A multicentre survey investigating the knowledge, behaviour, and attitudes of surgical healthcare professionals to frailty assessment in emergency surgery: DEFINE(surgery).

PURPOSE: Screening for frailty in people admitted with emergency surgical pathology can initiate timely referrals to enhanced perioperative services such as intensive care and geriatric medicine. However, there has been little research exploring surgical healthcare professionals' opinions to frailty assessment, or accuracy in identification. This study aimed to assess the knowledge, behaviour, and attitudes of healthcare professionals to frailty assessment in emergency surgical admissions. METHODS: We designed a cross-sectional multicentre study developed by a multiprofessional team of surgeons, geriatricians, and supported by patients. A semi-structured survey examined attitudes and behaviours. Knowledge was assessed by comparing respondents' accuracy in scoring twenty-two surgical case vignettes using the Clinical Frailty Scale. RESULTS: Eleven hospitals across England, Wales, and Scotland participated. Two hundred and eleven clinicians responded-20.4% junior doctors, 43.6% middle grade doctors, 24.2% senior doctors, 11.4% nurses and physician associates. Respondents strongly supported perioperative frailty assessment. Most were already assessing for frailty, although frequently not using a standardised tool. There was a strong call for more frailty education. Participants scored 2175 vignettes with 55.4% accurately meeting the gold standard; accuracy improved to 87.3% when categorised into "not frail/mildly frail/severely frail" and 94% when dichotomised to "not frail/frail". CONCLUSION: Frailty assessment is well supported by healthcare professionals working in surgery. However, standardised tools are not routinely being used, and only half of respondents could accurately identify frailty. Better education around frailty assessment is needed for healthcare professionals working in surgery to improve perioperative pathway for people living with frailty.

Genome-wide association studies and Mendelian randomization analyses provide insights into the causes of early-onset colorectal cancer.

BACKGROUND: The incidence of early-onset colorectal cancer (EOCRC; diagnosed <50 years of age) is rising globally; however, the causes underlying this trend are largely unknown. CRC has strong genetic and environmental determinants, yet common genetic variants and causal modifiable risk factors underlying EOCRC are unknown. We conducted the first EOCRC-specific genome-wide association study (GWAS) and Mendelian randomization (MR) analyses to explore germline genetic and causal modifiable risk factors associated with EOCRC. PATIENTS AND METHODS: We conducted a GWAS meta-analysis of 6176 EOCRC cases and 65 829 controls from the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), the Colorectal Transdisciplinary Study (CORECT), the Colon Cancer Family Registry (CCFR), and the UK Biobank. We then used the EOCRC GWAS to investigate 28 modifiable risk factors using two-sample MR. RESULTS: We found two novel risk loci for EOCRC at 1p34.1 and 4p15.33, which were not previously associated with CRC risk. We identified a deleterious coding variant (rs36053993, G396D) at polyposis-associated DNA repair gene MUTYH (odds ratio 1.80, 95% confidence interval 1.47-2.22) but show that most of the common genetic susceptibility was from noncoding signals enriched in epigenetic markers present in gastrointestinal tract cells. We identified new EOCRC-susceptibility genes, and in addition to pathways such as transforming growth factor (TGF) ß, suppressor of Mothers Against Decapentaplegic (SMAD), bone morphogenetic protein (BMP) and phosphatidylinositol kinase (PI3K) signaling, our study highlights a role for insulin signaling and immune/infection-related pathways in EOCRC. In our MR analyses, we found novel evidence of probable causal associations for higher levels of body size and metabolic factors-such as body fat percentage, waist circumference, waist-to-hip ratio, basal metabolic rate, and fasting insulin-higher alcohol drinking, and lower education attainment with increased EOCRC risk. CONCLUSIONS: Our novel findings indicate inherited susceptibility to EOCRC and suggest modifiable lifestyle and metabolic targets that could also be used to risk-stratify individuals for personalized screening strategies or other interventions.

