Search

--01 I would like to express my deep concern regarding Archbishop Joseph Naumann of Kansas City, Kansas and his stance against the renewal of the Catholic Campaign for Human Development, […]

We describe the demographics, clinical and molecular epidemiology of extended-spectrum β-lactamase (ESBL) Escherichia colibloodstream infections (BSI) in Central Australia.

ABSTRACTIntroductionUnfractionated heparin is a widely used anticoagulant in critically ill patients. It has a well-established safety profile and remains an attractive option for clinicians due to its short half-life and reversibility. Heparin has a unique pharmacokinetic profile, which contributes to significant inter-patient and intra-patient variability in effect. The variability in anticoagulant effect combined with heparin’s short half-life mean close monitoring is required for clinical efficacy and preventing adverse effects. To optimize heparin use in critically ill patients, effective monitoring assays and dose adjustment strategies are needed.Areas CoveredThis paper explores the use of heparin as an anticoagulant and optimal approaches to monitoring in critically ill patients.Expert opinionConventional monitoring assays for heparin dosing have significant limitations. Emerging data appear to favor using anti-Xa assay monitoring for heparin anticoagulation, which many centers have successfully adopted as the standard. The anti-Xa assay appears have important benefits relative to the aPTT for heparin monitoring in critically ill patients, and should be considered for broader use.

This article explores the need for new approaches to naming and categorizing species. It highlights the efforts of scientists who are creating a comprehensive database of marine species and have discovered that many species names are repetitive. The article also mentions the excessive classification of species by biologist Louis Agassiz in the 19th century and the recent finding that giraffes are actually four distinct species. It emphasizes the vast number of undiscovered species and the challenges faced in taxonomy. The article concludes by suggesting the use of temporary identities and a departure from traditional type specimens in the field of taxonomy. [Extracted from the article]

The aim of this study was to investigate an in vitro dynamic bioreactor model by evaluating the antimicrobial effect of clinically relevant amoxicillin doses on polymicrobial microcosm biofilms derived from subgingival plaque. Biofilms from pooled subgingival plaque were grown for 108  hours in control and experimental dynamic biofilm reactors. Amoxicillin was subsequently infused into the experimental reactor to simulate the pharmacokinetic profile of a standard 500 mg thrice‐daily dosing regimen over 5 days and biofilms were assessed by live/dead staining, scanning electron microscopy, and quantitative polymerase chain reaction. Following establishment of the oral microcosm biofilms, confocal imaging analysis showed a significant increase in dead bacteria at 8 hours (p= 0.0095), 48 hours (p= 0.0070), 96 hours (p= 0.0140), and 120 hours (p< 0.0001) in the amoxicillin‐treated biofilms compared to the control biofilms. Nevertheless, viable bacteria remained in the center of the biofilm at all timepoints. Significant reductions/elimination in Campylobacter rectus, Tannerella forsythia, Aggregatibacter actinomycetemcomitans, and Peptostreptococcus anaerobiuswas observed among the amoxicillin‐treated biofilms at the 96 and 120 hour timepoints. A novel in vitro dynamic model of oral microcosm biofilms was effective in modeling the antimicrobial effect of a pharmacokinetically simulated clinically relevant dose of amoxicillin.

Important progress has been made toward unravelling the complex genetics underlying atrial fibrillation (AF). Initial studies were aimed to identify monogenic causes; however, it has become increasingly clear that the most common predisposing genetic substrate for AF is polygenic. Despite intensive investigations, there is robust evidence for rare variants for only a limited number of genes and cases. Although the current yield for genetic testing in early onset AF might be modest, there is an increasing appreciation that genetic culprits for potentially life-threatening ventricular cardiomyopathies and channelopathies might initially present with AF. The potential clinical significance of this recognition is highlighted by evidence that suggests that identification of a pathogenic or likely pathogenic rare variant in a patient with early onset AF is associated with an increased risk of death. These findings suggest that it might be warranted to screen patients with early onset AF for these potentially more sinister cardiac conditions. Beyond facilitating the early identification of genetic culprits associated with potentially malignant phenotypes, insight into underlying AF genetic substrates might improve the selection of patients for existing therapies and guide the development of novel ones. Herein, we review the evidence that links genetic factors to AF, then discuss an approach to using genetic testing for early onset AF patients in the present context, and finally consider the potential value of genetic testing in the foreseeable future. Although further work might be necessary before recommending uniform integration of genetic testing in cases of early onset AF, ongoing research increasingly highlights its potential contributions to clinical care.

