Fanconi Syndrome Induced by Concomitant HIV PrEP and Tacrolimus.

Fanconi syndrome (FS) is a severe grade of drug-induced proximal tubule toxicity. There are numerous causes for acquired FS, and drug toxicity is one of the most common. FS is known to be associated with the nucleoside reverse transcriptase inhibitor (NRTI) tenofovir disoproxil fumarate (TDF). TDF is often used in combination with emtricitabine (FTC) for preexposure prophylaxis (PrEP) of human immunodeficiency virus (HIV) infection. TDF/FTC-induced FS has been observed as a dose-related phenomenon that is directly correlated to kidney function, high levels of absorption of the drug into the proximal tubule, and interactions with other medications. This case report describes a patient who acquired FS after starting TDF/FTC for PrEP in the setting of chronic kidney disease (CKD) with concomitant tacrolimus therapy, a known nephrotoxic agent.

Perceptions of programs that orient non-practice faculty to the pharmacy profession: A pilot study.

INTRODUCTION: Faculty collaboration across disciplines plays an important role in pharmacy education, and in particular, the American Association of Colleges of Pharmacy (AACP) faculty survey asks whether colleges/schools of pharmacy (C/SOPs) have programs available to orient non-practice faculty to the profession of pharmacy. The purpose of this pilot study was to characterize perceptions of the importance and effectiveness of such programs, and to examine barriers to their successful implementation. METHODS: An online survey was developed to collect demographic information and perceived importance, effectiveness, and barriers of programs designed to orient non-practice faculty to the pharmacy profession. The survey was posted to the AACP Connect Council of Deans and Council of Faculties listservs and responses were gathered and analyzed using descriptive statistics. RESULTS: Responses from 157 individuals representing 90C/SOPs were collected. While the majority (82%) of respondents rated programs that orient non-practice faculty to the pharmacy profession as extremely or very important, only 17% rated such programs as extremely or very effective. Lack of time was identified as the primary barrier. Differences were identified between various interest groups, including practice vs. non-practice disciplines and administrators vs. non-administrators. CONCLUSIONS: Programs to orient non-practice faculty to the pharmacy profession were perceived to be important; however, such programs were found to lack efficacy.

Clostridium perfringens as an unusual cause of a prosthetic joint infection following total knee arthroplasty.

Prosthetic joint infections are a serious complication of prosthetic joint implantations. These infections are generally caused by gram-positive, aerobic pathogens, however anaerobic organisms have been rarely implicated. We describe the case of an adult male who developed a Clostridium perfringens prosthetic joint infection four weeks following a right total knee arthroplasty. The patient had recently had a revision of a vascular graft, and there was initial concern for infectious graft involvement. Our case highlights a successful management pathway that included staged surgical revisions and extended courses of clindamycin and metronidazole, which ultimately spared any vascular complications.

Combining oral anticoagulation and antiplatelet therapies: appropriate patient selection.

Anticoagulant therapy and antiplatelet therapy are used regularly for prevention of arterial and venous thrombosis, and combinations of the two drug classes are seen with relative frequency in clinical practice. While co-prescribing is as high as 39-55% in some real-world cohort studies, the number of patients that meet criteria for combination therapy based on the overall body of evidence is likely much lower. This may not always be realized by prescribers, and many patients may be continued on long term combination therapies that provide little additional benefit, and carry significant risk for harm. Given the heightened bleeding risk with combination therapies, prescribers should readily reassess the risk: benefit ratio in all patients on combination therapies. Combined antiplatelet and anticoagulant therapy should be used only in those with a low risk of bleeding who have a higher risk of thromboembolic disease events. Most patients with coronary artery disease, atrial fibrillation, peripheral arterial disease, or bioprosthetic cardiac valves will not benefit from combining antiplatelet and anticoagulant therapies. Conversely, patient populations more likely to derive benefit from antiplatelet-anticoagulant combinations include those with mechanical cardiac valves, patients undergoing percutaneous cardiac intervention who have another indication for anticoagulant therapy, and patients with recurrent thrombotic events while being treated with a single agent. This article will attempt to provide readers with a framework to assess which patient populations are likely to derive the greatest benefit with combination anticoagulant-antiplatelet therapies relative to the weighted risk for bleeding.