Role of the placenta in developmental programming: Observations from models using large animals.

Developmental programming, which proposes that "insults" or "stressors" during intrauterine or postnatal development can have not only immediate but also long-term consequences for healthy and productivity, has emerged as a major biological principle, and based on studies in many animal species also seems to be a universal phenomenon. In eutherians, the placenta appears to be programmed during its development, which has consequences for fetal growth and development throughout pregnancy, and likewise has long-term consequences for postnatal development, leading to programming of organ function of the offspring even into adulthood. This review summarizes our current understanding of the placenta's role in developmental programming, the mechanisms involved, and the challenges remaining.

Feasibility of individualised patient modelling for continuous vancomycin infusions in outpatient antimicrobial therapy, a retrospective study.

BACKGROUND: The area under the curve (AUC) to minimum inhibitory concentration (MIC) ratio is proposed as a therapeutic drug-monitoring parameter for dosing vancomycin continuous infusion in methicillin-resistant Staphylococcus aureus (MRSA) infection. Individualised pharmacokinetic-pharmacodynamic (PK/PD) calculation of AUC24 may better represent therapeutic dosing than current Therapeutic Drug Monitoring (TDM) practices, targeting a Steady State Concentration of 15-25 mg/L. AIM: To compare real world TDM practice to theoretical, individualised, PK/PD target parameters utilising Bayesian predictions to steady state concentrations (Css) for outpatients on continuous vancomycin infusions. METHOD: A retrospective single centre study was conducted at a tertiary hospital on adult patients, enrolled in an outpatient parenteral antimicrobial therapy (OPAT) program, receiving vancomycin infusions for MRSA infection. Retrospective Bayesian dosing was modelled to target PK/PD parameters and compared to real world data. RESULTS: Fifteen patients were evaluated with 53% (8/15) achieved target CSS during hospitalisation, and 83% (13/15) as outpatient. Median Bayesian AUC/MIC was 613 mg.h/L with CSS 25 mg/L. Patients suffering an Acute Kidney Injury (33%) had higher AUC0-24/MIC values. Retrospective Bayesian modelling demonstrated on median 250 mg/24 h lower doses than that administered was required (R2 = 0.81) which achieved AUC24/MIC median 444.8 (range 405-460) mg.h/L and CSS 18.8 (range 16.8-20.4) mg/L. CONCLUSION: Bayesian modelling could assist in obtaining more timely target parameters at lower doses for patients receiving continuous vancomycin infusion as part of an OPAT program, which may beget fewer adverse effects. Utilisation of personalised predictive modelling may optimise vancomycin prescribing, achieving earlier target concentrations as compared to empiric dosing regimens.

COVID-19 response in South African communities: Screening, testing, tracing and movement modelling.

In South Africa (SA), the first case of COVID-19 was reported on 5 March 2020 from a traveller who had returned from Italy. Increases in COVID-19 cases and deaths necessitated the design and implementation of community screening, testing, and tracing as a control strategy. The SA government's plans to implement community-based screening, testing, contact tracing and movement modelling during the early phases of the COVID-19 pandemic presented both opportunities and challenges. In this article, we present our experiences, opportunities and lessons for community-based COVID-19 response, anchoring these efforts in the primary healthcare system.

Need for caution when interpreting Xpert® MTB/RIF results for rifampin resistance among children.

BACKGROUND: Recommended by the World Health Organization as an initial diagnostic test for TB in children, Xpert® MTB/RIF is widely implemented in many countries, including Kenya.METHODS: Three hundred HIV-positive and negative children (<5 years) were enrolled in Kisumu County, Kenya, from October 2013 to August 2015. Multiple specimen types were collected from each child and tested using Xpert, liquid culture, and phenotypic drug susceptibility testing (DST). Samples positive for rifampin (RIF) resistance on Xpert were tested using line-probe assay and sequencing.RESULTS: Of 32 children with bacteriologically confirmed TB, 27 had positive Xpert results. Of these, 3/27 (11%, 95% CI 4-28) had RIF resistance detected on Xpert, but not by phenotypic DST, line-probe assay, or sequencing. For these three children, five Xpert tests showed RIF resistance; all five tests had semi-quantitative "very low" results and delay or absence of probe D signal, whereas no Xpert results with higher semi-quantitative results showed RIF resistance. All three children responded well to standard TB treatment.CONCLUSIONS: False RIF resistance may be detected in pediatric specimens. Further study is needed to determine if false RIF resistance is associated with low bacterial load.