Ballot dropboxes provide voters who fill out mail-in ballots with a secure and convenient method for returning their ballot. During the COVID-19 pandemic, the use of ballot dropboxes increased dramatically as voters sought to cast ballots safely and conveniently. In the wake of the 2020 election, ballot dropboxes have come under considerable scrutiny as many Republican-controlled state legislatures have sought to eliminate them or sharply reduce the number available and/or limit the hours in which they can be used by voters. This article uses novel data on the number of ballots collected in Georgia dropboxes paired with measures of how accessible these dropboxes were to voters in order to analyze how the allocation of dropboxes affected voting behavior in an election where voters could choose to vote in a variety of ways. When controlling for the number of potential users, dropboxes closer in distance to voters are used at higher rates. Individuals located closer to dropboxes are more likely to vote by mail and are less likely to fail to return requested mail-in ballots. Our findings carry important implications for election administrators seeking to make voting accessible by adding additional ballot dropboxes and for administrators seeking to adjust to mandated decreases in the number of dropboxes provided to voters. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) is a major health concern with a growing disease burden and inequalities in access to treatments. Glomerular filtration rate (GFR) is accepted as the best overall measure of kidney function and is considered the most important measure for medications cleared by the kidneys. In clinical practice, equations that estimate GFR using validated prediction equations are routinely used. This practice update was developed by a Working Group comprising clinical pharmacists representing the Society of Hospital Pharmacists of Australia (SHPA) Specialty Practice streams of Nephrology, Oncology and haematology, Critical care and Infectious diseases. It is intended to provide practical recommendations for clinical pharmacists who use equations to estimate GFR for medication dosing decisions. The limitations of the various equations in use — such as the Chronic Kidney Disease Epidemiology Collaboration (CKD‐EPI), the Cockcroft–Gault equation and Modification of Diet in Renal Disease — are summarised and compared to direct measures of kidney function using exogenous markers. The CKD‐EPI equation is recommended to be used routinely as a primary measure of kidney function. Dose adjustments should also consider medication‐specific, patient‐related, and disease‐related characteristics. Kidney function and the response to therapy should be continuously assessed by monitoring the signs, symptoms and disease outcomes, the emergence of adverse reactions or medication‐induced disorders and use therapeutic drug monitoring (if available) to adjust doses accordingly.

There is growing evidence that mitral valve prolapse (MVP) is associated with otherwise unexplained cardiac arrest (UCA). However, reports are hindered by the absence of a systematic ascertainment of alternative diagnoses.

A prolonged QT interval on the electrocardiogram is associated with an increased risk of the torsades de pointes form of ventricular arrhythmia resulting in syncope, sudden cardiac arrest or death, or misdiagnosis as a seizure disorder. The cause of QT prolongation can be congenital and inherited as an autosomal dominant variant, or it can be transient and acquired, often because of QT-prolonging drugs or electrolyte abnormalities. Automated measurement of the QT interval can be inaccurate, especially when the baseline electrocardiogram is abnormal, and manual verification is recommended. In this clinical practice update we provide practical tips about measurement of the QT interval, diagnosis, and management of congenital long QT syndrome and acquired prolongation of the QT interval. For congenital long QT syndrome, certain β-adrenergic-blocking drugs are highly effective, and implantable defibrillators are infrequently required. Many commonly prescribed drugs such as antidepressants and antibiotics can prolong the QT interval, and recommendations are provided on their safe use.

