Diuretic Use in Post-Kidney Transplant Patients: A Retrospective Chart Review.

BACKGROUND: The occurrence of delayed graft function (DGF) significantly enhances the possibility of both acute and chronic rejection of the transplanted organ, thereby reducing patient quality of life and survival rates. To prevent and manage oliguria in renal transplant patients, loop diuretics are presently commonly used. In our study, we assessed the possible impact of furosemide on the incidence of DGF among kidney transplant recipients. METHODS: A review of medical records was conducted to examine demographic characteristics and kidney transplant outcomes in an adult (older than 18 years old) population. The primary objective was to determine the incidence of delayed graft function (DGF), whereas the secondary objective was to compare the creatinine levels and estimated glomerular filtration rate (eGFR) at day 30 and day 90 post-transplantation in patients who were administered furosemide vs those who were not. RESULTS: This study included 330 patients who underwent kidney transplantation. Furosemide was administered to 169 (51.3%), whereas 161(48.7%) patients did not receive continued dose of diuretic postoperatively. The rate of DGF was significantly higher in patients who received furosemide than in those who did not (furosemide 44% vs 4%; P < .001). The eGFR was lower in the furosemide group compared to the no furosemide group at day 30 (56 ± 24 vs 71 ± 24 mL/min/1.73 m2, P < .001) and day 90 (66 ± 27 vs 78 ± 25 mL/min/1.73 m2, P < .001). CONCLUSIONS: Our results show that there is no benefit in treating an oliguric AKI with furosemide. Administration of furosemide, especially in high doses, may increase the risk of toxicity, delay dialysis, and increase the length of stay.

Vancomycin and daptomycin dosing recommendations in patients receiving home hemodialysis using Monte Carlo simulation.

BACKGROUND: Few drug dosing recommendations for patients receiving home hemodialysis (HHD) have been published which has hindered the adoption of HHD. HHD regimens vary widely and differ considerably from conventional, thrice weekly, in-center hemodialysis in terms of treatment frequency, duration and blood and dialysate flow rates. Consequently, vancomycin and daptomycin clearances in HHD are also likely to be different, consequently HHD dosing regimens must be developed to ensure efficacy and minimize toxicity when these antibiotics are used. Many HHD regimens are used clinically, this study modeled ten common HHD regimens and determined optimal vancomycin and daptomycin dosing for each HHD regimen. METHODS: Monte Carlo simulations using pharmacokinetic data derived from the literature and demographic data from a large HHD program treating patients with end stage kidney disease were incorporated into a one-compartment pharmacokinetic model. Virtual vancomycin and daptomycin doses were administered post-HHD and drug exposures were determined in 5,000 virtual patients receiving ten different HHD regimens. Serum concentration monitoring with subsequent dose changes was incorporated into the vancomycin models. Pharmacodynamic target attainment rates were determined for each studied dose. The lowest possible doses that met predefined targets in virtual patients were chosen as optimal doses. RESULTS: HHD frequency, total dialysate volumes and HHD durations influenced drug exposure and led to different dosing regimens to meet targets. Antibiotic dosing regimens were identified that could meet targets for 3- and 7-h HHD regimens occurring every other day or 4-5 days/week. HHD regimens with 3-day interdialytic periods required higher doses prior to the 3-day period. The addition of vancomycin serum concentration monitoring allowed for calculation of necessary dosing changes which increased the number of virtual subjects meeting pharmacodynamic targets. CONCLUSIONS: Doses of vancomycin and daptomycin that will meet desired pharmacodynamic targets in HHD are dependent on patient and HHD-specific factors. Doses used in conventional thrice weekly hemodialysis are unlikely to meet treatment goals. The antibiotic regimens paired with the HHD parameters studied in this analysis are likely to meet goals but require clinical validation.

International consensus recommendations for the use of prolonged-infusion beta-lactam antibiotics: Endorsed by the American College of Clinical Pharmacy, British Society for Antimicrobial Chemotherapy, Cystic Fibrosis Foundation, European Society of Clinical Microbiology and Infectious Diseases, Infectious Diseases Society of America, Society of Critical Care Medicine, and Society of Infectious Diseases Pharmacists: An executive summary.

