Angiotensin Receptor Blocker-Related Sprue-like Enteropathy: Review of Food and Drug Administration Adverse Event Reporting System.

BACKGROUND: Sprue-like enteropathy (SE) related to olmesartan use was first reported in 2012. In 2017, the manufacturer of Benicar paid $300 million for 2300 claims for olmesartan-related SE. OBJECTIVE: A study in 2019 suggested that SE was related to olmesartan and with the possibility of angiotensin receptor blocker (ARB) class effect. To further characterize this condition, our group examined reports of ARB-related SE to Food and Drug Administration Adverse Event Reporting System (FAERS). METHODS: All reports of ARB-related SE from January 2017 to December 2021 were downloaded from the FAERS database. Gastrointestinal adverse events including SE were reviewed. Reporter categories included physicians, pharmacists, other health care professionals, consumers, and attorneys. RESULTS: A total of 106 590 reports of ARB-related adverse effects were analyzed. Sprue-like enteropathy was identified in 4337 cases (4.1% of total reports). Of these, 4240 cases (98.0%) of ARB-related SE were reported in patients using products with olmesartan, and 97 cases of SE were reported for all other ARBs (eprosartan, losartan, telmisartan, irbesartan, valsartan, and candesartan). Reports of olmesartan-related SE increased rapidly in 2017, continued at a high rate in 2018 and 2019, and essentially stopped in 2020 and 2021. CONCLUSIONS AND RELEVANCE: Reports to FAERS for ARB-related SE are mostly related to olmesartan. There was a steep decline in reports of olmesartan-related SE following the lawsuit with potential of lawyer interference. There are reports of SE related to ARBs other than olmesartan, with increased physician awareness and the potential to discover a class effect with future studies.

A Summary of the Rare Reports of Osteonecrosis of the Jaw Associated With Tumor Necrosis-α Inhibitors in the United States Food and Drug Administration's Adverse Event Reporting System Database.

PURPOSE: Recent case reports highlight an association between osteonecrosis of the jaw (ONJ) and antitumor necrosis factor (anti-TNF) medications. Our study reviewed and described reports of anti-TNF associated ONJ reported to the United States of America's Food and Drug Administration Adverse Event Reporting System to explore this potential adverse drug reaction further. METHODS: Using the Food and Drug Administration Adverse Event Reporting System database, we identified reported cases of ONJ between 2010 and 2021. Cases were included in our study if they reported any prior or concomitant anti-TNF medication use. Additionally, only adults (age 18+) and reports from health-care professionals were included. Cases lacking subject age or gender were excluded. After duplicates were removed, a dataset was created and demographics were described including age, gender, and indication for use. Naranjo scoring was conducted to assess adverse drug reaction probability. Subject demographics were then separately described for cases without reported denosumab or bisphosphonate therapy history and compared to those with reported history or concomitant denosumab or bisphosphonate therapy. RESULTS: Over twenty thousand cases of ONJ were reported. Forty-four potential cases (0.22%) of anti-TNF medication-associated ONJ were identified and reviewed. Of these, female gender comprised 77.3% (35 cases) and there was an average age of 61.3 years ± 13.7 years. Twenty cases (45.5%) had no prior/concomitant bisphosphonate or denosumab therapy. Of these, 55% (11 cases) were female and the average age was 54.5 ± 17.3 years. Rheumatoid arthritis was the most frequent indication for use (5 cases, 25%) followed by inflammatory bowel disease (IBD) and psoriatic arthritis (4 cases each, 20%) in this cohort. CONCLUSIONS: Twenty potential cases of anti-TNF-associated ONJ without prior or concomitant medications known to be associated with ONJ were identified and described. Interestingly, male gender was more frequent and subjects were younger in these cases compared to those with prior/concomitant bisphosphonates or denosumab therapy. Naranjo scoring indicated a probable interaction for three cases. Further studies are needed to clarify the association of ONJ and anti-TNF therapy, including investigating potential mechanisms and reporting future cases with sufficient detail to assess possible confounding factors.

