Outcomes following acute poor-grade aneurysmal subarachnoid bleed - Is early definitive treatment better than delayed management?

BACKGROUND/OBJECTIVE: Patients with poor-grade subarachnoid bleed (World Federation of Neurosurgical Societies grades 4-5) often improve their neurocognitive function months after their ictus. However, it is essential to explore the timing of intervention and its impact on long-term outcome. We compared the long-term outcomes between immediate management within 24 h and delayed management after 24 h in patients following poor-grade subarachnoid bleed. METHODS: This was a retrospective population-based study, including patients with poor-grade subarachnoid bleed who received definitive management between 1 January 2011 and 31 December 2016 in a large tertiary neurocritical care unit. The primary outcome was adjusted odds ratio of favourable outcome (Glasgow Outcome Scale 4-5) for survivors at 12 months following discharge, as measured by the Glasgow Outcome Scale. The secondary outcomes included adjusted odds ratio of a favourable outcome at discharge, 3 months and 6 months following discharge and survival rate at 28 days, 3 months, 6 months and 12 months following haemorrhage. RESULTS: A total of 111 patients were included in this study: 53 (48%) received immediate management and 58 (52%) received delayed management. The mean time delay from referral to intervention was 14.9 ± 5.8 h in immediate management patients, compared to 79.6 ± 106.1 h in delayed management patients. At 12 months following discharge, the adjusted odds ratio for favourable outcome in immediate management versus delayed management patients was 0.96 (confidence interval (CI) = 0.17, 5.39; p = 0.961). At hospital discharge, 3 months and 6 months, the adjusted odds ratio for favourable outcome was 3.85 (CI = 1.38, 10.73; p = 0.010), 1.04 (CI = 0.22, 5.00; p = 0.956) and 0.98 (CI = 0.21, 4.58; p = 0.982), respectively. There were no differences in survival rate between the groups at 28 days, 3 months, 6 months and 12 months (71.7% in immediate management group vs. 82.8% in delayed management group at 12 months, p = 0.163). CONCLUSIONS: Immediate management and delayed management after poor-grade subarachnoid bleed are associated with similar morbidity and mortality at 12 months. Therefore, delaying intervention in poor-grade patients may be a reasonable approach, especially if time is needed to plan the procedure or stabilise the patient adequately.