Intravenous ß-lactam antibiotics remain a cornerstone in the management of bacterial infections due to their broad spectrum of activity and excellent tolerability. ß-lactams are well established to display time-dependent bactericidal activity, where reductions in bacterial burden are directly associated with the time that free drug concentrations remain above the minimum inhibitory concentration (MIC) of the pathogen during the dosing interval. In an effort to take advantage of these bactericidal characteristics, prolonged (extended and continuous) infusions (PI) can be applied during the administration of intravenous ß-lactams to increase time above the MIC. PI dosing regimens have been implemented worldwide, but implementation is inconsistent. We report consensus therapeutic recommendations for the use of ß-lactam PI developed by an expert international panel with representation from clinical pharmacy and medicine. This consensus guideline provides recommendations regarding pharmacokinetic and pharmacodynamic targets, therapeutic drug monitoring considerations, and the use of PI ß-lactam therapy in the following patient populations: severely ill and nonseverely ill adult patients, pediatric patients, and obese patients. These recommendations provide the first consensus guidance for the use of ß-lactam therapy administered as PIs and have been reviewed and endorsed by the American College of Clinical Pharmacy (ACCP), the British Society for Antimicrobial Chemotherapy (BSAC), the Cystic Fibrosis Foundation (CFF), the European Society of Clinical Microbiology and Infectious Diseases (ESCMID), the Infectious Diseases Society of America (IDSA), the Society of Critical Care Medicine (SCCM), and the Society of Infectious Diseases Pharmacists (SIDP).

International consensus recommendations for the use of prolonged-infusion beta-lactam antibiotics: Endorsed by the American College of Clinical Pharmacy, British Society for Antimicrobial Chemotherapy, Cystic Fibrosis Foundation, European Society of Clinical Microbiology and Infectious Diseases, Infectious Diseases Society of America, Society of Critical Care Medicine, and Society of Infectious Diseases Pharmacists.

Intravenous ß-lactam antibiotics remain a cornerstone in the management of bacterial infections due to their broad spectrum of activity and excellent tolerability. ß-lactams are well established to display time-dependent bactericidal activity, where reductions in bacterial burden are directly associated with the time that free drug concentrations remain above the minimum inhibitory concentration (MIC) of the pathogen during the dosing interval. In an effort to take advantage of these bactericidal characteristics, prolonged (extended and continuous) infusions (PIs) can be applied during the administration of intravenous ß-lactams to increase time above the MIC. PI dosing regimens have been implemented worldwide, but implementation is inconsistent. We report consensus therapeutic recommendations for the use of PI ß-lactams developed by an expert international panel with representation from clinical pharmacy and medicine. This consensus guideline provides recommendations regarding pharmacokinetic and pharmacodynamic targets, therapeutic drug-monitoring considerations, and the use of PI ß-lactam therapy in the following patient populations: severely ill and nonseverely ill adult patients, pediatric patients, and obese patients. These recommendations provide the first consensus guidance for the use of ß-lactam therapy administered as PIs and have been reviewed and endorsed by the American College of Clinical Pharmacy (ACCP), the British Society for Antimicrobial Chemotherapy (BSAC), the Cystic Fibrosis Foundation (CFF), the European Society of Clinical Microbiology and Infectious Diseases (ESCMID), the Infectious Diseases Society of America (IDSA), the Society of Critical Care Medicine (SCCM), and the Society of Infectious Diseases Pharmacists (SIDP).

Evaluation of Curricula Content on Kidney Disease in US Doctor of Pharmacy Programs.

Objective. Although pharmacists improve outcomes in the care of patients with kidney diseases and current guidelines advocate multidisciplinary care, pharmacist nephrology training is not well described. This study seeks to characterize required and elective coursework within US Doctor of Pharmacy curricula. This information will be valuable in identification and evaluation of educational gaps for pharmacists as best practices in the education and care of kidney diseases for pharmacists are established.Methods. This prospective, cross-sectional, descriptive study assessed current practices and trends in education on kidney diseases within Doctor of Pharmacy curricula at accredited programs in the United States through an electronic survey.Results. Forty-three percent (N=61) of all ACPE-accredited pharmacy institutions were represented in the survey. Content on kidney diseases was found to be taught in both required and elective coursework, and one-third of responding institutions offered advanced pharmacy practice experiences focused on kidney diseases. Variation was found in the amount of time allotted for the teaching of kidney diseases topics in pharmacy curricula and the types of experiential training offered. Six respondents reported offering postgraduate education that focused on kidney diseases. Most respondents were clinical faculty who had completed residency training and board certification.Conclusion. Given the complex interplay between kidney diseases and other health conditions, the increasing incidence and prevalence of kidney diseases, and the potential expansion of pharmacists' roles in the care of patients with kidney diseases, a review of current Doctor of Pharmacy curricula is necessary to guide any future optimization efforts to ensure practice-ready pharmacists.