Study Objective: The purpose of this study is to rank the factors that are most and least important to patients with symptomatic uterine fibroids when considering surgical treatment options. Materials and Methods: Using a best worst scaling (BWS) preference elicitation approach, participants completed an online survey to rank factors associated with fibroid surgical treatments. Survey content was based on a literature review and included the following factors: symptom relief; surgical complications; repeat treatment; recovery time; cosmetic effects; risk of spreading undiagnosed cancer; sexual outcomes; maintenance of child-bearing; continuation of menses; unpredictable menses; and location of procedure. Participants completed 11 BWS tasks. For each task, we presented participants with a subset of 5 factors from the possible 11, and participants chose the most important and least important factor. Participants’ responses were analyzed using conditional logistic regression to determine the relative importance of factors. Patient priorities were further explored via age and race. Results: 285 respondents with symptomatic uterine fibroids (69 physician-confirmed and 216 self-reported) who had not undergone prior surgical treatment completed the survey. Respondents were enrolled from two clinical sites (clinical site cohort) and an online consumer panel (panel cohort). Both cohorts identified symptom relief, cancer risk, repeat treatment and complications as the most important factors in selecting surgical treatment options and location of procedure, return to normal activities after surgery, and cosmetic effects like presence of a scar after the surgical treatment as the least important factors. Of note, younger women (≤ 40) placed greater importance on the ability to have children after the procedure. Conclusion: Information regarding the factors most and least important to patients with symptomatic uterine fibroids might inform development and regulatory evaluation of new technologies and procedures. Study results may be useful in efforts to develop a set of outcomes to include in future fibroids clinical studies.

Supplemental Digital Content is Available in the Text.

Do interpersonal relationships among and between representatives and senators affect legislative collaboration in the contemporary Congress? The extant literature on Congress suggests interpersonal dimensions of life on Capitol Hill should play a minimal role in the legislative process. However, research in other fields, including psychology, finds that relationships are crucially important within organizations. In addition, many contemporary accounts of congressional deal‐making highlight the role of personal relationships. Drawing on interviews with high‐level congressional staff, and data on CODEL trips taken by members of Congress, we show that interpersonal relationships help promote collaboration across the aisle. These findings have implications for how we understand the contours of conflict and cooperation on Capitol Hill.

Splice-site variants in cardiac genes may predispose carriers to potentially lethal arrhythmias. To investigate, we screened 1315 probands and first-degree relatives enrolled in the Canadian Hearts in Rhythm Organization (HiRO) registry. 10% (134/1315) of patients in the HiRO registry carry variants within 10 base-pairs of the intron-exon boundary with 78% (104/134) otherwise genotype negative. These 134 probands were carriers of 57 unique variants. For each variant, American College of Medical Genetics and Genomics (ACMG) classification was revisited based on consensus between nine in silico tools. Due in part to the in silico algorithms, seven variants were reclassified from the original report, with the majority (6/7) downgraded. Our analyses predicted 53% (30/57) of variants to be likely/pathogenic. For the 57 variants, an average of 9 tools were able to score variants within splice sites, while 6.5 tools responded for variants outside these sites. With likely/pathogenic classification considered a positive outcome, the ACMG classification was used to calculate sensitivity/specificity of each tool. Among these, Combined Annotation Dependent Depletion (CADD) had good sensitivity (93%) and the highest response rate (131/134, 98%), dbscSNV was also sensitive (97%), and SpliceAI was the most specific (64%) tool. Splice variants remain an important consideration in gene elusive inherited arrhythmia syndromes. Screening for intronic variants, even when restricted to the ±10 positions as performed here may improve genetic testing yield. We compare 9 freely available in silico tools and provide recommendations regarding their predictive capabilities. Moreover, we highlight several novel cardiomyopathy-associated variants which merit further study.

Fungal infections are common and frequently associated with clinical failure in patients receiving extracorporeal membrane oxygenation (ECMO). Antifungal drugs have physicochemical characteristics associated with a higher likelihood of sequestration onto ECMO circuitry potentially leading to a subtherapeutic drug concentration. The percentage of sequestration of the antifungal drugs—caspofungin, posaconazole, and voriconazole—was determined using an ex vivoECMO model. The circuits were primed with whole human blood, sodium chloride 0.9%, and human albumin solution. Serial 2 ml samples were taken at baseline, 0.5, 1, 2, 6, 12, and 24 hours after drug addition, paired with non-ECMO controls stored in a water bath at 37°C. Mean loss from the blood-primed ECMO circuits and controls at 24 hours relative to baseline were 80% and 61% for caspofungin (p= ns), 64% and 11% for posaconazole (p< 0.005), and 27% and 19% for voriconazole (p< 0.05). Calculated AUC0–24showed a 44% for caspofungin (p= ns), 30.6% posaconazole (p< 0.005), and 9% loss for voriconazole (p= 0.003) compared with the controls, suggesting therapeutic concentrations of these antifungal agents cannot be guaranteed with standard dosing in patients on ECMO. Posaconazole exhibited the greatest loss to the ECMO circuit correlating with both high lipophilicity and protein binding of the drug.