Transitions of Care in Medical Education: A Compilation of Effective Teaching Methods.

BACKGROUND AND OBJECTIVES: Transitioning patients safely from the inpatient environment back to an outpatient environment is an important component of health care, and multidisciplinary cooperation and formal processes are necessary to accomplish this task. This Transitions of Care (TOC) process is constantly being shaped in health care systems to improve patient safety, outcomes, and satisfaction. While there are many models that have been published on methods to improve the TOC process systematically, there is no clear roadmap for educators to teach TOC concepts to providers in training. This article reviews published data to highlight specific methods shown to effectively instill these concepts and values into medical students and residents. Formal, evidence-based, TOC curriculum should be developed within medical schools and residency programs. TOC education should ideally begin early in the education process, and its importance should be reiterated throughout the curriculum longitudinally. Curriculum should have a specific focus on recognition of common causes of hospital readmissions, such as medication errors, lack of adequate follow-up visits, and social/economic barriers. Use of didactic lectures, case-based workshops, role-playing activities, home visits, interprofessional activities, and resident-led quality improvement projects have all be shown to be effective ways to teach TOC concepts.

Severe Hyponatremia and Immune Nephritis Following an Initial Infusion of Nivolumab.

Anti-programmed cell death-1 (PD-1) antibodies pembrolizumab and nivolumab are becoming increasingly important in the treatment of melanoma and non-small cell lung cancer. These agents are known to induce many immune-related adverse events, but rapid-onset nephritis and immune-related hyponatremia have not been described to date. We describe the case of an adult patient who developed severe hyponatremia and rapid-onset nephritis following the first infusion of nivolumab for metastatic melanoma.

Chemical prophylaxis to prevent venous thromboembolism in morbid obesity: literature review and dosing recommendations.

Pharmacologic prophylaxis of deep vein thrombosis and venous thromboembolism (VTE) is an important aspect of medical care, particularly in the inpatient setting. Low-molecular weight heparins, heparin, and fondaparinux are commonly used agents to prevent VTE, each of which has well established dosing regimens in patients with normal body mass index. Dosing of these medications in morbidly obese populations (BMI > 40 kg/m(2)) is not as clearly defined in guidelines. This article reviews published data to support specific dosing regimens and monitoring strategies of these agents in this population. The most validated parenteral agent to prevent VTE in morbidly obese hospitalized patients is enoxaparin, dosed at 40 mg subcutaneously (SC) twice daily. If unfractionated heparin is utilized for prophylaxis in morbidly obese patients, a dose of 7500 units SC three times daily should be considered. Monitoring of anti-factor Xa levels to guide prophylactic dosing is an option, although the utility of this lab test is limited, as target anti-Xa ranges for VTE prophylaxis have not been universally defined and trials have not shown a clear link between anti-factor Xa levels and bleeding or thrombotic events. Additional studies are needed to clearly define the most appropriate dosing strategies in patients with moderate obesity (BMI 35-40 mg/m(2)) and those with extreme obesity (BMI > 60 mg/m(2)).

Assessing an enoxaparin dosing protocol in morbidly obese patients.

The effect of obesity on the pharmacokinetics of enoxaparin is not clearly understood and traditional treatment doses in morbidly obese patients (body mass index [BMI] > 40 kg/m(2)) can lead to over anticoagulation. Our institution developed an inpatient protocol with reduced enoxaparin doses (0.75 mg/kg/dose based on actual body weight) for patients with a weight >200 kg or BMI > 40 kg/m(2). The primary objective was to determine if modified enoxaparin treatment doses would achieve therapeutic anti-Xa levels (goal range 0.6-1.0 IU/mL) in morbidly obese patients. Thirty-one patients were included in our study and had a median body weight of 138 kg (range 105-197) and a median BMI of 46.2 kg/m(2) (range 40.1-62). The initial peak anti-Xa levels were in therapeutic range in 15 of 31 patients (48 %) with an initial mean anti-Xa level of 0.92 IU/mL. Twenty-four patients (77 %) achieved therapeutic anti-Xa levels in goal range during their hospitalization, with a mean enoxaparin dose of 0.71 mg/kg. Bleeding and thrombotic events were minimal and all patients that achieved an anti-Xa level in goal range did so with a dose less than 1 mg/kg of enoxaparin.

