Prevention of radiation dermatitis with skin hygiene and washing: a systematic review and meta-analysis.

PURPOSE: This systematic review and meta-analysis aims to evaluate the effects of washing in patients receiving radiotherapy (RT) on radiation dermatitis (RD) severity. METHODS: A literature search was performed using Ovid MEDLINE, Embase, and Cochrane databases between January 1, 1946, and January 31, 2023. Four randomized controlled trials (RCTs) studying the effects of washing with or without soap on RD were identified. A meta-analysis was conducted for clinician-reported outcomes using RevMan 5.4 and a narrative synthesis for patient-reported outcomes due to a lack of reported data amenable to quantitative comparison in accordance with the Synthesis Without Meta-analysis (SWiM) guidelines. The Cochrane Risk of bias (RoB2) and Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) criteria were used to assess risk of bias and certainty of evidence, respectively. RESULTS: Two RCTs met the inclusion criteria for meta-analysis. Washing with or without soap significantly reduced the incidence of severe RD (OR: 0.32, 95% CI: 0.19-0.55, p < 0.01) and moist desquamation (OR: 0.25, 95% CI: 0.12-0.52, p < 0.01). Two of four trials found an association between washing and reduced itching score (p = 0.38). Pain score was not found to be significantly different with or without washing in any of the four studies (p = 0.07). The two studies that assessed burn scores did not detect any difference between the washing group versus no washing group (p = 0.25). Washing was associated with improved quality of life (QoL) measures in one study. CONCLUSION: Washing with or without soap during RT resulted in less severe RD and less moist desquamation. Given the QoL benefits of washing, it should be advocated as part of routine skin care during RT.

Hemodialysis taping styles and their effect on reducing the chance of venous needle dislodgement.

INTRODUCTION: Vascular access complications are common among hemodialysis patients, although most are not immediately life-threatening. However, inconsistent taping techniques and incompatible detection mechanisms may lead to venous needle dislodgement (VND), which can lead to catastrophic blood loss. Taping technique does not always meet the recommended best practice and there may be no available protocol for new staff. METHODS: Three commonly used taping patterns (the Chevron, butterfly, and overlapping styles) were tested in a mechanical engineering laboratory to determine the forces that each method was capable of withstanding. RESULTS: While all taping styles were confirmed to have an adhesive force stronger than the inherent force from the venous jet flow of blood, the overlapping style was found to have limited capability beyond this minimum criterion. Both the butterfly and Chevron styles demonstrated excellent holding capability, with elongation of dislodgement particularly noted for the butterfly style, and slightly stronger hold noted for the Chevron style. The Chevron style may be better suited to lateral movements from all directions, due to the taping direction. CONCLUSIONS: We recommend that either the Chevron or butterfly style is used for dialysis needle taping, with the butterfly better suited to home dialysis (where monitors may be used) and the Chevron better suited for in-care patients who may present erratic movements. The overlapping style is not recommended for use.

Evolution of antiemetic studies for radiation-induced nausea and vomiting within an outpatient palliative radiotherapy clinic.

PURPOSE: Radiation-induced nausea and vomiting (RINV) is a common side effect of radiotherapy and can affect up to 50-80% of patients, potentially causing detrimental effects to physical health, clinical efficacy, and patient quality of life. Antiemetic drugs act on receptors involved in the emesis pathway to block the uptake of neurotransmitters and inhibit stimulation of vomiting centers in the brain to prevent and treat RINV. The most commonly prescribed antiemetics for RINV are 5-hydroxytryptamine receptor antagonists (5-HT3 RA). Guidelines describing the optimal management of RINV are produced by the Multinational Association for Supportive Care in Cancer, the European Society of Medical Oncology, the American Society of Clinical Oncology, and the National Comprehensive Cancer Network. This review will present findings from research on antiemetic management for RINV conducted at our center. METHODS: A selective review of research conducted in a palliative outpatient radiotherapy clinic relating to antiemetic management for RINV was performed. RESULTS: Several studies investigating the efficacy of different routes of administration, new antiemetic drug types, and novel combinations of antiemetics have been tested at our clinic to elucidate which approach provides the best response. These include studies on the use of ondansetron rapidly dissolving film, palonosetron, and the addition of a neurokinin-1 receptor antagonist to traditional 5-HT3 RA regimens. CONCLUSIONS: These studies provide a framework for future research and could potentially inform changes to future guidelines to include the use of these novel regimens and techniques.

