Low-dose prasugrel versus standard-dose ticagrelor in east Asian patients with acute coronary syndrome.

Low-dose prasugrel demonstrated a similar effectiveness profile to clopidogrel in East Asian ACS patients, but its comparison with another new-generation potent P2Y12 inhibitor, ticagrelor, remains unclear. To compare the effectiveness and safety of low-dose prasugrel against those of standard-dose ticagrelor in East Asian patients with ACS. This retrospective cohort study used Taiwan's National Health and Welfare Database. This study included ACS patients who underwent percutaneous coronary intervention and, at discharge between January 1, 2018 and December 31, 2020, were prescribed with low-dose prasugrel plus aspirin or standard-dose ticagrelor plus aspirin. Stabilized inverse probability of treatment weighting was used to balance the covariates across these two groups. The primary effectiveness outcome was a composite of acute myocardial infarction, ischemic stroke, and cardiovascular death; the secondary effectiveness outcome was each of the individual components of the primary outcome, transient ischemic attack, and repeat revascularization. The primary safety outcome was a composite of intracranial hemorrhage and gastrointestinal bleeding, and the two secondary safety outcomes were intracranial hemorrhage and gastrointestinal bleeding. A total of 24,807 patients were included in this study. Among them, 1,493 were low-dose prasugrel users and 23,314 were standard-dose ticagrelor users. No significant differences were found in primary effectiveness [HR: 0.97 (0.74-1.28)] or primary safety outcomes [HR: 1.22 (0.73-2.01)] between the two study groups. For East Asian patients with ACS, low-dose prasugrel provides comparable effectiveness without increasing bleeding risk compared to standard-dose ticagrelor. Low-dose prasugrel may be an appropriate alternative for East Asian populations.

The Impact of Pharmacist-Managed Service on Warfarin Therapy in Patients after Mechanical Valve Replacement.

Objective: To evaluate the impact of pharmacist interventions on international normalized ratio (INR) control during the warfarin initiation phase after mechanical valve replacement. Methods: This was a retrospective cohort study conducted in a cardiovascular surgery ward in a tertiary hospital from August 1, 2015, to July 31, 2019. Patients aged ≥20 years who were admitted for mechanical valve replacement were enrolled in this study and further classified into conventional and pharmacist-managed warfarin therapy (PMWT) groups. All participants were prospectively followed up until the first outpatient appointment after valve replacement. The effectiveness outcomes were time in therapeutic range (TTR), time to therapeutic INR, number of patients with therapeutic INR at discharge and at first outpatient appointment, and length of hospital stay. The safety outcome was the number of patients with any supratherapeutic INR during the hospital stay. Multivariate logistic regression analyses were also used to determine the predictors of a therapeutic INR at discharge or with any supratherapeutic INR during admission. Results: A total of 39 and 33 patients were enrolled in the conventional and PMWT groups, respectively. At discharge, 18 patients (46.2%) in the conventional group and 24 patients (72.7%) in the PMWT group had achieved the therapeutic INR (P=0.023). Compared to the conventional group, fewer patients in the PMWT group had supratherapeutic INR during hospital stay (35.9% vs. 9.0%, P=0.008). No significant differences were found in TTR, time to therapeutic INR, number of patients with therapeutic INR at return appointment, and length of stay between the study groups. In the multivariate regression analyses, PMWT predicted achieving therapeutic INR at discharge (odds ratio (OR) and 95% confidence interval (CI), 3.14 [1.08-9.14]) and was inversely associated with supratherapeutic INRs during admission (OR = 0.21 [0.05-0.82]). Conclusions: Among patients admitted for mechanical valve replacement, the implementation of PMWT was associated with optimal therapeutic INR at discharge and no supratherapeutic INR during admission. Therefore, pharmacist participation is essential for improving the quality of warfarin therapy.

Comparison of risk of acute kidney injury between patients receiving the combination of teicoplanin and piperacillin/tazobactam versus vancomycin and piperacillin/tazobactam.

