The concomitant use of ultra short beta-blockers with vasopressors and inotropes in critically ill patients with septic shock: A systematic review and meta-analysis of randomized controlled trials.

Background: Septic shock is associated with systemic inflammatory response, hemodynamic instability, impaired sympathetic control, and the development of multiorgan dysfunction that requires vasopressor or inotropic support. The regulation of immune function in sepsis is complex and varies over time. However, activating Beta-2 receptors and blocking Beta-1 receptors reduces the proinflammatory response by influencing cytokine production. Evidence that supports the concomitant use of ultra short beta-blockers with inotropes and vasopressors in patients with septic shock is still limited. This study aimed to evaluate the use of ultra short beta-blockers and its impact on the ICU related outcomes such as mortality, length of stay, heart rate control, shock resolution, and vasopressors/inotropes requirements. Methods: A systematic review and meta-analysis of randomized controlled trials including critically ill patients with septic shock who received inotropes and vasopressors. Patients who received either epinephrine or norepinephrine without beta-blockers "control group" were compared to patients who received ultra short beta-blockers concomitantly with either epinephrine or norepinephrine "Intervention group". MEDLINE and Embase databases were utilized to systematically search for studies investigating the use of ultra short beta-blockers in critically ill patients on either epinephrine or norepinephrine from inception to October 10, 2023. The primary outcome was the 28-day mortality. While, length of stay, heart rate control, and inotropes/ vasopressors requirements were considered secondary outcomes. Results: Among 47 potentially relevant studies, nine were included in the analysis. The 28-day mortality risk was lower in patients with septic shock who used ultra short beta-blockers concomitantly with either epinephrine or norepinephrine compared with the control group (RR (95%CI): 0.69 (0.53, 0.89), I2=26%; P=0.24). In addition, heart rate was statistically significantly lower with a standardized mean difference (SMD) of -22.39 (95% CI: -24.71, -20.06) among the beta-blockers group than the control group. The SMD for hospital length of stay and the inotropes requirement were not statistically different between the two groups (SMD (95%CI): -0.57 (-2.77, 1.64), and SMD (95%CI): 0.08 (-0.02, 0.19), respectively). Conclusion: The use of ultra short beta-blockers concomitantly with either epinephrine or norepinephrine in critically ill patients with septic shock was associated with better heart rate control and survival benefits without increment in the inotropes and vasopressors requirement.

Impacts of a Mail-Order Service for Refilling Prescriptions on Patient Satisfaction and Operational Load at a Comprehensive Cancer Center in Jordan.

BACKGROUND: Mail-order services for refilling prescriptions for medications have been established in many countries and have increased patient satisfaction. We developed a mail-order service for the outpatient pharmacy of a comprehensive cancer center in Jordan. OBJECTIVE: To describe the implementation of a mail-order service and to report the impact of the service on patient satisfaction and the pharmacy workload. METHODS: A multidisciplinary team was formed to plan a mail-order service for refilling prescriptions for medications, and a survey was designed to evaluate patient satisfaction with the service. Patients were instructed to call the refill call center and order their medications at least 48 hours before their refill is due. The pharmacy workflow for refilling prescriptions was evaluated, and the time required with and without the mail-order service was documented, with a calculation of the time saved. RESULTS: At 1 year after the mail-order service had been established, 14 200 prescriptions had been refilled through the service, with the majority (97.5%) dispensed within 48 hours of the order time. As per the survey conducted with 219 patients, on the overall satisfaction, 69.4% reported being highly satisfied with the service and 27.9% reported being satisfied. The problems reported with the service were delay in arrival (n = 23, 10.5%), medication-related errors (n = 9, 4.1%), cash-related error (n = 1, 0.45%), improper storage condition (n = 1, 0.45%), and delivery to the wrong address (n = 4, 1.8%). The service was also associated with reduced overall time for processing in the outpatient pharmacy service; for patients receiving their medications from the pharmacy, resulting in reduced patients' overall waiting time (from 11.4 to 8.2 minutes). The service resulted in saving of 0.4 full-time employee at 1 year of implementation. CONCLUSIONS: A mail-order service for refilling prescriptions within a hospital setting had positive outcomes on both patient satisfaction and the pharmacy workflow. The major issues were related to transportation and logistics.