Testing the efficacy and safety of BIO101, for the prevention of respiratory deterioration, in patients with COVID-19 pneumonia (COVA study): a structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: As of December, 1st, 2020, coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2, resulted in more than 1 472 917 deaths worldwide and death toll is still increasing exponentially. Many COVID-19 infected people are asymptomatic or experience moderate symptoms and recover without medical intervention. However, older people and those with comorbid hypertension, diabetes, obesity, or heart disease are at higher risk of mortality. Because current therapeutic options for COVID-19 patients are limited specifically for this elderly population at risk, Biophytis is developing BIO101 (20-hydroxyecdysone, a Mas receptor activator) as a new treatment option for managing patients with SARS-CoV-2 infection at the severe stage. The angiotensin converting enzyme 2 (ACE2) serves as a receptor for SARS-CoV-2. Interaction between ACE2 and SARS-CoV2 spike protein seems to alter the function of ACE2, a key player in the renin-angiotensin system (RAS). The clinical picture of COVID-19 includes acute respiratory distress syndrome (ARDS), cardiomyopathy, multiorgan dysfunction and shock, all of which might result from an imbalance of the RAS. We propose that RAS balance could be restored in COVID-19 patients through MasR activation downstream of ACE2 activity, with 20-hydroxyecdysone (BIO101) a non-peptidic Mas receptor (MasR) activator. Indeed, MasR activation by 20-hydroxyecdysone harbours anti-inflammatory, anti-thrombotic, and anti-fibrotic properties. BIO101, a 97% pharmaceutical grade 20-hydroxyecdysone could then offer a new therapeutic option by improving the respiratory function and ultimately promoting survival in COVID-19 patients that develop severe forms of this devastating disease. Therefore, the objective of this COVA study is to evaluate the safety and efficacy of BIO101, whose active principle is 20-hydroxyecdysone, in COVID-19 patients with severe pneumonia. TRIAL DESIGN: Randomized, double-blind, placebo-controlled, multi-centre, group sequential and adaptive which will be conducted in 2 parts. Part 1: Ascertain the safety and tolerability of BIO101 and obtain preliminary indication of the activity of BIO101, in preventing respiratory deterioration in the target population Part 2: Re-assessment of the sample size needed for the confirmatory part 2 and confirmation of the effect of BIO101 observed in part 1 in the target population. The study is designed as group sequential to allow an efficient run-through, from obtaining an early indication of activity to a final confirmation. And adaptive - to allow accumulation of early data and adapt sample size in part 2 in order to inform the final design of the confirmatory part of the trial. PARTICIPANTS: Inclusion criteria 1. Age: 45 and above 2. A confirmed diagnosis of COVID-19 infection, within the last 14 days, prior to randomization, as determined by PCR or other approved commercial or public health assay, in a specimen as specified by the test used. 3. Hospitalized, in observation or planned to be hospitalized due to COVID-19 infection symptoms with anticipated hospitalization duration ≥3 days 4. With evidence of pneumonia based on all of the following: a. Clinical findings on a physical examination b. Respiratory symptoms developed within the past 7 days 5. With evidence of respiratory decompensation that started not more than 4 days before start of study medication and present at screening, meeting one of the following criteria, as assessed by healthcare staff: a. Tachypnea: ≥25 breaths per minute b. Arterial oxygen saturation ≤92% c. A special note should be made if there is suspicion of COVID-19-related myocarditis or pericarditis, as the presence of these is a stratification criterion 6. Without a significant deterioration in liver function tests: a. ALT and AST ≤ 5x upper limit of normal (ULN) b. Gamma-glutamyl transferase (GGT) ≤ 5x ULN c. Total bilirubin ≤ 5×ULN 7. Willing to participate and able to sign an informed consent form (ICF). Or, when relevant, a legally authorized representative (LAR) might sign the ICF on behalf of the study participant 8. Female participants should be: at least 5 years post-menopausal (i.e., persistent amenorrhea 5 years in the absence of an alternative medical cause) or surgically sterile; OR a. Have a negative urine pregnancy test at screening b. Be willing to use a contraceptive method as outlined in inclusion criterion 9 from screening to 30 days after last dose. 9. Male participants who are sexually active with a female partner must agree to the use of an effective method of birth control throughout the study and until 3 months after the last administration of the investigational product. (Note: medically acceptable methods of contraception that may be used by the participant and/or partner include combined oral contraceptive, contraceptive vaginal ring, contraceptive injection, intrauterine device, etonogestrel implant, each supplemented with a condom, as well as sterilization and vasectomy). 10. Female participants who are lactating must agree not to breastfeed during the study and up to 14 days after the intervention. 11. Male participants must agree not to donate sperm for the purpose of reproduction throughout the study and until 3 months after the last administration of the investigational product. 12. For France only: Being affiliated with a European Social Security. Exclusion criteria 1. Not needing or not willing to remain in a healthcare facility during the study 2. Moribund condition (death likely in days) or not expected to survive for >7 days - due to other and non-COVID-19 related conditions 3. Participant on invasive mechanical ventilation via an endotracheal tube, or extracorporeal membrane oxygenation (ECMO), or high-flow Oxygen (delivery of oxygen at a flow of ≥16 L/min.). 4. Participant is not able to take medications by mouth (as capsules or as a powder, mixed in water). 5. Disallowed concomitant medication: Consumption of any herbal products containing 20-hydroxyecdysone and derived from Leuzea carthamoides; Cyanotis vaga or Cyanotis arachnoidea is not allowed (e.g. performance enhancing agents). 6. Any known hypersensitivity to any of the ingredients, or excipients of the study medication, BIO101. 7. Renal disease requiring dialysis, or known renal insufficiency (eGFR≤30 mL/min/1.73 m2, based on Cockcroft & Gault formula). 8. In France only: a. Non-affiliation to compulsory French social security scheme (beneficiary or right-holder). b. Being under tutelage or legal guardianship. Participants will be recruited from approximately 30 clinical centres in Belgium, France, the UK, USA and Brazil. Maximum patients' participation in the study will last 28 days. Follow-up of participants discharged from hospital will be performed through post-intervention phone calls at 14 (± 2) and 60 (± 4) days. INTERVENTION AND COMPARATOR: Two treatment arms will be tested in this study: interventional arm 350 mg b.i.d. of BIO101 (AP 20-hydroxyecdysone) and placebo comparator arm 350 mg b.i.d of placebo. Administration of daily dose is the same throughout the whole treatment period. Participants will receive the study medication while hospitalized for up to 28 days or until a clinical endpoint is reached (i.e., 'negative' or 'positive' event). Participants who are officially discharged from hospital care will no longer receive study medication. MAIN OUTCOMES: Primary study endpoint: The proportion of participants with 'negative' events up to 28 days. 'Negative' events are defined as respiratory deterioration and all-cause mortality. For the purpose of this study, respiratory deterioration will be defined as any of the following: Requiring mechanical ventilation (including cases that will not be intubated due to resource restrictions and triage). Requiring extracorporeal membrane oxygenation (ECMO). Requiring high-flow oxygen defined as delivery of oxygen at a flow of ≥16 L/min. Only if the primary endpoint is significant at the primary final analysis the following Key secondary endpoints will be tested in that order: Proportion of participants with events of respiratory failure at Day 28 Proportion of participants with 'positive' events at Day 28. Proportion of participants with events of all-cause mortality at Day 28 A 'positive' event is defined as the official discharge from hospital care by the department due to improvement in participant condition. Secondary and exploratory endpoints: In addition, a variety of functional measures and biomarkers (including the SpO2 / FiO2 ratio, viral load and markers related to inflammation, muscles, tissue and the RAS / MAS pathways) will also be collected. RANDOMIZATION: Randomization is performed using an IBM clinical development IWRS system during the baseline visit. Block-permuted randomization will be used to assign eligible participants in a 1:1 ratio. In part 1, randomization will be stratified by RAS pathway modulator use (yes/no) and co-morbidities (none vs. 1 and above). In Part 2, randomization will be stratified by centre, gender, RAS pathway modulator use (yes/no), co-morbidities (none vs. 1 and above), receiving Continuous Positive Airway Pressure/Bi-level Positive Airway Pressure (CPAP/BiPAP) at study entry (Yes/No) and suspicion of COVID-19 related myocarditis or pericarditis (present or not). BLINDING (MASKING): Participants, caregivers, and the study team assessing the outcomes are blinded to group assignment. All therapeutic units (TU), BIO101 b.i.d. or placebo b.i.d., cannot be distinguished in compliance with the double-blind process. An independent data-monitoring committee (DMC) will conduct 2 interim analyses. A first one based on the data from part 1 and a second from the data from parts 1 and 2. The first will inform about BIO101 safety, to allow the start of recruitment into part 2 followed by an analysis of the efficacydata, to obtain an indication of activity. The second interim analysis will inform about the sample size that will be required for part 2, in order to achieve adequate statistical power. Numbers to be randomised (sample size) Number of participants randomized: up to 465, in total Part 1: 50 (to obtain the proof of concept in COVID-19 patients). Part 2: 310, potentially increased by 50% (up to 465, based on interim analysis 2) (to confirm the effects of BIO101 observed in part 1). TRIAL STATUS: The current protocol Version is V 10.0, dated on 24.09.2020. The recruitment that started on September 1st 2020 is ongoing and is anticipated to finish for the whole study by March2021. TRIAL REGISTRATION: The trial was registered before trial start in trial registries: EudraCT , No. 2020-001498-63, registered May 18, 2020; and Clinicaltrials.gov, identifier NCT04472728 , registered July 15, 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Study protocol for a multicenter prospective cohort study on esophagogastric anastomoses and anastomotic leak (the Oesophago-Gastric Anastomosis Audit/OGAA).

