Happyhour, a Ste20 family kinase, implicates EGFR signaling in ethanol-induced behaviors.

The consequences of alcohol use disorders (AUDs) are devastating to individuals and society, yet few treatments are currently available. To identify genes regulating the behavioral effects of ethanol, we conducted a genetic screen in Drosophila and identified a mutant, happyhour (hppy), due to its increased resistance to the sedative effects of ethanol. Hppy protein shows strong homology to mammalian Ste20 family kinases of the GCK-1 subfamily. Genetic and biochemical experiments revealed that the epidermal growth factor (EGF)-signaling pathway regulates ethanol sensitivity in Drosophila and that Hppy functions as an inhibitor of the pathway. Acute pharmacological inhibition of the EGF receptor (EGFR) in adult animals altered acute ethanol sensitivity in both flies and mice and reduced ethanol consumption in a preclinical rat model of alcoholism. Inhibitors of the EGFR or components of its signaling pathway are thus potential pharmacotherapies for AUDs.

Call to action: The pharmacist's role in improving contraceptive knowledge and access.

Pharmacists have the knowledge and training to participate in contraceptive education and management and should feel empowered to do so. Advocating for legislation to expand the pharmacist's role in this setting can improve patient access to hormonal contraceptives. As the nation digests the Supreme Court's decision to overturn Roe vs. Wade, many health care providers have stopped to think about what our role will be in this uncertain future. Approximately, 20 states/jurisdictions have legislation in place that allows pharmacists to prescribe or dispense oral contraceptives without a prescription; broadening the scope of practice for pharmacists increases patients' access to care, and may improve overall adherence. When compared to clinician-initiated contraception, pharmacists were more likely to prescribe contraception to eligible women and had a higher rate of continuation at 12 months. In addition, pharmacists providing education to both patients and prescribers can help debunk misinformation on hormonal contraceptives which may impact access and adherence. With the recently changing federal-and in many instances state-legislation, pharmacists will need to seek out more opportunities to facilitate access to hormonal contraceptives and increase knowledge surrounding emergency contraceptive options and other medications used for reproductive health. Pharmacists have the knowledge and accessibility to assist in contraceptive care. Now, more than ever, pharmacists' involvement in hormonal contraceptive care will be a necessary step to ensure that our patients receive the appropriate care they deserve.

Is now our time? History to provider status for allied health professions and the path for pharmacists.

The designation of health care providers is limited to physicians, physician assistants, nurse practitioners, certified nurse midwives, nurse anesthetists, clinical psychologists, dietitians, and social workers. Pharmacists are not federally recognized health care providers and, therefore, are not eligible for cognitive service reimbursements. This commentary explains the intentions of adding pharmacists as Medicare Part B providers, evaluates current state pharmacist provider status, and calls pharmacists, technicians, and other key stakeholders to advocate on behalf of the profession of pharmacy. If federal provider status is granted to pharmacists, patients will gain better access to care, health spending will decline, and physician lead care teams will have an expert in medications readily available for consultation or other medication-related needs. Reimbursement would provide more resources to administer these needed services to more patients in areas with limited access to health care resources.

Publication rate and impact stratified by gender among pharmacists designated Fellow in the American College of Critical Care Medicine.