The MOBILISE study: utilisation of ambulatory pumps in the inpatient setting to administer continuous antibiotic infusions-a randomised controlled trial.

In the inpatient setting, antibiotics are generally administered via bedside pumps with multiple daily dosing. Utilisation of a continuous antibiotic infusion (CAI) instead might have patient and nursing satisfaction, workflow efficiencies and infection control benefits. We aimed to study the utilisation of CAI in the inpatient setting for routine antibiotic administration. Patients receiving a peripherally inserted central venous catheter (PICC) for antibiotic administration were screened for the study. The patients were randomised to either (1) standard pump and intermittent antibiotic administration (IAA) or (2) CAI via an ambulatory pump. An accelerometer placed on the ankle was used to assess patient activity. Nursing and patient satisfaction surveys were also carried out. Forty patients met the study criteria for enrolment with 21 patients being enrolled in the CAI arm of the study. One hundred and five days of accelerometer recordings were available for analysis. The geometric mean activity was 45 min/day in the standard arm and 64 min/day in the CAI arm. This represented a 42% (95% CI: -14 to 133%, p = 0.16) difference in activity between the two groups. Nursing staff reported that they spent less time throughout their shift attending the antibiotic line or pump in patients who were in the CAI arm of the study (p < 0.001). In addition, patients in this arm of the study were more likely to recommend this method of administration of antibiotics to a family member (p =0.0001). The MOBILISE study showed nursing and patient satisfaction when CAI were utilised in the inpatient setting. A statistically non-significant difference in mobility was seen. The trial was registered (28/03/2018) with the Australia New Zealand Clinical Trials Registry (ACTRN12618000452291).

Asymptomatic COVID-19 in South Africa - implications for the control of transmission.

Asymptomatic COVID-19 may contribute significantly to the pandemic trajectory based on global biological, epidemiological and modelling evidence. A retrospective analysis was done to determine the proportion of asymptomatic COVID-19 in the workplace during the lockdown period from 27 March to 31 May 2020. We found that nearly 45% of cases were asymptomatic at the time of the first test. This high proportion of asymptomatic COVID-19 cases has implications for interventions, such as enforcing quarantine of all close contacts of COVID-19 cases regardless of symptoms.

Le COVID-19 a symptomatique pourrait contribuer significativement à la trajectoire de la pandémie en se basant sur des preuves mondiales, biologique et épidémiologiques, et en modélisant les preuves. Une analyse rétrospective a été réalisée afin de décrire la proportion d'infections asymptomatiques de SARS-CoV-2 parmi les clusters essentiels sur les lieux de travail en Afrique du Sud où des investigations de flambée ont été réalisées durant la période de confinement très restrictive du 27 mars au 31 mai 2020. Près de 45% des cas étaient asymptomatique lors du premier test. Cette proportion élevée des cas de COVID-19 asymptomatiques a des implications en ce qui concerne les interventions nonpharmaceutique comme le renforcement de la quarantaine de tous les contacts étroits des cas de SARS-CoV-2 sans tenir compte des symptômes.

PRL3 enhances T-cell acute lymphoblastic leukemia growth through suppressing T-cell signaling pathways and apoptosis.