BACKGROUND/PURPOSE: To compare the risk of acute kidney injury (AKI) among patients receiving teicoplanin (TA) plus piperacillin/tazobactam (TZP) versus vancomycin (VAN) plus TZP. METHODS: This was a retrospective cohort study using electronic health records. Patients were included if a combination of glycopeptide and TZP or other selected ß-lactams were used during hospitalization. In the main analysis, two study groups were identified: TA + TZP and VAN + TZP. We used 1:1 propensity score matching to control for potential confounders, and hazard ratio (HR) of AKI between study groups was calculated. We further compared the risk of AKI between patients receiving VAN + TZP and VAN + ß-lactams as an auxiliary analysis to verify the validity of the study design. RESULTS: The final sample contained 211 pairs of patients receiving either TA + TZP or VAN + TZP. The median dosage of TA and VAN were 10.3 and 26.7 mg/kg/day, respectively. The median trough level of VAN was 12.3 mg/L. The AKI risk in the TA + TZP group was similar to that in the VAN + TZP group (12.3% vs. 11.4%; HR = 1.25 [0.72-2.18], p = 0.44). The auxiliary analysis showed a higher risk of AKI in the VAN + TZP group than in the VAN + ß-lactam group (13.2% vs. 9.6%; HR = 1.63 [1.04-2.55], p = 0.03). CONCLUSION: Our study results showed that the risk of AKI were similar for patients receiving TA + TZP and VAN + TZP. However, low VAN and high TA dose may play a role in this finding. Further investigation on the association between AKI and TA + TZP is required.

Longitudinal Effects of a Combined Program of Pelvic Floor Muscle Training and Yoga on Genitourinary Symptoms in Asian Women of Older Age: A Randomized Experimental Study.

This parallel-two-group randomized experimental study including a supervised group and an unsupervised group examined the longitudinal effects of pelvic floor muscle training (PFMT) combined with yoga on genitourinary symptoms and the health-related quality of life (HRQOL), and compared practice adherence rates of the two groups. A sample of women experiencing ≥1 genitourinary symptom(s) were recruited and assigned to a supervised group or an unsupervised group. The supervised group attended supervised group practice sessions and performed at-home practice of PFMT and yoga. The unsupervised group performed at-home practice of PFMT and yoga. Information was collected at five time points (n = 91). Generalized estimating equation procedures were used to examine the intervention effects. An independent t-test was conducted to compare the practice adherence rates. Both groups' genitourinary symptoms and HRQOL significantly improved over time. The supervised group displayed greater improvements in genitourinary symptoms and HRQOL and better adherence than did the unsupervised group.

Nephrotoxicity of teicoplanin-based combination therapy: focus on piperacillin/tazobactam and other anti-pseudomonal ß-lactams.

BACKGROUND: The concurrent use of vancomycin and piperacillin/tazobactam increases the risk of acute kidney injury (AKI) compared with vancomycin use with other anti-pseudomonal ß-lactams (OAPBs). Teicoplanin is a glycopeptide antibiotic with lower nephrotoxicity than that of vancomycin. Whether the concomitant use of teicoplanin and piperacillin/tazobactam also increases the risk of AKI remains unknown. OBJECTIVES: To evaluate the AKI risk between teicoplanin-piperacillin/tazobactam and teicoplanin-OAPBs. METHODS: This was a retrospective, propensity score-matched cohort study. Adult patients receiving teicoplanin-based combination therapy were included. OAPBs included cefepime, cefoperazone/sulbactam, ceftazidime, doripenem, imipenem/cilastatin and meropenem. Propensity score matching was performed to balance demographic and confounding factors. The primary endpoint was AKI during combination therapy. RESULTS: After propensity score matching, 954 patients (teicoplanin-piperacillin/tazobactam: teicoplanin-OAPBs, 1:3 matched, 243 pairs in total) were included for analysis. The mean age was 66.3 years in the matched cohort and 17.1% of patients had shock. Use of nephrotoxic medications (45.7% versus 48.7%) and baseline renal function (78.88 ± 31.26 versus 81.05 ± 31.53 mL/min/1.73 m2) were similar in the two groups. The median teicoplanin dose was 10.7 mg/kg in both groups. The groups did not differ significantly in terms of AKI risk (14.8% versus 14.2%, P = 0.815). However, the time to AKI appeared shorter in the teicoplanin-piperacillin/tazobactam group (4.64 ± 2.33 versus 6.29 ± 4.72 days, P = 0.039). CONCLUSIONS: The combination of teicoplanin and piperacillin/tazobactam was not associated with an increased risk of AKI compared with teicoplanin and OAPBs.