BACKGROUND: There are approximately 352,000 pharmacists practicing in the United States, with most (59%) being female. Editorial board membership and publications with a female as the first author in selected pharmacy journals has increased in the past 2 decades. This study determined whether these positive trends are also occurring in critical care pharmacy. OBJECTIVE: To report publication rate and publication impact stratified by male and female gender among pharmacists designated Fellow of Critical Care Medicine (FCCM). METHODS: Pharmacists designated FCCM from inception through the 2020 convocation year were identified in January 2021 using a list provided by the Society of Critical Care Medicine. Pharmacists were excluded if they were designated Master of Critical Care Medicine, did not have an active pharmacist license, or did not have data in the Scopus database. Data were collected in February 2021 including year of first publication, total number of publications, citations, and Hirsch index (h-index). RESULTS: A total of 134 pharmacists were evaluable, including 76 males (57%) and 58 females (43%). Males had an earlier first publication year than females (2005 vs. 2010; P < 0.001). Males have produced a higher number of publications per individual pharmacist (29 vs. 13; P = 0.002) and a similar number of publications per year (2 vs. 1; P = 0.05). When comparing publication impact, males generated more citations (384 vs. 139; P = 0.001) and had a higher h-index (10 vs. 6, P < 0.001). These trends persisted when data from only the past 5 years were used. CONCLUSION: There is statistically significant gender disparity in publication rate and impact. However, this disparity seems to be decreasing with time as the rate of females designated FCCM is increasing. This is consistent with an overall increase in the proportion of pharmacists who are female and deserves further exploration.

The Safety of Continuous Infusion Propofol in Mechanically Ventilated Adults With Coronavirus Disease 2019.

BACKGROUND: Propofol is commonly used to achieve ventilator synchrony in critically ill patients with coronavirus disease 2019 (COVID-19), yet its safety in this patient population is unknown. OBJECTIVE: To evaluate the safety, in particular the incidence of hypertriglyceridemia, of continuous infusion propofol in patients with COVID-19. METHODS: This was a retrospective study at 1 academic medical center and 1 affiliated teaching hospital in New York City. Adult, critically ill patients with COVID-19 who received continuous infusion propofol were included. Patients who received propofol for <12 hours, were transferred from an outside hospital while on mechanical ventilation, or did not have a triglyceride concentration obtained during the infusion were excluded. RESULTS: A total of 252 patients were included. Hypertriglyceridemia (serum triglyceride concentration ≥ 400 mg/dL) occurred in 38.9% of patients after a median cumulative dose of 4307 mg (interquartile range [IQR], 2448-9431 mg). The median time to triglyceride elevation was 3.8 days (IQR, 1.9-9.1 days). In the multivariable regression analysis, obese patients had a significantly greater odds of hypertriglyceridemia (odds ratio = 1.87; 95% CI = 1.10, 3.21). There was no occurrence of acute pancreatitis. The incidence of possible propofol-related infusion syndrome was 3.2%. CONCLUSION AND RELEVANCE: Hypertriglyceridemia occurred frequently in patients with COVID-19 who received propofol but did not lead to acute pancreatitis. Elevated triglyceride concentrations occurred more often and at lower cumulative doses than previously reported in patients without COVID-19. Application of these data may aid in optimal monitoring for serious adverse effects of propofol in patients with COVID-19.

The Safety and Efficacy of Desmopressin in Patients With Intracranial Hemorrhage and a History of Alcohol Use.

BACKGROUND: Patients with a history of alcohol use disorder are at an increased risk of hematoma expansion following intracranial hemorrhage (ICH) due to the effects of alcohol on platelet aggregation. Desmopressin (DDAVP) improves platelet aggregation and may decrease hematoma expansion in patients with ICH. However, DDAVP may also increase the risk of hyponatremia and thrombotic events. Evidence is limited regarding the safety and efficacy of DDAVP in alcohol use (AU)-associated ICH. METHODS: This was a retrospective chart review of adult patients with radiographic evidence of ICH and a confirmed or suspected history of alcohol use upon admission. Patients were categorized into groups based on DDAVP administration. Safety outcomes included hyponatremia (serum sodium <135 mEq/L or decrease in serum sodium of ≥ 5 mEq/L for patients with baseline sodium <135 mEq/L) within 24 hours of ICH and thrombotic events within 7 days of ICH. The primary efficacy outcome was the incidence of hematoma expansion, defined as any expansion of the hemorrhage noted on repeat imaging within 32 hours. RESULTS: In total, 52 patients were included in the safety analysis (27 DDAVP and 25 non-DDAVP). Although hyponatremia was numerically higher in the DDAVP group, there was no significant difference between groups (19.2% vs 4.2%, P = 0.192). Thrombotic complications were similar between the DDAVP and non-DDAVP groups (11.1% vs. 8%, P = 1.0). Thirty-nine patients met criteria for hemostatic efficacy analysis. There was no difference in hematoma expansion between the DDAVP and non-DDAVP groups (23.1% vs 34.6%, P = 0.71) and these findings were consistent after adjusting for differences in baseline characteristics (OR 0.63, 95% CI 0.1-3.3). CONCLUSION: The administration of DDAVP was not associated with adverse safety events, but did not significantly reduce the incidence of hematoma expansion in patients with AU-associated ICH.

