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Kidney transplantation improves quality of life and reduces the risk of mortality. A majority of the success of kidney transplantation is attributable to the calcineurin inhibitors (CNIs), cyclosporine and tacrolimus, and their ability to reduce acute rejection rates. However, long-term graft survival rates have not improved over time, and although controversial, evidence does suggest a role of chronic CNI toxicity in this failure to improve outcomes. Consequently, there is interest in reducing or removing CNIs from immunosuppressive regimens in an attempt to improve outcomes. Several strategies exist to spare calcineurin inhibitors, including use of agents such as mycophenolate mofetil (MMF), mycophenolate sodium (MPS), sirolimus, everolimus or belatacept to facilitate late calcineurin inhibitor withdrawal, beyond 6 mo post-transplant; or using these agents to plan early withdrawal within 6 mo; or to avoid the CNIs all together using CNI-free regimens. Although numerous reviews have been written on this topic, practice varies significantly between centers. This review organizes the data based on patient characteristics (i.e., the baseline immunosuppressive regimen) as a means to aid the practicing clinician in caring for their patients, by matching up their situation with the relevant literature. The current review, the first in a series of two, examines the potential of immunosuppressive agents to facilitate late CNI withdrawal beyond 6 mo post-transplant, and has demonstrated that the strongest evidence resides with MMF/MPS. MMF or MPS can be successfully introduced/maintained to facilitate late CNI withdrawal and improve renal function in the setting of graft deterioration, albeit with an increased risk of acute rejection and infection. Additional benefits may include improved blood pressure, lipid profile and serum glucose. Sirolimus has less data directly comparing CNI withdrawal to an active CNI-containing regimen, but modest improvement in short-term renal function is possible, with an increased risk of proteinuria, especially in the setting of baseline renal dysfunction and/or proteinuria. Renal outcomes may be improved when sirolimus is used in combination with MMF. Although data with everolimus is less robust, results appear similar to those observed with sirolimus.

Background:The use of adjunct, non-opioid agents is integral for pain control following total hip and knee arthroplasty. Literature comparing safety profiles of intravenous acetaminophen versus opioids is lacking.Objective:To determine whether there is a difference in frequency and type of adverse effects between intravenous acetaminophen–treated and non-intravenous acetaminophen–treated patients. Primary safety endpoints included any adverse effect noted in the electronic medical record post-surgically. Secondary endpoints included changes in laboratory values, vital signs, and pain scores.Methods:This is a retrospective, matched, cohort study with data collected from electronic medical records. Adverse effects were collected from progress notes, nursing notes, and post-operative notes. Mean pain score was measured by the 11-point visual analog scale over a 72-h period.Results:A total of 609 patients who underwent a total hip or knee replacement were included. In all, 406 patients were treated with intravenous acetaminophen, and 203 patients received medication management without intravenous acetaminophen. More patients treated with intravenous acetaminophen experienced an adverse effect compared to patients who did not receive intravenous acetaminophen (91.63% versus 84.73%; p = 0.012). Mean cumulative acetaminophen exposure was similar in the intravenous acetaminophen group (7704.89 ± 2558.6 versus 7260.1 ± 3016.09 mg; p = 0.07). Mean opioid use was similar in the intravenous acetaminophen group as compared to the non-intravenous acetaminophen group (209.61 ± 555.09 versus 163.89 ± 232.44 mg; p = 0.152). Significantly higher mean pain scores were found in the intravenous acetaminophen group during the 72-h post-surgery period as compared with non-intravenous acetaminophen-treated patients.Conclusion:The increased utilization of intravenous acetaminophen in multimodal pain management did not result in an improved safety or tolerability profile or reduced opioid utilization in orthopedic patients.

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Introduction Chlorpromazine is a first-generation antipsychotic used for behavioral problems in pediatric patients. However, other therapies may demonstrate both improved outcomes and fewer side effects. Within our institution, chlorpromazine has been the standard medication used for treatment of pediatric agitation. The study objective was to evaluate the appropriateness of chlorpromazine use (including efficacy, appropriate dosing, drug interactions, and tolerability) to optimize the treatment of pediatric agitation. Methods Data regarding drug interactions, patient behavior, dosing, and side effects was collected for each patient administered chlorpromazine from January 2019 through June 2019. Data were analyzed using descriptive statistics assessing the incidence of drug-drug interactions (DDIs), incidences of inefficacy, inappropriate dosing, and side effects. Results A total of 70 patients and 130 administrations of oral or intramuscular chlorpromazine were evaluated. Of these administrations, 49 (38%) resulted in a DDI. Eighteen (14%) administrations were ineffective for managing symptoms of agitation. Eleven (8%) administrations were dosed inappropriately, and 46 (35%) administrations resulted in side effects possibly caused by chlorpromazine. Discussion Results from this study demonstrate opportunities for improvement in patient care due to instances of drug interactions, inefficacy, inappropriate dosing, and side effects with the use of chlorpromazine.