Peri-operative cardiac arrest: epidemiology and clinical features of patients analysed in the 7th National Audit Project of the Royal College of Anaesthetists.

The 7th National Audit Project of the Royal College of Anaesthetists studied peri-operative cardiac arrest in the UK, a topic of importance to patients, anaesthetists and surgeons. Here we report the results of the 12-month registry, from 16 June 2021 to 15 June 2022, focusing on epidemiology and clinical features. We reviewed 881 cases of peri-operative cardiac arrest, giving an incidence of 3 in 10,000 anaesthetics (95%CI 3.0-3.5 per 10,000). Incidence varied with patient and surgical factors. Compared with denominator survey activity, patients with cardiac arrest: included more males (56% vs. 42%); were older (median (IQR) age 60.5 (40.5-80.5) vs. 50.5 (30.5-70.5) y), although the age distribution was bimodal, with infants and patients aged > 66 y overrepresented; and were notably more comorbid (73% ASA physical status 3-5 vs. 27% ASA physical status 1-2). The surgical case-mix included more weekend (14% vs. 11%), out-of-hours (19% vs. 10%), non-elective (65% vs. 30%) and major/complex cases (60% vs. 28%). Cardiac arrest was most prevalent in orthopaedic trauma (12%), lower gastrointestinal surgery (10%), cardiac surgery (9%), vascular surgery (8%) and interventional cardiology (6%). Specialities with the highest proportion of cases relative to denominator activity were: cardiac surgery (9% vs. 1%); cardiology (8% vs. 1%); and vascular surgery (8% vs. 2%). The most common causes of cardiac arrest were: major haemorrhage (17%); bradyarrhythmia (9%); and cardiac ischaemia (7%). Patient factors were judged a key cause of cardiac arrest in 82% of cases, anaesthesia in 40% and surgery in 35%.

The incidence of potentially serious complications during non-obstetric anaesthetic practice in the United Kingdom: an analysis from the 7th National Audit Project (NAP7) activity survey.

Complications and critical incidents arising during anaesthesia due to patient, surgical or anaesthetic factors, may cause harm themselves or progress to more severe events, including cardiac arrest or death. As part of the 7th National Audit Project of the Royal College of Anaesthetists, we studied a prospective national cohort of unselected patients. Anaesthetists recorded anonymous details of all cases undertaken over 4 days at their site through an online survey. Of 416 hospital sites invited to participate, 352 (85%) completed the survey. Among 24,172 cases, 1922 discrete potentially serious complications were reported during 1337 (6%) cases. Obstetric cases had a high reported major haemorrhage rate and were excluded from further analysis. Of 20,996 non-obstetric cases, 1705 complications were reported during 1150 (5%) cases. Circulatory events accounted for most complications (616, 36%), followed by airway (418, 25%), metabolic (264, 15%), breathing (259, 15%), and neurological (41, 2%) events. A single complication was reported in 851 (4%) cases, two complications in 166 (1%) cases and three or more complications in 133 (1%) cases. In non-obstetric elective surgery, all complications were 'uncommon' (10-100 per 10,000 cases). Emergency (urgent and immediate priority) surgery accounted for 3454 (16%) of non-obstetric cases but 714 (42%) of complications with severe hypotension, major haemorrhage, severe arrhythmias, septic shock, significant acidosis and electrolyte disturbances all being 'common' (100-1000 per 10,000 cases). Based on univariate analysis, complications were associated with: younger age; higher ASA physical status; male sex; increased frailty; urgency and extent of surgery; day of the week; and time of day. These data represent the rates of potentially serious complications during routine anaesthesia care and may be valuable for risk assessment and patient consent.

Peri-operative cardiac arrest: management and outcomes of patients analysed in the 7th National Audit Project of the Royal College of Anaesthetists.