Management of Hepatic Coagulopathy in Bleeding and Nonbleeding Patients: An Evidence-Based Review.

Patients with varying degrees of hepatic dysfunction often present with presumed bleeding diathesis based on interpretation of routine measures of coagulation (prothrombin time [PT], international normalized ratio [INR], and activated partial thromboplastin time). However, standard markers of coagulation do not reflect the actual bleeding risk in this population and may lead to inappropriate administration of hemostatic agents and blood products. The concept of "rebalanced hemostasis" explains both the risk of bleeding and clotting seen in patients with liver dysfunction. The role of pharmacologic agents and blood products for prevention of bleeding during high-risk procedures and treatment of clinically significant bleeding remains unclear. Viscoelastic measurements of the clotting cascade provide information about platelets, fibrinogen/fibrin polymerization, coagulation factors, and fibrinolysis that might better represent hemostasis in vivo and may better inform management strategies. Due to the paucity of available data, firm recommendations for the use of blood products and pharmacologic agents in patients with hepatic coagulopathies are lacking, and thus, these products should not be routinely administered. Traditional laboratory tests such as PT/INR should not be the sole determinant of potential interventions. Rather, clinicians should assess factors such as the severity of bleed or bleeding risk of the procedure, the patient's risk of thromboembolism, and the strength of available evidence for specific agents and blood products to guide decision-making.

Characteristics of Calls to a COVID-19 Mental Health Hotline in the First Wave of the Pandemic in New York.

This report describes the development, implementation and outcomes of a "COVID-19 Anxiety Hotline," designed to address the community's mental health crisis provoked by the coronavirus pandemic. The service was specifically designed using survey data regarding the effects of the COVID-19 pandemic on its staff and community members. Callers had around-the-clock direct access to mental healthcare providers at no cost. Quantitative analysis showed that nearly three out of four callers experienced new onset anxiety and insomnia driven by fear of exposure, and had difficulty accessing mental health care. In addition to immediate support, referral to tele-mental health care was provided to 86% of callers. Qualitative analysis indicates the effectiveness of immediate support and appropriate referrals using a tele-health platform. Our report indicates that the service was utilized by the general population, by health care workers, and rapidly provided referrals to individuals with limited access to mental health care during the pandemic.

A Low-Dose 4F-PCC Protocol for DOAC-Associated Intracranial Hemorrhage.

PURPOSE: Current guidelines favor 4F-PCC over plasma for reversal of warfarin. Uncertainty remains on the hemostatic effectiveness and thrombotic risk of 4F-PCC for direct-acting oral anticoagulants (DOACs), particularly in patients with intracranial hemorrhage (ICH). This study sought to evaluate the effectiveness and safety of a lower dose protocol of 25 units/kg 4F-PCC for the management of DOAC-associated ICH in a real-world setting. MATERIALS AND METHODS: This was a retrospective study of adult patients who received at least one dose of 4F-PCC from March 2014 to December 2015 for DOAC-associated ICH. The primary outcome was hemostatic effectiveness within 24 hours. The secondary outcome was thromboembolic events within 14 days. RESULTS: Twenty-two patients received 4F-PCC for DOAC-associated ICH and were included in the analysis. Hemostasis was evaluable in 19 patients with post-4F-PCC imaging available and occurred in 18/19 (94.7%) patients. Thromboembolism occurred in 2 out of 22 patients (9.1%). CONCLUSIONS: The use of a lower dose protocol of 25 units/kg of 4F-PCC resulted in high rates of hemostasis in patients with DOAC-associated ICH. Two patients developed thrombotic events within 14 days of 4F-PCC administration.