Factors to influence the accuracy of albumin adjusted free valproic acid concentration.

BACKGROUND: Therapeutic drug monitoring (TDM) is recommended during treatment with valproic acid (VPA), as is the measurement of free VPA concentration (MfVPA). However, MfVPA is unavailable in many institutions. Based on the highly protein-bound characteristics of VPA, an albumin-adjusted formula has been proposed to predict free VPA concentration (PfVPA). Nevertheless, the factors affecting the accuracy of this formula remain unknown, as does the concordance between MfVPA and PfVPA. METHODS: Adult patients receiving VPA and undergoing TDM were enrolled. Free and total serum concentration (TVPA) were categorized as subtherapeutic, therapeutic, or supratherapeutic based on the reference range of 5-15 and 50-100 µg/mL, respectively. Concordance was defined as MfVPA and PfVPA, or MfVPA and TVPA, falling within the same category. Multivariate logistic regression with generalized estimating equation was adopted to identify factors affecting concordance, and the receiver operating characteristic curve was applied to determine the cutoff values of predictors. RESULTS: A total of 98 data points from 51 participants were included for analysis. The concordance of MfVPA and PfVPA, and MfVPA and TVPA, was 72% and 44%, respectively. Blood urea nitrogen (BUN) (0.97 [0.95-0.99], P = 0.01) and TVPA (0.97 [0.95-0.99], P = 0.02) had a significant influence on the concordance of MfVPA and PfVPA. The cutoff values of TVPA and BUN for the accuracy of the albumin-adjusted formula were 56.4 µg/mL and 51.05 mg/dL, respectively. CONCLUSION: If MfVPA is not available, the albumin-adjusted formula should be applied before VPA dosage adjustment when TVPA is < 56.4 µg/mL and BUN is < 51.05 mg/dL.

Pharmacokinetics and dosing of vancomycin in patients undergoing sustained low efficiency daily diafiltration (SLEDD-f): A prospective study.

BACKGROUND/PURPOSE: The pharmacokinetics of vancomycin in patients who undergo sustained low efficiency daily diafiltration (SLEDD-f) is not clear. This study aimed to determine the appropriate vancomycin dosage regimen for patients receiving SLEDD-f. METHODS: This prospectively observational study enrolled critically ill patients older than 18 years old that used SLEDD-f as renal replacement therapy and received vancomycin treatment. An 8-h SLEDD-f was performed with FX-60 (high-flux helixone membrane, 1.4 m2). Serial blood samples were collected before, during, and after SLEDD-f to analyse vancomycin serum concentrations. Effluent fluid samples (a mixture of dialysate and ultrafiltrate) were also collected to determine the amount of vancomycin removal. RESULTS: Seventeen patients were enrolled, and 10 completed the study. The amount of vancomycin removal was 447.4 ± 88.8 mg (about 78.4 ± 18.4% of the dose administered before SLEDD-f). The vancomycin concentration was reduced by 57.5 ± 14.9% during SLEDD-f, and this reduction was followed by a rebound with duration of one to three hours. The elimination half-life of vancomycin decreased from 64.1 ± 35.7 h before SLEDD-f to 7.0 ± 3.0 h during SLEDD-f. CONCLUSION: Significant amount of vancomycin removed during SLEDD-f. Despite the existence of post-dialysis rebound, a sufficient supplemental dose is necessary to maintain therapeutic range.