Weak circadian rhythm increases neutropenia risk among breast cancer patients undergoing adjuvant chemotherapy.

PURPOSE: Severe neutropenia is a common dose-limiting side effect of adjuvant breast cancer chemotherapy. We aimed to test the hypothesis that weak circadian rhythm is associated with an increased risk of neutropenia using a cohort study. METHODS: We consecutively recruited 193 breast cancer patients who received adjuvant chemotherapy (5-fluorouracil, epirubicin, and cyclophosphamide followed by docetaxel; doxorubicin and cyclophosphamide; docetaxel and cyclophosphamide). Participants wore a wrist actigraph continuously for 168 h at the beginning of chemotherapy. Values of percent rhythm and double amplitude below medians represented weak circadian rhythm. Mesor measured the mean activity level and acrophase symboled the peak time of the rhythm. We used Cox proportional hazard regression model to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) of grade 4 neutropenia and febrile neutropenia in relation to actigraphy-derived parameters. RESULTS: Low levels of percent rhythm (HR:2.59, 95% CI 1.50-4.72), double amplitude (HR:2.70, 95% CI 1.51-4.85), and mesor (HR: 2.48, 95% CI 1.44-4.29) were positively associated with the risk of grade 4 neutropenia during chemotherapy. Low levels of percent rhythm (HR: 2.41, 95% CI 1.02-5.69) and double amplitude (HR:2.49, 95% CI 1.05-5.90) were also associated with increased risks of febrile neutropenia. The HRs for acrophase were not statistically significant. CONCLUSIONS: This study provides the first epidemiological evidence that increased risks of grade 4 neutropenia and febrile neutropenia are associated with weak circadian rhythm among adjuvant breast cancer patients. The results suggest that circadian rhythm might be one potential target for the prevention of chemotherapy-induced neutropenia among cancer patients.

Comparative analysis of neutropenia in patients receiving prolonged treatment with ceftaroline.

Objectives: Ceftaroline is often used in durations greater than that studied in clinical trials. Several retrospective, non-comparative studies have suggested a higher than anticipated incidence of neutropenia in patients receiving prolonged treatment with ceftaroline. We sought to determine if ceftaroline was associated with neutropenia by comparing the incidence with ceftaroline treatment with treatment with several comparative antibiotics. Methods: Patients receiving 14 or more consecutive days of treatment with ceftaroline were compared with patients receiving cefazolin, daptomycin, linezolid, nafcillin or vancomycin (control group). The primary outcome was the development of neutropenia. Multivariate logistic regression and propensity score weighting using inverse probability weights with regression adjustment were used to control for confounding variables. Results: A total of 753 patients were included (53 that received ceftaroline and 700 that received a comparative antibiotic). Ceftaroline was associated with a greater incidence of neutropenia as compared with the control group (17.0% versus 3.9%, P < 0.001). Several covariates were also associated with neutropenia and included younger age, lower baseline absolute neutrophil count, liver disease and bone and joint infections. After controlling for these confounders, receipt of ceftaroline continued to be associated with the development of neutropenia (adjusted OR 3.97, P = 0.003). Analysis after propensity score weighting confirmed this finding. Conclusions: The results of this study suggest that prolonged treatment with ceftaroline is associated with a greater incidence of neutropenia as compared with other antibiotics that are often used for treatment of staphylococcal infections. Careful monitoring of absolute neutrophil count is recommended in patients receiving >14 days of ceftaroline.

Daptomycin non-susceptible, vancomycin-intermediate Staphylococcus aureus endocarditis treated with ceftaroline and daptomycin: case report and brief review of the literature.

We report a case of clearance of persistent bacteremia due to daptomycin non-susceptible, vancomycin-intermediate Staphylococcus aureus native mitral valve endocarditis with a combination of ceftaroline and daptomycin, in an 81-year-old medically complex patient who was not an operative candidate.