Prolonged activated partial thromboplastin time after prophylactic-dose unfractionated heparin in the post-operative neurosurgical setting: case series and management recommendations.

Primary brain tumors, both benign and malignant, pose a high risk of perioperative venous thromboembolism (VTE) due to the development of a prothrombotic state. Perioperative pharmacologic thromboprophylaxis with subcutaneous (SC) unfractionated heparin (UFH) has significantly reduced VTE associated morbidity. Recent reports suggest an association between prolonged activated partial thromboplastin time (aPTT) due to prophylactic SC UFH and increased bleeding risk. We present three patients with normal baseline coagulation parameters in whom pharmacologic thromboprophylaxis with SC UFH resulted in a marked prolongation of the aPTT, leading to adverse outcomes in two patients. These cases demonstrate the uncertain kinetics of SC UFH and effect on aPTT, suggesting the significance of routine aPTT monitoring in high-risk settings. Given the wide variation in presentations of therapeutic or supratherapeutic values of aPTT in the perioperative neurosurgical setting, we propose a practical standardized approach to the evaluation and management of aPTT prolongation following prophylactic SC UFH administration.

Using known drug interactions to manage supratherapeutic calcineurin inhibitor concentrations.

OBJECTIVES: To summarize the available body of evidence guiding the management of supratherapeutic concentrations of calcineurin inhibitors (CNI) using cytochrome P450 (CYP450) enzyme inducers. METHODS: A nondate restricted literature search within MEDLINE, Embase, and Scopus was performed using the terms "cyclosporine," "tacrolimus," "calcineurin inhibitor," "toxicity," "pharmacokinetics," "carbamazepine," "rifampin," "phenytoin," and "phenobarbital." Additional references were identified from a review of all included citations. All English-language reports that describe the management of supratherapeutic CNI concentrations with interventions targeting metabolic induction using CYP450 enzyme inducers were evaluated. RESULTS: A total of 10 publications were identified in which a CYP450 enzyme inducer was utilized intentionally to enhance CNI clearance in the setting of supratherapeutic concentrations; 7 case reports describe the use of phenytoin and 3 case reports describe the use of phenobarbital. Patient demographics, dosing strategies employed, and reported efficacy across this series of publications are heterogeneous; however, both agents appear to be well-tolerated when used in this setting. CONCLUSIONS: There is a paucity of published data on the use of CYP450 enzyme inducers for the management of supratherapeutic CNI concentrations. While routine use of this approach cannot be recommended, thorough risk-benefit analyses should be performed in the management of each such clinical scenario.

Efficacy of Nonpharmacological Antishivering Interventions: A Systematic Analysis.

