Abbreviated Urine Collection Compared With 24-Hour Urine Collection for Measuring Creatinine Clearance in Adult Critically Ill Patients: A Systematic Review.

OBJECTIVE: To evaluate the accuracy of abbreviated urine collection (≤12 hours) compared with 24-hour urine collection for measuring creatinine clearance (CrCl) in critically ill adult patients. DATA SOURCES: We searched PubMed, Embase, Web of Science, Google Scholar, and ProQuest Dissertations and Thesis Global; screened reference lists of included studies; and contacted the authors when needed. English studies only were considered with no restriction on dates. STUDY SELECTION AND DATA EXTRACTION: After duplicate removal, 2 reviewers screened titles/abstracts, reviewed full-text articles, and extracted data independently. Studies that compared abbreviated versus 24-hour urine collection for measuring CrCl were included. We assessed the risk of bias using the QUADAS-2 tool. We extracted correlation coefficients, mean prediction errors (ME)-as a measure of bias, and root mean squared prediction errors (RMSE)-as a measure of precision. DATA SYNTHESIS: Five studies were included, comprising 528 adult critically ill adults from surgical, medical, and trauma intensive care units (ICUs). Three studies had high risk of bias, and 2 had low risk. The studies evaluated different durations of urine collection, including 30-minute, 2-hour, 4-hour, 6-hour, and 12-hour. Mean 24-hour CrCl ranged from 57 mL/min/1.73 m2 to 103 mL/min. Abbreviated urine collection led to CrCl that correlated well with the 24-hour measured CrCl (correlation coefficient ranged from 0.8 to 0.95). Mean prediction error ranged from 5 mL/min/1.73 m2 to 16 mL/min (from 8% to 25% of the 24-hour CrCl). Root mean squared prediction error calculated from 1 study was 30.5 mL/min/1.73 m2. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Abbreviated urine collection is used to measure CrCl for renal drug dosing in critically ill patients, but its accuracy is not well-established. CONCLUSIONS: Abbreviated urine collection may overestimate CrCl compared with 24-hour urine collection. Larger, well-conducted studies are needed to evaluate the accuracy of CrCl measured using different durations of urine collection in critically ill patients.

A survey on the knowledge and attitudes of pharmacists towards the application of antimicrobial therapeutic drug monitoring and its challenges in Qatar.

INTRODUCTION: Therapeutic drug monitoring (TDM) is an integral part of pharmaceutical care. Antimicrobials are amongst the most commonly monitored medications. Therefore, identifying the gaps in antimicrobial pharmacokinetics and TDM knowledge and skills among pharmacists is crucial to optimize TDM application. RESEARCH QUESTION: What is the current knowledge, attitudes and perceived barriers of pharmacists in Qatar towards the application of antimicrobial TDM? STUDY DESIGN: Cross-sectional survey. METHODS: The psychometric validation of the survey underwent 3 stages: domain identification and item generation, content validation, and pilot test. The survey was divided into 4 domains (participant characteristics, knowledge, attitudes, and perceived barriers). It was developed in Survey Monkey and distributed to all pharmacists in Hamad Medical Corporation (HMC) hospitals via email. Data was analyzed using IBM Statistical Package for the Social Sciences (SPSS). Categorical and quantitative variables were expressed as frequencies with percentages and medians with interquartile ranges, respectively. Mann-Whitney U-test was used to test the effect of demographic and professional parameters on the knowledge scores. P values less than 0.05 were considered significant. RESULTS: Forty-nine responses were collected. The median age of respondents was 34 years and 51% of them were males. Most respondents were clinical pharmacists (47%). On average, 44% of knowledge questions were correct, whereas 32% were incorrect and 23% were not sure of the answer. The median knowledge score was 5 out of 10 (interquartile range 2.5-6). Participants with post-graduate degrees or prior pharmacokinetic training showed trends towards higher knowledge scores. Online pharmacokinetics calculators were the most frequently used dose adjustment method. The top perceived barriers for the implementation of antimicrobial TDM were lack of knowledge and lack of educational sessions. CONCLUSIONS: Albeit pharmacists in Qatar had modest level of knowledge about antimicrobial TDM, they had positive attitudes towards TDM and its implications in the clinical practice. Future plans should include providing TDM-related education activities.