Optimal antipseudomonal ꞵ-lactam drug dosing recommendations in critically-ill Asian patients receiving CRRT.

INTRODUCTION: The average body weight is smaller in Asian patients compared with Western patients, but influence of body weight in antibiotic dosing is unknown. This study was to predict the optimal ceftazidime, cefepime, meropenem, piperacillin/tazobactam doses in Asian patients undergoing continuous venovenous hemofiltration (CVVH). METHODS: Monte Carlo simulations (MCS) were performed using published Asian demographics and pharmacokinetics parameters in 5000 virtual patients at three CVVH effluent rates (Qeff; 20, 30, 40 mL/kg/h). Various dosing regimens were assessed for the probability of target attainments using 60% fT > 1 × MIC or 4xMIC and neurotoxicity risk at 48-h using suggested neurotoxicity thresholds. RESULTS: Ceftazidime 1 g q12h, meropenem 1 g q12h, and piperacillin/tazobactam 3.375 g q6h were optimal for all Qeff settings against fT > 1 × MIC. Cefepime 2 g q24h and 2 g q12h were optimal at 20 and 30-40 mL/kg/h respectively. For the aggressive PD target (4 × MIC), optimal ceftazidime regimens were 1.25 g q8h (20-30 mL/kg/h) and 1.5 g q8h (40 mL/kg/h). Cefepime 2 g q8h and meropenem 1 g q8h were optimal at all Qeff settings. No simulated piperacillin doses attained the aggressive PD target. Increased neurotoxicity risk was predicted with ceftazidime and cefepime doses attaining the efficacy. CONCLUSION: MCS enabled the prediction of optimal ß-lactam dosing regimens for Asian patients receiving CVVH at varying Qeff. Clinical validation is warranted.

Comparison of antimicrobial dosing recommendations in patients receiving intermittent hemodialysis among drug information resources.

WHAT IS KNOWN AND OBJECTIVE: Tertiary drug information resources are frequently consulted for the optimal antimicrobial dosing in intermittent hemodialysis (IHD) patients. Yet, significant discrepancy may exist in dosing recommendations between resources. This study was to evaluate the consistency of antimicrobial dosing recommendations in IHD among four different drug information resources and the relevance of referenced pharmacokinetic studies. METHODS: Dosing recommendations of 29 commonly prescribed antimicrobials in IHD patients were collected from Micromedex, LexiComp, Clinical Pharmacology and Drug Prescribing in Renal Impairment to compare dosing categorization and the total daily dose (TDD). Significant dosing discrepancies were defined as ≥30% difference. Referenced pharmacokinetic studies were evaluated for their relevance in current practice, using sample size, hemodialyzer types, the use of optimal pharmacodynamic targets and the consideration of different interdialytic dosing periods. RESULTS AND DISCUSSION: A significant variation was found both in dosing categorization and recommended doses between resources. Seventeen drugs were compared for TDD with significant dosing discrepancy in 8 drugs. Among 42 referenced pharmacokinetic studies, 40 were evaluated. Mean patient numbers of pharmacokinetic studies were 13 ranging from 3 to 70. Sixty per cent of studies utilized contemporary hemodialyzers (e.g., high-flux and/or high efficiency). The optimal pharmacodynamic targets and the impact of different interdialytic intervals were assessed only in 27.5% and 7.5% respectively. WHAT IS NEW AND CONCLUSION: Inconsistent antimicrobial dosing recommendations for IHD patients exist among four well-established resources. Many referenced pharmacokinetic studies utilized outdated or less pharmacodynamically relevant study methods. Newer studies are warranted to reflect contemporary dialysis practice and assess its impact on optimal antimicrobial dosing.