Impact of high plasma concentrations of linezolid in Taiwanese adult patients- therapeutic drug monitoring in improving adverse drug reactions.

BACKGROUND: Previous studies have shown that the development of thrombocytopenia was associated with the elevated plasma concentration of linezolid, but little is known about the relationship between other uncommon adverse drug reactions (ADRs) and plasma concentration. The appropriate dosing adjustment has remained controversial. This prospective observational study was conducted to investigate the association between the plasma concentration of linezolid, ADRs, and clinical outcomes. METHODS: Adult patients on linezolid treatment undergoing at least one therapeutic drug monitoring (TDM) were enrolled. The association between linezolid concentrations and ADRs was examined by multivariate Cox regression model. Predictors of linezolid concentrations was determined by linear regression model. The cut-off point of linezolid concentration and the effect of dosing adjustments based on TDM was also explored. RESULTS: Of 50 patients enrolled in the study, plasma concentrations were 1.5-3 times higher than what was described in the prescribing information. The median minimum concentration (Cmin) was significantly higher in patients with thrombocytopenia compared to patients without thrombocytopenia (13.0 vs. 7.2 µg/mL, P = 0.0273), and a higher median maximum concentration was also observed in patients with lactic acidosis (33.0 vs. 27.5 µg/mL, P = 0.0420). The Cmin was elevated in patients with advanced age and severely impaired renal function. Dosing adjustment tailored by early TDM with the upper limit of Cmin 9 µg/mL may improve platelet counts. CONCLUSION: Elevated linezolid concentrations were associated with thrombocytopenia and lactic acidosis. TDM-guided dosing adjustment could be considered as a pragmatic way to mitigate thrombocytopenia.

Effects of Retzius sparing on robot-assisted laparoscopic prostatectomy: a systematic review with meta-analysis.

BACKGROUND: To comprehensively evaluate the efficacy and safety of Retzius sparing (RS) for men undergoing robot-assisted laparoscopic prostatectomy (RARP). METHODS: We searched four electronic databases and reference lists of relevant studies for eligible research published before March 11, 2019. After quality assessment, eligible studies were synthesized for relevant outcomes, including positive surgical margin (PSM), continence, incontinence, complication, console time, and hospital stay. RESULTS: Two randomized clinical trials and four observational studies were included in this study. Quantitative syntheses revealed significantly higher PSM rates in RS-RARP compared with conventional RARP (c-RARP) (odds ratio [OR] 1.68, p = 0.02). Furthermore, we found significantly higher PSM rates at the anterior site in RS-RARP compared with c-RARP (OR 4.34, p = 0.03) and significantly lower incontinence rates in RS-RARP in the first month (OR 0.30, p < 0.001) and 12th month (OR 0.25, p < 0.001). CONCLUSIONS: Our syntheses revealed higher PSM rates in the RS-RARP group, especially in the anterior aspect. However, RS-RARP had superior functional outcome of urinary continence and lower console time than did c-RARP with equivalent complication rates. Thus, we suggest that operators pay more attention to making clear surgical margins if the lesion is in anterior prostate when performing RS-RARP.

Clinical and economic impact of clinical pharmacist intervention in a hematology unit.