Variation in Fluid and Vasopressor Use in Shock With and Without Physiologic Assessment: A Multicenter Observational Study.

OBJECTIVES: To characterize the association between the use of physiologic assessment (central venous pressure, pulmonary artery occlusion pressure, stroke volume variation, pulse pressure variation, passive leg raise test, and critical care ultrasound) with fluid and vasopressor administration 24 hours after shock onset and with in-hospital mortality. DESIGN: Multicenter prospective cohort study between September 2017 and February 2018. SETTINGS: Thirty-four hospitals in the United States and Jordan. PATIENTS: Consecutive adult patients requiring admission to the ICU with systolic blood pressure less than or equal to 90 mm Hg, mean arterial blood pressure less than or equal to 65 mm Hg, or need for vasopressor. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: Of 1,639 patients enrolled, 39% had physiologic assessments. Use of physiologic assessment was not associated with cumulative fluid administered within 24 hours of shock onset, after accounting for baseline characteristics, etiology and location of shock, ICU types, Acute Physiology and Chronic Health Evaluation III, and hospital (beta coefficient, 0.04; 95% CI, -0.07 to 0.15). In multivariate analysis, the use of physiologic assessment was associated with a higher likelihood of vasopressor use (adjusted odds ratio, 1.98; 95% CI, 1.45-2.71) and higher 24-hour cumulative vasopressor dosing as norepinephrine equivalent (beta coefficient, 0.37; 95% CI, 0.19-0.55). The use of vasopressor was associated with increased odds of in-hospital mortality (adjusted odds ratio, 1.88; 95% CI, 1.27-2.78). In-hospital mortality was not associated with the use of physiologic assessment (adjusted odds ratio, 0.86; 95% CI, 0.63-1.18). CONCLUSIONS: The use of physiologic assessment in the 24 hours after shock onset is associated with increased use of vasopressor but not with fluid administration.

Evaluation of Vasopressor Exposure and Mortality in Patients With Septic Shock.

OBJECTIVES: The objectives of this study were to: 1) determine the association between vasopressor dosing intensity during the first 6 hours and first 24 hours after the onset of septic shock and 30-day in-hospital mortality; 2) determine whether the effect of vasopressor dosing intensity varies by fluid resuscitation volume; and 3) determine whether the effect of vasopressor dosing intensity varies by dosing titration pattern. DESIGN: Multicenter prospective cohort study between September 2017 and February 2018. Vasopressor dosing intensity was defined as the total vasopressor dose infused across all vasopressors in norepinephrine equivalents. SETTING: Thirty-three hospital sites in the United States (n = 32) and Jordan (n = 1). PATIENTS: Consecutive adults requiring admission to the ICU with septic shock treated with greater than or equal to 1 vasopressor within 24 hours of shock onset. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Out of 1,639 patients screened, 616 were included. Norepinephrine (93%) was the most common vasopressor. Patients received a median of 3,400 mL (interquartile range, 1,851-5,338 mL) during the 24 hours after shock diagnosis. The median vasopressor dosing intensity during the first 24 hours of shock onset was 8.5 µg/min norepinephrine equivalents (3.4-18.1 µg/min norepinephrine equivalents). In the first 6 hours, increasing vasopressor dosing intensity was associated with increased odds ratio of 30-day in-hospital mortality, with the strength of association dependent on concomitant fluid administration. Over the entire 24 hour period, every 10 µg/min increase in vasopressor dosing intensity was associated with an increased risk of 30-day mortality (adjusted odds ratio, 1.33; 95% CI, 1.16-1.53), and this association did not vary with the amount of fluid administration. Compared to an early high/late low vasopressor dosing strategy, an early low/late high or sustained high vasopressor dosing strategy was associated with higher mortality. CONCLUSIONS: Increasing vasopressor dosing intensity during the first 24 hours after septic shock was associated with increased mortality. This association varied with the amount of early fluid administration and the timing of vasopressor titration.

Evaluating the Predictive Value of Lactate in Patients With Cancer Having Septic Shock.