Esophagectomy is a mainstay in curative treatment for esophageal cancer; however, the reported techniques and outcomes can vary greatly. Thirty-day mortality of patients with an intact anastomosis is 2-3% as compared to 17-35% in patients who have an anastomotic leak. The subsequent management of leaks postesophagectomy has great global variability with little consensus on a gold standard of practice. The aim of this multicentre prospective audit is to analyze current techniques of esophagogastric anastomosis to determine the effect on the anastomotic leak rate. Leak rates and leak management will be assessed to determine their impact on patient outcomes. A 12-month international multicentre prospective audit started in April 2018 and is coordinated by a team from the West Midlands Research Collaborative. This will include patients undergoing esophagectomy over 9 months and encompassing a 90-day follow-up period. A pilot data collection period occurred at four UK centers in 2017 to trial the data collection form. The audit standards will include anastomotic leak and the conduit necrosis rate should be less than 13% and major postoperative morbidity (Clavien-Dindo Grade III or more) should be less than 35%. The 30-day mortality rate should be less than 5% and the 90-day mortality rate should be less than 8%. This will be a trainee-led international audit of esophagectomy practice. Key support will be given by consultant colleagues and anesthetists. Individualized unit data will be distributed to the respective contributing sites. An overall anonymized report will be made available to contributing units. Results of the audit will be published in peer-reviewed journals with all collaborators fully acknowledged. The key information and results from the audit will be disseminated at relevant scientific meetings.