BACKGROUND: Medication errors can lead to preventable adverse drug events and associated hospitalization and healthcare cost to patients. Pharmacotherapy in patients with hematologic malignancies is more complex than that in general medicine patients. This study evaluated the clinical and economic impact of clinical pharmacist intervention in a hematology unit. METHODS: This retrospective study compared the number of pharmacist interventions and the economic impact for one year before and after a clinical pharmacist was deployed in a hematology unit. The clinical pharmacist joined the ward rounds and gave patient counseling and recommendations on medication use. For pharmacist intervention analysis, we compared the number and type of interventions. For cost analysis, we calculated the cost savings, estimated the cost avoidance, and compared the benefit-cost ratio between the two periods. RESULTS: The average length of hospitalization reduced from 19.27 days to 16.69 days after clinical pharmacist deployment. The rate of pharmacist interventions in medication orders increased from 143 out of 42,501 prescriptions (0.34%) to 826 out of 44,175 prescriptions (1.87%) (P < 0.00001). The calculated cost savings (NT$37,080 and NT$252,280), cost avoidance (NT$582,100 and NT$2,304,600), and benefit-cost ratio (0.77 and 3.19) increased after clinical pharmacist deployment. CONCLUSION: This study demonstrated that the number of interventions significantly increased after clinical pharmacist deployment. This service could reduce medication errors, preventable adverse drug events, and costs of both medications and potential adverse drug events.

Effects of transabdominal preperitoneal and totally extraperitoneal inguinal hernia repair: an update systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Compared with open herniorrhaphy, laparoscopic herniorrhaphy can yield more favorable clinical outcomes. However, previous studies failed to give definite answer for comparison between laparoscopic inguinal hernia repair approaches. This study aimed to systematically determine the differences in recurrence rate, duration of return to work, pain, surgery duration, and duration of hospital stay between transabdominal preperitoneal (TAPP) and totally extraperitoneal (TEP) approach for inguinal hernia. METHODS: PubMed, Embase, and Cochrane Library (including the Cochrane Central Register of Controlled Trials) abstracts up to September 2017 were searched for randomized controlled trials (RCTs) comparing TAPP or TEP hernia repairing. The hernia recurrence rate, time to return to work, analgesic consumption, surgery duration, hospital stay, and the pain score were recorded with subgroup analysis of the hernia type. RESULTS: Sixteen RCTs that randomized 1519 patients with hernia into TEP and TAPP repair groups were analyzed in this study. The results revealed that TEP repair resulted in shorter hospital stay of primary cases (MD - 0.87, 95% CI - 1.67 to - 0.07) but was associated with a longer operative duration in recurrent hernia group (MD 3.35, 95% CI 0.16 - 6.54). CONCLUSIONS: TEP and TAPP have their own advantages. TEP repair reduces short-term postoperative pain more effectively than TAPP repair and results in shorter hospital stay of primary cases. In contrast, TAPP repair is correlated with shorter surgery duration. These findings show that shared decision-making regarding both approaches of laparoscopic hernia repair may be needed.

Effect of Extracorporeal Membrane Oxygenation on the New Vancomycin Dosing Regimen in Critically Ill Patients Receiving Continuous Venovenous Hemofiltration.

BACKGROUND: The optimal dosing regimen of vancomycin for critically ill patients receiving continuous venovenous hemofiltration (CVVH) remains controversial, not to mention those with concurrent use of extracorporeal membrane oxygenation (ECMO). We aimed to determine if a new dosing regimen can achieve the target vancomycin trough concentration (Ctrough) of 10-20 mcg/mL in patients receiving CVVH with or without ECMO. METHODS: We conducted a retrospective study by enrolling patients who received vancomycin while undergoing CVVH. The vancomycin dosing regimen was 15-20 mg/kg as the loading dose and 7.5 mg/kg every 12 hours as the maintenance doses. Serum concentration was determined after at least 4 doses of vancomycin were given. RESULTS: A total of 38 patients were enrolled, of which 21 were also on ECMO. The ultrafiltration rate of CVVH was 30.6 ± 5.5 mL·kg·h with the Ctrough of 14.7 ± 3.5 mcg/mL. Ctrough was within the target range in 82% of patients. All CVVH-only patients achieved the target concentration, whereas only 76.2% of those with concurrent ECMO did (P = 0.031). CONCLUSIONS: All patients receiving CVVH achieved the target Ctrough with this new dosing regimen, but those with concurrent ECMO did not. Ctrough must be more closely monitored in patients using ECMO simultaneously.