To describe whether contemporary dosing of antifungal drugs achieves therapeutic exposures in critically ill patients that are associated with optimal outcomes. Adequate antifungal therapy is a key determinant of survival of critically ill patients with fungal infections. Critical illness can alter an antifungal agents’ pharmacokinetics, increasing the risk of inappropriate antifungal exposure that may lead to treatment failure and/or toxicity.

Supplemental Digital Content is Available in the Text.

ObjectiveTo evaluate the stability of temocillin solution in two elastomeric infusion devices – Easypump II LT 270–27- S and Dosi-Fusor L25915-250D1 for OPAT administration during 14 days of 5°C±3°C fridge storage followed by 24 hour exposure at an in-use temperature of 32°C, when reconstituted with 0.3% citrate buffer at pH7.MethodsStability testing was conducted in accordance with standard protocols in the UK National Health Service Yellow Cover Document (YCD). A stability indicating assay method was applied using a high-performance liquid chromatography (HPLC) system with a photodiode array detector. Low (500 mg/240 mL), intermediate (4000 mg/240 mL) and high (6000 mg/240 mL) temocillin concentrations were tested in triplicate devices with duplicate samples taken at 11 time points during fridge storage and subsequent in-use temperature exposure.ResultThe percentage of temocillin remaining after 14 days of fridge storage was greater than 97% in both devices and at all concentrations tested. During subsequent in-use temperature exposure, a 95% stability limit was achieved for 12 hours except for the high concentration (25 mg/mL) in the Dosi-Fusor device. It met this criterion for only 10 hours — the percent of temocillin remaining at 12 hours was 94.5%. However, for all devices and the doses tested, the degradation of temocillin was <9% at the end of 24 hours in-use temperature exposure.ConclusionTemocillin reconstituted with 0.3% citrate buffer at pH7 in elastomeric infusion devices can be stored in a fridge (2°C–8°C) for 14 days meeting the YCD acceptance criteria. Considering <5% degradation, the current data supports twice daily dosing of temocillin within the OPAT setting. In jurisdictions where a <10% degradation limit is acceptable, once daily dosing with 24-hour continuous infusion may be considered. Temocillin is a useful alternative to other broad-spectrum anti-Gram-negative agents currently utilised in the OPAT setting and supports the wider antimicrobial stewardship agenda.

Practitioners frequently submit tissue and fluid samples to pathologists--typically employed at academic institutions, state laboratories, or private diagnostic laboratories--to assist them in the diagnosis of infectious diseases, inflammatory or metabolic [...]

Patients with hemodynamically tolerated ventricular tachycardia (VT) and minimally reduced left ventricular ejection fraction (LVEF) remain a group that presents a prognostic and therapeutic dilemma.