The 7th National Audit Project of the Royal College of Anaesthetists studied peri-operative cardiac arrest in the UK, a topic of importance to patients, anaesthetists and surgeons. We report the results of the 12-month registry phase, from 16 June 2021 to 15 June 2022, focusing on management and outcomes. Among 881 cases of peri-operative cardiac arrest, the initial rhythm was non-shockable in 723 (82%) cases, most commonly pulseless electrical activity. There were 665 (75%) patients who survived the initial event and 384 (52%) who survived to hospital discharge. A favourable functional outcome (based on modified Rankin Scale score) was reported for 249 (88%) survivors. Outcomes varied according to arrest rhythm. The highest rates of survival were seen for bradycardic cardiac arrests with 111 (86%) patients surviving the initial event and 77 (60%) patients surviving the hospital episode. The lowest survival rates were seen for patients with pulseless electrical activity, with 312 (68%) surviving the initial episode and 156 (34%) surviving to hospital discharge. Survival to hospital discharge was worse in patients at the extremes of age with 76 (40%) patients aged > 75 y and 9 (45%) neonates surviving. Hospital survival was also associated with surgical priority, with 175 (88%) elective patients and 176 (37%) non-elective patients surviving to discharge. Outcomes varied with the cause of cardiac arrest, with lower initial survival rates for pulmonary embolism (5, 31%) and bone cement implantation syndrome (9, 45%), and hospital survival of < 25% for pulmonary embolism (0), septic shock (13, 24%) and significant hyperkalaemia (1, 20%). Overall care was rated good in 464 (53%) cases, and 18 (2%) cases had overall care rated as poor. Poor care elements were present in a further 245 (28%) cases. Care before cardiac arrest was the phase most frequently rated as poor (92, 11%) with elements of poor care identified in another 186 (21%) cases. These results describe the management and outcomes of peri-operative cardiac arrest in UK practice for the first time.

The 7th National Audit Project (NAP7) baseline survey of individual anaesthetists: preparedness for and experiences of peri-operative cardiac arrest.

The Royal College of Anaesthetists' 7th National Audit Project baseline survey assessed knowledge, attitudes, practices and experiences of peri-operative cardiac arrests among UK anaesthetists and Anaesthesia Associates. We received 10,746 responses, representing a 71% response rate. In-date training in adult and paediatric advanced life support was reported by 9646 (90%) and 7125 (66%) anaesthetists, respectively. There were 8994 (84%) respondents who were confident in leading a peri-operative cardiac arrest, with males more confident than females, but only 5985 (56%) were confident in leading a debrief and 7340 (68%) communicating with next of kin. In the previous two years, 4806 (46%) respondents had managed at least one peri-operative cardiac arrest, of which 321 (7%) and 189 (4%) of these events involved a child or an obstetric patient, respectively. Respondents estimated the most common causes of peri-operative cardiac arrest to be hypovolaemia, hypoxaemia and cardiac ischaemia, with haemorrhage coming fifth. However, the most common reported causes for the most recently attended peri-operative cardiac arrest were haemorrhage; (927, 20%); anaphylaxis (474, 10%); and cardiac ischaemia (397, 9%). Operating lists or shifts were paused or stopped after 1330 (39%) cardiac arrests and 1693 (38%) respondents attended a debrief, with 'hot' debriefs most common. Informal wellbeing support was relatively common (2458, 56%) and formal support was uncommon (472, 11%). An impact on future care delivery was reported by 196 (4%) anaesthetists, most commonly a negative psychological impact. Management of a peri-operative cardiac arrest during their career was reported by 8654 (85%) respondents. The overall impact on professional life was more often judged positive (2630, 30%) than negative (1961, 23%), but impact on personal life was more often negative.

Organisation of UK hospitals and anaesthetic departments in the treatment of peri-operative cardiac arrest: an analysis from the 7th National Audit Project (NAP7) local co-ordinator baseline survey.

We report the results of the Royal College of Anaesthetists' 7th National Audit Project organisational baseline survey sent to every NHS anaesthetic department in the UK to assess preparedness for treating peri-operative cardiac arrest. We received 199 responses from 277 UK anaesthetic departments, representing a 72% response rate. Adult and paediatric anaesthetic care was provided by 188 (95%) and 165 (84%) hospitals, respectively. There was no paediatric intensive care unit on-site in 144 (87%) hospitals caring for children, meaning transfer of critically ill children is required. Remote site anaesthesia is provided in 182 (92%) departments. There was a departmental resuscitation lead in 113 (58%) departments, wellbeing lead in 106 (54%) and departmental staff wellbeing policy in 81 (42%). A defibrillator was present in every operating theatre suite and in all paediatric anaesthesia locations in 193 (99%) and 149 (97%) departments, respectively. Advanced airway equipment was not available in: every theatre suite in 13 (7%) departments; all remote locations in 103 (57%) departments; and all paediatric anaesthesia locations in 23 (15%) departments. Anaesthetic rooms were the default location for induction of anaesthesia in adults and children in 148 (79%) and 121 (79%) departments, respectively. Annual updates in chest compressions and in defibrillation were available in 149 (76%) and 130 (67%) departments, respectively. Following a peri-operative cardiac arrest, debriefing and peer support programmes were available in 154 (79%) and 57 (29%) departments, respectively. While it is likely many UK hospitals are very well prepared to treat anaesthetic emergencies including cardiac arrest, the survey suggests this is not universal.

