Identification and characterization of critical values in therapeutic drug monitoring: a retrospective analysis.

Therapeutic drug monitoring (TDM) is a crucial clinical practice that improves pharmacological effectiveness and prevent severe drug-related adverse events. Timely reporting and intervention of critical values during TDM are essential for patient safety. In this study, we retrospectively analyzed the laboratory data to provide an overview of the incidence, distribution pattern and biochemical correlates of critical values during TDM. A total of 19,110 samples were tested for nine drug concentrations between January 1, 2019, and December 31, 2020. Of these, 241 critical values were identified in 165 patients. The most common critical values were vancomycin trough (63.4%), followed by tacrolimus trough (16.9%) and digoxin (15.2%). The primary sources of drug critical values were the department of general intensive care unit (ICU), cardiology, and surgery ICU. At baseline or the time of critical value, significant differences were found between the vancomycin, digoxin, and tacrolimus groups in terms of blood urea nitrogen (BUN), creatinine, N-terminal Pro-B-Type Natriuretic Peptide (NT-proBNP), and lymphocyte percentage, P < 0.05. Therefore, it is important to prioritize and closely monitor drug concentrations to reduce laboratory critical values during TDM.

Epidemiology and outcomes of bloodstream infections in severe burn patients: a six-year retrospective study.

BACKGROUND: Infection is the leading cause of morbidity and mortality among burn patients, and bloodstream infection (BSI) is the most serious. This study aimed to evaluate the epidemiology and clinical outcomes of BSI in severe burn patients. METHODS: Clinical variables of all patients admitted with severe burns (≥ 20% total body surface area, %TBSA) were analyzed retrospectively from January 2013 to December 2018 at a teaching hospital. The Kaplan-Meier method was utilized for plotting survival curves. Multivariate logistic regression and Cox regression model were also performed. RESULTS: A total of 495 patients were evaluated, of whom 136 (27.5%) had a BSI. The median time from the patients being burned to BSI was 8 days. For BSI onset in these patients, 47.8% (65/136) occurred in the first week. The most frequently isolated causative organism was A. baumannii (22.7%), followed by methicillin-resistant Staphylococcus aureus (18.7%) and K. pneumoniae (18.2%), in patients with BSI. Multivariate logistic regression analysis showed that %TBSA (p = 0.023), mechanical ventilation (p = 0.019), central venous catheter (CVC) (p < 0.001) and hospital length of stay (27d vs 50d, p < 0.001) were independent risk factors associated with BSI. Cox regression model showed that acute kidney injury (HR, 12.26; 95% CI 2.31-64.98; p = 0.003) and septic shock (HR, 4.36; 95% CI 1.16-16.34; p = 0.031) were identified as independent predictors of 30-day mortality of BSI in burn patients. CONCLUSIONS: Multidrug resistant gram-negative bacteria were the main pathogens of BSI in severe burn patients. Accurate evaluation of risk factors for BSI and the mortality of BSI in severe burn patients may improve early appropriate management.

Effect of prior receipt of antibiotics on the pathogen distribution: a retrospective observational cohort study on 27,792 patients.

