Applying the antecedent, behaviour, and consequence taxonomy to unintentional firearm injury as determined by a collaborative firearm injury database.

BACKGROUND: Unintentional firearm injury (UFI) remains a significant problem in the USA with respect to preventable injury and death. The antecedent, behaviour and consequence (ABC) taxonomy has been used by law enforcement agencies to evaluate unintentional firearm discharge. Using an adapted ABC taxonomy, we sought to categorise civilian UFI in our community to identify modifiable behaviours. METHODS: Using a collaborative firearm injury database (containing both a university-based level 1 trauma registry and a metropolitan law enforcement database), all UFIs from August 2008 through December 2021 were identified. Perceived threat (antecedent), behaviour and injured party (consequence) were identified for each incident. RESULTS: During the study period, 937 incidents of UFI were identified with 64.2% of incidents occurring during routine firearm tasks. 30.4% of UFI occurred during neglectful firearm behaviour such as inappropriate storage. Most injuries occurred under situations of low perceived threat. UFI involving children was most often due to inappropriate storage of weapons, while cleaning a firearm was the most common behaviour in adults. Overall, 16.5% of UFI involved injury to persons other than the one handling the weapon and approximately 1.3% of UFI resulted in mortality. CONCLUSIONS: The majority of UFI occurred during routine and expected firearm tasks such as firearm cleaning. Prevention programmes should not overlook these modifiable behaviours in an effort to reduce UFIs, complications and deaths.

A complex ePrescribing antimicrobial stewardship-based (ePAMS+) intervention for hospitals: mixed-methods feasibility trial results.

BACKGROUND: Antibiotic resistant infections cause over 700,000 deaths worldwide annually. As antimicrobial stewardship (AMS) helps minimise the emergence of antibiotic resistance resulting from inappropriate use of antibiotics in healthcare, we developed ePAMS+ (ePrescribing-based Anti-Microbial Stewardship), an ePrescribing and Medicines Administration (EPMA) system decision-support tool complemented by educational, behavioural and organisational elements. METHODS: We conducted a non-randomised before-and-after feasibility trial, implementing ePAMS+ in two English hospitals using the Cerner Millennium EPMA system. Wards of several specialties were included. Patient participants were blinded to whether ePAMS+ was in use; prescribers were not. A mixed-methods evaluation aimed to establish: acceptability and usability of ePAMS+ and trial processes; feasibility of ePAMS+ implementation and quantitative outcome recording; and a Fidelity Index measuring the extent to which ePAMS+ was delivered as intended. Longitudinal semi-structured interviews of doctors, nurses and pharmacists, alongside non-participant observations, gathered qualitative data; we extracted quantitative prescribing data from the EPMA system. Normal linear modelling of the defined daily dose (DDD) of antibiotic per admission quantified its variability, to inform sample size calculations for a future trial of ePAMS+ effectiveness. RESULTS: The research took place during the SARS-CoV-2 pandemic, from April 2021 to November 2022. 60 qualitative interviews were conducted (33 before ePAMS+ implementation, 27 after). 1,958 admissions (1,358 before ePAMS+ implementation; 600 after) included 24,884 antibiotic orders. Qualitative interviews confirmed that some aspects of ePAMS+ , its implementation and training were acceptable, while other features (e.g. enabling combinations of antibiotics to be prescribed) required further development. ePAMS+ uptake was low (28 antibiotic review records from 600 admissions; 0.047 records per admission), preventing full development of a Fidelity Index. Normal linear modelling of antibiotic DDD per admission showed a residual variance of 1.086 (log-transformed scale). Unavailability of indication data prevented measurement of some outcomes (e.g. number of antibiotic courses per indication). CONCLUSIONS: This feasibility trial encountered unforeseen circumstances due to contextual factors and a global pandemic, highlighting the need for careful adaptation of complex intervention implementations to the local setting. We identified key refinements to ePAMS+ to support its wider adoption in clinical practice, requiring further piloting before a confirmatory effectiveness trial. TRIAL REGISTRATION: ISRCTN Registry ISRCTN13429325, 24 March 2022.