Patient characteristics, anaesthetic workload and techniques in the UK: an analysis from the 7th National Audit Project (NAP7) activity survey.

Detailed contemporary knowledge of the characteristics of the surgical population, national anaesthetic workload, anaesthetic techniques and behaviours are essential to monitor productivity, inform policy and direct research themes. Every 3-4 years, the Royal College of Anaesthetists, as part of its National Audit Projects (NAP), performs a snapshot activity survey in all UK hospitals delivering anaesthesia, collecting patient-level encounter data from all cases under the care of an anaesthetist. During November 2021, as part of NAP7, anaesthetists recorded details of all cases undertaken over 4 days at their site through an online survey capturing anonymous patient characteristics and anaesthetic details. Of 416 hospital sites invited to participate, 352 (85%) completed the activity survey. From these, 24,177 reports were returned, of which 24,172 (99%) were included in the final dataset. The work patterns by day of the week, time of day and surgical specialty were similar to previous NAP activity surveys. However, in non-obstetric patients, between NAP5 (2013) and NAP7 (2021) activity surveys, the estimated median age of patients increased by 2.3 years from median (IQR) of 50.5 (28.4-69.1) to 52.8 (32.1-69.2) years. The median (IQR) BMI increased from 24.9 (21.5-29.5) to 26.7 (22.3-31.7) kg.m-2 . The proportion of patients who scored as ASA physical status 1 decreased from 37% in NAP5 to 24% in NAP7. The use of total intravenous anaesthesia increased from 8% of general anaesthesia cases to 26% between NAP5 and NAP7. Some changes may reflect the impact of the COVID-19 pandemic on the anaesthetic population, though patients with confirmed COVID-19 accounted for only 149 (1%) cases. These data show a rising burden of age, obesity and comorbidity in patients requiring anaesthesia care, likely to impact UK peri-operative services significantly.

Heat ameliorative measures in Murrah buffalo (Bubalus bubalis) heifers during summer: effect on microclimate, thermal comfort, and behavior.

Water buffalo (Bubalus bubalis) is the mainstay of milk production in Asian countries including India. However, the hot climate of the country remains the biggest bottleneck to exploit the potential of this species. Therefore, a study was conducted to assess the effect of heat ameliorative measures on microclimate, thermal comfort, and behavior of Murrah buffalo heifers during summer. Buffalo heifers (n = 24) between the age of 15 and 20 months with a mean body weight of 363.75 ± 11.27 kg were randomly grouped into four treatments based on their age and body weight. The heifers kept in the shed without any cooling served as CON (control), while the animals of group CJ were tied with a cooling jacket. The buffalo heifers of the CJF group were subjected to the cooling jacket with forced air ventilation, whereas the intermittent (10 min at 2-h intervals) sprinkling followed by forced air ventilation was practiced in group SF between 900 and 1800 h throughout the experiment. The microclimatic variables were low in the sheds of groups CJ, CJF, and SF than the CON. The physiological responses such as rectal temperature, skin temperature, respiration rate, and pulse rate were reduced in groups CJ, CJF, and SF than the CON at 1400 h. The serum cortisol was less in the CJF and SF than those of CON group. The animals of the CJ, CJF, and SF groups spent more time for feeding and rumination with less frequent longer bouts. The extended periods of lying followed by shorter standing and idling were observed in groups CJ, CJF, and SF when compared with the CON. It may be therefore concluded that cooling jacket and intermittent sprinkling in combination with forced air ventilation might be helpful in improving the micro-environment, thermal comfort, and behavior of buffalo heifers particularly under tropical climates during summer.

Methods of the 7th National Audit Project (NAP7) of the Royal College of Anaesthetists: peri-operative cardiac arrest.