A qualitative study on the roles and responsibilities of nurse consultants in Hong Kong.

This study aims to explore the roles and responsibilities of seven newly appointed nurse consultants (NCs) in various clinical specialties in Hong Kong as a pioneer project. Qualitative approaches using direct observation and semi-structured interviews were adopted with two full-day observations on the seven NCs plus 56 semi-structured interviews of NCs, nurses, doctors and patients. Five major NCs' roles and responsibilities had been identified, namely providing expert practice, initiating service development, leading education, guiding continuous quality improvement (CQI) and conducting research and providing evidence-based practice. The seven NCs within this study have by and large achieved building professional excellence, respect and trust within their own spheres. It is strongly recommended that the NC post be formally established in the new Nurses Career Structure to enable expert clinical nurses to develop a clinical career to contribute to service and patient care to its maximum.

The impact on patient health and service outcomes of introducing nurse consultants: a historically matched controlled study.

BACKGROUND: The position of nurse consultant (NC) was introduced in Hong Kong by the Hospital Authority in January 2009. Seven NCs were appointed in five clinical specialties: diabetes, renal, wound and stoma care, psychiatrics, and continence. This was a pilot to explore the impact of the introduction of NCs on patient health and service outcomes. METHODS: The present paper describes a historically matched controlled study. A total of 280 patients, 140 in each cohort under NC or non-NC care, participated in the study. The patient health and service outcomes of both cohorts were evaluated and compared: accident and emergency visits, hospital admissions, length of hospital stays, number of acute complications, number of times of treatment or regimen altered by nurses according to patient's condition, glycated haemoglobin A1c (HbA1c) levels, urea and urea-to-creatinine ratios, and number of wound dressings for patients in corresponding specialty units. A patient satisfaction instrument was also used to assess the NC cohort. RESULTS: The study showed that patients under NC care had favourable patient health and service outcomes compared with those under non-NC care. The NC cohort also reported a high level of patient satisfaction. CONCLUSIONS: The study demonstrates that the introduction of NCs in specialty units may have a positive impact on patients' health and service outcomes. The high level of patient satisfaction scores indicates that patients appreciate the care they are receiving with the introduction of NCs.

Eculizumab Use in a Temporarily Dialysis-Dependent Patient With Shiga Toxin-Producing Escherichia Coli Hemolytic Uremic Syndrome With Neurological Complications.

Shiga toxin-producing Escherichia coli hemolytic uremic syndrome (STEC-HUS) is the most common cause of acute renal failure in children, and it is associated with thrombocytopenia and hemolytic anemia. Although this disease primarily affects the kidney, it can also contribute to cellular damage in other organ systems, such as the CNS. Eculizumab is a monoclonal antibody that binds to complement proteins to prevent complement-mediated intravascular hemolysis in atypical HUS. In STEC-HUS, complement activation also occurs by Shiga toxin, and previous cases of eculizumab use in the setting of neurological involvement have been shown to be successful. We report the successful use of eculizumab in the setting of typical STEC-HUS-induced neurological symptoms including seizure, altered mental status, and left arm weakness. The patient also experienced concomitant renal failure requiring dose adjustment for hemodialysis. Following 2 doses of eculizumab, our patient was discharged to an inpatient rehabilitation facility with resolution of her renal injury, seizures, and altered mentation without adverse effects from eculizumab throughout the admission. Based on our case study, it appears that eculizumab may be given during or between hemodialysis without dose adjustment.

Rapid Deployment of Multiple Tactics to Address Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine Uptake in Healthcare Employees With a Focus on Those Who Identify as Black, Indigenous, and People of Color.