Mesenteric Panniculitis, Sclerosing Mesenteritis and Mesenteric Lipodystrophy: Descriptive Review of a Rare Condition.

Mesenteric panniculitis (MP) is the preferred nomenclature for a continuum of inflammatory diseases of the mesentery. The diagnosis of MP is often based on the appearance of a mass-like structure at the root of the mesentery. Characteristic histology includes focal fat necrosis, chronic inflammation, and sometimes mesenteric fibrosis. At present, robust literature related to diagnosis and management of MP are limited. MP is postulated to be an immune-mediated chronic inflammatory and/or a paraneoplastic disease. A personal or family history of other autoimmune diseases is commonly apparent. Several inciting events have been identified that possibly act as triggers in the development of the disease. Trauma, abdominal surgery, infection, and various cancers have been associated with mesenteric panniculitis. There are several diagnostic and histologic criteria that aid in making the diagnosis of MP. The differential diagnosis for a mesenteric mass includes neoplastic disease, and a biopsy may be indicated to rule out other conditions. While cases of MP with a short duration of symptoms, or spontaneously regression may occur, some patients experience prolonged periods of pain, fever, and alterations in bowel habit, causing significant morbidity. A variety of medical therapies have been suggested for MP. Only two, thalidomide and low-dose naltrexone, have been prospectively evaluated. For patients with chronic MP, good responses to prolonged corticosteroid treatment have been reported. Novel therapies include thalidomide and low-dose naltrexone. Hormonal and immunomodulatory therapies are also used based on small case series, but these treatments may have significant side effects. Surgical intervention is not curative and is avoided except for relief of focal bowel obstruction secondary to fibrotic forms of the disease.

Complications and Management of Eptifibatide-Induced Thrombocytopenia.

BACKGROUND: Eptifibatide is used in acute coronary syndromes to reversibly block platelet aggregation by inhibiting the platelet glycoprotein IIb/IIIa receptor. A serious adverse effect of eptifibatide is a profound drop in platelet count, termed eptifibatide-induced thrombocytopenia (EIT). OBJECTIVE: To provide insight into the types of complications and management of EIT. METHODS: Cases of EIT submitted to the Food and Drug Administration adverse event reporting system were evaluated. Data analyses included management of EIT, complications of thrombocytopenia, initial platelets, and platelet nadir following eptifibatide. RESULTS: 103 cases of EIT were reported from January 2010 to 2019; 57 cases met the Naranjo scale and were included. Only 37 of those cases contained information on how EIT was managed. Eptifibatide administration was withheld in all 37 of those cases. Platelet transfusions were administered in 20 cases (54%). Two cases were managed with steroids (5.4%), and 1 case used intravenous immunoglobulin G to reverse EIT (2%). The median initial platelet count prior to administration of eptifibatide was 207 000 cells/mm3 (SD = 69 000; n = 27), and median platelet nadir was 9000 cells/mm3 (SD = 19 000; n = 35) The majority of complications of EIT included bleeding events (16/28, 57%). Delayed procedures, prolonged stay, allergic reactions, and thrombosis were each reported in 3 patients (10.75%). CONCLUSION AND RELEVANCE: Most cases of EIT were managed by withholding eptifibatide with platelet transfusion if necessary. The majority of complications included bleeding. However, significant procedure delays, prolonged hospital stay, thrombosis, and allergic reactions were also reported.

Rapid Review: Nonsteroidal Anti-inflammatory Agents and Aminosalicylates in COVID-19 Infections.

In the current COVID-19 pandemic, there has been concern regarding the use of ibuprofen and other nonsteroidal anti-inflammatory agents by COVID-19 infected patients. Aminosalicylates (5-ASAs) are structurally similar and have anti-inflammatory functions that resemble those of nonsteroidal anti-inflammatory agents. Since 5-ASAs are a mainstay treatment for inflammatory bowel disease, the authors review the pharmacology of both classes of drugs and discuss the potential relevance of 5-ASAs in the ongoing discussion of medication use in patients infected with COVID-19.