Cardiac arrest in the peri-operative period is rare but associated with significant morbidity and mortality. Current reporting systems do not capture many such events, so there is an incomplete understanding of incidence and outcomes. As peri-operative cardiac arrest is rare, many hospitals may only see a small number of cases over long periods, and anaesthetists may not be involved in such cases for years. Therefore, a large-scale prospective cohort is needed to gain a deep understanding of events leading up to cardiac arrest, management of the arrest itself and patient outcomes. Consequently, the Royal College of Anaesthetists chose peri-operative cardiac arrest as the 7th National Audit Project topic. The study was open to all UK hospitals offering anaesthetic services and had a three-part design. First, baseline surveys of all anaesthetic departments and anaesthetists in the UK, examining respondents' prior peri-operative cardiac arrest experience, resuscitation training and local departmental preparedness. Second, an activity survey to record anonymised details of all anaesthetic activity in each site over 4 days, enabling national estimates of annual anaesthetic activity, complexity and complication rates. Third, a case registry of all instances of peri-operative cardiac arrest in the UK, reported confidentially and anonymously, over 1 year starting 16 June 2021, followed by expert review using a structured process to minimise bias. The definition of peri-operative cardiac arrest was the delivery of five or more chest compressions and/or defibrillation in a patient having a procedure under the care of an anaesthetist. The peri-operative period began with the World Health Organization 'sign-in' checklist or first hands-on contact with the patient and ended either 24 h after the patient handover (e.g. to the recovery room or intensive care unit) or at discharge if this occured earlier than 24 h. These components described the epidemiology of peri-operative cardiac arrest in the UK and provide a basis for developing guidelines and interventional studies.

Microclimate modification in Murrah buffalo (Bubalus bubalis) heifers during summer: Effect on intake, growth and hematobiochemistry.

The present investigation evaluated the effect of microclimate modification on feed intake, growth performance, and hemato-biochemical profile of Murrah buffalo (Bubalus bubalis) heifers during summer. Twenty-four buffalo heifers, between 15 and 20 months of age with an average body weight of 363.75 ± 11.27 kg, were randomly assigned to 4 groups based on their age and body weight. The heifers of the T0 (control) group were kept under the shed without any cooling treatment, while the animals in group T1 were tied with a cooling jacket. Buffalo heifers of group T2 were subjected to a cooling jacket with forced ventilation and animals in group T3 were treated with intermittent sprinkling (10 min., at 2 h intervals) and forced ventilation between 9.00 AM and 6.00 PM during the experiment. The ambient temperature inside the shed and core body temperature were reduced in groups T1, T2, and T3 compared to T0. Heifers had higher dry matter intake when subjected to cooling treatments T1, T2, and T3, whereas water intake was reduced in T2 and T3 groups. The animals in T2 and T3 groups attained higher average daily weight gain, while the feed conversion was better in the T3 group compared to T0. The hematological measures such as hemoglobin, total erythrocyte count, and total leucocyte count were found higher in T0. The serum glucose, sodium, and potassium levels increasedand alkaline phosphatase activity decreased in groups T1, T2 and T3 when compared with T0. It can be concluded that the provision of intermittent sprinkling and cooling jacket in combination with forced ventilation could improve the microclimate, which in turn could enhance the performance of Murrah heifers during hot summer days in the tropics.

Factors influencing water intake in dairy cows: a review.

Water is a very critical nutrient in the diet of lactating animals as it performs several functions, viz., transfer of nutrients and excretions of waste products produced during metabolism, digestion, and body temperature regulation of all living organisms. Besides growth, other parameters like milk production, reproduction, adaptive potential, and feed consumption are also influenced by water status in feed and body reserves. Water intake in dairy cows is influenced directly or indirectly by several factors; direct factors include animal-related factors such as breed, body size, physiological stage, age, health, stress, and ecological adaptations and environmental factors, viz., season of the year, environmental temperature, humidity, wind speed, and precipitation. These factors significantly influence the drinking water intake of dairy cows. Nonetheless, different managemental practices such as rearing type, feeding practices, housing, water availability, and its quality can also affect water intake indirectly. However, overall understanding of these factors affecting water intake in dairy cows could help to improve the dairy husbandry practices and subsequently health, production, and welfare of dairy cows.