The weekend effect in status epilepticus: a national cohort study.

Higher mortality following admission to hospital at the weekend has been reported for several conditions. It is unclear whether this variation is due to differences in patients or their care. Status epilepticus mandates hospital admission and usually critical care: its study might provide new insights into the nature of any weekend effect. We studied 20,922 adults admitted to UK critical care with status epilepticus from 2010 to 2015. We used multiple logistic regression to evaluate the association between weekend admission and in-hospital mortality, comparing university hospitals with other hospitals. There were 2462 in-hospital deaths (12%). There was no difference in mortality after weekend admission to university hospitals, adjusted odds ratio (95%CI) 0.99 (0.84-1.16), p = 0.89. Mortality was less after weekend admission than after admissions Monday to Friday in hospitals not associated with a university, adjusted odds ratio (95%CI) 0.74 (0.64-0.87), p = 0.0001. There is no evidence that adults admitted to UK critical care at the weekend in status epilepticus are more likely to die than similar patients admitted during the week.

Guidelines for the safe practice of total intravenous anaesthesia (TIVA): Joint Guidelines from the Association of Anaesthetists and the Society for Intravenous Anaesthesia.

Guidelines are presented for safe practice in the use of intravenous drug infusions for general anaesthesia. When maintenance of general anaesthesia is by intravenous infusion, this is referred to as total intravenous anaesthesia. Although total intravenous anaesthesia has advantages for some patients, the commonest technique used for maintenance of anaesthesia in the UK and Ireland remains the administration of an inhaled volatile anaesthetic. However, the use of an inhalational technique is sometimes not possible, and in some situations, inhalational anaesthesia is contraindicated. Therefore, all anaesthetists should be able to deliver total intravenous anaesthesia competently and safely. For the purposes of simplicity, these guidelines will use the term total intravenous anaesthesia but also encompass techniques involving a combination of intravenous infusion and inhalational anaesthesia. This document is intended as a guideline for safe practice when total intravenous anaesthesia is being used, and not as a review of the pros and cons of total intravenous anaesthesia vs. inhalational anaesthesia in situations where both techniques are possible.

Natural Enemy Abundance in Southeastern Blueberry Agroecosystems: Distance to Edge and Impact of Management Practices.

Natural enemies are valuable components of agroecosystems as they provide biological control services to help regulate pest populations. Promoting biocontrol services can improve sustainability by decreasing pesticide usage, which is a major challenge for the blueberry industry. Our research is the first to compare natural enemy populations in managed (conventional and organic) and unmanaged blueberry systems, in addition to the effects of non-crop habitat. We conducted our study in 10 blueberry orchards during the growing season across the major blueberry producing counties in Georgia, United States. To estimate the spatial distribution of natural enemies, we conducted suction sampling at three locations in each orchard: within the forested border, along the edge of blueberry orchard adjacent to forested border, and within the interior of the blueberry orchard. Natural enemies maintained higher abundance over the season in unmanaged areas when compared with organic or conventional production systems. In the conventional orchards, natural enemies were more abundant in the surrounding non-crop area compared with the interior of the orchard. Populations were more evenly distributed in less intensive systems (organic and unmanaged). Our results indicate spatial structure in natural enemy populations is related to management practice, and less intensive management can retain higher abundance of natural enemies in blueberry systems. Considerations must be made towards promoting ecologically based management practices to sustain natural enemy populations and potentially increase the delivery of biological control services.