Size Matters: The Influence of Patient Size on Antibiotics Exposure Profiles in Critically Ill Patients on Continuous Renal Replacement Therapy.

(1) Purpose of this study: To determine whether patient weight influences the probability of target attainment (PTA) over 72 h of initial therapy with beta-lactam (cefepime, ceftazidime, piperacillin/tazobactam) and carbapenem (imipenem, ertapenem, meropenem) antibiotics in the critical care setting. This is the first paper to address the question of whether patient size affects antibiotic PTA in the ICU. (2) Methods: We performed a post hoc analysis of Monte Carlo simulations conducted in virtual critically ill patients receiving antibiotics and continuous renal replacement therapy. The PTA was calculated for each antibiotic on the following pharmacodynamic (PD) targets: (a) were above the target organism's minimum inhibitory concentration (≥%fT≥1×MIC), (b) were above four times the MIC (≥%fT≥4×MIC), and (c) were always above the MIC (≥100%fT≥MIC) for the first 72 h of antibiotic therapy. The PTA was analyzed in patient weight quartiles [Q1 (lightest)-Q4 (heaviest)]. Optimal doses were defined as the lowest dose achieving ≥90% PTA. (3) Results: The PTA for fT≥1×MIC led to similarly high rates regardless of weight quartiles. Yet, patient weight influenced the PTA for higher PD targets (100%fT≥MIC and fT≥4×MIC) with commonly used beta-lactams and carbapenems. Reaching the optimal PTA was more difficult with a PD target of 100%fT≥MIC compared to fT≥4×MIC. (4) Conclusions: The Monte Carlo simulations showed patients in lower weight quartiles tended to achieve higher antibiotic pharmacodynamic target attainment compared to heavier patients.

Imipenem/Relebactam Ex Vivo Clearance during Continuous Renal Replacement Therapy.

(1) Purpose of this study: determination of adsorption and transmembrane clearances (CLTM) of imipenem and relebactam in ex vivo continuous hemofiltration (CH) and continuous hemodialysis (CHD) models. These clearances were incorporated into a Monte Carlo Simulation (MCS), to develop drug dosing recommendations for critically ill patients requiring continuous renal replacement therapy (CRRT); (2) Methods: A validated ex vivo bovine blood CH and CHD model using two hemodiafilters. Imipenem/relebactam and urea CLTM at different ultrafiltrate/dialysate flow rates were evaluated in both CH and CHD. MCS was performed to determine dose recommendations for patients receiving CRRT; (3) Results: Neither imipenem nor relebactam adsorbed to the CRRT apparatus. The CLTM of imipenem, relebactam, and urea approximated the effluent rates (ultrafiltrate/dialysate flow rates). The types of hemodiafilter and effluent rates did not influence CLTM except in a dialysis flow rate of 1 L/h and 6 L/h in the CHD with relebactam (p < 0.05). Imipenem and relebactam 200 mg/100 mg every 6 h were sufficient to meet the standard time above the MIC pharmacodynamic targets in the modeled CRRT regimen of 25 kg/mL/h. (4) Conclusions: Imipenem and relebactam are not removed by adsorption to the CRRT apparatus, but readily cross the hemodiafilter membrane in CH and CHD. Dosage adjustment of imipenem/relebactam is likely required for critically ill patients receiving CRRT.

Drug dosing considerations in continuous renal replacement therapy.

Acute kidney injury (AKI) is a common complication in critically ill patients, which is associated with increased in-hospital mortality. Delivering effective antibiotics to treat patients with sepsis receiving continuous renal replacement therapy (RRT) is complicated by variability in pharmacokinetics, dialysis delivery, lack of primary literature, and therapeutic drug monitoring. Pharmacokinetic alterations include changes in absorption, distribution, protein binding (PB), metabolism, and renal elimination. Drug absorption may be significantly changed due to alterations in gastric pH, perfusion, gastrointestinal motility, and intestinal atrophy. Volume of distribution for hydrophilic drugs may be increased due to volume overload. Estimation of renal clearance is challenged by the effective delivery of RRT. Drug characteristics such as PB, volume of distribution, and molecular weight impact removal of the drug by RRT. The totality of these alterations leads to reduced exposure. Despite our best knowledge, therapeutic drug monitoring of patients receiving continuous RRT demonstrates wide variability in antimicrobial concentrations, highlighting the need for expanded monitoring of all drugs. This review article will focus on changes in drug pharmacokinetics in AKI and dosing considerations to attain antibiotic pharmacodynamic targets in critically ill patients receiving continuous RRT.