Short-term effect of foot-and-mouth disease (FMD) vaccination on the milk yield in the Deoni and crossbred cows.

Biannual vaccination of the cattle with inactivated foot-and-mouth disease (FMD) vaccine is the control strategy in endemic countries. Reduction in the milk yield is one of the main reasons for poor compliance of the cattle owners to FMD vaccination. As it can adversely affect the herd immunity, the present study aimed to quantify the losses in the milk yield post-FMD vaccination. Retrospective data on the milk yield (kg) recordings, days in milk, parity, and age at vaccination of the Deoni and crossbred cows were collected from 10 days before (-10) to 10 days after (+10) FMD vaccination (dpv). Days in milk were categorized into three stages of lactation for Deoni and crossbred cows. Age (month) was categorized into four classes. Least squares means of the milk yield were generated after adjusting for year, age, parity, and stage of lactation. Based on exploratory data analysis, the corrected milk yield records from -2 to +2 dpv for 5 years comprising 614 data points on Deoni cows (n=54) and 488 data points on crossbred cows (n=55) were used for the final analysis. Because of the correlated errors on the corrected milk yield, linear mixed model ANOVA was done by fitting dpv as fixed effect and cow as random effect, and the results revealed the effect of dpv was non-significant (P>0.05) in either breed. With respect to dpv 0, a marginal reduction of 90 g in the corrected milk yield in the Deoni cow was recorded on dpv 1, while the reduction was about 360 g on dpv 0 as compared dpv -1 in the crossbred cow. It was concluded that FMD vaccination caused a transient non-significant reduction in the milk yield in the Deoni and crossbred cows.

Developing classification criteria for skin-predominant dermatomyositis: the Delphi process.

BACKGROUND: The European League Against Rheumatism/American College of Rheumatology classification criteria for inflammatory myopathies are able to classify patients with skin-predominant dermatomyositis (DM). However, approximately 25% of patients with skin-predominant DM do not meet two of the three hallmark skin signs and fail to meet the criteria. OBJECTIVES: To develop a set of skin-focused classification criteria that will distinguish cutaneous DM from mimickers and allow a more inclusive definition of skin-predominant disease. METHODS: An extensive literature review was done to generate items for the Delphi process. Items were grouped into categories of distribution, morphology, symptoms, antibodies, histology and contextual factors. Using REDCap™, participants rated these items in terms of appropriateness and distinguishing ability from mimickers. The relevance score ranged from 1 to 100, and the median score determined a rank-ordered list. A prespecified median score cut-off was decided by the steering committee and the participants. There was a pre-Delphi and two rounds of actual Delphi. RESULTS: There were 50 participating dermatologists and rheumatologists from North America, South America, Europe and Asia. After a cut-off score of 70 during the first round, 37 of the initial 54 items were retained and carried over to the next round. The cut-off was raised to 80 during round two and a list of 25 items was generated. CONCLUSIONS: This project is a key step in the development of prospectively validated classification criteria that will create a more inclusive population of patients with DM for clinical research. What's already known about this topic? Proper classification of patients with skin-predominant dermatomyositis (DM) is indispensable in the appropriate conduct of clinical/translational research in the field. The only validated European League Against Rheumatism/American College of Rheumatology criteria for idiopathic inflammatory myopathies are able to classify skin-predominant DM. However, a quarter of amyopathic patients still fail the criteria and does not meet the disease classification. What does this study add? A list of 25 potential criteria divided into categories of distribution, morphology, symptomatology, pathology and contextual factors has been generated after several rounds of consensus exercise among experts in the field of DM. This Delphi project is a prerequisite to the development of a validated classification criteria set for skin-predominant DM.

Variation in esophageal anastomosis technique-the role of collaborative learning.