Early linezolid-associated lactic acidosis in a patient with Child's class C liver cirrhosis and end stage renal disease.

Linezolid, an oxazolidinone antibiotic, does not required dose adjustment in patients with Child's class A and B liver cirrhosis. The dose adjustment data for Child's class C liver cirrhosis is inadequate. We reported a case of Child's class C liver cirrhosis, in which lactic acidosis, an adverse effect related to prolonged use, occurred only after two weeks of linezolid treatment. A 63-year old male had underlying diseases, such as end-stage renal disease (ESRD) and Child's class C liver cirrhosis, and was admitted for hepatic encephalopathy management and liver transplantation evaluation. Spontaneous bacterial peritonitis and septic shock occurred during admission. Because ascites culture revealed vancomycin-resistant Enterococci (VRE), daptomycin was initially prescribed. Subsequently, VRE bacteremia occurred, and infective endocarditis was confirmed. Following treatment failure with daptomycin use, intravenous linezolid (600 mg q12h) was added for synergic effect. VRE bacteremia quickly resolved following linezolid treatment, and vasopressor use was reduced. Despite stable hemodynamics, lactic acidosis still persisted, and linezolid therapeutic drug monitoring was ordered. High linezolid trough concentration (49 mg/L) was found by therapeutic drug monitoring, and linezolid-associated lactic acidosis was highly suspected. Therefore, linezolid treatment was stopped and patient's lactic acid level returned to normal after one week. VRE bacteremia recurred after discontinuation of linezolid; therefore, linezolid was re-prescribed at the lower dose (600 mg). Linezolid trough concentration was within the therapeutic range this time (6.1 mg/L), and lactic acidosis did not occur when linezolid dose was reduced. Therefore, empirically decreased dose and therapeutic drug monitoring should be considered in patients with Child's class C liver cirrhosis and ESRD.

Correlates of Nocturia and Relationships of Nocturia With Sleep Quality and Glycemic Control in Women With Type 2 Diabetes.

PURPOSES: To explore correlates of nocturia, compare sleep quality and glycemic control for women with and without nocturia, and examine relationships of nocturia with sleep quality and glycemic control in women with diabetes. DESIGN: This study was a cross-sectional, correlational study with data collected from 275 women with type 2 diabetes. METHODS: Data were collected using a structured questionnaire. Multivariate logistic regression analyses were used to identify correlates. Chi-squared tests were used to identify candidate variables for the first logistic regression model. A one-way analysis of variance was used to compare sleep quality and glycemic control for women with and those without nocturia. Pearson correlations were used to examine the relationships of nocturia with sleep quality and glycemic control. FINDINGS: Of the 275 participants, 124 (45.1%) had experienced nocturia (at least two voids per night). Waist circumference, parity, time since diagnosis of diabetes, sleep quality, and increased daytime urinary frequency were correlated with nocturia after adjusting for age. Compared to women without nocturia, women who had nocturia reported poorer sleep quality. A significant correlation was found between the number of nocturnal episodes and sleep quality. CONCLUSIONS: Nocturia and poor sleep are common among women with diabetes. The multifactorial nature of nocturia supports the delivered management and treatments being targeted to underlying etiologies in order to optimize women's symptom management. Interventions aimed at modifiable correlates may include maintaining a normal body weight and regular physical exercise for maintaining a normal waist circumference, and decreasing caffeine consumption, implementing feasible modifications in sleeping environments and maintaining sleep hygiene to improve sleep quality. CLINICAL RELEVANCE: Healthcare professionals should screen for nocturia and poor sleep and offer appropriate nonpharmacological lifestyle management, behavioral interventions, or pharmacotherapy for women with diabetes.