BACKGROUND: In the third quarter of 2021, government entities enacted vaccine requirements across multiple employment sectors, including healthcare. Experience from previous vaccination campaigns within healthcare emphasize the need to translate community modalities of vaccine outreach and education that partner with Black communities, Indigenous communities, and communities of Color stakeholders to increase vaccine confidence broadly. METHODS: This was an observational feasibility study conducted from August through October 2021 that deployed and measured the effect of a multimodal approach to increasing vaccine uptake in healthcare employees. Vaccine data were acquired through the Center for Disease Control Immunization Information Systems across Oregon and Washington. Rates of complete vaccination before the intervention were compared with rates after as a measure of feasibility of this intervention. These data were subdivided by race/ethnicity, age, gender, and job class. Complete vaccination was defined as completion of a 2-dose mRNA SARS-CoV-2 vaccine series or a 1-dose adenoviral vector SARS-CoV-2 vaccine. RESULTS: Overall preintervention and postintervention complete vaccination rates were 83.7% and 93.5%, respectively. Of those employees who identified as a certain race, black employees demonstrated the greatest percentage difference increase, 18.5% (preintervention, 72.1%; postintervention, 90.6%), followed by Hispanic employees, 14.1% (preintervention, 79.4%; postintervention, 93.5%), and employees who identify as 2 or more races, 13.9% (preintervention, 78.7%; postintervention, 92.6%). CONCLUSIONS: We found that a multimodal approach to improving vaccination uptake in employees was feasible. For organizations addressing vaccine requirements for their workforce, we recommend a multimodal strategy to increase vaccine confidence and uptake.

p21-Activated kinase-1 promotes aggressive phenotype, cell proliferation, and invasion in gestational trophoblastic disease.

Gestational trophoblastic disease (GTD) includes hydatidiform mole (HM), which can develop persistent gestational trophoblastic neoplasia requiring chemotherapy; choriocarcinoma, which is a frankly malignant tumor; placental site trophoblastic tumor; and epithelioid trophoblastic tumor. p21-Activated kinases (PAKs) promote malignant tumor progression. Therefore, this study investigated PAK1, PAK2, and p-PAK2 Ser(20) in the pathogenesis of GTD. By real-time PCR, PAK1 mRNA was significantly higher in HMs, particularly metastatic HMs (P = 0.046) and HMs that developed persistent disease (P = 0.011), when compared with normal placentas. By immunohistochemistry, significantly increased cytoplasmic PAK1 immunoreactivity in cytotrophoblasts was also detected in HMs (P = 0.042) and choriocarcinomas (P = 0.003). In addition, HMs that developed persistent disease displayed higher PAK1 immunoreactivity than those that regressed (P = 0.016), and elevated PAK1 immunoreactivity was observed in placental site trophoblastic tumors. Indeed, there was significant positive correlation between PAK1 expression and the proliferative indices Ki-67 (P = 0.016) and MCM7 (P = 0.026). Moreover, higher PAK1 mRNA and protein expression was confirmed in the choriocarcinoma cell-lines JEG-3 and JAR; however, PAK2 mRNA and p-PAK2 immunoreactivity showed a similar expression pattern in normal first trimester placentas and GTD. Knockdown of PAK1 in JEG-3 and JAR reduced cell proliferation, migration, and invasion ability, up-regulated p16, and down-regulated vascular endothelial growth factor and MT1-MMP expression. This is the first report revealing the involvement of PAK1 in the pathogenesis and clinical progress of GTD.

Knowledge of and attitude to contraception among migrant woman workers in mainland China.

AIMS: The aims of this paper were to determine the level of knowledge and attitude of contraception and their relationships among Chinese migrant woman workers. BACKGROUND: Studies on psychosocial variables that lead to reproductive health behaviours among Chinese migrant woman workers in China remain limited. DESIGN: A cross-sectional, descriptive and correlational design. PARTICIPANTS: One hundred and ninety young woman workers of a factory in Guangdong, a representative city of factory base in mainland China, voluntarily participated in the study with a response rate of 63%. METHODS: Data were collected through self-administered questionnaires consisting of a socio-demographic sheet, the Contraceptive Knowledge Scale and the Contraceptive Attitude Scale. Pearson product moment correlation coefficient test was employed to examine the relationships between the contraceptive knowledge and attitude, with level of significance set at p<0·05. RESULTS: The Chinese migrant woman workers demonstrated lower contraceptive knowledge and less favourable contraceptive attitude compared with previous studies of adolescents in Taiwan and women seeking abortion in Hong Kong. Although it was a weak correlation, contraceptive knowledge was statistically associated with contraceptive attitudes among the respondents (r=0·276, p<0·001). Respondents' age, education level and working experience were significantly positively correlated with the contraceptive knowledge. CONCLUSIONS: Young Chinese migrant workers reported in the current study are found to be at higher sexual risk, when compared to the adolescents in Taiwan and Hong Kong women seeking abortion. Early educational intervention for reproductive health in particular contraception and its usage to these young women is indicated. RELEVANCE TO CLINICAL PRACTICE: Migrant woman workers in mainland demonstrated poor knowledge and unfavourable attitudes towards contraception, especially for the younger, single and less educated group. Greater effort is necessary to promote young migrant women's knowledge and attitude towards contraception and sexual health.