OBJECTIVE: We performed a systematic review of the published evidence regarding nonpharmacologic antishivering interventions in various clinical settings. DATA SOURCES: Studies through November 2014 were identified using predefined search terms in electronic databases, including PubMed, the Cochrane Library, EMBASE: Excerpta Medica (Ovid), and Web of Science. STUDY SELECTION: All identified articles were critically analyzed by applying prespecified criteria. We included experimental trials with comparable baseline data investigating the antishivering efficacy of nonpharmacological interventions in subjects without underlying thermoregulatory dysfunction. DATA EXTRACTION: Sixty-five publications (3,361 subjects) were analyzed by the type of clinical setting, intervention, comparison, and study design. In addition, each study underwent a standardized study quality assessment. DATA SYNTHESIS: Nonpharmacological interventions consisted of active cutaneous warming (forced-air warming, electric heating pad/blanket, radiant heating, and water-circulating mattress), body core warming (fluid or gas warming system), passive cutaneous warming (space blankets or towels), and electroacupuncture. Identified clinical settings included perioperative settings without induced hypothermia (60 of 77 comparisons), perioperative settings with induced hypothermia (8 of 77), and induced hypothermia without anesthesia (9 of 77). Active cutaneous warming was the most commonly studied intervention, and it was associated with the highest prevalence of positive results when compared with controls in all three clinical settings. In contrast, passive cutaneous warming and body core warming showed conflicting efficacy. Comparison evaluations among different antishivering interventions were limited due to the paucity and heterogeneity of studies directly comparing different interventions against one another. CONCLUSION: This systematic review of the effectiveness of nonpharmacological antishivering methods delineates active cutaneous warming as the most effective nonpharmacologic antishivering intervention in the perioperative and induced hypothermia settings.

Genome-wide association and genetic functional studies identify autism susceptibility candidate 2 gene (AUTS2) in the regulation of alcohol consumption.

Alcohol consumption is a moderately heritable trait, but the genetic basis in humans is largely unknown, despite its clinical and societal importance. We report a genome-wide association study meta-analysis of ∼2.5 million directly genotyped or imputed SNPs with alcohol consumption (gram per day per kilogram body weight) among 12 population-based samples of European ancestry, comprising 26,316 individuals, with replication genotyping in an additional 21,185 individuals. SNP rs6943555 in autism susceptibility candidate 2 gene (AUTS2) was associated with alcohol consumption at genome-wide significance (P = 4 × 10(-8) to P = 4 × 10(-9)). We found a genotype-specific expression of AUTS2 in 96 human prefrontal cortex samples (P = 0.026) and significant (P < 0.017) differences in expression of AUTS2 in whole-brain extracts of mice selected for differences in voluntary alcohol consumption. Down-regulation of an AUTS2 homolog caused reduced alcohol sensitivity in Drosophila (P < 0.001). Our finding of a regulator of alcohol consumption adds knowledge to our understanding of genetic mechanisms influencing alcohol drinking behavior.

Cryoprecipitate for Alteplase-Related Hemorrhagic Conversion of Acute Ischemic Stroke.

Background: Evidence to support cryoprecipitate for reversal of alteplase-related hemorrhagic conversion of acute ischemic stroke is limited. Guidelines recommend cryoprecipitate as first line treatment, followed by aminocaproic acid as a conditional recommendation with very low-quality evidence. The purpose of this case series was to describe the use of cryoprecipitate for alteplase-related hemorrhagic conversion of acute ischemic stroke. Methods: This was an IRB-approved retrospective case series of adults who received cryoprecipitate for an alteplase-related hemorrhagic conversion of acute ischemic stroke at two comprehensive stroke centers within a large academic medical center. Thromboembolism at 14 days and hemostasis within 24 hours were collected. The outcomes of cryoprecipitate alone vs cryoprecipitate with aminocaproic acid (C + A) were also described. Results: A total of 19 patients were included. Thrombosis occurred in 1/19 (5%) and hemostasis occurred in 4/14 (29%) of evaluable patients. In-hospital mortality was seen in 9/19 (47%) patients. Seventy four percent (14/19) of patients received concomitant blood products other than cryoprecipitate and 63% received a concomitant reversal agent. Thirteen patients received cryoprecipitate alone and six received C + A. Thrombosis was seen in 1/13 (8%) vs 0/6 (0%) and hemostasis occurred in 2/11 (18%) and 2/3 (67%) evaluable cryoprecipitate vs C + A patients respectively. Conclusion: Cryoprecipitate was associated with a low rate of thrombosis and hemostasis for alteplase-associated hemorrhagic conversion of acute ischemic stroke. There was significant heterogeneity in treatment regimens, including the use of and dosing of adjunctive aminocaproic acid and monitoring of fibrinogen levels.