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy of thymocytes and is largely driven by the NOTCH/MYC pathway. Yet, additional oncogenic drivers are required for transformation. Here, we identify protein tyrosine phosphatase type 4 A3 (PRL3) as a collaborating oncogenic driver in T-ALL. PRL3 is expressed in a large fraction of primary human T-ALLs and is commonly co-amplified with MYC. PRL3 also synergized with MYC to initiate early-onset ALL in transgenic zebrafish and was required for human T-ALL growth and maintenance. Mass-spectrometry phosphoproteomic analysis and mechanistic studies uncovered that PRL3 suppresses downstream T-cell phosphorylation signaling pathways, including those modulated by VAV1, and subsequently suppresses apoptosis in leukemia cells. Taken together, our studies have identified new roles for PRL3 as a collaborating oncogenic driver in human T-ALL and suggest that therapeutic targeting of the PRL3 phosphatase will likely be a useful treatment strategy for T-ALL.

Increased care at discharge from COVID-19: The association between pre-admission frailty and increased care needs after hospital discharge; a multicentre European observational cohort study.

BACKGROUND: The COVID-19 pandemic has placed significant pressure on health and social care. Survivors of COVID-19 may be left with substantial functional deficits requiring ongoing care. We aimed to determine whether pre-admission frailty was associated with increased care needs at discharge for patients admitted to hospital with COVID-19. METHODS: Patients were included if aged over 18 years old and admitted to hospital with COVID-19 between 27 February and 10 June 2020. The Clinical Frailty Scale (CFS) was used to assess pre-admission frailty status. Admission and discharge care levels were recorded. Data were analysed using a mixed-effects logistic regression adjusted for age, sex, smoking status, comorbidities, and admission CRP as a marker of severity of disease. RESULTS: Thirteen hospitals included patients: 1671 patients were screened, and 840 were excluded including, 521 patients who died before discharge (31.1%). Of the 831 patients who were discharged, the median age was 71 years (IQR, 58-81 years) and 369 (44.4%) were women. The median length of hospital stay was 12 days (IQR 6-24). Using the CFS, 438 (47.0%) were living with frailty (≥ CFS 5), and 193 (23.2%) required an increase in the level of care provided. Multivariable analysis showed that frailty was associated with an increase in care needs compared to patients without frailty (CFS 1-3). The adjusted odds ratios (aOR) were as follows: CFS 4, 1.99 (0.97-4.11); CFS 5, 3.77 (1.94-7.32); CFS 6, 4.04 (2.09-7.82); CFS 7, 2.16 (1.12-4.20); and CFS 8, 3.19 (1.06-9.56). CONCLUSIONS: Around a quarter of patients admitted with COVID-19 had increased care needs at discharge. Pre-admission frailty was strongly associated with the need for an increased level of care at discharge. Our results have implications for service planning and public health policy as well as a person's functional outcome, suggesting that frailty screening should be utilised for predictive modelling and early individualised discharge planning.

Intra-operative diabetes insipidus associated with cervical spine traction during staged scoliosis surgery.

A 15-year-old boy with cerebral palsy and epilepsy presented for a posterior spinal fusion as part of staged repair of thoracolumbar scoliosis. Total intravenous anaesthesia was induced and maintained with propofol, remifentanil and ketamine. Following prone positioning, cervical traction was applied. Polyuria developed intra-operatively, from 4 to 18 ml.kg-1.h-1. There was a corresponding rise in plasma sodium concentration from 132 to 145 mmol.l-1. Haemodynamic stability was maintained with boluses of Hartmann's solution and a noradrenaline infusion. Given the possibility of diabetes insipidus due to reduced cerebral perfusion pressure, the cervical traction was removed. This initially showed a good response with a transient reduction in polyuria to 3 ml.kg-1.h-1 before rising to 8 ml.kg-1.h-1. Subsequently, a vasopressin infusion was started with normalisation of diuresis and plasma sodium concentration by the end of surgery. Diabetes insipidus is an endocrine disorder related to lack of production or insensitivity to vasopressin. In the peri-operative period, it is mainly associated with pituitary surgery and rarely with spinal surgery. To the authors' knowledge, this is only the second report of diabetes insipidus associated with staged scoliosis surgery. Cervical traction should be considered as a potential cause of intra-operative diabetes insipidus.