PURPOSE: Limited studies evaluated the predictive value of serum lactate (LA) in critically ill patients with cancer. The main objective of this study was to evaluate the predictive validity of LA single measurements as well as LA clearance in predicting mortality in patients with cancer having septic shock. The study also aimed to determine the LA measurement over the first 24 hours with the highest predictability for hospital mortality. MATERIALS AND METHODS: A retrospective cohort study of adult patients with cancer having septic shock and LA measurements during the first 24 hours. Three receiver-operating characteristic (ROC) curves were constructed to evaluate the predictive validity for hospital mortality of LA at baseline, at 6 hours and at 24 hours after identifying septic shock. The ROC with the largest area under the curve was analyzed to determine LA level with the highest predictability for hospital mortality. In addition, the ability of LA normalization (LA <2 mmol/L at 6 hours and at 24 hours) and the degree of LA elimination (>10% and >20% at 24 hours) to predict hospital mortality were evaluated by determining the predictive values for each clearance end point. RESULTS: The study included 401 patients. LA >2.5 mmol/L at 24 hours showed the largest area under the ROC curve to predict hospital mortality (ROC area: 0.648; 95% confidence interval: 0.585-0.711) with a sensitivity of 58.4% and specificity of 62.8%. The LA normalization, LA clearance >10%, and LA clearance >20% were also predictors of hospital mortality, with the highest sensitivity for LA normalization at 6 hours (74%) and LA normalization at 24 hours (73.4%). CONCLUSION: In patients with cancer having septic shock, LA >2.5 mmol/L at 24 hours of septic shock had the highest predictability for hospital mortality. The LA normalization and clearance were also predictors of hospital mortality. However, all LA end points were not strong predictors.

Fixed-dose combination associated with faster time to smear conversion compared to separate tablets of anti-tuberculosis drugs in patients with poorly controlled diabetes and pulmonary tuberculosis in Qatar.

BACKGROUND: Diabetes is associated with increased risk of tuberculosis (TB) treatment failure, death, and relapse compared to patients without diabetes. Current TB regimens are available as fixed dose combination (FDC) and separate tablets (ST), in which using the former is purported to make it easier to adhere and complete treatment. So far there are no studies assessing the performance of FDC compared to ST in diabetic patients with pulmonary TB. METHODOLOGY: A retrospective cohort study was conducted, and included eight hospitals in Qatar in which patients diagnosed with pulmonary TB received rifampin, isoniazid, pyrazinamide, and ethambutol (as FDC or ST) given as directly observed therapy. Sputum smears for acid fast bacilli were tested weekly. We included patients admitted between December 2012 and December 2015, ≥18 years old, diagnosed with TB with pretreatment positive sputum smears, and having diabetes. Patients with Mycobacterium tuberculosis that was resistant to any first-line drug were excluded. Blood glucose was monitored closely and controlled to < 180 md/dL using oral hypoglycemic agents and/or insulin. We assessed the effectiveness of TB regimens by comparing time to confirmed negative smears between those treated with FDC or ST, and the impact of adding metformin. RESULTS: 103 patients met inclusion criteria. Mean age and body mass index were 45.6 ± 9.1 years and 22.1 ± 3.6 kg/m2, respectively. Fifty-four (52%) patients received the FDC. There was no difference between groups in baseline characteristics and sputum bacillary loads. Patients prescribed FDC showed faster times to sputum smear conversion compared to ST (32 ± 19 vs. 46 ± 31 days, p = 0.01). The difference was greater among patients with pretreatment bacillary load of 3+ (FDC 36.6 ± 19.5 vs. ST 56.1 ± 28.8, p = 0.008). Receipt of metformin≥2000 mg/day altered the difference in time to smear conversion (FDC 30.7 ± 13.4 vs. ST 62 ± 35.5, p = 0.016), which was of greatest difference in those with pretreatment bacillary load 3+ and who received metformin≥2000 mg/day (FDC 36 ± 12.1 vs. ST 92.2 ± 26 days, p = 0.001). CONCLUSION: Patients with diabetes and prescribed FDC showed faster smear conversion during treatment for pulmonary TB compared to ST which was more pronounced in those with 3+ bacillary load pretreatment and which appeared to be modified by higher dose metformin.