Concordance Between Active Partial Thromboplastin Time and Anti-Factor Xa Assays in Neurocritically Ill Patients Receiving Subcutaneous Heparin Prophylaxis.

Background: Laboratory monitoring is not recommended when subcutaneous unfractionated heparin (SQ-UFH) is administered at prophylactic doses. However, aPTT prolongation and associated hemorrhage has been reported in the neurocritically ill. At our institution, Neuroscience Intensive Care Unit (Neuro-ICU) patients with prolonged aPTT are further evaluated with a follow up aPTT and anti-factor Xa. Purpose: The purpose of this study was to describe concordance between aPTT and anti-factor Xa in neurocritically ill patients receiving prophylactic SQ-UFH with evidence of aPTT prolongation. Methods: A retrospective chart review of adult patients admitted to the Neuro-ICU from June 2017 to June 2019 was performed. Patients were included if they received SQ-UFH with aPTT levels and at least one anti-factor Xa level drawn within one hour of each other. Concordance between paired aPTT and anti-factor Xa was evaluated using Cohen's weighted kappa. Results: Forty two patients with 56 paired aPTT and anti-factor Xa levels were included. The most prescribed SQ-UFH regimen was 5000 units every 8 hours (60.7%) and anti-factor Xa levels were drawn a median (IQR) of 5.7 (3.1-10.7) hours after the SQ-UFH dose. Only 16 (28.6%) pairs were in concordance. The analysis showed a weighted kappa of .09; 95% CI [-.05 to .22] indicating poor agreement. Conclusions: In neurocritically ill patients receiving prophylactic SQ-UFH with aPTT prolongation, there was poor concordance between aPTT and anti-factor Xa. This suggests that aPTT prolongation may not be solely driven by heparin activity and further evaluation of mechanistic drivers for coagulopathy in this population is necessary.

Antiplatelet therapy and outcomes after aneurysmal subarachnoid hemorrhage: A systematic review and meta-analysis.

BACKGROUND: The efficacy of antiplatelet therapy (APT) after aneurysmal subarachnoid hemorrhage (aSAH) remains unclear. We performed a systematic review and meta-analysis to summarize the associations of APT use after aSAH with outcomes. METHODS: We searched published medical literature to identify cohort studies involving adults with aSAH. The exposure was APT use after aSAH. Outcome measures were good functional outcome (modified Rankin Score 0-2 or Glasgow Outcome Scale 4-5), delayed cerebral ischemia (infarcts on neuroimaging), and intracranial hemorrhage. After assessing study heterogeneity and publication bias, we performed a meta-analysis using random-effects models to assess the strength of association between APT and SAH outcomes. RESULTS: A total of 14 studies with 4228 aSAH patients were included. APT after aSAH was associated with good functional outcome (pooled relative risk, 1.08; 95% confidence interval, [CI], 1.02-1.15; I2 = 45%, p for heterogeneity = 0.04), but there was no relationship with delayed cerebral ischemia (pooled relative risk, 0.80; 95% confidence interval, [CI], 0.63-1.02; I2 = 61%, p for heterogeneity <0.01) or intracranial hemorrhage (pooled relative risk, 1.50; 95% confidence interval, [CI], 0.98-2.31; I2 = 0, p for heterogeneity =0.71). In additional analyses, APT resulted in good functional outcomes in endovascularly-treated patients. When stratified by type of medication, aspirin, clopidogrel, and ticlopidine were associated with good functional outcomes. CONCLUSIONS: APT after aSAH was associated with a modest improvement in functional outcome, but there was no relationship with delayed cerebral ischemia or intracranial hemorrhage.

Efficacy spectrum of antishivering medications: meta-analysis of randomized controlled trials.

