were asked if anti-reflux medication including proton-pump inhibitor was taken and responded to GERD questionnaire. The validated Korean version of GERD-Q questionnaire was utilized. Laparoscopic sleeve gastrectomy was performed in the usual manner, with or without omentopexy. Omentopexy was defined as the suturing the stapled stomach to the omentum which must include upper part of the sleeve. Electric medical and surgical records were evaluated by the surgeons who were specialized in gastrointestinal surgery. The primary outcome was GERD incidence evaluated by three criteria: LA classification on esophagogastroduod enoscopy, GERD-Q score and anti-reflux medication history. Results During the study period, 106 and 62 patients were enrolled in the LSG with omentopexy group (LSGO) and LSG without omentopexy group (LSGWO) respectively. The baseline demographics did not significantly differ from each group. The mean age of LSGO group was 37.8 years (standardized deviation [SD] 11.0 years] and that of LSGWO group was 38.4 years [SD 10.9 years] (p=0.959). The LSGO and LSGWO groups were comprised of 34.0% and 35.5% men (p=0.868). There were no significant differences in surgical outcomes and postoperative complications between two groups. On GERD, there was no significant difference in LA classification and anti-reflux medication proportion between two groups after postoperative 1 year. However, LSGO group showed significantly less GERD-Q score (mean, SD; 6.57, 1.56) than LSGWO group (mean, SD; 7.91, 3.0) (p=0.02), which represented less subjective GERD symptoms in LSGO group. Conclusion People with obesity who underwent laparoscopic sleeve gastrectomy combined with omentopexy showed less GERD symptoms 1 year after operation than those who without omentopexy.

Translating Molecular Biology Discoveries to Develop Targeted Cancer Interception in Barrett's Esophagus.

Esophageal adenocarcinoma (EAC) is a rapidly increasing lethal tumor. It commonly arises from a metaplastic segment known as Barrett's esophagus (BE), which delineates the at-risk population. Ample research has elucidated the pathogenesis of BE and its progression from metaplasia to invasive carcinoma; and multiple molecular pathways have been implicated in this process, presenting several points of cancer interception. Here, we explore the mechanisms of action of various agents, including proton pump inhibitors, non-steroidal anti-inflammatory drugs, metformin, and statins, and explain their roles in cancer interception. Data from the recent AspECT trial are discussed to determine how viable a multipronged approach to cancer chemoprevention would be. Further, novel concepts, such as the repurposing of chemotherapeutic drugs like dasatinib and the prevention of post-ablation BE recurrence using itraconazole, are discussed.

Pharmacogenetic Testing for the Pediatric Gastroenterologist: Actionable Drug-Gene Pairs to Know.

Gastroenterologists represent some of the earlier adopters of precision medicine through pharmacogenetic testing by embracing upfront genotyping for thiopurine S-methyltransferase nucleotide diphosphatase (TPMT) before prescribing 6-mercaptopurine or azathioprine for the treatment of inflammatory bowel disease. Over the last two decades, pharmacogenetic testing has become more readily available for other genes relevant to drug dose individualization. Common medications prescribed by gastroenterologists for conditions other than inflammatory bowel disease now have actionable guidelines, which can improve medication efficacy and safety; however, a clear understanding of how to interpret the results remains a challenge for many clinicians, precluding wide implementation of genotype-guided dosing for drugs other than 6-mercaptopurine and azathioprine. Our goal is to provide a practical tutorial on the currently available pharmacogenetic testing options and a results interpretation for drug-gene pairs important to medications commonly used in pediatric gastroenterology. We focus on evidence-based clinical guidelines published by the Clinical Pharmacogenetics Implementation Consortium (CPIC®) to highlight relevant drug-gene pairs, including proton pump inhibitors and selective serotonin reuptake inhibitors and cytochrome P450 (CYP) 2C19, ondansetron and CYP2D6, 6-mercaptopurine and TMPT and Nudix hydrolase 15 (NUDT15), and budesonide and tacrolimus and CYP3A5.

Medication misuse and overuse in community-dwelling persons with dementia.

Persons with dementia (PWD) have high rates of polypharmacy. While previous studies have examined specific types of problematic medication use in PWD, we sought to characterize a broad spectrum of medication misuse and overuse among community-dwelling PWD. We included community-dwelling adults aged ≥66 in the Health and Retirement Study from 2008 to 2018 linked to Medicare and classified as having dementia using a validated algorithm. Medication usage was ascertained over the 1-year prior to an HRS interview date. Potentially problematic medications were identified by: (1) medication overuse including over-aggressive treatment of diabetes/hypertension (e.g., insulin/sulfonylurea with hemoglobin A1c < 7.5%) and medications inappropriate near end of life based on STOPPFrail and (2) medication misuse including medications that negatively affect cognition and medications from 2019 Beers and STOPP Version 2 criteria. To contextualize, we compared medication use to people without dementia through a propensity-matched cohort by age, sex, comorbidities, and interview year. We applied survey weights to make our results nationally representative. Among 1441 PWD, median age was 84 (interquartile range = 78-89), 67% female, and 14% Black. Overall, 73% of PWD were prescribed ≥1 potentially problematic medication with a mean of 2.09 per individual in the prior year. This was notable across several domains, including 41% prescribed ≥1 medication that negatively affects cognition. Frequently problematic medications included proton pump inhibitors (PPIs), non-steroidal anti-inflammatory drugs (NSAIDs), opioids, antihypertensives, and antidiabetic agents. Problematic medication use was higher among PWD compared to those without dementia with 73% versus 67% prescribed ≥1 problematic medication (p = 0.002) and mean of 2.09 versus 1.62 (p < 0.001), respectively. Community-dwelling PWD frequently receive problematic medications across multiple domains and at higher frequencies compared to those without dementia. Deprescribing efforts for PWD should focus not only on potentially harmful central nervous system-active medications but also on other classes such as PPIs and NSAIDs.