What Happens on Call Doesn't Stay on Call. The Effects of In-house Call on Acute Care Surgeons' Sleep and Burnout: Results of the Surgeon Performance (SuPer) Trial.

OBJECTIVE: We sought to quantify the effects of in-house call(IHC) on sleep patterns and burnout among acute care surgeons (ACS). BACKGROUND: Many ACS take INC, which leads to disrupted sleep and high levels of stress and burnout. METHODS: Physiological and survey data of 224 ACS with IHC were collected over 6 months. Participants continuously wore a physiological tracking device and responded to daily electronic surveys. Daily surveys captured work and life events as well as feelings of restfulness and burnout. The Maslach Burnout Inventory (MBI) was administered at the beginning and end of the study period. RESULTS: Physiological data were recorded for 34,135 days, which includes 4389 nights of IHC. Feelings of moderate, very, or extreme burnout occurred 25.7% of days and feelings of being moderately, slightly, or not at all rested occurred 75.91% of days. Decreased amount of time since the last IHC, reduced sleep duration, being on call, and having a bad outcome all contribute to greater feelings of daily burnout ( P <0.001). Decreased time since last call also exacerbates the negative effect of IHC on burnout ( P <0.01). CONCLUSIONS: ACS exhibit lower quality and reduced amount of sleep compared with an age-matched population. Furthermore, reduced sleep and decreased time since the last call led to increased feelings of daily burnout, accumulating in emotional exhaustion as measured on the MBI. A reevaluation of IHC requirements and patterns as well as identification of countermeasures to restore homeostatic wellness in ACS is essential to protect and optimize our workforce.

Does acute kidney injury alerting improve patient outcomes?

BACKGROUND: Electronic alerts (e-alerts) for Acute Kidney Injury (AKI) have been implemented into a variety of different Electronic Health Records (EHR) systems worldwide in order to improve recognition and encourage early appropriate management of AKI. We were interested in the impact on patient safety, specialist referral and clinical management. METHODS: All patients admitted to our institution with AKI were included in the study. We studied AKI progression, dialysis dependency, length of hospital stay, emergency readmission, ICU readmission, and death, before and after the introduction of electronic alerts. The impact on prescription of high risk drugs, fluid administration, and referral to renal services was also analysed. RESULTS: After the introduction of the e-alert, progression to higher AKI stage, emergency readmission to hospital and death during admission were significantly reduced. More prescriptions were stopped for drugs that adversely affect renal function in AKI and there was a significant increase in the ICU admissions and in the number of patients having dialysis, especially in earlier stages. Longer term mortality, renal referrals, and fluid alteration did not change significantly after the AKI e-alert introduction. CONCLUSIONS: AKI e-alerts can improve clinical outcomes in hospitalised patients.

Sustainable medicines use in clinical practice: A clinical pharmacological view on eco-pharmaco-stewardship.

Climate change continues to pose a dangerous threat to human health. However, not only is health impacted by this crisis, healthcare itself adds to the problem, through significant contributions to greenhouse gas emissions. In the UK, the National Health Service (NHS) is responsible for an estimated 4% of the overall national carbon footprint. Medicines account for a quarter of this and whilst they are vital for health now, through sustainable use they can also positively influence the environmental health of the future. In this review, we explore how clinical pharmacologists and other health care professionals can practice sustainable medicines use or eco-pharmaco-stewardship. We will discuss current and near future environmental practices within the NHS, which we suspect will resonate with other health systems. We will suggest approaches for championing eco-pharmaco-stewardship in drug manufacturing, clinical practice and patient use, to achieve a more a sustainable healthcare system.

Coping with COVID: Preparing prescribers during the pandemic.