BACKGROUND: There have been no systematic studies of microbiological differences before and after antibiotics treatment. The aim of this study was to evaluate the effect of prior receipt of antibiotics on the microorganism distribution. METHODS: A retrospective, observational cohort study was conducted in a 3200-bed tertiary, referral, teaching hospital in eastern China. During a 2-year period, all hospitalized patients treated with antimicrobial agents were enrolled in this study. Among 48,692 patients evaluated, the 27,792 (57.1%) who were sampled within 2 days before or after administration of the first dose of antimicrobial agents were included. Distribution of clinical specimens and the microorganism were compared between before and after antibiotic drug treatment groups. RESULTS: Compared to specimens taken after antibiotics exposure, specimens taken before antibiotics exposure had a higher proportion of blood and urine specimens and a higher culture positive rate (all P < 0.001). Higher percentages of Staphylococcus aureus (9.9% vs. 8.5%, P = 0.041), non-fermenting bacteria (27.7% vs. 19.9%, P < 0.001), and fungi (8.4% vs. 4.0%, P < 0.001) were isolated from the group after antibiotics exposure, while the percentages of Streptococcus spp. (4.8% vs. 2.7%, P < 0.001), Haemophilus influenzae (2.3% vs. 0.8%, P < 0.001), and Moraxella catarrhalis (0.7% vs. 0.1%, P < 0.001) were higher in the group before antibiotics exposure. Further analysis found significant differences of microbes derived from respiratory secretions, blood or urine samples. We found, after antibiotics exposure, the separation rate of non-fermenting bacteria was significantly increased (all P < 0.05), and the separation rate of Candida spp. was higher, with statistical significance in airway secretion and urine samples (both P < 0.05), but the separation rate of Staphylococcus aureus among the three groups was not affected by antibiotics. In addition, the isolation rate of Streptococcus spp. in blood and urine samples decreased significantly (both P < 0.05) after antibiotics exposure. Interestingly, no statistical difference was found for microbes isolated from body fluid specimens between the two groups. CONCLUSIONS: The outcome revealed that antibiotic-insensitive organisms such as non-fermentative bacteria and fungi were more frequently isolated after antibiotics exposure. However, this trend might be specimen dependent and was not obvious in body fluid specimens.

Trends and patterns of five antihypertensive drug classes between 2007 and 2012 in China using hospital prescription data.

PURPOSE: To examine prescription trends and patterns in five antihypertensive drug classes during 2007 - 2012 in China. METHODS: A retrospective time series data was investigated from 2007 to 2012. Prescription data of five classes of antihypertensive drugs (calcium channel blockers (CCBs), angiotensin receptor blockers (ARBs), angiotensin-converting enzyme inhibitors (ACEIs), ß-blockers, and diuretics) were accessed from the Hospital Prescription Analysis Program Database, including 59 hospitals in four cities in China. The drugs were coded using the Anatomic Chemical Therapeutic (ATC) classification. Quantities were standardized using the defined daily dose (DDD) measurement methodology. RESULTS: The total number of DDDs of the five classes of antihypertensive drugs prescribed in the sample hospitals increased by 83.3% and the total cost of antihypertensive drugs increased by 92.4% from 2007 to 2012. During the whole study period, CCBs, ARBs, ACEIs, ß-blockers, and diuretics represented in DDDs 42.8%, 28.3%, 13.3%, 10.8%, and 4.8%, respectively, of the total five classes of anti-hypertensive drugs. The average annual increase rate of ARBs, ß-blockers, CCBs, ACEIs, and diuretics, in DDDs, was 23.4%, 13.3%, 13.2%, 1.4%, and -4.2%, respectively CONCLUSIONS: The consumption of the five classes of antihypertensive drugs in China nearly doubled from 2007 to 2012. The top-prescribed antihypertensive drug classes were CCBs and ARBs, and the latter increased most rapidly.

Appropriateness of administration of nasogastric medication and preliminary intervention.

A utilization study was performed in a 2200-bed tertiary care teaching hospital. Data mining was performed on all nasogastric medication prescriptions for patients hospitalized in 2011. Nurses were interviewed by questionnaire. A PDCA (Plan-Do-Check-Act) cycle was used for continuous quality improvement. The proportion of patients with nasogastric tubes (NGT) was 3.2%. A large number of medical orders (n = 6261) involved nasogastric medications with a package insert particularly noting that they should not be crushed or opened (group 1) or medications without a specific formulation recommendation in the package insert but having evidence discouraging NGT dosing (group 2). Of the nasogastrically administered sustained-release or controlled-release formulations, a sustained-release sodium valproate tablet formulation was the most prescribed drug and a sustained-release 2.5 mg felodipine tablet was prescribed with the highest proportion of NGT dosing [NGT/(NGT + oral) = 12.3%]. Among the nasogastrically administered enteric-coated formulations, a myrtol-standardized enteric-coated capsule formulation was the most prescribed drug and a pantoprazole tablet formulation was prescribed with the highest proportion of NGT dosing [NGT/(NGT + oral) = 19.3%]. Proportions of NGT dosing for amiodarone and carbamazepine (group 2) were 4.8% and 6.3%, respectively. The percentage of nurses with adequate knowledge about pharmaceutical dosage formulations was 60%. The rate of answering correctly as to whether medications in group 1 could be crushed or opened was only 30%. Awareness of evidence discouraging NGT dosing of medications in group 2 was zero. Most nurses (90%) left physicians and pharmacists with the entire responsibility for knowledge and decision-making concerning route of drug administration. After a 3-month preliminary intervention, irrational medical orders involving nasogastric administration of medications in group 1 were successfully abolished. The rate of answering correctly as to whether medications in group 1 could be crushed or opened increased to 100%. This utilization study indicates poor awareness concerning nasogastric administration of medication on the part of physicians and nurses, and preliminary intervention measures were efficient in improving knowledge through team cooperation and effort.