Advances in radiotherapy in bone metastases in the context of new target therapies and ablative alternatives: A critical review.

In patients with bone metastases (BM), radiotherapy (RT) is used to alleviate symptoms, reduce the risk of fracture, and improve quality of life (QoL). However, with the emergence of concepts like oligometastases, minimal invasive surgery, ablative therapies such as stereotactic ablative RT (SABR), radiosurgery (SRS), thermal ablation, and new systemic anticancer therapies, there have been a paradigm shift in the multidisciplinary approach to BM with the aim of preserving mobility and function survival. Despite guidelines on using single-dose RT in uncomplicated BM, its use remains relatively low. In uncomplicated BM, single-fraction RT produces similar overall and complete response rates to RT with multiple fractions, although it is associated with a higher retreatment rate of 20% versus 8%. Complicated BM can be characterised as the presence of impending or existing pathologic fracture, a major soft tissue component, existing spinal cord or cauda equina compression and neuropathic pain. The rate of complicated BM is around 35%. Unfortunately, there is a lack of prospective trials on RT in complicated BM and the best dose/fractionation regimen is not yet established. There are contradictory outcomes in studies reporting BM pain control rates and time to pain reduction when comparing SABR with Conventional RT. While some studies showed that SABR produces a faster reduction in pain and higher pain control rates than conventional RT, other studies did not show differences. Moreover, the local control rate for BM treated with SABR is higher than 80% in most studies, and the rate of grade 3 or 4 toxicity is very low. The use of SABR may be preferred in three circumstances: reirradiation, oligometastatic disease, and radioresistant tumours. Local ablative therapies like SABR can delay change or use of systemic therapy, preserve patients' Qol, and improve disease-free survival, progression-free survival and overall survival. Moreover, despite the potential benefit of SABR in oligometastatic disease, there is a need to establish the optial indication, RT dose fractionation, prognostic factors and optimal timing in combination with systemic therapies for SABR. This review evaluates the role of RT in BM considering these recent treatment advances. We consider the definition of complicated BM, use of single and multiple fractions RT for both complicated and uncomplicated BM, reirradiation, new treatment paradigms including local ablative treatments, oligometastatic disease, systemic therapy, physical activity and rehabilitation.

Differential expression and phosphorylation of Pak1 and Pak2 in ovarian cancer: effects on prognosis and cell invasion.

Ovarian cancer is a gynecological malignancy with high mortality. Therefore, the identification of novel prognostic and therapeutic targets is important. p21-activated kinases (Paks) are involved in cytoskeleton reorganization. This study investigated the clinical significance of total and phosphorylated (p) Pak1 and Pak2 as well as their functional roles in ovarian cancer. Expressions of Pak1, p-Pak1 Thr(212), Pak2 and p-Pak2 Ser(20) in ovarian normal and cancerous cell lines as well as in clinical samples of ovarian tumors were evaluated. The effects of Pak1 and Pak2 on ovarian cancer cell functions were determined. Pak1, p-Pak1 and p-Pak2 were overexpressed in ovarian cancer cell lines, and clinical samples of ovarian cancers were compared with benign ovarian lesions/inclusion cysts. Similar Pak2 expression levels were observed among normal and cancerous cell lines and clinical samples. After multiple testing correction, high Pak1 and nuclear p-Pak1 expression in ovarian cancers was significantly associated with histological type and tumor grade, respectively. Pak1 and p-Pak1 expression was associated with poor overall and disease-free survival. Pak1 was an independent prognostic factor. Knockdown of Pak1 and Pak2 in ovarian cancer cell lines reduced cell migration and invasion but did not affect cell proliferation and apoptosis. Knockdown of Pak1 also reduced p38 activation and downregulated vascular endothelial growth factor. Conversely, ectopic Pak1 overexpression enhanced ovarian cancer cell migration and invasion in a kinase-dependent manner, along with increased p38 activation. Our findings suggest that Pak1, p-Pak1 and p-Pak2 play important roles in ovarian carcinogenesis. Pak1 and p-Pak1 may be potential prognostic markers and therapeutic molecular targets in ovarian cancer.