Septic arthritis post anterior cruciate ligament reconstruction due to Clostridioides difficile.

Clostridioides difficile is an obligate anaerobe ubiquitous in the environment and is of particular interest in the healthcare setting as a cause of healthcare associated infection usually presenting with colitis. Extracolonic manifestations of C. difficile infection are less common with only rare reports of septic arthritis primarily in the setting of relative or overt immunocompromise. This report details the case of a 31-year-old immunocompetent male presenting with clinical features of septic arthritis, three weeks post right knee anterior cruciate ligament (ACL) reconstruction using a native hamstring tendon graft. C. difficile was isolated from two different samples of the synovial tissue from a subsequent arthroscopic washout and synovectomy. The ACL graft was retained. The isolate underwent whole genome sequencing and was found to be tcdA and tcdB gene deficient. Susceptibility testing showed susceptibility to benzylpenicillin and metronidazole. The patient received a two-week course of intravenous benzylpenicillin and four weeks of oral metronidazole. At one-year post cessation of antibiotics the patient has no clinical evidence of recurrence. This is the first known reported case of C. difficile septic arthritis in an immunocompetent patient. It demonstrates successful treatment of post-ACL septic arthritis with a graft retention strategy.

A multisectoral investigation of a neonatal unit outbreak of Klebsiella pneumoniae bacteraemia at a regional hospital in Gauteng Province, South Africa.

BACKGROUND: Rates of healthcare-associated infections (HAIs) among babies born in developing countries are higher than among those born in resource-rich countries, as a result of suboptimal infection prevention and control (IPC) practices. Following two reported deaths of neonates with carbapenem-resistant Klebsiella pneumoniae bloodstream infections (BSIs), we conducted an outbreak investigation in a neonatal unit of a regional hospital in Gauteng Province, South Africa. OBJECTIVES: To confirm an outbreak of K. pneumoniae BSIs and assess the IPC programme in the neonatal unit. METHODS: We calculated total and organism-specific BSI incidence risks for culture-confirmed cases in the neonatal unit for baseline and outbreak periods. We conducted a clinical record review for a subset of cases with K. pneumoniae BSI that had been reported to the investigating team by the neonatal unit. An IPC audit was performed in different areas of the neonatal unit. We confirmed species identification and antimicrobial susceptibility, and used polymerase chain reaction for confirmation of carbapenemase genes and pulsed-field gel electrophoresis (PFGE) for typing of submitted clinical isolates. RESULTS: From January 2017 to August 2018, 5 262 blood cultures were submitted, of which 11% (560/5 262) were positive. Of 560 positive blood cultures, 52% (n=292) were positive for pathogenic organisms associated with healthcare-associated BSIs. K. pneumoniae comprised the largest proportion of these cases (32%; 93/292). The total incidence risk of healthcare-associated BSI for the baseline period (January 2017 - March 2018) was 6.8 cases per 100 admissions, and that for the outbreak period (April - September 2018) was 10.1 cases per 100 admissions. The incidence risk of K. pneumoniae BSI for the baseline period was 1.6 cases per 100 admissions, compared with 5.0 cases per 100 admissions during the outbreak period. Average bed occupancy for the entire period was 118% (range 101 - 133%), that for the baseline period was 117%, and that for the outbreak period was 121%. In a subset of 12 neonates with K. pneumoniae bacteraemia, the median (interquartile range (IQR)) gestational age at birth was 27 (26 - 29) weeks, and the median (IQR) birth weight was 1 100 (880 - 1 425) g. Twelve bloodstream and 31 colonising K. pneumoniae isolates were OXA-48-positive. All isolates were genetically related by PFGE analysis (89% similarity). Inadequate IPC practices were noted, including suboptimal adherence to aseptic technique and hand hygiene (57% overall score in the neonatal intensive care unit), with poor monitoring and reporting of antimicrobial use (pharmacy score 55%). CONCLUSIONS: Overcrowding and inadequate IPC and antimicrobial stewardship contributed to a large outbreak of BSIs caused by genetically related carbapenemase-producing K. pneumoniae isolates in the neonatal unit.