Domperidone is Commonly Prescribed With QT-Interacting Drugs: Review of a Community-based Practice and a Postmarketing Adverse Drug Event Reporting Database.

INTRODUCTION: Domperidone, a peripheral D2 dopamine receptor antagonist, has efficacy for treatment of nausea, dyspepsia, and gastroparesis. Domperidone prolongs the QT interval (QTc), and may cause life-threatening arrhythmias. METHODS: Electronic medical records for all patients receiving domperidone in the NorthShore University HealthSystem from January 1, 2008 to December 1, 2013 were reviewed. All concomitant medications were noted. The coadministration of QT-interacting medications was determined. Electrocardiogram (EKG) evaluation before and during domperidone therapy was noted. A query of the FDA Adverse Event Reporting System (FAERS) database was also performed. Individual reports from the FAERS Web site from January 2008 to June 2014 were downloaded and analyzed. The database was queried for all reports of adverse events with domperidone. Coadministration of QT-interacting medications was noted. Cardiac events that potentially were related to prolongation of the QTc were examined. RESULTS: In total, 108 of 155 patients (69.7%) were coprescribed QT-interacting drugs along with domperidone. Fifty-nine of 155 patients (38.1%) underwent a baseline EKG and 9 (15.3%) had prolongation of the QTc at initiation. Forty patients (25.8%) had a follow-up EKG and 13 (32.5%) had prolongation of the QTc. All 13 were coprescribed QT-interacting medications. On the FAERS, 221 nonfatal cardiac events were reported in domperidone patients; of these, 162 (73.3%) occurred in patients receiving QT-interacting medications. Coprescription occurred in 53 of 151 deaths (35.1%) and in 16 of 61 cardiac arrests (26.2%). CONCLUSIONS: Coprescribing of QT-prolonging medications and inconsistent EKG monitoring occur in patients receiving domperidone, placing these patients at risk for arrhythmias.

Attitudes and Usage of the Food and Drug Administration Adverse Event Reporting System Among Gastroenterology Nurse Practitioners and Physician Assistants.

The Food and Drug Administration Adverse Event Reporting System (FAERS) is used for postmarketing pharmacovigilance. Our study sought to assess attitudes and usage of the FAERS among gastroenterology nurse practitioners (NPs) and physician assistants (PAs). A survey was administered at the August 2012 Principles of Gastroenterology for the Nurse Practitioner and Physician Assistant course, held in Chicago, IL. Of the 128 respondents, 123 (96%) reported a specialty in gastroenterology or hepatology and were included in analysis. Eighty-nine participants were NPs and 32 PAs, whereas 2 did not report their profession. Although 119 (98%) agreed or strongly agreed with the statement that accurately reporting adverse drug reactions is an important process to optimize patient safety, the majority of participants (54% NPs and 81% PAs) were unfamiliar with the FAERS. In addition, only 20% of NPs and 9% of PAs reported learning about the FAERS in NP or PA schooling. Our study shows enthusiasm among gastroenterology NPs and PAs for the reporting of adverse drug reactions, coupled with a lack of familiarity with the FAERS. This presents an opportunity for enhanced education about reporting of adverse drug reactions for gastroenterology NPs and PAs.

Biosimilars: the need, the challenge, the future: the FDA perspective.