Virtual Care? Telepharmacy in Critical Care Settings for Patient-Centered Care and Multidisciplinary Collaboration: A Scoping Review of Activities, Benefits, Economic Impact, Challenges, and Knowledge Gaps.

Background: Very few studies have investigated telepharmacy (TP) in critical care. This scoping review undertook this task. Methods: We searched the following five electronic databases (PubMed, Embase, WoS, Scopus, CINAHL). Data were extracted from the articles and mapped out. Arksey and O'Malley's 6-step framework was used, and data synthesis identified activities, benefits, economic impact, challenges, and knowledge gaps of TP in critical care. Results: Out of 77 reports retrieved, 14 were included in the review as per inclusion criteria. Eight studies (57%) were published since 2020, and 9 (64%) were from the United States. Tele-ICU was in place before TP implementation in six studies (43%). TP used a range of synchronous/asynchronous communications. Studies reported wide assortment of reactive/scheduled TP activities. Patient outcomes were evaluated in one study of sedation-related TP interventions but they were not different despite improved compliance with sedation protocol. Most common clinical interventions/drugs included glycemic, electrolyte, and antimicrobial therapy management and antithrombotic agents among others. Acceptance of TP interventions was 75% or more in four studies and 51-55% in two studies. Benefits of TP included resolved drug-related problems, increased compliance with guidelines, maintained interactions with other health care providers, and patient safety among others. Three studies (21%) reported cost avoidance with TP interventions. Challenges included communication, intervention documentation, tracking implementation of recommendations, and monetary/financial and legislative/regulatory issues. Knowledge gaps comprised lack of frameworks for implementation/evaluation of TP in critical care, methodological aspects, lack of patient-specific outcomes, as well as institution/health-system aspects, and documentation systems, cost, legislative, and sustainability issues. Conclusions: TP in critical care is underpublished, and comprehensive frameworks for its implementation and evaluation remain lacking. Assessments are needed to evaluate the effect of TP in critical care on patient-specific outcomes, its economic and legal dimensions, methods to sustain it, as well as the role of documentation systems, collaboration models, and institutional characteristics.

Efficacy and safety of insulin glargine 300 units/mL vs insulin degludec in patients with type 1 and type 2 diabetes: a systematic review and meta-analysis.

Background: Ultra-long-acting insulin analogs [insulin degludec (IDeg) and insulin glargine 300 units/mL (IGla-300)] offer a longer duration of action with less risk of hypoglycemia compared to other long-acting insulins. However, data about the comparative efficacy and safety are inconsistent. Methods: We searched CENTRAL, PubMed, Embase, ICTRP Search Portal, and ClinicalTrials.gov on 7 October 2022. Randomized controlled trials (RCTs) comparing the safety and efficacy of IDeg (100 or 200 units/mL) and IGla-300 in patients with type 1 or type 2 diabetes were included. Three review authors independently selected trials, assessed the risk of bias, extracted data, and evaluated the overall certainty of the evidence using GRADE. The primary outcomes were the change in glycated hemoglobin (HbA1c) and any hypoglycemia; the secondary outcomes were the change in fasting plasma glucose (FPG) and severe and nocturnal hypoglycemia. Results: Four open-label RCTs were included (2727 participants), 3 parallel and 1 cross-over. Overall, the risk of bias assessment yielded some concern or high risk. There was a comparable change in HbA1c from baseline to the end of treatment, a mean difference of 0.07% (95% confidence interval (CI) 0.06 - 0.19; p = 0.29; 3 trials; 2652 patients; very low-certainty evidence), and a comparable rate of any hypoglycemia, rate ratio 1.02 (95% CI 0.8 - 1.3; p = 0.87; 3 trials; 2881 patients; very low-certainty evidence). IDeg resulted in more reduction in FPG compared to IGla-300, mean difference of 10.27 mg/dL (95% CI 7.25 - 13.29; p < 0.001; 3 trials; 2668 patients; low-certainty evidence). Similar rates of nocturnal and severe hypoglycemia were observed, rate ratio of 1.13 (95% CI 0.72 - 1.78; p = 0.54; 3 trials; 2668 patients; very low-certainty evidence) and 1.4 (95% CI 0.41 - 4.73; p = 0.59; 2 trials; 1952 patients; very low-certainty evidence), respectively. Conclusion: There is no evidence of a difference between IDeg and IGla-300 in the mean change in HbA1c and the risk of anytime, nocturnal, and severe hypoglycemia. IDeg appeared to cause a higher reduction in FPG compared to IGla-300. However, this finding should be interpreted with caution due to the small number of trials included and their high risk of bias. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022364891, identifier CRD42022364891.