Use of angiotensin converting enzyme inhibitors in patients receiving therapeutic plasma exchange with a centrifuge-based apheresis system.

Angiotensin-converting enzyme inhibitors (ACEi) are frequently used antihypertensive medications with additional advantages such as reducing proteinuria and cardiovascular events. ACEi are commonly held at least 24 hours before a therapeutic plasma exchange (TPE) to reduce possibility of adverse events (AEs) including adverse drug reactions (ADR). The objective of this study was to determine if ACEi use increases the risk of ADR in patients receiving TPE with a conventional centrifuge-based apheresis system. This is a retrospective chart review study (n = 252; 52% male). Binary logistic regression was used to analyze the association of ACEi use and AEs. Of 171 patients who had AE during TPE, only 38 patients were taking ACEi. There was no significant association between ACEi use and AEs after adjustments (odds ratio = 0.885, 95% confidence interval: 0.468, 1.674). Our results suggest that risk of AEs is not higher in patients taking ACEi receiving TPE using a centrifuge-based machine. Randomized controlled prospective trials may be needed to further investigate this matter.

Assessment of literacy and numeracy skills related to medication labels in patients on chronic in-center hemodialysis.

OBJECTIVES: Patients on hemodialysis have complicated medication regimens requiring the ability to accurately interpret medication information. Literacy and numeracy skills have been shown to differ by the types of materials provided to patients. The aims of this study were to determine prescription and over-the-counter medication label understanding and to assess the prevalence of low health literacy regarding medication labeling among in-center hemodialysis patients. DESIGN, SETTING AND PARTICIPANTS: The Medication Literacy and Numeracy in Dialysis (MedLitD) tool is an assessment of a person's ability to read and understand medication labels. A comparison with the Rapid Estimate of Adult Literacy in Medicine Short Form (REALM-SF), an established literacy tool, was conducted to determine if there were differences in the literacy results from the 2 tools that could be leveraged to target education initiatives for this specialized population. RESULTS: A total of 110 patients receiving hemodialysis from 3 dialysis facilities in the Capital Region of upstate New York were enrolled in the study. Most patients (77%) achieved a maximum REALM-SF score, indicating a high level of literacy proficiency; however, their MedLitD scores varied. Patients who were 65 years and older had lower scores on the MedLitD tool compared with younger patients. Gender, education, and the number of medications did not influence the MedLitD scores. Only 16% of all participants correctly answered the question asking for an indication of the phosphate binder (PB), although the most patients were currently taking PBs. CONCLUSION: A continuum of medication literacy levels exists among patients on hemodialysis. Appropriate evaluation of medication literacy should be done to better inform individualized education and counseling.

Neuroimaging-Based Deep Learning in Autism Spectrum Disorder and Attention-Deficit/Hyperactivity Disorder.

Deep learning (DL) is a kind of machine learning technique that uses artificial intelligence to identify the characteristics of given data and efficiently analyze large amounts of information to perform tasks such as classification and prediction. In the field of neuroimaging of neurodevelopmental disorders, various biomarkers for diagnosis, classification, prognosis prediction, and treatment response prediction have been examined; however, they have not been efficiently combined to produce meaningful results. DL can be applied to overcome these limitations and produce clinically helpful results. Here, we review studies that combine neurodevelopmental disorder neuroimaging and DL techniques to explore the strengths, limitations, and future directions of this research area.

Harmonizing antibiotic regimens with renal replacement therapy.