In response to the COVID-19 pandemic, Health Education England (HEE) and the University of Birmingham provided National Health Service (NHS) staff free access to SCRIPT, a national eLearning programme for safer prescribing and therapeutics. The eLearning was particularly for those returning to work or being redeployed. In the year March 2020-21, 3412 users registered to access portfolios and opened an aggregate of 17 198 modules. Each user completed a median of 2 (range 1-50, interquartile range [IQR] 1-7) assessed learning modules. Marks improved from pre-test to post-test by a median of 2 (IQR 0-3) marks out of 10. The most frequently selected modules were Adherence and Concordance (1109 users), Fluids (981 users) and Diabetic Emergencies (818 users). A total of 878 users accessed the unassessed COVID-19 module. The SCRIPT modules provided standardised education in core principles relating to prescribing and therapeutics, and were used by professionals from many healthcare disciplines.

Assessment of Discharge Analgesic Prescription Patterns for Hospitalized Patients With Rib Fractures.

INTRODUCTION: There is a paucity of data describing opioid prescribing patterns for trauma patients. We investigated pain medication regimens prescribed at discharge for patients with traumatic rib fractures, as well as potential variables predictive of opioid prescribing. METHODS: A single-center, retrospective analysis was performed of 337 adult patients presenting with ≥1 traumatic rib fractures between January and December 2019. The primary outcome was oral morphine milligram equivalents (MME) prescribed on discharge. A multivariable logistic regression analysis was performed to determine factors independently associated with above median (150) MME prescription at discharge. RESULTS: The majority of patients were male (68.8%) with a median age of 53 y. Blunt trauma accounted for 97.3% of cases with a median Injury Severity Score(ISS) of 10. Locoregional pain procedures were utilized in 16.9% of patients. Opioids were the most common analgesic prescribed at discharge, and 74.1% of patients prescribed opioids on discharge were also prescribed a non-opioid adjunct. On multivariable analysis, daily MME prescribed during hospitalization (OR 1.01, 95% CI 1.01-1.02, P < 0.01) and number of rib fractures (OR 2.26, 95% CI 1.36-3.74, P < 0.01) were predictive of high MME prescribed on discharge. CONCLUSIONS: For patients with traumatic rib fractures, daily MME during hospitalization and number of rib fractures were predictive of high MME prescribing on discharge. Further prospective studies evaluating strategies for pain management and protocolized approaches to opioid prescribing are needed to reduce unnecessary and inappropriate opioid use in this patient population.

Effectiveness of clinical decision support in controlling inappropriate red blood cell and platelet transfusions, speciality specific responses and behavioural change.

BACKGROUND: Electronic clinical decision support (CDS) within Electronic Health Records has been used to improve patient safety, including reducing unnecessary blood product transfusions. We assessed the effectiveness of CDS in controlling inappropriate red blood cell (RBC) and platelet transfusion in a large acute hospital and how speciality specific behaviours changed in response. METHODS: We used segmented linear regression of interrupted time series models to analyse the instantaneous and long term effect of introducing blood product electronic warnings to prescribers. We studied the impact on transfusions for patients in critical care (CC), haematology/oncology (HO) and elsewhere. RESULTS: In non-CC or HO, there was significant and sustained decrease in the numbers of RBC transfusions after introduction of alerts. In CC the alerts reduced transfusions but this was not sustained, and in HO there was no impact on RBC transfusion. For platelet transfusions outside of CC and HO, the introduction of alerts stopped a rising trend of administration of platelets above recommended targets. In CC, alerts reduced platelet transfusions, but in HO alerts had little impact on clinician prescribing. CONCLUSION: The findings suggest that CDS can result in immediate change in user behaviour which is more obvious outside specialist settings of CC and HO. It is important that this is then sustained. In CC and HO, blood transfusion practices differ. CDS thus needs to take specific circumstances into account. In this case there are acceptable reasons to transfuse outside of these crude targets and CDS should take these into account.