The Effect of Different Carbapenem Antibiotics (Ertapenem, Imipenem/Cilastatin, and Meropenem) on Serum Valproic Acid Concentrations.

BACKGROUND: Carbapenem antibiotics (CBPMs) may significantly reduce the serum concentration of valproic acid (VPA), but the extent of this effect among various CBPMs is unknown. This study compared the extent and onset of the interactions among ertapenem, imipenem/cilastatin, and meropenem. METHODS: A 5-year retrospective study was performed. Hospitalized patients over 18 years old who received VPA and a CBPM concurrently were enrolled via the pharmacy computer system. Patients who lacked VPA serum concentration measurements before or during CBPMs' use, had concurrent medication(s) that might interfere with VPA metabolism, or had a history of liver cirrhosis were excluded. Total VPA serum concentrations before and during CBPMs' use and after its discontinuation were recorded, and differences among various CBPMs were analyzed. RESULTS: Fifty-two patients were included in this analysis. Irrespective of the route of administration, VPA serum concentrations were subtherapeutic in 90% of the subjects during CBPMs' use. There was a significant decrease (P < 0.001) in VPA serum concentrations during the use of CBPMs: 72% ± 17%, 42% ± 22%, and 67% ± 19% in the ertapenem (N = 9), imipenem/cilastatin (N = 17), and meropenem (N = 26) groups, respectively. The effect of ertapenem and meropenem on VPA was significantly more expressed than that of imipenem/cilastatin (P < 0.005). The onset of this drug interaction occurred within 24 hours of CBPMs' administration, and VPA serum concentrations returned to 90% of baseline within 7 days of CBPMs' discontinuation along with a 20% increase in VPA dose. Increasing VPA dose during the use of ertapenem or meropenem did not result in elevating VPA serum concentrations to therapeutic levels during the combined therapy period. CONCLUSIONS: CBPMs reduced VPA serum concentration within 24 hours of administration by approximately 60%. Ertapenem and meropenem had a greater effect on VPA serum concentration than imipenem/cilastatin. Because of the dramatic reduction of VPA serum concentration during CBPMs' use, concomitant use of VPA and CBPMs should be avoided.

Acute Hepatotoxicity of Intravenous Amiodarone: Case Report and Review of the Literature.

Amiodarone is a class III antiarrhythmic drug widely used for the treatment of both supraventricular and ventricular arrhythmias in intensive care unit. Hepatotoxicity of amiodarone is usually mild and delayed onset. Acute hepatotoxicity is a rare side effect and usually correlated to intravenous form use. In this case, acute hepatocellular injury occurred within 24 hours after the administration of intravenous amiodarone. Liver enzyme significantly improved after holding intravenous amiodarone use. Because ventricular arrhythmia persisted and side effects occurred to alternative therapy, low dose of oral amiodarone was resumed and hepatotoxicity did not occur afterward. Acute hepatotoxicity of intravenous amiodarone is possibly related to polysorbate 80, the solubilizer of amiodarone infusion or higher dose. As a result, when intravenous amiodarone is prescribed, closely monitoring liver enzyme is highly suggested. If acute hepatitis takes place secondary to intravenous amiodarone, oral therapy should not be resumed afterward. If there is no alternative treatment, lower dose of oral amiodarone (≤200 mg/d) could be tried and should monitor liver function regularly.

Clopidogrel-Associated Neutropenia: Case Report and Review of the Literature.

Clopidogrel is a second generation of thienopyridine, which has antiplatelet effect by inhibiting P2Y12 receptor. Hematologic adverse effect is very uncommon during clopidogrel use, but some cases of clopidogrel-associated neutropenia were reported in the past decade. Until now, there was no summary data to delineate the clinical course and safe alternatives of this event. We report 2 cases of clopidogrel-associated neutropenia and review other 10 case reports from 2000 to 2014. The median onset of neutropenia was 22 days, and the recovery time was 4 days after receiving granulocyte-colony-stimulating factor. Bone marrow studies in 6 cases all showed hypocellular or toxic damage. Six cases used cilostazol, prasugrel, or ticagrelor as safe alternatives. Closely monitoring blood cell counts is highly suggested in the first month after using clopidogrel. Newer P2Y12 inhibitors, especially ticagrelor, could be effective and safe alternatives if patients had a history of clopidogrel-associated neutropenia.