Nosocomial COVID-19 infection: examining the risk of mortality. The COPE-Nosocomial Study (COVID in Older PEople).

BACKGROUND: Hospital admissions for non-coronavirus disease 2019 (COVID-19) pathology have decreased significantly. It is believed that this may be due to public anxiety about acquiring COVID-19 infection in hospital and the subsequent risk of mortality. AIM: To identify patients who acquire COVID-19 in hospital (nosocomial COVID-19 infection (NC)) and their risk of mortality compared to those with community-acquired COVID-19 (CAC) infection. METHODS: The COPE-Nosocomial Study was an observational cohort study. The primary outcome was the time to all-cause mortality (estimated with an adjusted hazard ratio (aHR)), and secondary outcomes were day 7 mortality and the time-to-discharge. A mixed-effects multivariable Cox's proportional hazards model was used, adjusted for demographics and comorbidities. FINDINGS: The study included 1564 patients from 10 hospital sites throughout the UK, and one in Italy, and collected outcomes on patients admitted up to April 28th, 2020. In all, 12.5% of COVID-19 infections were acquired in hospital; 425 (27.2%) patients with COVID died. The median survival time in NC patients was 14 days compared with 10 days in CAC patients. In the primary analysis, NC infection was associated with lower mortality rate (aHR: 0.71; 95% confidence interval (CI): 0.51-0.98). Secondary outcomes found no difference in day 7 mortality (adjusted odds ratio: 0.79; 95% CI: 0.47-1.31), but NC patients required longer time in hospital during convalescence (aHR: 0.49, 95% CI: 0.37-0.66). CONCLUSION: The minority of COVID-19 cases were the result of NC transmission. No COVID-19 infection comes without risk, but patients with NC had a lower risk of mortality compared to CAC infection; however, caution should be taken when interpreting this finding.

Herb species inclusion in grazing swards for dairy cows-A systematic review and meta-analysis.

A systematic review and meta-analysis were conducted to estimate the effect of herb species on milk production and urinary nitrogen (UN) excretion from grazing dairy cows. Grazing swards consisting of herb species grown with either a grass species or a grass and legume (multispecies swards) were compared with non-herb-containing swards consisting of a grass species grown as a monoculture or grass-legume swards (simple swards). A literature search was completed using the online databases CAB Direct, Web of Science, and Google Scholar, using the search strategy "dairy cow", "herb OR forb OR phorb", and "grazing". Milk production data, variance, and sample size were required for eligibility. In all, 116 studies were identified. Following eligibility screening, 11 papers from 6 journals, published between 2006 and 2018, were available for analysis. Studies were from New Zealand (N = 7), Australia (N = 3), and the United States (N = 1). The population was either Holstein Friesian or Holstein Friesian × Jersey dairy cows, with a range in mean daily milk yield (MY) from 12.1 kg to 34.7 kg (mean = 18.6 kg). A total of 25 comparisons were used for milk production analysis, with 324 and 284 cows included in multispecies and simple sward groups respectively. Data analysis was conducted in R using a random effects, robust variance estimation model (R Foundation for Statistical Computing, Vienna, Austria). Heterogeneity was reported using the I2 statistic. Milk production was significantly increased. Analysis of MY resulted in a weighted mean difference (WMD) of +1.20 kg/d (95% CI = 0.90, 1.49; I2 = 4%). Fat and protein kg were also significantly increased (WMD +0.06 kg/d; CI = 0.01, 0.11). Urinary nitrogen excretion was estimated from milk urea nitrogen when reported (n = 6). A WMD of -28.1 g of N/d (95% CI = -81.1, 24.9) was generated, with heterogeneity high among studies (I2 = 75%). This meta-analysis shows the potential benefits of multispecies swards. Although we saw no significant difference in UN excretion, an increase in milk production was found.