Harmonizing and improving European education in prescribing: An overview of digital educational resources used in clinical pharmacology and therapeutics.

AIM: Improvement and harmonization of European clinical pharmacology and therapeutics (CPT) education is urgently required. Because digital educational resources can be easily shared, adapted to local situations and re-used widely across a variety of educational systems, they may be ideally suited for this purpose. METHODS: With a cross-sectional survey among principal CPT teachers in 279 out of 304 European medical schools, an overview and classification of digital resources was compiled. RESULTS: Teachers from 95 (34%) medical schools in 26 of 28 EU countries responded, 66 (70%) of whom used digital educational resources in their CPT curriculum. A total of 89 of such resources were described in detail, including e-learning (24%), simulators to teach pharmacokinetics and/or pharmacodynamics (10%), virtual patients (8%), and serious games (5%). Together, these resources covered 235 knowledge-based learning objectives, 88 skills, and 13 attitudes. Only one third (27) of the resources were in-part or totally free and only two were licensed open educational resources (free to use, distribute and adapt). A narrative overview of the largest, free and most novel resources is given. CONCLUSION: Digital educational resources, ranging from e-learning to virtual patients and games, are widely used for CPT education in EU medical schools. Learning objectives are based largely on knowledge rather than skills or attitudes. This may be improved by including more real-life clinical case scenarios. Moreover, the majority of resources are neither free nor open. Therefore, with a view to harmonizing international CPT education, more needs to be learned about why CPT teachers are not currently sharing their educational materials.

EurOP2E - the European Open Platform for Prescribing Education, a consensus study among clinical pharmacology and therapeutics teachers.

PURPOSE: Sharing and developing digital educational resources and open educational resources has been proposed as a way to harmonize and improve clinical pharmacology and therapeutics (CPT) education in European medical schools. Previous research, however, has shown that there are barriers to the adoption and implementation of open educational resources. The aim of this study was to determine perceived opportunities and barriers to the use and creation of open educational resources among European CPT teachers and possible solutions for these barriers. METHODS: CPT teachers of British and EU medical schools completed an online survey. Opportunities and challenges were identified by thematic analyses and subsequently discussed in an international consensus meeting. RESULTS: Data from 99 CPT teachers from 95 medical schools were analysed. Thirty teachers (30.3%) shared or collaboratively produced digital educational resources. All teachers foresaw opportunities in the more active use of open educational resources, including improving the quality of their teaching. The challenges reported were language barriers, local differences, lack of time, technological issues, difficulties with quality management, and copyright restrictions. Practical solutions for these challenges were discussed and include a peer review system, clear indexing, and use of copyright licenses that permit adaptation of resources. CONCLUSION: Key challenges to making greater use of CPT open educational resources are a limited applicability of such resources due to language and local differences and quality concerns. These challenges may be resolved by relatively simple measures, such as allowing adaptation and translation of resources and a peer review system.

COVID-19: to be or not to be; that is the diagnostic question.

Since the first cases in December 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread across the globe, resulting in the COVID-19 pandemic. Early clinical experiences have demonstrated the wide spectrum of SARS-CoV-2 presentations, including various reports of atypical presentations of COVID-19 and possible mimic conditions.This article summarises the current evidence surrounding atypical presentations of COVID-19 including neurological, cardiovascular, gastrointestinal, otorhinolaryngology and geriatric features. A case from our hospital of pneumocystis pneumonia initially suspected to be COVID-19 forms the basis for a discussion surrounding mimic conditions of COVID-19. The dual-process model of clinical reasoning is used to analyse the thought processes used to make a diagnosis of COVID-19, including consideration of the variety of differential diagnoses.While SARS-CoV-2 is likely to remain on the differential diagnostic list for a plethora of presentations for the foreseeable future, clinicians should be cautious of ignoring other potential diagnoses due to availability bias. An awareness of atypical presentations allows SARS-CoV-2 to be a differential so that it can be appropriately investigated. A knowledge of infectious mimics prevents COVID-19 from overshadowing other diagnoses, hence preventing delayed diagnosis or even misdiagnosis and consequent adverse outcomes for patients.