Background and Objective: Prolonged infusion of ceftolozane/tazobactam (C/T) is a strategy used to increase achievement of pharmacokinetic/pharmacodynamic targets for the treatment of multi- or extensively drug-resistant MDR/XDR Gram-negative microorganisms. The objective of this study was to describe our therapeutic drug monitoring (TDM) experience of C/T administered by prolonged infusion or intermittent infusion to patients with MDR/XDR Pseudomonas aeruginosainfections. Our outcomes of interest were pharmacokinetic/pharmacodynamic target achievement and clinical cure. Methods: Patients with MDR/XDR P. aeruginosainfections treated with C/T were enrolled between February 2018 and February 2020. Blood samples were obtained as part of a TDM program. The pharmacokinetic/pharmacodynamic therapeutic target of C/T was defined as 100% of the duration of the dosing interval that free concentrations are above the minimum inhibitory concentration (MIC) (100 %ƒT ≥ MIC) of the causative pathogen. Dose changes were performed according to TDM results. Results: Forty patients were included: 13 (32.5%) with a proven MDR and 27 (67.5%) with a XDR P. aeruginosainfection. C/T was administered by prolonged infusion in 32 (80%) patients and by intermittent infusion in 8 (20%) patients. Lower doses were administered in the prolonged infusion compared to the intermittent infusion group [3 (9.4%) vs. 5 (62.5%] patients received a dose of 9 g/day (ceftolozane 2 g + tazobactam 1 g, every 8 h; p= 0.004). All patients achieved the pharmacokinetic/pharmacodynamic target and C/T concentrations exceeded 10 × MIC in > 50% of patients in both groups. TDM-recommended dose reductions occurred in 19 (47.5%) patients, being 16 (84.2%) in the prolonged infusion group. A high proportion of patients achieved clinical cure (82.5%). Conclusions: The administration of C/T by prolonged infusion with TDM-guided dosing allowed the achievement of a pharmacokinetic/pharmacodynamic target even at lower doses. C/T showed a high efficacy for treating MDR/XDR P. aeruginosainfections.

Clinical studies investigating the benefits of beta-lactam therapeutic drug monitoring (TDM) among critically ill patients are hindered by small patient groups, variability between studies, patient heterogeneity, and inadequate use of TDM. Accordingly, definitive conclusions regarding the efficacy of TDM remain elusive. To address these challenges, we propose an innovative approach that leverages data-driven methods to unveil the concealed connections between therapy effectiveness and patient data, collected through a randomized controlled trial (DRKS00011159; 10th October 2016). Our findings reveal that machine learning algorithms can successfully identify informative features that distinguish between healthy and sick states. These hold promise as potential markers for disease classification and severity stratification, as well as offering a continuous and data-driven “multidimensional” Sequential Organ Failure Assessment (SOFA) score. The positive impact of TDM on patient recovery rates is demonstrated by unraveling the intricate connections between therapy effectiveness and clinically relevant data via machine learning.

Optimal antibiotic therapy for critically ill patients can be complicated by the altered physiology associated with critical illness. Antibiotic pharmacokinetics and exposures can be altered driven by the underlying critical illness and medical interventions that critically ill patients receive in the intensive care unit. Furthermore, pathogens that are usually isolated in the intensive care unit are commonly less susceptible and “resistant” to common antibiotics. Indeed, antibiotic dosing that does not consider these unique differences will likely fail leading to poor clinical outcomes and the emergence of antibiotic resistance in the intensive care unit. The aims of this narrative review were to describe the pharmacokinetics of beta-lactam antibiotics in critically ill patients, to highlight pharmacokinetic/pharmacodynamic targets for both non-critically ill and critically ill patients, and to discuss important strategies that can be undertaken to optimize beta-lactam antibiotic dosing for critically ill patients in the intensive care unit.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) encompasses a group of conditions characterized by right ventricular fibrofatty infiltration, with a predominant arrhythmic presentation. First described in the late 1970s and early 1980s, it is now frequently recognized to have biventricular involvement. The prevalence is ∼1:2,000 to 1:5,000, depending on geographic location, and it has a slight male predominance. The diagnosis of ARVC is determined on the basis of fulfillment of task force criteria incorporating electrophysiological parameters, cardiac imaging findings, genetic factors, and histopathologic features. Risk stratification of patients with ARVC aims to identify those who are at increased risk of sudden cardiac death or sustained ventricular tachycardia. Factors including age, sex, electrophysiological features, and cardiac imaging investigations all contribute to risk stratification. The current management of ARVC includes exercise restriction, β-blocker therapy, consideration for implantable cardioverter-defibrillator insertion, and catheter ablation. This review summarizes our current understanding of ARVC and provides clinicians with a practical approach to diagnosis and management.

With the remarkable growth of disability- and rehabilitation-related research in the last decade, it is imperative that we support the highest quality research possible. With cuts in research funding, rehabilitation [...]

