Proton pump inhibitors: Understanding the associated risks and benefits of long-term use.

PURPOSE: Proton pump inhibitors (PPIs) are widely prescribed medications. Various adverse clinical effects of PPIs have been reported in the literature, particularly over the past decade. The purpose of this article is to review published data primarily describing adverse effects associated with PPI use and to help clinicians determine which patients may still benefit from therapy despite safety concerns. SUMMARY: Associations between PPIs and the following have been described: bone fracture, acute and chronic kidney disease, gastrointestinal infections, deficiencies in vitamin B12 and magnesium, and coronavirus disease 2019 and respiratory infections. For inclusion in this review, studies must have evaluated potential adverse events associated with PPIs as a primary or secondary objective. Increased risks of bone fracture, acute and chronic kidney disease, gastrointestinal infections, and magnesium deficiency were consistently reported, albeit mostly in studies involving low-quality data (case-control and/or observational studies) and subject to bias. In the only pertinent randomized controlled trial to date, chronic pantoprazole use was associated with a greater risk of enteric infections relative to placebo use; there was no significant between-group difference in any other adverse event evaluated. PPIs continue to be recommended by the American College of Gastroenterology as a first-line treatment for management of gastroesophageal reflux disease and in the acute period following upper gastrointestinal and ulcer bleeding. CONCLUSION: Higher-quality data is needed to better understand PPI-associated risks of the adverse effects listed above. Until then, clinicians may consider greater vigilance with PPI use; however, the data does not demonstrate a need for wide adoption of de-escalation strategies solely out of safety concerns.

Unfractionated heparin infusion for treatment of venous thromboembolism based on actual body weight without dose capping.

Controversy exists regarding the use of dose capping of weight-based unfractionated heparin (UFH) infusions in obese and morbidly obese patients. The primary objective of this study was to compare time to first therapeutic activated partial thromboplastin time (aPTT) in hospitalized patients receiving UFH for acute venous thromboembolism (VTE) among three body mass index (BMI) cohorts: non-obese (< 30 kg/m2), obese (30-39.9 kg/m2), and morbidly obese (⩾ 40 kg/m2). In this single-center, retrospective cohort study, patients were included if they ⩾ 18 years of age, had a documented VTE, and were on an infusion of UFH for at least 24 hours. Weight-based UFH doses were calculated using actual body weight. A total of 423 patients met the inclusion criteria, with 230 (54.4%), 146 (34.5%), and 47 (11.1%) patients in the non-obese, obese, and morbidly obese cohorts, respectively. Median times to therapeutic aPTT were 16.4, 16.6, and 17.1 hours in each cohort. Within 24 hours, the cumulative incidence rates for therapeutic aPTT were 70.7% for the non-obese group, 69.9% for the obese group, and 61.7% for the morbidly obese group (obese vs non-obese: HR = 1.02, 95% CI: 0.82-1.26, p = 0.88; morbidly obese vs non-obese: HR = 0.87, 95% CI: 0.62-1.21, p = 0.41). There was no significant difference in major bleeding events between BMI groups (obese vs non-obese, p = 0.91; morbidly obese vs non-obese, p = 0.98). Based on our study, heparin dosing based on actual body weight without a dose cap is safe and effective.

Comparison of intravenous and oral definitive antibiotic regimens in hospitalised patients with Gram-negative bacteraemia from a urinary tract infection.

OBJECTIVES: Transitioning patients from intravenous (IV) to oral antibiotic therapy has been shown to be a successful approach for several infections. However, minimal data exist evaluating outcomes following transition from to oral antibiotics for patients with bacteraemia secondary to a urinary tract infection (UTI). This study compared treatment failures between patients treated exclusively with IV antibiotics and those transitioned from IV to oral antibiotics for bacteraemia secondary to UTI. METHODS: This single-centre, retrospective cohort study included hospitalised, non-critically ill adult patients treated with culture-susceptible antibiotic therapy for 7-21 days. Patients were divided into two cohorts based on the route of definitive antibiotic administration. Treatment failure was a composite outcome of death and recurrence of the index micro-organism within 21 days following negative blood cultures. RESULTS AND DISCUSSION: Among the 346 patients enrolled, 82 (23.7%) were in the IV cohort and 264 (76.3%) were in the IV-to-oral cohort. A total of six treatment failures occurred; 2 (2.4%) in the IV cohort and 4 (1.5%) in the oral transition cohort (hazard ratio=0.62, 95% confidence interval 0.11-3.39; P=0.58). All failures were due to recurrence of the index organism. Secondary outcomes demonstrated a significantly higher rate of IV line-associated complications in the IV cohort (P=0.03) and a favourable hospital length of stay in the oral cohort (P<0.001). Patients transitioned from IV to oral antibiotics based on culture-susceptibility data experienced similarly low rates of treatment failure as those who received exclusive IV therapy.

Transition of Intravenous Treprostinil to Oral Therapy in a Patient with Functional Class IV Chronic Thromboembolic Pulmonary Hypertension.