Induction of Labor in an Intubated Patient With Coronavirus Disease 2019 (COVID-19).

BACKGROUND: In the global coronavirus disease 2019 (COVID-19) pandemic, to date, delivery of critically ill pregnant patients has predominantly been by cesarean. CASE: A 27-year-old pregnant woman was admitted to a 166-bed community hospital at 33 weeks of gestation with acute hypoxemic respiratory failure secondary to COVID-19. She underwent mechanical ventilation for 9 days. While ventilated, she underwent induction of labor, resulting in a successful forceps assisted-vaginal birth. She was extubated on postpartum day 5 and discharged on postpartum day 10. The neonate was intubated for 24 hours but was otherwise healthy and discharged home at 36 2/7 weeks postmenstrual age. CONCLUSION: Critically ill patients requiring mechanical ventilation, in this case due to COVID-19, may undergo induction of labor and vaginal delivery when carefully selected.

Contraceptive self-efficacy and contraceptive knowledge of Hong Kong Chinese women with unplanned pregnancy.

AIM AND OBJECTIVES: The purpose of this study was to explore contraceptive practice, the level of knowledge and self-efficacy of contraception among Chinese women with unplanned pregnancy and to determine the relationships between these variables. BACKGROUND: The construct of self-efficacy can be employed as a theory to design a nursing intervention to prevent sexually active women from unplanned pregnancy. Only a few western studies have investigated the relationships between self-efficacy and contraception behaviour yet none targeted at the Chinese population. DESIGN: Cross-sectional survey. METHODS: This study employed a cross-sectional survey design. A convenience sample of 117 eligible Chinese females completed all the questionnaires, which included the Chinese version of the Contraceptive Self-efficacy Scale and Contraceptive Knowledge Scale. RESULTS: The findings in this study suggested that younger, unmarried women at the lower income group, who adopted male condoms are at risk for unplanned pregnancy. The sample demonstrated an above medium level of knowledge and self-efficacy in contraception. However, no significant relationship was found between contraceptive self-efficacy and knowledge (p>0.05). CONCLUSIONS: Contraceptive obstacles were revealed by participants' moderate level of contraceptive self-efficacy and contraceptive knowledge. The relationship between contraceptive knowledge of specific methods and contraceptive self-efficacy need further exploration in future studies. RELEVANCE TO CLINICAL PRACTICE: The dominant use of male condoms by the sample of this study sheds light on future direction in the development of educational programmes and contraceptive promotion strategies appropriate for women with unplanned pregnancy.

Disruption of sleep, sleep-wake activity rhythm, and nocturnal melatonin production in breast cancer patients undergoing adjuvant chemotherapy: prospective cohort study.

OBJECTIVE: This prospective cohort study captured the patterns of sleep, sleep-wake activity rhythm, and first-morning urinary melatonin in breast cancer patients undergoing adjuvant chemotherapy. METHODS: Breast cancer patients undergoing adjuvant chemotherapy wore wrist actigraph for 168 h and collected first-morning void urine samples before treatment, during the first, and at the last cycle of chemotherapy. We converted actigraphy data into sleep duration, sleep efficiency, nighttime total wake time, percent rhythm, F-statistic, amplitude, mesor, and acrophase. We then assessed urinary 6-sulfatoxymelatonin (aMT6s) levels. RESULTS: This cohort contained 180 participants. Compared with the baseline, sleep efficiency during the first and last cycle decreased by 10.16% [95% confidence interval (95% CI): 5.85%, 14.47%] and 5.01% (95% CI: 0.50%, 9.53%), respectively. Similarly, percent rhythm decreased by 27.20% (95% CI: 19.95%, 34.45%) during the first cycle and 21.20% (95% CI: 13.52, 28.89) during the last cycle. Taking the baseline as the reference, aMT6s levels during the first and last cycle decreased by 11.27% (95% CI: 0.37%, 22.16%) and 14.74% (95% CI: 2.34, 27.11), respectively. CONCLUSION: The first administration of adjuvant chemotherapy is associated with sleep disturbance and sleep-wake activity rhythm disruption among breast cancer patients, while the disturbance and disruption during the last cycle are less severe; nevertheless, repeated administration of chemotherapy results in progressive impairment of nocturnal melatonin production.