The Hidden Burden of Mental Health Outcomes Following Firearm-related Injures.

OBJECTIVES: Examine the effect of different types of firearms on readmission due to acute stress disorder (ASD) and/or post-traumatic stress disorder (PTSD) in firearm-injury victims. BACKGROUND: Survivors of firearm-related injuries suffer long-term sequelae such as disability, work loss, and deterioration in the quality of life. There is a paucity of data describing the long-term mental health outcomes in these patients. METHODS: We performed a 5-year (2011-2015) analysis of the Nationwide Readmission Database. All adult patients with firearm injuries were stratified into 3 groups by firearm type: handgun, shotgun, and semiautomatic rifle. Outcome measures were the incidence and predictors of ASD/PTSD. RESULTS: A total of 100,704 victims of firearm-related injuries were identified, of which 13.3% (n = 13,393) were readmitted within 6 months of index hospitalization, 6.7% (n = 8970) of these due to ASD/PTSD. Mean age was 34 ±â€Š14 years, 88% were men. Of those readmitted due to ASD/PTSD, 24% (n = 2153) sustained a handgun-related injury on index hospitalization, 12% (n = 1076) shotgun, and 64% (n = 5741) semiautomatic gun (P = 0.039). On regression analysis, semiautomatic gun and shotgun victims had higher odds of developing ASD/PTSD upon readmission [odds ratio (OR): 2.05 (1.10-4.12) and OR: 1.41 (1.08-2.11)] compared to handgun. Female sex [OR: 1.79 (1.05-3.05)] and younger age representing those younger than 25 years [OR: 4.66 (1.12-6.74)] were also independently associated with higher odds of ASD/PTSD. CONCLUSIONS: Apart from the lives lost, survivors of semiautomatic rifle- and shotgun-related injuries suffer long-term mental health sequalae. These secondary and debilitating mental health outcomes are important considerations for capturing the overall burden of the disease.

The European Association for Clinical Pharmacology and Therapeutics-25 years' young and going strong.

Clinical pharmacology as a scientific discipline and medical specialty was unarguably born in the twentieth century. Whilst pharmacology-the science behind the treatment of disease-had been in evolution since at least medieval times, the clinical discipline of pharmacology has had a more recent genesis and rather insidious evolution. During the 1900s, there were some clear father (parent) figures of clinical pharmacology in Europe that emerged and were responsible for the development of the specialty in this continent. This was a time when there were parallel developments in geographically dispersed academic departments (around the globe), during an age of excitement in drug discovery and clinical application of new therapeutic agents. It was the meeting of minds of some of these progenitors of the specialty that led to the development of the European Association for Clinical Pharmacology and Therapeutics (EACPT) 25 years ago arising from a working party supported by the World Health Organization in Europe. The EACPT now includes all major national organizations for clinical pharmacology in Europe, representing over 4000 individual professionals interested in clinical pharmacology and therapeutics. The EACPT has a major interest in promoting the safe use of medicines across Europe and internationally and has supported these aims since 1995, through biennial international scientific congresses and summer schools with delegates and presenters from around the world as well as various working group activities. In this article, the current executive committee members of EACPT recall this history, describe the evolution of the association over the last quarter of a century, and provide an update on the activities and ambitions of the association today.

Osler Centenary Papers: William Osler in medical education.