Early enteral nutrition in critically ill patients: ESICM clinical practice guidelines

PURPOSE: To provide evidence-based guidelines for early enteral nutrition (EEN) during critical illness. METHODS: We aimed to compare EEN vs. early parenteral nutrition (PN) and vs. delayed EN. We defined "early" EN as EN started within 48 h independent of type or amount. We listed, a priori, conditions in which EN is often delayed, and performed systematic reviews in 24 such subtopics. If sufficient evidence was available, we performed meta-analyses; if not, we qualitatively summarized the evidence and based our recommendations on expert opinion. We used the GRADE approach for guideline development. The final recommendations were compiled via Delphi rounds. RESULTS: We formulated 17 recommendations favouring initiation of EEN and seven recommendations favouring delaying EN. We performed five meta-analyses: in unselected critically ill patients, and specifically in traumatic brain injury, severe acute pancreatitis, gastrointestinal (GI) surgery and abdominal trauma. EEN reduced infectious complications in unselected critically ill patients, in patients with severe acute pancreatitis, and after GI surgery. We did not detect any evidence of superiority for early PN or delayed EN over EEN. All recommendations are weak because of the low quality of evidence, with several based only on expert opinion. CONCLUSIONS: We suggest using EEN in the majority of critically ill under certain precautions. In the absence of evidence, we suggest delaying EN in critically ill patients with uncontrolled shock, uncontrolled hypoxaemia and acidosis, uncontrolled upper GI bleeding, gastric aspirate >500 ml/6 h, bowel ischaemia, bowel obstruction, abdominal compartment syndrome, and high-output fistula without distal feeding access.

Limonene in exhaled breath is elevated in hepatic encephalopathy.

Breath samples were taken from 31 patients with liver disease and 30 controls in a clinical setting and proton transfer reaction quadrupole mass spectrometry (PTR-Quad-MS) used to measure the concentration of volatile organic compounds (VOCs). All patients had cirrhosis of various etiologies, with some also suffering from hepatocellular cancer (HCC) and/or hepatic encephalopathy (HE). Breath limonene was higher in patients with No-HCC than with HCC, median (lower/upper quartile) 14.2 (7.2/60.1) versus 3.6 (2.0/13.7) and 1.5 (1.1/2.3) nmol mol-1 in controls. This may reflect disease severity, as those with No-HCC had significantly higher UKELD (United Kingdom model for End stage Liver Disease) scores. Patients with HE were categorized as having HE symptoms presently, having a history but no current symptoms and having neither history nor current symptoms. Breath limonene in these groups was median (lower/upper quartile) 46.0 (14.0/103), 4.2 (2.6/6.4) and 7.2 (2.0/19.1) nmol mol-1, respectively. The higher concentration of limonene in those with current symptoms of HE than with a history but no current symptoms cannot be explained by disease severity as their UKELD scores were not significantly different. Longitudinal data from two patients admitted to hospital with HE show a large intra-subject variation in breath limonene, median (range) 18 (10-44) and 42 (32-58) nmol mol-1.

Elimination characteristics of post-operative isoflurane levels in alveolar exhaled breath via PTR-MS analysis.

Isoflurane (1-chloro-2,2,2-trifluoroethyl difluoromethyl ether), C3H2ClF5O, is a commonly used inhalation anaesthetic. Using a proton transfer reaction mass spectrometer (PTR-MS) we have detected isoflurane in the breath of patients several weeks following major surgery. That isoflurane is detected in the breath of patients so long after being anaesthetised raises questions about when cognitive function has fully returned to a patient. Temporal profiles of isoflurane concentrations in breath are presented for five patients (F/M 3/2, mean age 50 years, min-max 36-58 years) who had undergone liver transplant surgery. In addition, results from a headspace analysis of isoflurane are presented so that the product ions resulting from the reactions of H3O+ with isoflurane in PTR-MS could be easily identified in the absence of the complex chemical environment of breath. Six product ions were identified. In order of increasing m/z (using the 35Cl isotope where appropriate) these are [Formula: see text] (m/z 51), CHFCl+ (m/z 67), CF3CHCl+ (m/z 117), C3F4OCl+ (m/z 163), C3H2F4OCl+ (m/z 165), and C3F4OCl+ H2O (m/z 183). No protonated parent was detected. For the headspace study both clean air and CO2 enriched clean air (4% CO2) were used as buffer gases in the drift tube of the PTR-MS. The CO2 enriched air was used to determine if exhaled breath would affect the product ion branching ratios. Importantly no significant differences were observed, and therefore for isoflurane the product ion distributions determined in a normal air mixture can be used for breath analysis. Given that PTR-MS can be operated under different reduced electric fields (E/N), the dependence of the product ion branching percentages for isoflurane on E/N (96-138 Td) are reported.