Prospective evaluation of vancomycin pharmacokinetics in a heterogeneous critically ill population.

Rich pharmacokinetic data on vancomycin in critically ill patients are lacking. The purpose of this study was to evaluate the pharmacokinetics of vancomycin in this population using rich pharmacokinetic sampling. Nineteen critically ill patients received individualized vancomycin doses by intermittent infusion to achieve target trough concentrations (15-20 mg/L). Blood samples were collected following the third or later dose of vancomycin. Serial blood samples were collected at 30 min following initiation of the vancomycin infusion; at the end of the infusion; serially at 60, 120, 300, and 480 min after the infusion finished; and immediately prior to the next dose. Vancomycin concentration-time profiles at steady state were fit to a noncompartmental model to determine the pharmacokinetic parameters. Vancomycin trough concentration was correlated to AUC0-24 (r = 0.83, P < 0.001). Total body weight was a predictor of volume of distribution (r = 0.43, P = 0.03). Age, serum creatinine, and creatinine clearance (CrCl) were found to be predictors for vancomycin clearance (r = -0.67, -0.52, and, 0.72, respectively). CrCl was the best predictor of vancomycin systemic clearance, and addition of other variables to a multivariate model failed to improve model fit. Vancomycin trough concentration may not be an adequate surrogate of AUC0-24. Additional research is needed to determine dosing strategies to optimize AUC0-24 while limiting toxicity.

Review and Validation of Bayesian Dose-Optimizing Software and Equations for Calculation of the Vancomycin Area Under the Curve in Critically Ill Patients.

BACKGROUND: Vancomycin area under the concentration-time curve (AUC) has been linked to efficacy and safety. An accurate method of calculating the AUC is needed. METHODS: Bayesian dose-optimizing software programs available for clinician use and first-order pharmacokinetic equations were evaluated for their ability to estimate vancomycin AUC. A previously published rich pharmacokinetic data set of 19 critically ill patients was used for validation of the AUC estimation. The AUC estimated using subsets of the full data set by Bayesian software and equations was compared with the reference AUC. Accuracy (ratio of estimated AUC to the reference AUC) and bias (percentage difference of estimated AUC to reference AUC) were calculated. RESULTS: Five Bayesian dose-optimizing software programs (Adult and Pediatric Kinetics [APK], BestDose, DoseMe, InsightRx, and Precise PK) and two first-order pharmacokinetic equations were included. Of the Bayesian programs, InsightRx was the most adaptable, visually appealing, easiest to use, and had the most company support. Utilizing only the trough, accuracy (range 0.79-1.03) and bias (range 5.1-21.2%) of the Bayesian dose-optimizing software were variable. Precise PK and BestDose had the most accurate estimates with the accuracy values of BestDose exhibiting the most variability of all the programs; however, both programs were more difficult to use. Precise PK was the least biased (median 5.1%). Using a single nontrough value produced similar results to that of the trough for most programs. The addition of a second level to the trough improved the accuracy and bias for DoseMe and InsightRx but not Precise PK and BestDose. APK did not reliably estimate the AUC with input of two levels. Using two levels, the pharmacokinetic equations produced similar or better accuracy and bias as compared with Bayesian software. CONCLUSION: Bayesian dose-optimizing software using one or more vancomycin levels and pharmacokinetic equations utilizing two vancomycin levels produce similar estimates of the AUC.