Pharmacokinetics of vancomycin in adults receiving extracorporeal membrane oxygenation.

BACKGROUND/PURPOSE: Extracorporeal membrane oxygenation (ECMO) alters the pharmacokinetics (PK) of vancomycin in neonates; but data on adults is limited. METHODS: This is a prospective, matched cohort, single center, pharmacokinetic study. For each adult patient who received vancomycin therapy in the ECMO group (with either centrifugal pump or roller pump), a control patient was matched by age (≥ 60 years or < 60 years), gender, and creatinine clearance (CLCr) in intensive care units. After vancomycin was administered for at least four doses, serial blood samples were drawn at 0.5 hours, 1 hour, 2 hours, 3 hours, 5 hours, 7 hours, 11 hours, 23 hours, 35 hours, and 47 hours post vancomycin infusion according to the dosing intervals. The serum concentration-time profile was fitted to a noncompartment model and a nonlinear mixed effect model to determine the PK parameters. RESULTS: Twenty-two critically ill adults without renal replacement therapy were enrolled. There were no significant differences between the ECMO group and the matched group in demographics, renal function, and PK parameters. However, vancomycin clearance in the roller pump group was significantly lower than that in the matched control (0.83 ± 0.43 mL/min/kg vs. 0.97 ± 0.43 mL/min/kg, p = 0.002). CONCLUSION: Vancomycin clearance in patients receiving ECMO with a roller pump was significantly lower than that in the matched cohort. Vancomycin PK parameters in patients on ECMO with a centrifugal pump were comparable to those in the matched control group.

Correction: The effectiveness of problem based learning in improving critical thinking, problem-solving and self-directed learning in first-year medical students: A meta-analysis.

[This corrects the article DOI: 10.1371/journal.pone.0277339.].

The effect of pharmacist-led medication therapy management in the multidisciplinary care of acute kidney injury survivors.

BACKGROUND: The Acute Disease Quality Initiative advocates multidisciplinary care for the survivors of acute kidney injury (AKI). The bundled care strategy recognizes the role of pharmacists. However, their specific contributions in this context remain underexplored. METHODS: This retrospective study examined the efficacy of pharmacist-led post-AKI pharmaceutical care in outpatient settings at a single center. Adults with recent AKI during hospitalization, maintaining an estimated glomerular filtration rate <45 mL/min/1.73 m2 postdischarge, were enrolled in a multidisciplinary team care program from March 2022 to January 2023, with a 6-month follow-up period. Pharmacist-delivered care adhered to international multidisciplinary consensus guidelines. Efficacy was evaluated by analyzing medication-related recommendations, medication adherence, nephrotoxic drug utilization, and renoprotective medication usage before and after the intervention. RESULTS: A total of 40 patients were referred to the pharmacist-managed clinic. Of these, 33 patients (mean age, 63 ± 15 years; 60.6% male) attended the clinic. Nineteen patients completed follow-up visits. The pharmacist provided 14 medication-related recommendations to relevant physicians, with 10 of these recommendations (71.4%) being accepted. There was a significant decrease in the use of modifiable nephrotoxic drugs (p = 0.03). However, no significant improvements were noted in medication adherence or the utilization of renoprotective medications. CONCLUSION: Our study underscores the potential benefits of pharmacist-led post-AKI bundled care strategy in outpatient settings. We observed a significant reduction in the utilization of modifiable nephrotoxic drugs, indicating the effectiveness of pharmacist interventions in optimizing medication regimens to mitigate renal harm.