Augmented Renal Clearance Using Population-Based Pharmacokinetic Modeling in Critically Ill Pediatric Patients.

OBJECTIVES: The objectives of this study were to: 1) evaluate the prevalence of augmented renal clearance in critically ill pediatric patients using vancomycin clearance; 2) derive the pharmacokinetic model that best describes vancomycin clearance in critically ill pediatric patients; and 3) correlate vancomycin clearance with creatinine clearance estimated by modified Schwartz or Cockcroft-Gault. DESIGN: Retrospective, two-center, cohort study from 2003 to 2016. SETTING: Clinical drug monitoring services in the PICUs at two tertiary care, teaching hospitals. PATIENTS: Children from 1 to 21 years old. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Identify patients with augmented renal clearance (vancomycin clearance ≥ 130 mL/min/1.73 m used as definition of augmented renal clearance). Derive final population-based pharmacokinetic model and estimate individual patient pharmacokinetic parameters. Compare estimated glomerular filtration rate (modified Schwartz or Cockcroft-Gault depending on age < or ≥ 17 yr) with vancomycin clearance. Augmented renal clearance was identified in 12% of 250 total subjects. The final population-based pharmacokinetic model for vancomycin clearance (L/hr) was 0.118 × weight (e). Median vancomycin clearance in those with versus without augmented renal clearance were 141.3 and 91.7 mL/min/1.73 m, respectively (p < 0.001). By classification and regression tree analysis, patients who were more than 7.9 years old were significantly more likely to experience augmented renal clearance (17% vs 4.6% in those ≤ 7.9 yr old; p = 0.002). In patients with augmented renal clearance, 79% of 29 had vancomycin trough concentrations less than 10 µg/mL, compared with 52% of 221 in those without augmented renal clearance (p < 0.001). Vancomycin clearance was weakly correlated to the glomerular filtration rate estimated by the modified Schwartz or Cockcroft-Gault method (Spearman R = 0.083). CONCLUSIONS: Augmented renal clearance was identified in one of 10 critically ill pediatric patients using vancomycin clearance, with an increase of approximately 50 mL/min/1.73 m in those with augmented renal clearance. As augmented renal clearance results in subtherapeutic antibiotic concentrations, optimal dosing is essential in those exhibiting augmented renal clearance.

Predictors of ICU Admission in Patients With Cancer and the Related Characteristics and Outcomes: A 5-Year Registry-Based Study.

OBJECTIVE: To identify factors predictive of admission of patients with cancer to an ICU. In addition, the study aimed to describe the characteristics and outcomes, both short-term and long-term, of patients with cancer admitted to the ICU. DESIGN: Retrospective case-control study, utilizing the institution's cancer registry. SETTING: Comprehensive cancer center. PATIENTS: Patients with cancer. The case group consisted of patients who required ICU admission during the study period, whereas the control group consisted of patients who did not require ICU admission. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: The patient characteristics and outcomes were recorded. Univariate and multivariate analyses were conducted to determine factors associated with ICU admission. The registry included 10,792 patients, and among those, 2,439 patients (22.6%) required ICU admission after a median of 10.1 months (interquartile range, 3.28-25.2). The following factors were associated with ICU admission: hematologic malignancy (odds ratio, 1.51; 95% CI, 1.26-1.81), chemotherapy (odds ratio, 1.74; 95% CI, 1.48-2.03), advanced cancer (odds ratio, 2.57; 95% CI, 1.44-4.60), and smoking (odds ratio, 1.38; 95% CI, 1.20-1.61). The most common ICU admission diagnoses were sepsis (21.5%) and respiratory insufficiency/failure (25.7%). The ICU mortality was 36.5%, whereas the 1-year and 5-year survival rates were 22.8% and 14.2%, respectively. CONCLUSION: In a comprehensive cancer center, about one fourth of the patients required ICU admission. Addressing modifiable risk factors associated with ICU admission is essential to potentially reduce ICU admissions and improve long-term survival.

Vancomycin pharmacokinetics and predicted dosage requirements in pediatric cancer patients.