Brugada syndrome (BrS) is a cardiac arrhythmia disorder associated with sudden death in young adults. With the exception of SCN5A, encoding the cardiac sodium channel NaV1.5, susceptibility genes remain largely unknown. Here we performed a genome-wide association meta-analysis comprising 2,820 unrelated cases with BrS and 10,001 controls, and identified 21 association signals at 12 loci (10 new). Single nucleotide polymorphism (SNP)-heritability estimates indicate a strong polygenic influence. Polygenic risk score analyses based on the 21 susceptibility variants demonstrate varying cumulative contribution of common risk alleles among different patient subgroups, as well as genetic associations with cardiac electrical traits and disorders in the general population. The predominance of cardiac transcription factor loci indicates that transcriptional regulation is a key feature of BrS pathogenesis. Furthermore, functional studies conducted on MAPRE2, encoding the microtubule plus-end binding protein EB2, point to microtubule-related trafficking effects on NaV1.5 expression as a new underlying molecular mechanism. Taken together, these findings broaden our understanding of the genetic architecture of BrS and provide new insights into its molecular underpinnings.

Supplemental Digital Content is Available in the Text.

Supplemental Digital Content is available in the text.

IMPORTANCE: Calcium-release deficiency syndrome (CRDS), which is caused by loss-of-function variants in cardiac ryanodine receptor 2 (RyR2), is an emerging cause of ventricular fibrillation. However, the lack of complex polymorphic/bidirectional ventricular tachyarrhythmias during exercise stress testing (EST) may distinguish it from catecholaminergic polymorphic ventricular tachycardia (CPVT). Recently, in the first clinical series describing the condition, mouse and human studies showed that the long-burst, long-pause, short-coupled ventricular extra stimulus (LBLPS) electrophysiology protocol reliably induced CRDS ventricular arrhythmias. Data from larger populations with CRDS and its associated spectrum of disease are lacking. OBJECTIVE: To further insight into CRDS through international collaboration. DESIGN, SETTING, AND PARTICIPANTS: In this multicenter observational cohort study, probands with unexplained life-threatening arrhythmic events and an ultrarare RyR2 variant were identified. Variants were expressed in HEK293 cells and subjected to caffeine stimulation to determine their functional impact. Data were collected from September 1, 2012, to March 6, 2021, and analyzed from August 9, 2015, to March 6, 2021. MAIN OUTCOMES AND MEASURES: The functional association of RyR2 variants found in putative cases of CRDS and the associated clinical phenotype(s). RESULTS: Of 10 RyR2 variants found in 10 probands, 6 were loss-of-function, consistent with CRDS (p.E4451del, p.F4499C, p.V4606E, p.R4608Q, p.R4608W, and p.Q2275H) (in 4 [67%] male and 2 [33%] female probands; median age at presentation, 22 [IQR, 8-34] years). In 5 probands with a documented trigger, 3 were catecholamine driven. During EST, 3 probands with CRDS had no arrhythmias, 1 had a monomorphic couplet, and 2 could not undergo EST (deceased). Relatives of the decedents carrying the RyR2 variant did not have EST results consistent with CPVT. After screening 3 families, 13 relatives were diagnosed with CRDS, including 3 with previous arrhythmic events (23%). None had complex ventricular tachyarrhythmias during EST. Among the 19 confirmed cases with CRDS, 10 had at least 1 life-threatening event at presentation and/or during a median follow-up of 7 (IQR, 6-18) years. Two of the 3 device-detected ventricular fibrillation episodes were induced by a spontaneous LBLPS-like sequence. β-Blockers were used in 16 of 17 surviving patients (94%). Three of 16 individuals who were reportedly adherent to β-blocker therapy (19%) had breakthrough events. CONCLUSIONS AND RELEVANCE: The results of this study suggest that calcium-release deficiency syndrome due to RyR2 loss-of-function variants mechanistically and phenotypically differs from CPVT. Ventricular fibrillation may be precipitated by a spontaneous LBLPS-like sequence of ectopy; however, CRDS remains difficult to recognize clinically. These data highlight the need for better diagnostic tools and treatments for this emerging condition.

Supplemental Digital Content is available in the text.