Poor awareness of preventing aspirin-induced gastrointestinal injury with combined protective medications.

AIM: To investigate prescribing pattern in low-dose aspirin users and physician awareness of preventing aspirin-induced gastrointestinal (GI) injury with combined protective medications. METHODS: A retrospective drug utilization study was conducted in the 2nd Affiliated Hospital, School of Medicine, Zhejiang University. The hospital has 2300 beds and 2.5 million outpatient visits annually. Data mining was performed on all aspirin prescriptions for outpatients and emergency patients admitted in 2011. Concomitant use of proton-pump inhibitors (PPIs), histamine 2-receptor antagonists (H2RA) and mucoprotective drugs (MPs) were analyzed. A defined daily dose (DDD) methodology was applied to each MP. A further investigation was performed in aspirin users on combination use of GI injurious medicines [non-steoid anti-inflammatory drugs (NSAIDs), corticosteroids and clopidogrel and warfarin] or intestinal protective drugs (misoprostol, rebamipide, teprenone and gefarnate). Data of major bleeding episodes were derived from medical records and adverse drug reaction monitoring records. The annual incidence of major GI bleeding due to low-dose aspirin was estimated for outpatients. RESULTS: Prescriptions for aspirin users receiving PPIs, H2RA and MPs (n = 1039) accounted for only 3.46% of total aspirin prescriptions (n = 30 015). The ratios of coadministration of aspirin/PPI, aspirin/H2RA, aspirin/MP and aspirin/PPI/MP to the total aspirin prescriptions were 2.82%, 0.12%, 0.40% and 0.12%, respectively. No statistically significant difference was observed in age between patients not receiving any GI protective medications and patients receiving PPIs, H2RA or MPs. The combined medication of aspirin and PPI was used more frequently than that of aspirin and MPs (2.82% vs 0.40%, P < 0.05) and aspirin/H2RA (2.82% vs 0.12%, P < 0.05). The values of DDDs of MPs in descending order were as follows: gefarnate, hydrotalcite > teprenone > sucralfate oral suspension > L-glutamine and sodium gualenate granules > rebamipide > sucralfate chewable tablets. The ratio of MP plus aspirin prescriptions to the total MP prescriptions was as follows: rebamipide (0.47%), teprenone (0.91%), L-glutamine and sodium gualenate granules (0.92%), gefarnate (0.31%), hydrotalcite (1.00%) and sucralfate oral suspension (0.13%). Percentages of prescriptions containing aspirin and intestinal protective drugs among the total aspirin prescriptions were: rebamipide (0.010%), PPI/rebamipide (0.027%), teprenone (0.11%), PPI/teprenone (0.037%), gefarnate (0.017%), and PPI/gefarnate (0.013%). No prescriptions were found containing coadministration of aspirin and other NSAIDs. Among the 3196 prescriptions containing aspirin/clopidogrel, 3088 (96.6%) prescriptions did not contain any GI protective medicines. Of the 389 prescriptions containing aspirin/corticosteroids, 236 (60.7%) contained no GI protective medicines. None of the prescriptions using aspirin/warfarin (n = 22) contained GI protective medicines. Thirty-five patients were admitted to this hospital in 2011 because of acute hemorrhage of upper digestive tract induced by low-dose aspirin. The annual incidence rates of major GI bleeding were estimated at 0.25% for outpatients taking aspirin and 0.5% for outpatients taking aspirin/warfarin, respectively. CONCLUSION: The prescribing pattern of low-dose aspirin revealed a poor awareness of preventing GI injury with combined protective medications. Actions should be taken to address this issue.