OBJECTIVES: Shivering after anesthesia or in the critical care setting is frequent, can be prolonged, and has the potential for serious adverse events and worsening outcomes. Furthermore, there are conflicting published data and clinical protocols on how to best treat shivering. In this study, we aimed to critically analyze the published evidence of antishivering medications. DATA SOURCES: We systematically reviewed, categorized, and analyzed all literature on antishivering medications published in English. Target key words and study types were determined and major scientific databases (PubMed, EMBASE, the Cochrane Controlled Trials Register, Ovid-Medline, and JAMA Evidence) and individual target journals were systematically searched up to August 1, 2011. STUDY SELECTION: Publications were categorized by the pharmacological intervention used, regardless of whether the subjects were ventilated, underwent surgery, received anesthesia, or received additional medications. Randomized, double-blinded, placebo-controlled trials investigating antishivering treatment were extracted and evaluated for clinical and statistical homogeneity and, if suitable, included in a subsequent meta-analysis using linear comparisons calculating shivering risk-reduction ratios. DATA EXTRACTION: A total of 41 individual and eight combination antishivering medications were tested in 124 publications containing 208 substudies and recruiting a total of 9,668 subjects. Among those, 80 publications containing 119 substudies were identified as randomized, double-blinded, placebo-controlled of which 94 substudies were subjected to linear comparison analysis. DATA SYNTHESIS: Study drug frequencies, calculated pooled risk benefits, and pooled numbers needed to treat of the five most frequently studied and efficacious medications were clonidine (22 studies; risk ratio: 1.6, numbers needed to treat: 4), meperidine (16; 2.2, 2), tramadol (8; 2.2, 2), nefopam (7; 2.1, 2), and ketamine (7; 1.8, 3). CONCLUSIONS: There is significant heterogeneity in the literature with respect to study methods and efficacy testing of antishivering treatments. Clonidine, meperidine, tramadol, nefopam, and ketamine were the most frequently reported pharmacological interventions and showed a variable degree of efficacy in randomized, double-blinded, placebo-controlled trials.

Timing of susceptibility-based antifungal drug administration in patients with Candida bloodstream infection: correlation with outcomes.

OBJECTIVES: We sought to determine the impact of timing of appropriate antifungal therapy, as assessed by susceptibility results, on patient survival. METHODS: Patients ≥16 years of age with first episodes of candidaemia during 2001-09 were included. Clinical data were collected retrospectively, including time to appropriate antifungal therapy and patient survival. RESULTS: The study population included 446 patients [243 (54%) female, mean age 53 years] with candidaemia, 380 (85%) of whom had antifungal susceptibility data. Candida albicans was the most common pathogen (221, 50%) followed by Candida glabrata (99, 22%), Candida parapsilosis (59, 13%), Candida tropicalis (48, 11%) and Candida krusei (6, 1%). Appropriate antifungal therapy consisted of fluconazole (177, 40%), an echinocandin (125, 28%), amphotericin B (41, 9%) and voriconazole (6, 1%); 97 (22%) failed to receive appropriate antifungal therapy. The 30 day mortality was 34% (151/446) and there was no clear relationship between time from positive culture to receipt of appropriate antifungal therapy and 30 day survival. On multivariable Cox regression, increased APACHE II score [hazard ratio (HR) 1.11, 95% CI 1.09-1.13, P<0.001], cirrhosis (HR 2.15, 95% CI 1.48-3.13, P<0.001) and HIV infection (HR 2.03, 95% CI 1.11-3.72, P=0.02) were independent predictors of mortality. A secondary analysis requiring patients in the early treatment group to have received ≥24 h of effective antifungal therapy did show a significant mortality benefit to receiving antifungal treatment within 72 h of a positive blood culture being drawn (30 day mortality for early treatment: 27% versus 40%, P=0.004; HR for mortality with delayed treatment on multivariable analysis: 1.41, 95% CI 1.01-1.98, P=0.045). CONCLUSIONS: Candida bloodstream infection is associated with high mortality, despite timely receipt of appropriate antifungal therapy.