Cable television should maintain public access, and the best way to do this is by viewer activity instead of government regulation. The 1992 Cable Television Consumer Protection and Competition Act has regulations from the Federal Communications Commission which constitute censorship in the name of public access. Viewers could regulate content better by such methods as counter programming and lockboxes for blocking out channels.

Background:The β-Lactam Infusion Group (BLING) III study is a prospective, multicentre, open, phase 3 randomised controlled trial comparing continuous infusion with intermittent infusion of β-lactam antibiotics in 7000 critically ill patients with sepsis.

The research aim was to conduct a systematic review of the literature regarding the pharmacokinetics (PK) and dosing of antimicrobials in prolonged intermittent renal replacement therapy (PIRRT), a hybrid form of dialysis becoming increasingly utilised in critical care. A literature review was performed using PubMed from database inception to October 2020 according to the PRISMA guidelines. All papers published in English language were included in the review. Two researchers independently conducted literature searches, screened abstracts and full text and came to agreement as to which articles were suitable for inclusion before compiling the relevant data into a spreadsheet. The types of papers retrieved varied between case reports, single and multiple dose pharmacokinetic studies and Monte Carlo simulations. A total of 149 articles were found in the initial literature review and via other sources. Of these papers, 50 articles were deemed eligible for inclusion. These studies included one to 34 patients. PIRRT settings varied between institutions, including filter surface area, duration of PIRRT and type of dialyser used. With the exception of vancomycin and meropenem, few antimicrobials had sufficient data available from which reasonable empiric dosing regimens can be recommended. There is limited data to guide dosing of antimicrobials during PIRRT. More studies are required to understand how dosing can be optimised in this population of critically ill patients.

To summarise the evidence on pharmacist‐led antifungal stewardship (AFS) programs in the hospital setting and to evaluate their impact on the quality of antifungal prescribing and infection management, antifungal usage and clinical outcomes. A systematic review of English‐language studies identified in MEDLINE and EMBASE was performed on 27 November 2020 and conducted in accordance with PRISMA. Search terms included ‘antifungal agent’, ‘invasive fungal infection’, ‘antimicrobial stewardship’, ‘patient care bundles’ and ‘pharmacist’. Eligible studies describing pharmacist‐led quality improvement intervention(s) implemented in the hospital setting targeted at optimising systemic antifungal prescribing. Six hundred and forty‐six studies were identified, and seven met inclusion criteria. Five were dedicated to optimising candidaemia management, one at optimising intensive care unit prescribing of caspofungin and one on antifungal prescribing in haematology and oncology units. All studies measured varied metrics relating to quality of prescribing and infection management, reporting improvement in proportion of effective antifungal therapy (n= 1/1), appropriate antifungal selection (n= 1/1), dosing (n= 2/3), management of drug–drug interactions (n= 1/1) and reduced time to antifungal initiation (n= 4/4). Studies that implemented a candidaemia bundle of care reported improvements in composite bundle adherence (n= 2/2), with greatest improvement in ophthalmological consultation (n= 4/4), echocardiography (n= 2/2) and infectious diseases consultation (n= 3/3). There was reduction in antifungal expenditure (n= 4/4) and consumption (n= 2/4). Pharmacist‐led AFS programs did not influence clinical outcomes. Available evidence suggests that pharmacist‐led AFS interventions can improve the quality and timeliness of antifungal prescribing and reduce antifungal usage. Further research is required to assess the impact on clinical and microbiological outcomes.

AbstractVentricular repolarisation can be influenced by hormonal milieu which may mimic long QT syndrome. We describe a series of patients referred for genetic testing for diagnosed long QT syndrome where a detailed clinical workup demonstrated endocrinopathies as the cause of presumed “gene negative” long QT syndrome and QT prolongation.

Background:Nosocomial pneumonia in the critical care setting is associated with increased morbidity, significant crude mortality rates and high health care costs. Ventilator-associated pneumonia represents about 80% of nosocomial pneumonia cases in intensive care units (ICUs). Wide variance in incidence of nosocomial pneumonia and diagnostic techniques used has been reported, while successful treatment remains complex and a matter of debate.