Using models to shape measles control and elimination strategies in low- and middle-income countries: A review of recent applications.

After many decades of vaccination, measles epidemiology varies greatly between and within countries. National immunization programs are therefore encouraged to conduct regular situation analyses and to leverage models to adapt interventions to local needs. Here, we review applications of models to develop locally tailored interventions to support control and elimination efforts. In general, statistical and semi-mechanistic transmission models can be used to synthesize information from vaccination coverage, measles incidence, demographic, and/or serological data, offering a means to estimate the spatial and age-specific distribution of measles susceptibility. These estimates complete the picture provided by vaccination coverage alone, by accounting for natural immunity. Dynamic transmission models can then be used to evaluate the relative impact of candidate interventions for measles control and elimination and the expected future epidemiology. In most countries, models predict substantial numbers of susceptible individuals outside the age range of routine vaccination, which affects outbreak risk and necessitates additional intervention to achieve elimination. More effective use of models to inform both vaccination program planning and evaluation requires the development of training to enhance broader understanding of models and where feasible, building capacity for modelling in-country, pipelines for rapid evaluation of model predictions using surveillance data, and clear protocols for incorporating model results into decision-making.

Varicella Related Hospital Admissions in Ireland

Aim The aim of this study was to evaluate trends in admissions for patients with primary varicella infection in Irish hospitals. Methods The Hospital Inpatient Enquiry System was evaluated from Irish hospitals from 2005-2016 for patients with primary varicella infection. Results There were 2717 admissions with primary varicella infection. The average annual number of admissions was 226 for an incidence of 4.87/100,000. Average length of stay (ALOS) was 5-days. Sixty-two (2.5%) patients required intensive-care with an ALOS of 26-days. The most common secondary diagnoses were cellulitis, volume-depletion and streptococcal infection. The number of admissions due to streptococcal infection and cellulitis significantly increased over the period. Conclusion Chickenpox places a consistent burden on Irish healthcare, accounting for in excess of 1100 acute and 160 intensivecare bed days annually. This study adds weight to the argument that universal varicella vaccine should be considered and provides baseline epidemiology to determine vaccine effectiveness in the future.

Slow Acceptance of Universal Antiretroviral Therapy (ART) Among Mothers Enrolled in IMPAACT PROMISE Studies Across the Globe.

The PROMISE trial enrolled asymptomatic HIV-infected pregnant and postpartum women not eligible for antiretroviral treatment (ART) per local guidelines and randomly assigned proven antiretroviral strategies to assess relative efficacy for perinatal prevention plus maternal/infant safety and maternal health. The START study subsequently demonstrated clear benefit in initiating ART regardless of CD4 count. Active PROMISE participants were informed of results and women not receiving ART were strongly recommended to immediately initiate treatment to optimize their own health. We recorded their decision and the primary reason given for accepting or rejecting the universal ART offer after receiving the START information. One-third of participants did not initiate ART after the initial session, wanting more time to consider. Six sessions were required to attain 95% uptake. The slow uptake of universal ART highlights the need to prepare individuals and sensitize communities regarding the personal and population benefits of the "Treat All" strategy.

Listeria Meningitis in an Immunocompetent Child: Case Report and Literature Review

We present a case of a 23 month-old boy presenting with fever, irritability and diarrhea who subsequently developed symptoms of photophobia and lethargy. Cerebrospinal fluid culture grew Listeria monocytogenes. Immunology investigations were normal. This patient had a complete and uncomplicated recovery. Listeria meningitis is a rare presentation in immunocompetent children, but should be considered in the setting of diarrhea, failure to respond to cephalosporin therapy, or suspected immunodeficiency.