William Osler combined many excellent characteristics of a clinical educator being a scientific scholar, a motivational speaker and writer and a proficient physician. As we celebrate his life a century on, many of his educational ideals are as pertinent today as they were in those Victorian times. Osler's contributions to modern medicine go beyond his legacy of quotable aphorisms to a doctor, educator and leader whose proponent use of bedside teaching, careful clinical methods, and clinicopathological correlation was a great inspiration for students and junior doctors. He was also a great advocate of patient-centred care-listening to and closely observing his patients, an important message for modern medicine as the reliance on investigations strains modern healthcare systems. This review of Osler's contribution to medical education summarises his development as an educator and provides reflection on his influences to modern clinical education.

The 'top 100' drugs and classes in England: an updated 'starter formulary' for trainee prescribers.

AIMS: Prescribing is a complex skill required of doctors and, increasingly, other healthcare professionals. Use of a personal formulary can help to develop this skill. In 2006-9, we developed a core list of the 100 most commonly prescribed drugs. Our aim in the present study was to update this 'starter formulary' to ensure its continued relevance for prescriber training. METHODS: We analysed large contemporary primary and secondary care datasets to identify the most frequently prescribed medicinal products. Items were classified into natural groups, broadly following their British National Formulary classification. The resulting drug groups were included in the core list if they comprised ≥0.1% prescriptions in both settings or ≥0.2-0.3% prescriptions in one setting. Drugs from emergency guidelines that did not qualify by prescribing frequency completed the list. RESULTS: Over 1 billion primary care items and approximately 1.8 million secondary care prescriptions were analysed. The updated list comprises 81 drug groups commonly prescribed in both settings; six from primary care; seven from secondary care; and six from emergency guidelines. Eighty-eight per cent of the formulary was unchanged. Notable changes include entry of newer anti-epileptics and dipeptidyl peptidase-4 inhibitors and exit of phenytoin and thiazolidinediones. CONCLUSIONS: The relative stability of the core drug list over 9 years and the current update ensure that learning based on this list remains relevant to practice. Trainee prescribers may be encouraged to use this 'starter formulary' to develop a sound basis of prescribing knowledge and skills that they can subsequently apply more widely.

Use of ultrasound in diagnosing postoperative small-bowel intussusception in pediatric surgical oncology patients: a single-center retrospective review.

BACKGROUND: Postoperative intussusception can be a complication of abdominal surgery and often poses a diagnostic dilemma. OBJECTIVE: The purpose of this study was to evaluate the utility of ultrasonography in the diagnosis of intussusception in children who had recently undergone resection of a primary solid tumor. MATERIALS AND METHODS: We performed a retrospective review of all pediatric surgical oncology patients undergoing laparotomy for excision of an abdominal tumor at our institution from 1995 to 2015. We reviewed those with documented postoperative intussusception. In addition we searched the radiology database for all ultrasound examinations requested to rule out postoperative intussusception during our study interval. We analyzed demographics, primary diagnosis, surgical procedure, presentation, diagnostic investigations and definitive treatment. RESULTS: At our institution 852 laparotomies for abdominal tumor resection were performed during the study period, resulting in 10 postoperative intussusceptions (1.2% of cases), of which half were following neuroblastoma resection and the other half following nephrectomy for Wilms tumor. Postoperative intussusception was suspected if the patient had increasing nasogastric output, abdominal distension or feeding intolerance. Ultrasound was used to diagnose intussusception in 9/10 cases, on postoperative day 6 (standard deviation [SD] 5.6 days) on average, with a sensitivity of 89% (8/9; one false negative; 95% confidence interval [CI] 0.52, 1.00) and a specificity of 100% (no false positives; 95% CI 0.96, 1.00). CONCLUSION: Ultrasound was highly accurate in diagnosing postoperative intussusception in children who underwent resection of retroperitoneal tumors.

Pediatric contrast-enhanced ultrasound in the United States: a survey by the Contrast-Enhanced Ultrasound Task Force of the Society for Pediatric Radiology.