Introduction: Critically ill patients with acute kidney injury often require renal replacement therapy and antibiotic therapy. Mortality rates are high in these patients, possibly due to ineffective dosing due to altered pharmacokinetic profiles and drug removal by renal replacement therapy. Areas covered: The main types of renal replacement therapies are intermittent hemodialysis, prolonged intermittent renal replacement therapy and continuous renal replacement therapy. Each of these renal replacement therapies may have drastic, yet different, effects on antibiotic serum concentration profiles. Moreover, three antibiotic administration strategies are often used: (1) standard infusion; (2) extended infusion; and (3) continuous infusion. A literature review was conducted on Medline in December 2019 to identify pertinent research. Expert opinion: Renal replacement therapies used in the treatment of acute kidney injury in critically ill patients usually complicates antibiotic use. Although antibiotic toxicity can be seen, most studies find that these patients do not receive sufficient antibiotic doses to achieve desired pharmacodynamic targets. Clinicians should dose antibiotics to match renal replacement therapy drug clearance characteristics to antibiotic pharmacodynamic profiles.

Contrasting PTH Response of Denosumab Use in Dialysis Patients: A Report of 2 Cases.

A common complication of end-stage renal disease (ESRD) is mineral and bone disorder. Yet, many anti-osteoporotic drugs are contraindicated in ESRD patients. Denosumab, a monoclonal antibody, does not require renal dose adjustment. However, its use is uncertain due to a lack of safety and efficacy of data in this population. Two hemodialysis patient cases of contrasting responses in parathyroid hormone (PTH) after denosumab administration were observed. Patient 1, a 62-years-old male received denosumab 60 mg at Day 0. His calcium decreased from 8.8 mg/dL to 6.8 mg/dL on Day 30. The PTH level increased from 265 pg/mL to 372 pg/mL after 30 days. Calcium and PTH levels approached normal range after increasing doses of vitamin D/calcium supplements, and calcitriol. Patient 2, a 72-years-old male on hemodialysis also received denosumab 60 mg on Day 0. His baseline calcium and PTH were 9.2 mg/dL and 420 pg/mL, respectively. On Day 30, his calcium level decreased (6.8 mg/dL) but, PTH level drastically increased (>5,000 pg/mL). Denosumab commonly causes hypocalcemia and hyperparathyroidism since it inhibits osteoclast activation, reduces calcium release from bone and increases PTH levels as a compensatory mechanism. With a wait-and-watch approach, Patient 2's levels approached the normal range (calcium 9.6 mg/dL and PTH 274 pg/mL at Day 90).

Safety and Efficacy of Direct Oral Anticoagulants for Atrial Fibrillation in Patients with Renal Impairment.

Direct oral anticoagulants (DOACs) are gaining popularity for patients with nonvalvular atrial fibrillation (AF) for stroke prevention. Less bleeding risk with comparable stroke prevention compared to warfarin was shown. DOACs have predictable anticoagulant effects, infrequent monitoring requirements and less drug-food interactions compared to warfarin. However, safety and efficacy data of DOACs in patients with chronic kidney disease (CKD) are limited. This is a retrospective study to evaluate thromboembolic and bleeding events in patients with AF (with/without CKD) in October 2010 and July 2017. A total of 495 patients were included and only 150 patients had CKD. Our study found that patients with renal impairment on a DOAC do not have a higher incidence of bleeding events. It showed significant increase in thromboembolic events in CKD patients with dabigatran compared to CKD patients with apixaban with odds ratio of 6.58 (95%CI 1.35-32.02, p = 0.02).

Drug Dosing Considerations in Critically Ill Patients Receiving Continuous Renal Replacement Therapy.

Acute kidney injury is very common in critically ill patients requiring renal replacement therapy. Despite the advancement in medicine, the mortality rate from septic shock can be as high as 60%. This manuscript describes drug-dosing considerations and challenges for clinicians. For instance, drugs' pharmacokinetic changes (e.g., decreased protein binding and increased volume of distribution) and drug property changes in critical illness affecting solute or drug clearance during renal replacement therapy. Moreover, different types of renal replacement therapy (intermittent hemodialysis, prolonged intermittent renal replacement therapy or sustained low-efficiency dialysis, and continuous renal replacement therapy) are discussed to describe how to optimize the drug administration strategies. With updated literature, pharmacodynamic targets and empirical dosing recommendations for commonly used antibiotics in critically ill patients receiving continuous renal replacement therapy are outlined. It is vital to utilize local epidemiology and resistance patterns to select appropriate antibiotics to optimize clinical outcomes. Therapeutic drug monitoring should be used, when possible. This review should be used as a guide to develop a patient-specific antibiotic therapy plan.