Centralization of care has improved outcomes in esophagogastric (EG) cancer surgery. However, specialist surgical centers often work within clinical silos, with little transfer of knowledge and experience. Although variation exists in multiple dimensions of perioperative care, the differences in operative technique are rarely studied. An esophageal anastomosis workshop was held to identify areas of common and differing practice within the operative technique. Surgeons showed videos of their anastomosis technique by open and minimally invasive surgery. Each video was followed by a discussion. Surgeons from 10 different EG cancer centers attended. Eight key technical differences and learning points were identified and discussed: the optimum diameter of the gastric conduit; avoiding ischemia in the gastric conduit; minimizing esophageal trauma; the use of an esophageal mucosal collar; omental wrapping; intraoperative leak testing; ideal diameter of the circular stapler and the growing use of linear stapled anastomoses. The workshop received positive feedback from participants and on 2 years follow-up, 40% stated that they believed that the learning of tips and techniques during the workshop has contributed to lowering their anastomotic leak rate. Many differences exist in surgical technique. The reasons for, and crucially the significance of, these differences must be discussed and examined. Workshops provide a forum for peer-to-peer collaborative learning to reflect on one's own practice and improve surgical technique. These changes can, in turn, generate incremental improvements in patient care and postoperative outcomes.

Three-Dimensional-Printed Electrochemical Sensor for Simultaneous Dual Monitoring of Serotonin Overflow and Circular Muscle Contraction.

Serotonin (5-HT) is a key signaling molecule within the mucosal epithelium of the intestinal wall and has been shown to be an important modulator of motility. At present, no single approach has been established for simultaneous dual measurement of 5-HT overflow and circular muscle contraction. We developed a 3D-printed carbon black/polylactic acid (PLA) electrochemical sensor, which had a geometry suitable for ex vivo measurement in the anorectum. The device was characterized for sensitivity and stability for 5-HT measurements as well as suitability for accurate tracking of anorectal contractions. The 3D-printed electrochemical sensor had a linear range in physiological concentrations of 5-HT (1-10 µM) present within the intestinal tract and a limit of detection of 540 nM. The sensor was stable for 5-HT measurement following ex vivo tissue measurements. There was a signficant correlation in the amplitude and duration of individual contractions when comparing the measurements using an isometric force transducer and 3D-printed electrochemical sensor. Finally, in the presence of 1 µM fluoxetine, the sensor was able to monitor a reduction in contractility as well as an increase in 5-HT overflow as predicted. Overall, the 3D-printed sensor has the ability to conduct dual simultaneous measurements of 5-HT overflow and contractility. This single device will have significant potential for clinical measurements of anorectum function and signaling that can direct therapeutic management of patients with bowel disorders.

Evaluation of the reliability and validity of the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) in paediatric cutaneous lupus among paediatric dermatologists and rheumatologists.

BACKGROUND: The Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) is a reliable outcome measure for cutaneous lupus erythematosus (CLE) in adults used in clinical trials. However, it has not been validated in children, limiting clinical trials for paediatric CLE. OBJECTIVES: This study aimed to validate the CLASI in paediatrics. METHODS: Eleven paediatric patients with CLE, six dermatologists and six rheumatologists participated. The physicians were trained to use the CLASI and Physician's Global Assessment (PGA), and individually rated all patients using both tools. Each physician reassessed two randomly selected patients. Within each physician group, the intraclass correlation coefficient (ICC) was calculated to assess the reliability of each measure. RESULTS: CLASI activity scores demonstrated excellent inter- and intrarater reliability (ICC > 0·90), while the PGA activity scores had good inter-rater reliability (ICC 0·73-0·77) among both specialties. PGA activity scores showed excellent (ICC 0·89) and good intrarater reliability (ICC 0·76) for dermatologists and rheumatologists, respectively. Limitations of this study include the small sample size of patients and potential recall bias during the physician rerating session. CONCLUSIONS: CLASI activity measurement showed excellent inter- and intrarater reliability in paediatric CLE and superiority over the PGA. These results demonstrate that the CLASI is a reliable and valid outcome instrument for paediatric CLE.

Outbreak report of investigation and control of an outbreak of Panton-Valentine Leukocidin-positive methicillin-sensitive Staphylococcus aureus (PVL-MSSA) infection in neonates and mothers.