BACKGROUND: The United States Food and Drug Administration (FDA) recently approved an ultrasound (US) contrast agent for intravenous and intravesical administration in children. OBJECTIVE: Survey the usage, interest in and barriers for contrast-enhanced US among pediatric radiologists. MATERIALS AND METHODS: The Contrast-Enhanced Ultrasound Task Force of the Society for Pediatric Radiology (SPR) surveyed the membership of the SPR in January 2017 regarding their current use and opinions about contrast-enhanced US in pediatrics. RESULTS: The majority (51.1%, 166) of the 325 respondents (26.7% of 1,218) practice in either a university- or academic affiliated group. The most widely used US contrast agent was Lumason® 52.3% (23/44). While lack of expertise and training were reported barriers, all respondents who are not currently using US contrast agents are considering future use. CONCLUSION: Interest in pediatric contrast US is very high. Education and training are needed to support members who plan to adopt contrast US into practice.

Hydroxycarbamide versus chronic transfusion for maintenance of transcranial doppler flow velocities in children with sickle cell anaemia-TCD With Transfusions Changing to Hydroxyurea (TWiTCH): a multicentre, open-label, phase 3, non-inferiority trial.

BACKGROUND: For children with sickle cell anaemia and high transcranial doppler (TCD) flow velocities, regular blood transfusions can effectively prevent primary stroke, but must be continued indefinitely. The efficacy of hydroxycarbamide (hydroxyurea) in this setting is unknown; we performed the TWiTCH trial to compare hydroxyurea with standard transfusions. METHODS: TWiTCH was a multicentre, phase 3, randomised, open-label, non-inferiority trial done at 26 paediatric hospitals and health centres in the USA and Canada. We enrolled children with sickle cell anaemia who were aged 4-16 years and had abnormal TCD flow velocities (≥ 200 cm/s) but no severe vasculopathy. After screening, eligible participants were randomly assigned 1:1 to continue standard transfusions (standard group) or hydroxycarbamide (alternative group). Randomisation was done at a central site, stratified by site with a block size of four, and an adaptive randomisation scheme was used to balance the covariates of baseline age and TCD velocity. The study was open-label, but TCD examinations were read centrally by observers masked to treatment assignment and previous TCD results. Participants assigned to standard treatment continued to receive monthly transfusions to maintain 30% sickle haemoglobin or lower, while those assigned to the alternative treatment started oral hydroxycarbamide at 20 mg/kg per day, which was escalated to each participant's maximum tolerated dose. The treatment period lasted 24 months from randomisation. The primary study endpoint was the 24 month TCD velocity calculated from a general linear mixed model, with the non-inferiority margin set at 15 cm/s. The primary analysis was done in the intention-to-treat population and safety was assessed in all patients who received at least one dose of assigned treatment. This study is registered with ClinicalTrials.gov, number NCT01425307. FINDINGS: Between Sept 20, 2011, and April 17, 2013, 159 patients consented and enrolled in TWiTCH. 121 participants passed screening and were then randomly assigned to treatment (61 to transfusions and 60 to hydroxycarbamide). At the first scheduled interim analysis, non-inferiority was shown and the sponsor terminated the study. Final model-based TCD velocities were 143 cm/s (95% CI 140-146) in children who received standard transfusions and 138 cm/s (135-142) in those who received hydroxycarbamide, with a difference of 4·54 (0·10-8·98). Non-inferiority (p=8·82 × 10(-16)) and post-hoc superiority (p=0·023) were met. Of 29 new neurological events adjudicated centrally by masked reviewers, no strokes were identified, but three transient ischaemic attacks occurred in each group. Magnetic resonance brain imaging and angiography (MRI and MRA) at exit showed no new cerebral infarcts in either treatment group, but worsened vasculopathy in one participant who received standard transfusions. 23 severe adverse events in nine (15%) patients were reported for hydroxycarbamide and ten serious adverse events in six (10%) patients were reported for standard transfusions. The most common serious adverse event in both groups was vaso-occlusive pain (11 events in five [8%] patients with hydroxycarbamide and three events in one [2%] patient for transfusions). INTERPRETATION: For high-risk children with sickle cell anaemia and abnormal TCD velocities who have received at least 1 year of transfusions, and have no MRA-defined severe vasculopathy, hydroxycarbamide treatment can substitute for chronic transfusions to maintain TCD velocities and help to prevent primary stroke. FUNDING: National Heart, Lung, and Blood Institute, National Institutes of Health.