Antibiotic Exposure Profiles in Trials Comparing Intensity of Continuous Renal Replacement Therapy.

OBJECTIVES: To determine whether the probability of target attainment over 72 hours of initial therapy with beta-lactam (cefepime, ceftazidime, piperacillin/tazobactam) and carbapenem (imipenem, meropenem) antibiotics were substantially influenced between intensive and less-intensive continuous renal replacement therapy groups in the Acute Renal Failure Trial Network trial and The RENAL Replacement Therapy Study trial. DESIGN: The probability of target attainment was calculated using pharmacodynamic targets of percentage of time that free serum concentrations (fT): 1) were above the target organism's minimum inhibitory concentration (≥ fT > 1 × minimum inhibitory concentration); 2) were above four times the minimum inhibitory concentration (≥ % fT > 4 × minimum inhibitory concentration); and 3) were always above the minimum inhibitory concentration (≥ 100% fT > minimum inhibitory concentration) for the first 72 hours of antibiotic therapy. Demographic data and effluent rates from the Acute Renal Failure Trial Network and RENAL Replacement Therapy Study trials were used. Optimal doses were defined as the dose achieving greater than or equal to 90% probability of target attainment. SETTING: Monte Carlo simulations using demographic data from Acute Renal Failure Trial Network and RENAL Replacement Therapy Study trials. PATIENTS: Virtual critically ill patients requiring continuous renal replacement therapy. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The pharmacodynamic target of fT greater than 1 × minimum inhibitory concentration led to similarly high rates of predicted response with antibiotic doses often used in continuous renal replacement therapy. Achieving 100% fT greater than minimum inhibitory concentration is a more stringent benchmark compared with T greater than 4 × minimum inhibitory concentration with standard antibiotic dosing. The intensity of effluent flow rates (less intensive vs intensive) did not substantially influence the probability of target attainment of antibiotic dosing regimens regardless of pharmacodynamic target. CONCLUSIONS: Antibiotic pharmacodynamic target attainment rates likely were not meaningfully different in the low- and high-intensity treatment arms of the Acute Renal Failure Trial Network and RENAL Replacement Therapy Study Investigators trials.

Assessment of literacy and numeracy skills related to non-steroidal anti-inflammatory drug labels.

BACKGROUND: Non-steroidal anti-inflammatory drugs are widely used and have a potential for over-the-counter misuse. Limited health literacy is associated with poor health outcomes. Identification of new strategies to assess literacy and numeracy could be useful in targeting effective education initiatives. OBJECTIVE: To characterize numeracy and literacy skills related to non-steroidal anti-inflammatory drug labels in primary care patients. METHODS: Patients were recruited and consented over an 8-month period after their regular primary care visit. Demographic information was collected and two instruments were administered to assess literacy and numeracy skills: (1) a medication label literacy instrument focused on non-steroidal anti-inflammatory drugs (MedLit-NSAID) and (2) a general healthy literacy-screening tool, the Newest Vital Sign. Two questions on the MedLit-NSAID instrument evaluated understanding of the Food and Drug Administration medication guide for non-steroidal anti-inflammatory drugs and the Food and Drug Administration approved over-the-counter label. RESULTS: A total of 145 patients were enrolled. Mean MedLit-NSAID and Newest Vital Sign scores were 6.8 (scale range 0-8) and 4.2 (scale range 0-6), respectively. Higher education level was associated with higher scores for both tools (p ⩽ 0.05). Total MedLit-NSAID scores on average were higher in females compared with males (6.5 vs 6, p = 0.05). Patients with decreased kidney function (n = 18) had significantly lower MedLit-NSAID scores (p ⩽ 0.05). Test-retest scores were not significantly different for MedLit-NSAID (p = 0.32). The correlation between the tools was 0.54 and internal consistency MedLit-NSAID was 0.61. CONCLUSION: A medication information focused instrument provided specific information to assess health literacy related to non-steroidal anti-inflammatory drug labels. This information could be utilized to develop patient education initiatives for medication label comprehension.