PURPOSE: To determine the pharmacokinetic parameters and compare pharmacodynamic target attainment at different dosing strategies of vancomycin in pediatric cancer patients. METHODS: Pediatric patients who received vancomycin and had at least two steady-state concentrations taken within the same dosing interval were identified. Vancomycin minimum inhibitory concentrations (MICs) for methicillin resistant staphylococcus aureus (MRSA) isolates from our institution were determined using E-test. The population-based pharmacokinetic modeling was performed using NONMEM 7.2. A one-compartment model with first-order kinetics was used to estimate clearance (CL) and volume of distribution (Vd). Monte Carlo simulations (N = 9800) were performed to compare area-under-the-curve over 24 h (AUC24)/MIC and trough concentration at different doses. RESULTS: Forty-nine patients, with 120 vancomcyin serum concentrations, were included in the analysis, mean age was 6 ± 2.5 (SD) years, mean weight was 19.6 ± 6.9(SD) kg, mean baseline serum creatinine was 0.4 ± 0.11(SD) mg/dl, and mean initial vancomycin dose was 205 mg/day (range 100-460). Final model pharmacokinetic parameters were: CL (L/h) = 0.381 × weight(0.75) and Vd (L) = 0.663 × weight. Mean baseline (±SD) vancomycin CL was 0.20 ± 0.07 L/h/kg and Vd 0.66 ± 0.001 L/kg. . Renal function, sex, age, stay in the intensive care unit, and co-administration of nephrotoxic medications did not have an effect on the calculated parameters. Using Monte Carlo simulation with reported MICs, a dose of 60 mg/kg/day achieved AUC24/MIC ≥400 and trough concentration ≥15 mcg/mL in only 21.5% and 11% of virtual subjects, respectively. CONCLUSIONS: Higher than usual vancomycin doses may be required to treat serious MRSA infections in pediatric patients. The currently recommended dose of 60 mg/kg/day is unlikely to achieve the targets in most subjects. The optimal vancomycin dosing in pediatric cancer patients requires further investigations.

Rifampicin as adjunct to colistin therapy in the treatment of multidrug-resistant Acinetobacter baumannii.

OBJECTIVE: To evaluate the available evidence regarding the efficacy and safety of rifampicin, as adjunct to colistin, in the treatment of multidrug resistant Acinetobacter baumannii (MDR-AB). DATA SOURCES: We searched MEDLINE (1966 to January 2014) using the following search terms: A baumannii, drug resistance, treatment, colistin, and rifampicin and combinations. In addition, the bibliographies of relevant articles were searched for additional citations. STUDY SELECTION AND DATA EXTRACTION: The search was limited to English-language references and adults. Studies in which colistin was not administered intravenously were excluded. In addition, we excluded meeting abstracts and single case reports. DATA SYNTHESIS: The search strategy identified 5 observational studies and 2 randomized controlled trials that evaluated the combination of intravenous colistin and rifampicin for the treatment of MDR-AB. All observational studies included a small sample size, and the microbiological clearance associated with the combination therapy ranged from 60% to 100%. The randomized controlled trials reported reduced time to microbiological clearance and higher microbiological eradication rate in the colistin/rifampicin group compared with colistin alone. However, there was no difference between both groups in the overall mortality, infection-related mortality, and the length of stay. Furthermore, rifampicin was associated with a higher incidence of hepatotoxicity. CONCLUSIONS: Studies evaluating the combination of rifampicin and colistin in the treatment of MDR-AB are limited. The currently available evidence does not support the addition of rifampicin to colistin because of the lack of improved clinical outcomes with the combination therapy and the risk of rifampicin-induced hepatotoxicity.

Adverse drug events resulting in admission to the intensive care unit in oncology patients: Incidence, characteristics and associated cost.