Prescribing Safety Assessment 2016: Delivery of a national prescribing assessment to 7343 UK final-year medical students.

AIMS: Newly graduated doctors write a large proportion of prescriptions in UK hospitals but recent studies have shown that they frequently make prescribing errors. The prescribing safety assessment (PSA) has been developed as an assessment of competence in relation to prescribing and supervising the use of medicines. This report describes the delivery of the PSA to all UK final-year medical students in 2016 (PSA2016). METHODS: The PSA is a 2-hour online assessment comprising eight sections which cover various aspects of prescribing defined within the outcomes of undergraduate education identified by the UK General Medical Council. Students sat one of four PSA 'papers', which had been standard-set using a modified Angoff process. RESULTS: A total of 7343 final-year medical students in all 31 UK medical schools sat the PSA. The overall pass rate was 95% with the pass rates for the individual papers ranging from 93 to 97%. The PSA was re-sat by 261 students who had failed and 80% of those candidates passed. The internal consistency (Cronbach's alpha) of the four papers ranged from 0.74 to 0.77 (standard error of measurement 4.13-4.24%). There was a statistically significant variation in performance between medical school cohorts (F = 32.6, P < 0.001) and a strongly positive correlation in performance for individual schools between PSA2015 and PSA2016 (r = 0.79, 95% CI 0.61-0.90; P < 0.01). CONCLUSIONS: PSA2016 demonstrated the feasibility of delivering a standardized national prescribing assessment online. The vast majority of UK final-year medical students were able to meet a prespecified standard of prescribing competence.

Hospital acquired Acute Kidney Injury is associated with increased mortality but not increased readmission rates in a UK acute hospital.

BACKGROUND: Acute Kidney Injury (AKI) has evoked much interest over the past decade and is reported to be associated with high inpatient mortality. Preventable death and increased readmission rates related to AKI have been the focus of considerable interest. METHODS: We studied hospital acquired AKI in all emergency hospital admissions, except transfers from ICU to ICU or patients known to renal services, to ascertain mortality and readmission rates, and trackable modifiable factors for death, using cox regression and Kaplan Meier survival curves. Data was extracted from the electronic patient records and a series of case notes reviewed. Admissions were included between April 2006 and March 2010 (and patients followed up until September 2011). RESULTS: Overall incidence of AKI was 2.2%, (AKI stage 1, 61%, stage 2,27% and stage 3, 12%). In patients who sustain in-hospital AKI, 34% die in hospital, 42% are dead at 90 days and 48% at 1 year post discharge, compared to 12% 1 year mortality in patients without AKI. In multivariable analyses, AKI is an independent risk factor for in-hospital mortality (Hazard Ratio 1.6: 95% confidence intervals 1.43-1.75: P < 0.001), death within 90 days of discharge (Hazard Ratio 1.5: 95% confidence intervals 1.3-1.9: P < 0.001) and subsequent mortality beyond 90 days (Hazard Ratio 2.9: 95% confidence intervals 2.7-3.1: P < 0.001) after adjustment for co-morbidities and peak C-reactive protein. Thirty percent of the patients who died in the first 90 days post discharge and had AKI, also had malignancy. Readmission rates at 30 and 90 days were not increased by AKI after adjustment for co-morbidities and peak C-reactive protein. CONCLUSIONS: A significant proportion of deaths in the first 90 days post-discharge may not be avoidable, due to malignancy and other end-stage disease. Readmission rates were not higher in patients who had had AKI.