Risk of serotonin syndrome in acutely ill patients receiving linezolid and opioids concomitantly: a retrospective cohort study.

Introduction: Linezolid is an oxazolidinone antibiotic with a reversible, non-selective, monoamine oxidase inhibitory effect. Combining linezolid with serotonergic agents may increase serotonin syndrome (SS) risk.Linezolid is recommended in patients with suspected or confirmed resistant Gram-positive bacterial infections, especially if vancomycin cannot be used. However, it is unclear whether co-administration of linezolid with opioids increases the risk of serotonin syndrome. Research objective: To establish whether combining linezolid with opioids will increase the incidence of SS in acutely ill patients. Methods: This was a retrospective observational study. All adult patients who were admitted and received linezolid between March and September 2020 were included in the study. The primary outcome was the prevalence of SS, as defined by Hunter's criteria. Results: The study included 106 patients, most whom were males (91.5%). More than half of the cohort (56.6%) received a concomitant opioid agent. Morphine and fentanyl were the most prescribed opioids (37.7% and 34%, respectively). Among patients who received opioids, only one patient (1.6%) had spontaneous clonus. However, this patient developed spontaneous clonus post cardiac arrest, which made an association with the linezolid-opioids combination less likely. Conclusion: In this study, the incidence of SS was low in acutely ill patients who received concomitant linezolid and opioids. However, larger prospective studies are required to confirm this finding.

Preemptive Dose Adjustment Effect on the Quality of Anticoagulation Management in Warfarin Patients With Drug Interactions: A Retrospective Cohort Study.

One strategy to manage patients on warfarin starting an interacting drug is to increase the frequency of monitoring. Another strategy is to adjust warfarin dose around the time patient is started on an interacting medication, which is known as "preemptive warfarin dose adjustment." The main objective of this study is to compare preemptive to nonpreemptive strategy and their impact on the quality of anticoagulation management. This is a retrospective cohort study performed at the pharmacist-managed anticoagulation clinic in a tertiary hospital in the State of Qatar. Over a 4-year period, 340 patients were evaluated, and 58 warfarin-drug interaction encounters were identified. Mean age of the patients was (57.7 ± 13.7), and 50% of them were females. Preemptive dose adjustment was used in 17 (29.3%) cases. Incidence of out-of-target international normalized ratio (INR) was statistically lower in the preemptive arm compared to the control group (41.2% [7/17] vs 69.2% [27/39], P = .048). Incidence of extreme out-of-target INR was numerically lower in the preemptive arm compared to the control but did not reach statistical significance (11.8% [2/17] vs 29.3% [12/41], P = .139). Change in frequency of INR monitoring was not different between the 2 groups. However, overall frequency of INR monitoring after onset/discontinuation of interacting medication increased compared to baseline (7 [9] vs 21 [16] days, P < .001). Preemptive strategy was shown in our study to decrease incidence of the out-of-target INR visits, although patients remained in need for close monitoring.

Torsemide versus furosemide after acute decompensated heart failure: a retrospective observational study.