PURPOSE: Describe the incidence, characteristics and cost of adverse drug events that necessitate admission to the intensive care unit in oncology patients. METHODS: This was a prospective observational 5-months study at a medical/surgical intensive care unit of a comprehensive teaching cancer center. Patients admitted to the intensive care unit were screened to determine whether the admission was due to an adverse drug event. The adverse drug events were characterized based on the suspected medication, system involved and preventability. Patient demographics, length of stay, mortality and the total patient charges during their intensive care unit stay were recorded. RESULTS: During the study period, 249 patients were screened and an adverse drug event was the primary cause of 57 (22.9%) admissions. The most common medications associated with an adverse drug event requiring intensive care unit admission were antineoplastics (n = 37), analgesics (n = 9) and anticoagulants (n = 4). Ten adverse drug events were considered preventable. The average length of stay for patients with adverse drug events resulting in intensive care unit admission was 6.2 days ±9.8 (SD) and the mortality rate was 28.1%. Hematological malignancy was independently associated with adverse drug events resulting in intensive care unit admission. The average patient charges for the intensive care unit stay was US$11,692 ± 17,529 (SD), which corresponded to about US$1.5 million in annual patient charges for a 12-bed intensive care unit at a cancer institution. CONCLUSIONS: Adverse drug events resulting in intensive care unit admission in oncology patients are common and often associated with significant morbidity, mortality, and cost.

Bias in artificial intelligence algorithms and recommendations for mitigation.

The adoption of artificial intelligence (AI) algorithms is rapidly increasing in healthcare. Such algorithms may be shaped by various factors such as social determinants of health that can influence health outcomes. While AI algorithms have been proposed as a tool to expand the reach of quality healthcare to underserved communities and improve health equity, recent literature has raised concerns about the propagation of biases and healthcare disparities through implementation of these algorithms. Thus, it is critical to understand the sources of bias inherent in AI-based algorithms. This review aims to highlight the potential sources of bias within each step of developing AI algorithms in healthcare, starting from framing the problem, data collection, preprocessing, development, and validation, as well as their full implementation. For each of these steps, we also discuss strategies to mitigate the bias and disparities. A checklist was developed with recommendations for reducing bias during the development and implementation stages. It is important for developers and users of AI-based algorithms to keep these important considerations in mind to advance health equity for all populations.

Bayesian method application: Integrating mathematical modeling into clinical pharmacy through vancomycin therapeutic monitoring.

The most recent consensus guidelines for dosing and monitoring vancomycin recommended the use of area-under-the-curve with Bayesian estimation for therapeutic monitoring. As this is a modern concept in the practice of clinical pharmacy, the main objective of this review is to introduce the fundamentals of Bayesian estimation and its mathematical application as it relates to vancomycin therapeutic drug monitoring. In addition, we aim to identify pharmacokinetic (PK) software programs that incorporate Bayesian estimation for vancomycin dosing and to describe the PK models utilized in those software programs for the adult population. Twelve software programs that utilize Bayesian estimation were identified, which included: Adult and Pediatric Kinetics, Best Dose, ClinCalc, DoseMeRx, ID-ODS, InsightRx, MwPharm++, NextDose, PrecisePK, TDMx, Tucuxi, and VancoCalc. The software programs varied in the population PK models used as the Bayesian a priori. With the presence of various vancomycin Bayesian software programs, it is important to choose those that utilize PK models reflective of the specific patient population.

Impact of Clinical Pharmacy Services on Patient Management in the Chemotherapy Infusion Clinics: A 5-Year Study at a Comprehensive Cancer Center.

BACKGROUND: Chemotherapy requires careful dosing and monitoring and is associated with numerous adverse events. There is limited data describing the impact of clinical pharmacists in the chemotherapy ambulatory setting. OBJECTIVE: This study aimed to evaluate the impact of clinical pharmacy services on patient management in the adult chemotherapy infusion clinics. METHODS: This was a 5-year retrospective study that utilized the pharmacy electronic documentation system to determine the type of interventions and adverse drug events (ADEs) reported by the clinical pharmacists in the chemotherapy infusion clinics. Interventions were described based on the type of intervention and medication involved. ADEs were evaluated based on the type of ADE, the suspected medication, and the required management. RESULTS: During the study period, 3,279 interventions and 1,445 ADEs were reported. The most common interventions involved dose adjustments (51%), followed by addition (23%) or discontinuation (21%) of prescribed medications. Carboplatin (20%) and zoledronic acid (14%) were the most common medications that required pharmacist interventions. The most common types of ADEs were hematologic (22%) and infusion-related reactions (20%). Docetaxel was the most common medication associated with ADEs (20%). Among the reported ADEs, most required adding supportive care (44%), followed by adjusting chemotherapy doses (22%). CONCLUSION: Clinical pharmacy services at the chemotherapy infusion clinics play an important role in optimizing the chemotherapy regimens as well as identifying and managing ADEs. Future studies should be directed to measure the impact of these services on patient outcomes as well as, physicians and pharmacy operational workload and cost savings.