BACKGROUND: In January 2011, there was an outbreak of Panton-Valentine Leukocidin-positive methicillin-sensitive Staphylococcus aureus (PVL-MSSA) infection in a neonatal unit (NNU). We describe the investigation and control of an outbreak of PVL-MSSA infection in neonates. SETTING: Neonatal unit in West London. METHODS: We performed descriptive and analytical (case-control study) epidemiological investigations. Microbiological investigations including screening of MSSA isolates by PCR for the presence of the luk-PV, mecA and mecC genes and comparison of isolate with Pulsed field gel electrophoresis (PFGE). Control measures were also introduced. RESULTS: Sixteen babies were infected/colonised with the outbreak strain. Of these, one baby developed blood stream infection, 12 developed skin pustules and four babies were colonised. Four mothers developed breast abscesses. Eighty-seven babies in the unit were screened and 16 were found to have same PVL-MSSA strain (spa type t005, belonging to MLST clonal complex 22). Multivariate analysis showed gestational age was significantly lower in cases compared to controls (mean gestational age: 31.7 weeks v 35.6 weeks; P = 0.006). Length of stay was significantly greater for cases, with a median of 25 days, compared to only 6 days for controls (P = 0.01). Most (88%) cases were born through caesarean section, compared to less than half of controls. (P = 0.002). No healthcare worker carriers and environmental source was identified. The outbreak was controlled by stopping new admissions to unit and reinforcing infection control precautions. The outbreak lasted for seven weeks. No further cases were reported in the following year. CONCLUSIONS: Infection control teams have to be vigilant for rising prevalence of particular S. aureus clones in their local community as they may cause outbreaks in vulnerable populations in healthcare settings such as NNUs.

First-in-human study of LY3039478, an oral Notch signaling inhibitor in advanced or metastatic cancer.

Background: Deregulated Notch signaling due to mutation or overexpression of ligands and/or receptors is implicated in various human malignancies. γ-Secretase inhibitors inhibit Notch signaling by preventing cleavage of transmembrane domain of Notch protein. LY3039478 is a novel, potent Notch inhibitor decreases Notch signaling and its downstream biologic effects. In this first-in-human study, we report the safety, pharmacokinetic (PK) profile, pharmacodynamic effects, and antitumor activity of LY3039478 in patients with advanced or metastatic cancer. Methods: This phase I, open-label, multicenter, nonrandomized, and dose-escalation phase study determined and confirmed the recommended phase II dose of LY3039478 (oral dose: 2.5-100 mg, thrice weekly (TIW) on a 28-day cycle). The primary objectives are to determine (part A) and confirm (part B) a recommended phase II dose that may be safely administered to patients with advanced or metastatic cancer, and secondary objectives include evaluation of safety, tolerability, PK parameters, and preliminary antitumor activity of LY3039478. Results: A total of 110 patients were treated with LY3039478 monotherapy between 31 October 2012 and 15 July 2016. Dose-limiting toxicities were thrombocytopenia, colitis, and nausea. Most adverse events were gastrointestinal. The recommended phase II dose was 50 mg TIW, because of its better tolerability compared with 75 mg. The PKs of LY3039478 appeared dose proportional. Pharmacodynamic data indicate an ∼80% inhibition of plasma Aß, and >50% inhibition of Notch-regulated genes hairy and enhancer of split-1, cyclin D1, and Notch-regulated ankyrin repeat at 45-100-mg dose. Clinical activity (tumor necrosis, metabolic response, or tumor shrinkage) was observed in patients with breast cancer, leiomyosarcoma, and adenoid cystic carcinoma. Conclusion: Potent inhibition of Notch signaling by LY3039478 was well tolerated at doses associated with target engagement, and demonstrated evidence of clinical activity in heavily pretreated patients. Further investigation with LY3039478 as monotherapy and in combination with targeted agent or chemotherapy is ongoing. Clinicaltrials.gov ID: NCT01695005.

The American Orthopaedic Association's Own the Bone® database: a national quality improvement project for the treatment of bone health in fragility fracture patients.

The American Orthopaedic Association initiated the Own the Bone (OTB) quality improvement program in 2009. Herein we show that the data collected through this program is similar to that collected in other large studies. Thus, the OTB registry functions as an externally valid cohort for studying fragility fracture patients. INTRODUCTION: The American Orthopedic Association initiated the Own the Bone (OTB) quality improvement program in 2009 to improve secondary prevention of fragility fractures. In this study, we present a summary of the data collected by the OTB program and compare it to data from other large fragility fracture registries with an aim to externally validate the OTB registry. METHODS: The OTB registry contained 35,038 unique cases of fragility fracture as of September, 2016. We report the demographics, presenting fracture characteristics, past fracture history, and bone mineral density (BMD) data and compare these to data from large fragility fracture studies across the world. RESULTS: Seventy-three percent of the patients in the OTB registry were female, Caucasian, and post-menopausal. In 54.4% of cases, patients had a hip fracture; spine fractures were the second most common fracture type occurring in 11.1% of patients. Thirty-four percent of the patients had a past history of fragility fracture, and the most common sites were the spine and hip. The average femoral neck T-score was - 2.06. When compared to other studies, the OTB database showed similar findings with regard to patient age, gender, race, BMI, BMD profile, prior fracture history, and family history of fragility fractures. CONCLUSION: OTB is the first and largest multi-center voluntary fragility fracture registry in the USA. The data collected through the OTB program is comparable to that collected in international studies. Thus, the OTB registry functions as an externally valid cohort for further studies assessing the clinical characteristics, interventions, and outcomes achieved in patients who present with a fragility fracture in the USA.