OBJECTIVES: This article summarizes the brief history of the biosimilars industry, the FDA's regulations and guidance for biosimilars development, and the issues and challenges facing developers and regulators in bringing biosimilars to market. METHODS: Current literature, regulations, and FDA guidance documents were summarized and interpreted to define biosimilars and to present their financial and clinical implications. RESULTS: Some biologic agents that will lose patent protection during the next few years may be replaced with lower cost follow-on biologics. However, unlike generic drugs, biosimilars may be structurally and functionally different from the reference product they are designed to resemble. The FDA has yet to approve any agent via the abbreviated licensure pathway for biosimilars that was passed as part of the Affordable Care Act. The FDA has issued new guidance describing processes by which manufacturers may demonstrate either biosimilarity or interchangeability with an FDA-approved biologic agent, which is required for abbreviated licensure. Biosimilars approved in Europe consist of relatively small molecules; complex large-molecule biosimilars could be subjected to a rigorous and prolonged FDA approval process, which would defeat attempts to develop lower-cost versions of biologic drugs. CONCLUSIONS: Biosimilar development is a consequence of the financial success of biologic therapies and their eventual patent expiration. The pharmaceutical industry must now develop complex biosimilars that resemble FDA-approved biologic agents and invent analytical tools and end points to demonstrate similarity to regulatory authorities. Already in development is a new wave of "biobetter" or "biosuperior" drugs that mimic but also improve upon a biologic drug's chemistry, formulation, or delivery.

The Food and Drug Administration advisory committees and panels: how they are applied to the drug regulatory process.

Food and Drug Administration (FDA) advisory panels and committees play a critical role in advising the FDA on the safety and efficacy of medical devices and drugs marketed in the US. Advisory panel recommendations are used by the FDA to make decisions regarding medical products. Currently, the FDA utilizes over 50 advisory panels that serve the three major FDA centers, including the Centers for Biologics, Drugs and Device Products. Members of an advisory panel typically include academicians, clinicians, consumers, patients, and industry representatives. The FDA establishes the schedules for advisory panel meetings on an annual basis and a panel usually meets several times a year for two consecutive days in Washington, DC. Typically, the advisory panel discusses issues highlighted by the FDA and is then asked to vote a response to the questions posed in advance by the FDA. Advisory panel recommendations have a strong influence on FDA's decision to approve a product, as evidenced by the 214 Advisory Panels FDA convened between January 2008 to November 2012, during which advisory panel members voted to approve the product (or use of the product) ∼74% of the time, with FDA ultimately approving the medical product (or use of the product) ∼79% of the time. The ACG membership are encouraged to consider serving the public's interest by participating in an FDA advisory panel utilizing their expertise for the evaluation of a new drug or medical device, and providing advice about whether the product should be sold in the US.

Emerging pharmacotherapy trends in preventing and managing oral mucositis induced by chemoradiotherapy and targeted agents.

INTRODUCTION: The introduction of targeted therapy and immunotherapy has tremendously changed the clinical outcomes and prognosis of cancer patients. Despite innovative pharmacological therapies and improved radiotherapy (RT) techniques, patients continue to suffer from side effects, of which oral mucositis (OM) is still the most impactful, especially for quality of life. AREAS COVERED: We provide an overview of current advances in cancer pharmacotherapy and RT, in relation to their potential to cause OM, and of the less explored and more recent literature reports related to the best management of OM. We have analyzed natural/antioxidant agents, probiotics, mucosal protectants and healing coadjuvants, pharmacotherapies, immunomodulatory and anticancer agents, photobiomodulation and the impact of technology. EXPERT OPINION: The discovery of more precise pathophysiologic mechanisms of CT and RT-induced OM has outlined that OM has a multifactorial origin, including direct effects, oxidative damage, upregulation of immunologic factors, and effects on oral flora. A persistent upregulated immune response, associated with factors related to patients' characteristics, may contribute to more severe and long-lasting OM. The goal is strategies to conjugate individual patient, disease, and therapy-related factors to guide OM prevention or treatment. Despite further high-quality research is warranted, the issue of prevention is paramount in future strategies.

The metoclopramide black box warning for tardive dyskinesia: effect on clinical practice, adverse event reporting, and prescription drug lawsuits.