Vancomycin therapeutic monitoring by measured trough concentration versus Bayesian-derived area under the curve in critically ill patients with cancer.

The updated vancomycin guideline and recent studies suggested that trough concentrations may result in underestimation of the actual area under the curve (AUC), leading to excessive dosing and nephrotoxicity. With limited data available on critically ill cancer patients, this study aimed to compare the two methods in this patient population. This was a 5-year retrospective study on patients treated with vancomycin in the intensive care unit (ICU) of a comprehensive cancer center. The measured trough concentration was compared to Bayesian-derived AUC/minimum-inhibitory-concentration (MIC), considering MIC as 1. Trough concentrations of 15-20 mg/L and AUC of 400-600 mg h/L were considered the targeted goal. Multivariate analysis was performed to identify factors associated with an AUC below the targeted goal. During the study period, 316 patients were included. The mean age was 54 years ±16 (SD); most patients had solid tumors (75%), and 11% had neutropenia. A targeted goal AUC and trough were recorded in 128 (41%) patients and in 64 (20%) patients, respectively. Of the 128 patients with targeted goal AUC, 31 (24%) had targeted goal trough concentrations and 91 (71%) had trough concentrations below 15 mg/L. Furthermore, among the patients with targeted goal trough concentration (n = 64), 33 (52%) had higher than targeted goal AUC. Augmented renal clearance (ARC), defined as a calculated creatinine-clearance ≥130 ml/min, was associated with an AUC below the targeted goal. In a cohort of critically ill patients with cancer, over two-thirds of the patients with a targeted goal Bayesian AUC/MIC had trough concentrations below the targeted goal. ARC was associated with AUC below the targeted goal.

A Systematic Review and Meta-Analysis Evaluating Geographical Variation in Outcomes of Cancer Patients Treated in ICUs.

The reported mortality rates of cancer patients admitted to ICUs vary widely. In addition, there are no studies that examined the outcomes of critically ill cancer patients based on the geographical regions. Therefore, we aimed to evaluate the mortality rates among critically ill cancer patients and provide a comparison based on geography. DATA SOURCES: PubMed, EMBASE, and Web of Science. STUDY SELECTION: We included observational studies evaluating adult patients with cancer treated in ICUs. We excluded non-English studies, those with greater than 30% hematopoietic stem cell transplant or postsurgical patients, and those that evaluated a specific type of critical illness, stage of malignancy, or age group. DATA EXTRACTION: Two reviewers independently applied eligibility criteria, assessed quality, and extracted data. Studies were classified based on the continent in which they were conducted. Primary outcomes were ICU and hospital mortality. We pooled effect sizes by geographical region. DATA SYNTHESIS: Forty-six studies were included (n = 110,366). The overall quality of studies was moderate. Most of the published literature was from Europe (n = 22), followed by North America (n = 9), Asia (n = 8), South America (n = 5), and Oceania (n = 2). Pooled ICU mortality rate was 38% (95% CI, 33-43%); the lowest mortality rate was in Oceania (26%; 95% CI, 22-30%) and highest in Asia (51%; 95% CI, 44-57%). Pooled hospital mortality rate was 45% (95% CI, 41-49%), with the lowest in North America (37%; 95% CI, 31-43%) and highest in Asia (54%; 95% CI, 37-71%). CONCLUSIONS: More than half of cancer patients admitted to ICUs survived hospitalization. However, there was wide variability in the mortality rates, as well as the number of available studies among geographical regions. This variability suggests an opportunity to improve outcomes worldwide, through optimizing practice and research.