The impact of the acute respiratory distress syndrome on outcome after oesophagectomy.

BACKGROUND: The Acute Respiratory Distress Syndrome (ARDS) is a serious complication of major surgery and consumes substantial healthcare resources. Oesophagectomy is associated with high rates of ARDS. The aim of this study was to characterize patients and identify risk factors for developing ARDS after oesophagectomy. METHODS: A secondary analysis of data from 331 patients gathered during the Beta Agonists Lung Injury Prevention Trial was undertaken. Characteristics and outcomes of patients with early (first 72 h postoperatively) and late (after 72 h) ARDS were determined. Linear and multivariate regression analysis was used to study the differences between early and late ARDS and identify risk factors. RESULTS: ARDS was associated with more non-respiratory organ failure (early 44.1%, late 75.0%, no ARDS 27.6% P<0.001), longer ICU stay (mean early 12.1, late 20.2, no ARDS 7.3 days P<0.001) and longer hospital stay (mean early 18.1, late 24.5, no ARDS 14.2 days P<0.001) but no difference in mortality or quality of life. Older patients (OR 1.06 (1.00 to 1.13), P=0.045) and those with mid-oesophageal tumours (OR 7.48 (1.62-34.5), P=0.010) had a higher risk for ARDS. CONCLUSIONS: Early and late ARDS after oesophagectomy increases intensive care and hospital length of stay. Given the high incidence of ARDS, cohorts of patients undergoing oesophagectomy may be useful as models for studies investigating ARDS prevention and treatment. Further investigations aimed at reducing perioperative ARDS are warranted.

Volatile Biomarkers in Breath Associated With Liver Cirrhosis - Comparisons of Pre- and Post-liver Transplant Breath Samples.

BACKGROUND: The burden of liver disease in the UK has risen dramatically and there is a need for improved diagnostics. AIMS: To determine which breath volatiles are associated with the cirrhotic liver and hence diagnostically useful. METHODS: A two-stage biomarker discovery procedure was used. Alveolar breath samples of 31 patients with cirrhosis and 30 healthy controls were mass spectrometrically analysed and compared (stage 1). 12 of these patients had their breath analysed after liver transplant (stage 2). Five patients were followed longitudinally as in-patients in the post-transplant period. RESULTS: Seven volatiles were elevated in the breath of patients versus controls. Of these, five showed statistically significant decrease post-transplant: limonene, methanol, 2-pentanone, 2-butanone and carbon disulfide. On an individual basis limonene has the best diagnostic capability (the area under a receiver operating characteristic curve (AUROC) is 0.91), but this is improved by combining methanol, 2-pentanone and limonene (AUROC curve 0.95). Following transplant, limonene shows wash-out characteristics. CONCLUSIONS: Limonene, methanol and 2-pentanone are breath markers for a cirrhotic liver. This study raises the potential to investigate these volatiles as markers for early-stage liver disease. By monitoring the wash-out of limonene following transplant, graft liver function can be non-invasively assessed.

Central venous catheter-related bloodstream infections: improving post-insertion catheter care.

Patients with central venous catheters (CVCs) are at increased risk of bloodstream infections and sepsis-related death. CVC-related bloodstream infections (CRBSIs) are costly and account for a significant proportion of hospital-acquired infections. The aim of this audit was to assess current practice and staff knowledge of CVC post-insertion care and therefore identify aspects of CVC care with potential for improvement. We conducted a prospective audit over 28 consecutive days at a university teaching hospital investigating current practice of CVC post-insertion care in wards with high CVC usage. A multiple choice questionnaire on best practice of CVC insertion and care was distributed among clinical staff. Rates of breaches in catheter care and CRBSIs were calculated and statistical significance assumed when P<0.05. Data was recorded from 151 CVCs in 106 patients giving a total of 721 catheter days. In all, 323 breaches in care were identified giving a failure rate of 44.8%, with significant differences between intensive care unit (ICU) and non-ICU wards (P<0.001). Dressings (not intact) and caps and taps (incorrectly placed) were identified as the major lapses in CVC care with 158 and 156 breaches per 1000 catheter days, respectively. During the study period four CRBSIs were identified, producing a CRBSI rate of 5.5 per 1000 catheter days (95% confidence interval: 0.12-10.97). There are several opportunities to improve CVC post-insertion care. Future interventions to improve reliability of care should focus on implementing best practice rather than further education.