A comparative trial of anti-factor Xa levels versus the activated partial thromboplastin time for heparin monitoring.

OBJECTIVE: To determine if laboratory monitoring of intravenous (IV) unfractionated heparin (UFH) using an anti­activated factor X (anti­factor Xa) assay, as opposed to the activated partial thromboplastin time (aPTT), would result in a higher percentage of results within the goal range, fewer monitoring tests, and fewer dose adjustments. METHODS: Retrospective, single-center, cohort study conducted at a community teaching hospital. A newly implemented deep vein thrombosis/pulmonary embolism treatment protocol, in which patients' doses of IV UFH were adjusted based on blood plasma anti­factor Xa level monitoring, was compared with a deep vein thrombosis/pulmonary embolism protocol, in which patients' IV UFH doses were adjusted based on monitoring with the blood plasma aPTT. We reviewed the medical records of 186 patients (88 managed by the anti­factor Xa assay­based protocol and 98 managed by the aPTT-based protocol) to determine how often monitoring tests were within the goal range (aPTT, 75­110 sec; anti­factor Xa, 0.3­0.7 U/mL), in addition to how many UFH dose adjustments and monitoring tests were required for each patient within a 24-hour period. RESULTS: In patients undergoing IV UFH therapy whose blood plasma was monitored with anti­factor Xa assay levels, as opposed to the aPTT, there was a higher percentage of UFH test results within the goal range (69% vs 41%; P < 0.0001), fewer monitoring tests were needed (2.08 vs 2.73; P = 0.001), and fewer dose adjustments were required per 24-hour period (0.62 vs 1.47; P < 0.0001). CONCLUSIONS: Use of an anti­factor Xa assay­based UFH-monitoring protocol resulted in a higher percentage of within-range blood plasma heparin monitoring tests, fewer monitoring tests for the patient to achieve blood plasma monitoring tests within goal range, and fewer dose adjustments compared with a protocol based on blood plasma monitoring using the aPTT.

Antifactor Xa levels versus activated partial thromboplastin time for monitoring unfractionated heparin.

Intravenous unfractionated heparin (UFH) remains an important therapeutic agent, particularly in the inpatient setting, for anticoagulation. Historically, the activated partial thromboplastin time (aPTT) has been the primary laboratory test used to monitor and adjust UFH. The aPTT test has evolved since the 1950s, and the historical goal range of 1.5-2.5 times the control aPTT, which first gained favor in the 1970s, has fallen out of favor due to a high degree of variability in aPTT readings from one laboratory to another, and even from one reagent to another. As a result, it is now recommended that the aPTT goal range be based on a corresponding heparin concentration of 0.2-0.4 unit/ml by protamine titration or 0.3-0.7 unit/ml by antifactor Xa assay. Given that several biologic factors can influence the aPTT independent of the effects of UFH, many institutions have transitioned to monitoring heparin with antifactor Xa levels, rather than the aPTT. Clinical data from the last 10-20 years have begun to show that a conversion from aPTT to antifactor Xa monitoring may offer a smoother dose-response curve, such that levels remain more stable, requiring fewer blood samples and dosage adjustments. Given the minimal increased acquisition cost of the antifactor Xa reagents, it can be argued that the antifactor Xa is a cost-effective method for monitoring UFH. In this review, we discuss the relative advantages and disadvantages of the aPTT, antifactor Xa, and protamine titration tests, and provide a clinical framework to guide practitioners who are seeking to optimize UFH monitoring within their own institutions.