OBJECTIVES: We examined the effects of the black box warning about the risk of tardive dyskinesia (TD) with chronic use of metoclopramide on management of gastroparesis within a single clinical practice, and on reporting of adverse events. METHODS: Medical records of gastroparesis patients were evaluated for physician management choices. The FDA Adverse Event Reporting System (FAERS) was analyzed for event reports, and for lawyer-initiated reports, with metoclopramide from 2004 to 2010. Google Scholar was searched for court opinions against metoclopramide manufacturers. RESULTS: Before the black box warning, 69.8% of patients received metoclopramide for gastroparesis, compared with 23.7% after the warning. Gastroenterologists prescribed domperidone more often after than before the warning. Metoclopramide prescriptions decreased after 2008. Adverse event reporting increased after the warning. Only 3.6% of all FAERS reports but 70% of TD reports were filed by lawyers, suggesting a distortion in signal. Forty-seven legal opinions were identified, 33 from 2009-2010. CONCLUSIONS: The black box warning for metoclopramide has decreased its usage and increased its rate of adverse event reporting. Lawyer-initiated reports of TD hinder pharmacovigilance.

Relationship between mesenteric abnormalities on computed tomography and malignancy: clinical findings and outcomes of 359 patients.

BACKGROUND: Mesenteric abnormalities are detected on abdominal computed tomography (CT) performed for various indications. GOALS: Determine the risk of malignancy on follow-up of patients with these abnormalities without a preexisting malignancy. STUDY: Data were collected on all patients at NorthShore University HealthSystem with abdominal CT scan reports of mesenteric abnormalities labeled as "panniculitis" from January 2005 to April 2010. RESULTS: Three hundred fifty-nine patients were identified, 81 (22.6%) had a known malignancy at the time of the index abdominal CT scan. Nineteen (6.8%) of the 278 had a new diagnosis of malignancy on evaluation of the findings of the index CT scan. Among the 240 (86.33%) that did not have a notation of the abnormality in their medical record, 11 (4.58%) developed a malignancy during the study period. Sixty-eight of the 248 (24.46%) without a known malignancy had diseases associated with mesenteric abnormalities. The presence of these were associated with a reduction in the likelihood that the abnormalities are associated with new or delayed diagnosis of a malignancy (odds ratio, 0.197; 95% confidence interval, 0.0045-0.8501; P=0.013). Progression of underlying malignancy was unlikely in those where the mesenteric abnormalities did not worsen in appearance on follow-up CT scans (odds ratio, 0.03268; 95% confidence interval, 0.0028-0.3761; P=0.0061). CONCLUSIONS: In the presence of an underlying disease associated with these findings, the subsequent finding of a malignancy is less likely. In addition, neglect of these findings may result in delayed diagnosis of cancer.

Alleged isotretinoin-associated inflammatory bowel disease: disproportionate reporting by attorneys to the Food and Drug Administration Adverse Event Reporting System.

BACKGROUND: Some studies have purported to link isotretinoin prescribed for acne with the development of inflammatory bowel disease (IBD). OBJECTIVE: We sought to identify existence of disproportionate attorney-initiated reporting of isotretinoin-associated IBD in the Food and Drug Administration Adverse Event Reporting System (FAERS). METHODS: A total of 3,338,835 cases (2003-2011) were downloaded from the FAERS. These were queried for IBD cases reported with isotretinoin for a usage indication of acne while recording reporter category. Trends were analyzed over time for reports by attorneys for all medications compared with reports of IBD with isotretinoin. Signal inflation factor was calculated to determine the distortion of pharmacovigilance signals for IBD with isotretinoin. RESULTS: There were 2214 cases of IBD resulting from isotretinoin. Attorneys reported 1944 (87.8%) cases whereas physicians reported 132 (6.0%) and consumers reported 112 (5.1%) cases (P value < .01). For the entire FAERS, only 87,905 of the total 2,451,314 (3.6%) reports for all drug reactions during the same time period were reported by attorneys (P value < .01). The signal inflation factor for IBD with isotretinoin for attorney-initiated reports was 5.82, signifying a clear distortion. LIMITATIONS: The accuracy of reports was not ascertained. CONCLUSIONS: Attorney-initiated reports inflate the pharmacovigilance signal of isotretinoin-associated IBD in the FAERS.