BACKGROUND: Loop diuretics are recommended by clinical practice guidelines to treat volume overload in acute decompensated heart failure (ADHF). The effectiveness of switching furosemide to torsemide versus optimizing the furosemide dose following ADHF has not yet been evaluated. METHODS: This retrospective observational study aimed to assess the impact of switching furosemide to torsemide versus optimizing the furosemide dose after ADHF on HF-related hospitalization within 1 month and 6 months of discharge. The study included patients previously on furosemide admitted with ADHF to the Heart Hospital in Qatar between January 1, 2016 and June 30, 2017. The study included 2 groups: (1) patients discharged on torsemide; and (2) patients discharged on an optimized furosemide dose. Cox proportional hazard regression analysis was used to determine the association between diuretic use and hospitalization. RESULTS: Of the 232 patients included, 45 received torsemide and 187 received an optimized furosemide dose upon discharge. The majority of patients included were males (54%) with a mean age of 67 ± 12 years, and presented with HF with reduced ejection fraction (57%) and had a history of coronary artery disease (68%). The 1-month and 6-month HF-related hospitalization did not differ between the torsemide and optimized furosemide groups (aHR = 0.72; 95% CI 0.23-2.3, p = 0.57; aHR = 0.94, 95% CI 0.45-1.8, p = 0.87), respectively. CONCLUSION: Switching furosemide to torsemide after ADHF was not associated with reduced HF-related hospitalization compared to receiving an optimized furosemide dose. Larger prospective clinical trials are needed to confirm the findings of this study.

Clinical and Pharmacokinetic Outcomes of Peak-Trough-Based Versus Trough-Based Vancomycin Therapeutic Drug Monitoring Approaches: A Pragmatic Randomized Controlled Trial.

BACKGROUND: Vancomycin therapeutic drug monitoring (TDM) is based on achieving 24-h area under the concentration-time curve to minimum inhibitory concentration cure breakpoints (AUC24/MIC). Approaches to vancomycin TDM vary, with no head-to-head randomized controlled trial (RCT) comparisons to date. OBJECTIVES: We aimed to compare clinical and pharmacokinetic outcomes between peak-trough-based and trough-only-based vancomycin TDM approaches and to determine the relationship between vancomycin AUC24/MIC and cure rates. METHODS: A multicentered pragmatic parallel-group RCT was conducted in Hamad Medical Corporation hospitals in Qatar. Adult non-dialysis patients initiated on vancomycin were randomized to peak-trough-based or trough-only-based vancomycin TDM. Primary endpoints included vancomycin AUC24/MIC ratio breakpoint for cure and clinical effectiveness (therapeutic cure vs therapeutic failure). Descriptive, inferential, and classification and regression tree (CART) statistical analyses were applied. NONMEM.v.7.3 was used to conduct population pharmacokinetic analyses and AUC24 calculations. RESULTS: Sixty-five patients were enrolled [trough-only-based-TDM (n = 35) and peak-trough-based-TDM (n = 30)]. Peak-trough-based TDM was significantly associated with higher therapeutic cure rates compared to trough-only-based TDM [76.7% vs 48.6%; p value = 0.02]. No statistically significant differences were observed for all-cause mortality, neutropenia, or nephrotoxicity between the two groups. Compared to trough-only-based TDM, peak-trough-based TDM was associated with less vancomycin total daily doses by 12.05 mg/kg/day (p value = 0.027). CART identified creatinine clearance (CLCR), AUC24/MIC, and TDM approach as significant determinants of therapeutic outcomes. All patients [n = 19,100%] with CLCR ≤ 7.85 L/h, AUC24/MIC ≤ 1256, who received peak-trough-based TDM achieved therapeutic cure. AUC24/MIC > 565 was identified to be correlated with cure in trough-only-based TDM recipients [n = 11,84.6%]. No minimum AUC24/MIC breakpoint was detected by CART in the peak-trough-based group. CONCLUSION: Maintenance of target vancomycin exposures and implementation of peak-trough-based vancomycin TDM may improve vancomycin-associated cure rates. Larger scale RCTs are warranted to confirm these findings.