Lenalidomide as a novel therapy for gastrointestinal angiodysplasia in von Willebrand disease.

INTRODUCTION: Lenalidomide is a thalidomide analog with anti-angiogenic properties. Previous case reports suggest its efficacy in preventing gastrointestinal bleeding (GIB) secondary to angiodysplasia (AD) in hereditary haemorrhagic telangiectasia and potentially in reversing AD. We present the first case series to explore lenalidomide as a treatment for AD-related GIB in patients with von Willebrand disease (VWD). METHODS: A retrospective chart review was conducted to include patients with VWD, who were evaluated from 2010 to 2013 and who had received lenalidomide to treat recurrent GIB secondary to AD. All patients had failed single-agent use of antifibrinolytic agents. Patients were observed for at least 2 years on therapy. RESULTS: Five patients (3 males; 68.2 ± 4.9 years) with VWD (3 with type 3 and 1 each with types 1 and 2a) and AD were found. Sites of AD included the stomach, duodenum, jejunum and colon. Lenalidomide was started at 5 mg oral daily. Uptitration to 10 and 15 mg in 1 patient each was necessary due to recurrence of GIB. The mean number of endoscopies performed for control of GIB post lenalidomide was significantly lower compared to pretherapy (0.25 vs 5.50; P = .001). Mean bleed-free duration on lenalidomide was 12.6 ± 4.7 months. Three patients have reported no GIB on lenalidomide. CONCLUSION: This case series demonstrates significantly reduced number of endoscopies and increased bleed-free duration with lenalidomide treatment in selected patients with VWD and recurrent GIB from AD. Prospective multicenter trials are needed to further define the role of lenalidomide in the management of GIB from angiodysplasia and VWD.

Prospective Risk Factor Analysis for the Development of Post-operative Urinary Retention Following Ambulatory General Surgery.

AIMS: Post-operative urinary retention (POUR) is a common cause of unplanned admission following day-case surgery and has negative effects on both patient and surgical institution. We aimed to prospectively evaluate potential risk factors for the development of POUR following day-case general surgical procedures. METHODS: Over a 24-week period, consecutive adult patients undergoing elective day-case general surgery at a single institution were prospectively recruited. Data regarding urinary symptoms, comorbidities, drug history, surgery and perioperative anaesthetic drug use were collected. The primary outcome was the incidence of POUR, defined as an impairment of bladder voiding requiring either urethral catheterisation, unplanned overnight admission or both. Potential risk factors for the development of POUR were analysed by logistic regression. RESULTS: A total of 458 patients met the inclusion criteria during the study period, and data were collected on 382 (83%) patients (74.3% male). Sixteen patients (4.2%) experienced POUR. Unadjusted analysis demonstrated three significant risk factors for the development of POUR: age ≥ 56 years (OR 7.77 [2.18-27.78], p = 0.002), laparoscopic surgery (OR 3.37 [1.03-12.10], p = 0.044) and glycopyrrolate administration (OR 5.56 [2.00-15.46], p = 0.001). Male sex and lower urinary tract symptoms were not significant factors. Multivariate analysis combining type of surgery, age and glycopyrrolate use revealed that only age ≥ 56 years (OR 8.14 [2.18-30.32], p = 0.0018) and glycopyrrolate administration (OR 3.48 [1.08-11.24], p = 0.0370) were independently associated with POUR. CONCLUSIONS: Patients aged at least 56 years and/or requiring glycopyrrolate-often administered during laparoscopic procedures-are at increased risk of POUR following ambulatory general surgery.