Ischemic colitis with type I interferons used in the treatment of hepatitis C and multiple sclerosis: an evaluation from the food and drug administration adverse event reporting system and review of the literature.

OBJECTIVE: To better characterize the association between type I interferons and ischemic colitis (IC) in patients with the hepatitis C virus (HCV) and multiple sclerosis (MS), by analyzing reports submitted to the Food and Drug Administration (FDA) Adverse Event Reporting System (AERS) and the published literature. DATA SOURCES: A total of 2,562,390 reports of adverse events between January 2003 and June 2011 were downloaded from the FDA AERS. A literature review was performed on PubMed (January 1966-August 2012) using the MeSH terms interferon or interferon alfa or interferon beta and ischemic colitis separated by the Boolean operator "and" between the first 3 terms and the last term. Additional literature was identified by conducting a hand search of the reference list of the published literature identified in the initial search. STUDY SELECTION AND DATA EXTRACTION: Cases were restricted to those with an indication of HCV or MS, a primary suspect drug of a type I interferon, and a reaction of IC. Full-length reports were requested and organized by type of interferon, age, sex, concomitant drugs, and comorbidities. The Naranjo probability scale was used to define cases as definite, probable, possible, or doubtful drug-induced adverse events. DATA SYNTHESIS: Type I interferons, including interferon alfa (IFN-α) and interferon beta (IFN-ß), are approved for the treatment of HCV and MS. IFN-α has been shown to induce IC, but a relationship between type I interferons and IC has not been clarified in the medical literature. Fifty-six primary suspect reports of type I interferons associated with IC in patients with HCV or MS were identified from the FDA AERS. Seventeen cases were reported with IFN-α and 39 cases were reported with IFN-ß. The majority of the cases were in females (80%) and those between the ages of 50 and 65 years (52%). The Naranjo probability scale identified 13 probable and 4 possible cases of IFN-α-induced IC, and 19 probable and 20 possible cases of IFN-ß-induced IC. In the literature, 11 cases of IFN-α-induced IC were reported, while there were no reports with IFN-ß. CONCLUSIONS: Our study suggests a possible association between treatment with type I interferons and the development of IC. Further research to determine the mechanism of this association is warranted.

Medication-induced osteonecrosis of the jaw: a review of cases from the Food and Drug Administration Adverse Event Reporting System (FAERS).

BACKGROUND: Osteonecrosis of the jaw (ONJ) is a rare but serious adverse drug reaction (ADR) commonly associated with bisphosphonate and denosumab therapy. Prior research utilized an online, public FDA Adverse Event Reporting System (FAERS) Database to explore this ADR. This data identified and described several novel medications associated with ONJ. Our study aims to build upon the prior findings, reporting trends of medication induced ONJ over time and identifying newly described medications. METHODS: We searched the FAERS database for all reported cases of medication related osteonecrosis of the jaw (MRONJ) from 2010 to 2021. Cases lacking patient age or gender were excluded. Only adults (18 +) and reports from Healthcare Professions were included. Duplicate cases were removed. The top 20 medications were identified and described for April 2010-December 2014 and April 2015-January 2021. RESULTS: Nineteen thousand six hundred sixty-eight cases of ONJ were reported to the FAERS database from 2010-2021. 8,908 cases met inclusion criteria. 3,132 cases were from 2010-2014 and 5,776 cases from 2015-2021. Within the cases from 2010-2014, 64.7% were female and 35.3% were male, and the average age was 66.1 ± 11.1 years. Between 2015-2021, 64.3% were female and 35.7% were male, and the average age was 69.2 ± 11.5 years. Review of the 2010-2014 data identified several medications and drug classes associated with ONJ not previously described. They include lenalidomide, corticosteroids (prednisolone and dexamethasone), docetaxel and paclitaxel, letrozole, methotrexate, imatinib, and teriparatide. Novel drugs and classes described between 2015-2021 include palbociclib, pomalidomide, radium 223, nivolumab, and cabozantinib. DISCUSSION: While stricter inclusion criteria and removal of duplicate cases led to fewer overall identified cases of MRONJ when compared to prior research, our data represents a more reliable analysis of MRONJ reports to the FAERS database. Denosumab was the most frequently reported medication associated with ONJ. While unable to imply incidence rates from our data due to the nature of the FAERS database, our findings provide further description of the various medications associated with ONJ and elucidate patient demographics associated with the ADR. Additionally, our study identifies cases of several newly described drugs and drug classes that have not been previously described in literature.