Augmented renal clearance in critically ill patients with cancer (ARCCAN Study): A prospective observational study evaluating prevalence and risk factors.

Augmented renal clearance (ARC) is a phenomenon that has been associated with enhanced excretion of renally eliminated drugs, such as antimicrobials, which may result in subtherapeutic levels and potentially therapeutic failure. There has been limited data on ARC in critically ill patients with cancer. This study aimed to evaluate the prevalence of ARC and to identify risk factors associated with ARC in this patient population. This was a prospective study at an oncologic intensive care unit (ICU) which included adult patients with normal renal function, defined as serum creatinine ≤1 mg/dl and urine output >0.5 ml/kg/hr. The 24-hour creatinine clearance (ClCr) study was used to determine ClCr, starting on day 1 of ICU admission, for 5 days or until ICU transfer or death. ARC was defined as ClCr >130 ml/min/1.73 m2 . Univariate and multivariate logistic regression analyses were performed to identify risk factors for ARC. Over the study period, 363 patients were enrolled who completed an average of 2.8 ± 1.5(SD) days in the study and contributed 977 ClCr measurements. The mean age was 52 ± 16(SD) years old, the majority had solid tumors (n = 264, 73%), mean APACHE II was 21 ± 8(SD), and the major admission diagnosis was respiratory failure (n = 165, 45%). ARC was reported in 116 (32%) patients on at least one of the study days. Over the study period, the incidence of ARC ranged between 15.6% and 24.3%. Age was the only risk factor significantly associated with ARC (OR 1.028, 95% CI 1.005-1.051).

Capacity Building for Research in Critical Care: A Pilot Program in the Eastern Mediterranean Region.

Research productivity in the Eastern Mediterranean Region is relatively low in all fields, including critical care. We describe a capacity-building research program that was piloted with 11 clinicians from the Eastern Mediterranean Region, who had minimal research experience. The program was conducted over 1 year, with a structure that specifically addressed factors that contribute to low research productivity. We describe the structure of the program, the faculty involved, the feasibility, and challenges faced, as well as the impact of the program on research output. At a small scale, the program was generally feasible and demonstrated promising results. Evaluating the feasibility of conducting such a program over a longer period of time and with a larger group of participants is necessary since research capacity-building programs require multiple years to demonstrate a significant impact on research output.

Iatrogenic Toxicities in the Intensive Care Unit.

Drug-induced iatrogenic toxicities are common in critically ill patients and have been associated with increased morbidity and mortality. Early recognition and management of iatrogenic toxicities is essential; however, the diagnosis is usually complicated by the underlying critical illness, comorbidities, and administration of multiple medications. This article reviews several types of iatrogenic toxicities associated with medications that are commonly used in critically ill patients. The mechanism of the iatrogenic toxicities, clinical presentation, and diagnosis, as well as management are discussed.

ICU readmission of patients with cancer: Incidence, risk factors and mortality.

PURPOSE: Few studies evaluated ICU readmission in cancer patients. This study aimed to describe the incidence and risk factors for ICU readmission in cancer patients and the association with mortality. MATERIALS AND METHODS: A retrospective cohort study at a comprehensive cancer center, which included cancer patients who were discharged after their initial ICU admission over a 5-year period. The characteristics and outcomes of patients who required ICU readmission within 30 days of discharge were compared to those who did not require readmission during the study period. Multivariate analyses were performed to identify factors associated with readmission and to evaluate the association between readmission and mortality. RESULTS: Among 1582 patients discharged from the ICU, 313(19.8%) were readmitted after a median of 6 days. The most common readmission diagnoses were respiratory failure and sepsis. Mechanical ventilation (OR 5.80; 95% CI 4.29-7.84) and thrombocytopenia (OR 1.66; 95% CI 1.16-2.38), on the first ICU admission were associated with readmission. Readmission was associated with a higher risk of 28-day and 90-day mortality, (OR 3.02; CI 2.3-4.00) and (OR 3.47; 95% CI 2.69-4.49), respectively. CONCLUSIONS: ICU readmission was associated with increased mortality. Mechanical ventilation and thrombocytopenia at the first admission were associated with ICU readmission.