Chronic thromboembolic pulmonary hypertension (CTEPH) occurs when pulmonary emboli fail to resolve with anticoagulation. For patients with inoperable or residual CTEPH, riociguat is currently the only therapy approved by the United States Food and Drug Administration. However, some patients with CTEPH may require therapy beyond riociguat, such as intravenous prostacyclins, which can present significant administration challenges in patients with complex comorbid conditions. We describe a 42-year-old man with T12 paraplegia complicated by CTEPH (functional class IV with substantial right ventricular dysfunction) and severe pressure ulcers. In order to facilitate goals of care (hospital discharge to a skilled nursing facility where parenteral prostanoids could not be administered), he underwent rapid transition from intravenous treprostinil to oral selexipag in the form of a cross-taper over 6 days. The patient required readmission due to worsening symptoms and was transitioned back to intravenous treprostinil; he tolerated conversion to oral treprostinil for approximately 4 months, but it was subsequently discontinued due to nausea and modified goals of care. The patient underwent transition to hospice care 3 months later and eventually died from clinical deterioration. To our knowledge, this is the first report to describe transition from intravenous treprostinil to selexipag as well as conversion from parenteral treprostinil to oral treprostinil in a patient with CTEPH and illustrates the approaches to and potential issues with prostanoid transitions. Additional observations are necessary to better understand the relative roles of selexipag and oral treprostinil regarding comparative efficacy and tolerability.

Comparison of oral antibiotic failure rates in post-Roux-en-Y gastric bypass patients versus controls.

BACKGROUND: Due to the malabsorptive nature of the Roux-en-Y gastric bypass (RYGB), there is a potential for impaired absorption of oral medications. Clinical outcomes of patients who receive oral antibiotics after RYGB have not been adequately described in the literature. OBJECTIVES: The primary objective was composite therapeutic failure. Secondary objectives included comparing failure rates between antibiotic classes and at various time points since RYGB. SETTING: University hospital, United States. METHODS: Patients with a history of RYGB and controls who received an eligible oral antibiotic for urinary tract infection, skin and soft tissue infection, or community acquired pneumonia between April 1, 2008, and September 30, 2015, were included via retrospective chart review. Therapeutic failure rates between groups were compared and adjusted for body mass index and infection type. Failure rates among antibiotic classes and various time points since RYGB (0-1 yr, 1-1.9 yr, and≥2 yr) were also compared. RESULTS: A total of 58 RYGB and 128 controls met inclusion and exclusion criteria. Composite therapeutic failure occurred in the RYGB and control group in 14 (24.1%) and 20 patients (15.6%), respectively (P = .18; odds ratio, 1.8; 95% confidence interval .8-4.4). RYGB patients who received fluoroquinolones or sulfonamides had a significantly increased risk of therapeutic failure. CONCLUSIONS: RYGB was not associated with a statistically significant increased risk of composite therapeutic failure of oral antibiotics in the treatment of urinary tract infection, skin and soft tissue infection, or community acquired pneumonia compared with patients with no history of gastrointestinal resection. Further research is warranted to understand clinical outcomes of RYGB patients who receive oral antibiotics.

Mealtime Insulin Dosing by Carbohydrate Counting in Hospitalized Cardiology Patients: A Retrospective Cohort Study.

BACKGROUND: Carbohydrate counting may improve glycemic control in hospitalized cardiology patients by providing individualized insulin doses tailored to meal consumption. The purpose of this study was to compare glycemic outcomes with mealtime insulin dosed by carbohydrate counting versus fixed dosing in the inpatient setting. MATERIALS AND METHODS: This single-center retrospective cohort study included 225 adult medical cardiology patients who received mealtime, basal, and correction-scale insulin concurrently for at least 72 h and up to 7 days in the interval March 1, 2010-November 7, 2013. Mealtime insulin was dosed by carbohydrate counting or with fixed doses determined prior to meal intake. An inpatient diabetes consult service was responsible for insulin management. Exclusion criteria included receipt of an insulin infusion. The primary end point compared mean daily postprandial glucose values, whereas secondary end points included comparison of preprandial glucose values and mean daily rates of hypoglycemia. RESULTS: Mean postprandial glucose level on Day 7 was 204 and 183 mg/dL in the carbohydrate counting and fixed mealtime dose groups, respectively (unadjusted P=0.04, adjusted P=0.12). There were no statistical differences between groups on Days 2-6. Greater rates of preprandial hypoglycemia were observed in the carbohydrate counting cohort on Day 5 (8.6% vs. 1.5%, P=0.02), Day 6 (1.7% vs. 0%, P=0.01), and Day 7 (7.1% vs. 0%, P=0.008). No differences in postprandial hypoglycemia were seen. CONCLUSIONS: Mealtime insulin dosing by carbohydrate counting was associated with similar glycemic outcomes as fixed mealtime insulin dosing, except for a greater incidence of preprandial hypoglycemia. Additional comparative studies that include hospital outcomes are needed.