Pediatric Gastroesophageal Reflux Disease (GERD): A Literature Review

Background: Gastroesophageal reflux disease (GERD) is a condition where stomach contents reflux into the esophagus, causing discomfort and complications. It is most prevalent in infants (26.9%) and lesser in children under 10 (3.2%) and over 10 years old (10.1%). Discussion: GERD is caused by frequent relaxations of the lower esophageal sphincter (LES), allowing stomach contents to escape into the esophagus. Symptoms vary with age, with infants experiencing regurgitation and irritability, while older children may have heartburn and nausea. Diagnosis requires differentiating GERD from similar conditions and may involve various tests, though their primary use lacks sufficient evidence. Nonpharmacological treatments include thickened feeding, reducing feeding volume but increasing frequency and possibly eliminating cow's milk protein. Pharmacological treatments include Proton Pump Inhibitors (PPIs), and Histamine Receptor Antagonists (H2RAs), though their efficacy varies. Prokinetics are generally not recommended due to lack of evidence. If all these treatments fail, anti-reflux surgery such as fundoplication can be considered. Conclusion: The hallmark of GERD is the presence of esophagitis during endoscopy. However, Barrett’s esophagus is rare in pediatric GERD patients. Factors indicating a worse prognosis include early onset age, an initial GERD diagnosis, and the need for PPI or combination of H2RA and PPI treatment.

Hormone-Related and Drug-Induced Osteoporosis: A Cellular and Molecular Overview.

Osteoporosis resulting from an imbalance of bone turnover between resorption and formation is a critical health issue worldwide. Estrogen deficiency following a nature aging process is the leading cause of hormone-related osteoporosis for postmenopausal women, while glucocorticoid-induced osteoporosis remains the most common in drug-induced osteoporosis. Other medications and medical conditions related to secondary osteoporosis include proton pump inhibitors, hypogonadism, selective serotonin receptor inhibitors, chemotherapies, and medroxyprogesterone acetate. This review is a summary of the cellular and molecular mechanisms of bone turnover, the pathophysiology of osteoporosis, and their treatment. Nuclear factor-κβ ligand (RANKL) appears to be the critical uncoupling factor that enhances osteoclastogenesis. In contrast, osteoprotegerin (OPG) is a RANKL antagonist secreted by osteoblast lineage cells. Estrogen promotes apoptosis of osteoclasts and inhibits osteoclastogenesis by stimulating the production of OPG and reducing osteoclast differentiation after suppression of IL-1 and TNF, and subsequent M-CSF, RANKL, and IL-6 release. It can also activate the Wnt signaling pathway to increase osteogenesis, and upregulate BMP signaling to promote mesenchymal stem cell differentiation from pre-osteoblasts to osteoblasts rather than adipocytes. Estrogen deficiency leads to the uncoupling of bone resorption and formation; therefore, resulting in greater bone loss. Excessive glucocorticoids increase PPAR-2 production, upregulate the expression of Dickkopf-1 (DKK1) in osteoblasts, and inhibit the Wnt signaling pathway, thus decreasing osteoblast differentiation. They promote osteoclast survival by enhancing RANKL expression and inhibiting OPG expression. Appropriate estrogen supplement and avoiding excessive glucocorticoid use are deemed the primary treatment for hormone-related and glucocorticoid-induced osteoporosis. Additionally, current pharmacological treatment includes bisphosphonates, teriparatide (PTH), and RANKL inhibitors (such as denosumab). However, many detailed cellular and molecular mechanisms underlying osteoporosis seem complicated and unexplored and warrant further investigation.

Vertebral Compression Fractures in Very Early Onset Inflammatory Bowel Disease.

Patients with VEOIBD receiving care at a single tertiary center were prospectively enrolled in a longitudinal data repository. Retrospective chart review was performed to identify clinical characteristics and comorbidities. Those with clinically apparent vertebral compression fractures subsequently underwent an additional chart review focused on bone health. Three out of 216 (1.4%) patients with VEOIBD had symptomatic vertebral compression fractures. Of the 3 patients with vertebral compression fractures, all had Crohn's disease, 2 had monogenic inflammatory bowel disease, and all reported back pain. One patient notably had a normal dual-energy X-ray absorptiometry, highlighting a potential limitation of dual-energy X-ray absorptiometry to identify increased skeletal fragility in this population. Risk factors for suboptimal bone health included chronic inflammation secondary to poorly controlled inflammatory bowel disease, substantial glucocorticoid exposure, chronic use of other medications associated with suboptimal bone health including proton pump inhibitors and granulocyte colony-stimulating factor, and solid organ transplant. Patients treated with bisphosphonates had improved clinical outcomes, with resolution of back pain and increased bone mineral density. Vertebral compression fracture should be considered in the differential diagnosis of patients with VEOIBD and back pain, especially in those with other risk factors for suboptimal bone health. Treatment of compression fractures with bisphosphonates resulted in resolution of back pain and improved bone density.