A Historical Perspective of Healthcare Disparity and Infectious Disease in the Native American Population.

The incidence and severity of COVID-19 infections have been disproportionately high in Native American populations. Native Americans are a high-risk group for COVID-19 because of a variety of healthcare disparities. Historically, these populations suffered excessively during previous epidemics in the United States (US). Several epidemics occurred when disease-naïve indigenous peoples were exposed to European settlers with herd immunity. Native American populations had four times higher mortality in the 1918 Spanish flu epidemic. Deaths from H1N1 infections were higher in Native Americans and most cases and deaths from the Hantavirus pulmonary syndrome (HPS) occurred in Native Americans. Other infectious diseases, including HIV, hepatitis A and hepatitis C are more also common. Diabetes, alcoholism and cardiovascular diseases, all risk factors for severity and mortality in COVID-19 infection, are also more common in this group. Addressing the root causes of enhanced risk in Native American populations will improve outcomes from COVID-19 and future pandemics.

A Case Report of Diffuse Alveolar Hemorrhage Coexisting With Immunoglobulin A (IgA) Nephropathy.

Immunoglobulin A (IgA) nephropathy is the most common cause of primary glomerulonephritis worldwide. IgA vasculitis (formerly known as Henoch-Schonlein purpura) typically presents with IgA nephropathy on renal biopsy in addition to extrarenal symptoms like purpura, abdominal pain, and arthritis. Diffuse alveolar hemorrhage (DAH) is the most common pulmonary complication, but this is rarely seen. In this case report, we describe a 35-year-old male with chronic untreated hepatitis B infection who presented with pulmonary-renal syndrome. He was found to have clinical findings of DAH and concomitant IgA nephropathy on renal biopsy, without having any other typical manifestations of IgA vasculitis. This shows that IgA nephropathy should be considered in the differential diagnosis of DAH and emphasizes the importance of a renal biopsy in patients presenting with pulmonary-renal syndrome.

Cost Analysis of Implementing an Exercise Program for Fall and Fracture Prevention in Older Adults on Proton Pump Inhibitor Therapy.

Purpose: Falls have significant financial impact. Proton pump inhibitor (PPI) therapy is associated with an increased risk of falls and fractures. Exercise programs have been shown to decrease risk of falls in the elderly population and are recommended by the U.S. Preventive Services Task Force for patients over age 65 to reduce falls. Our study aimed to explore the potential financial benefit of implementing three different Centers for Disease Control and Prevention-recommended exercise-based interventions for fall prevention (Tai Chi, Stepping On, and Otago Exercise Program) in ≥65-year-old patients on PPI therapy. Methods: A Markov model was developed to predict the financial implications of fall-related outcomes in the study population. Net cost of the intervention was deducted from the financial savings predicted for fall avoidance relative to the fall reduction conferred by the intervention. Sensitivity analysis was performed on a range of odds ratios between falling and PPI use. Results: Exercise-based interventions were found to offer financial savings when fall reduction rates exceeded 5%, irrespective of variable odds ratios between PPI use and fall rate. Hypothetical implementation of an exercise-based intervention for PPI users ≥65 years of age was estimated to result in annual fall- and fracture-related savings ranging from $10,317.35 to $18,766.28 per individual. Findings suggested an estimated annual reduction in U.S. health care costs of $18 billion to $85 billion. Conclusions: Implementing an exercise-based fall prevention program for elderly PPI users represents a possible strategy to mitigate health care costs in the United States. Future prospective studies are recommended.