'Warning: allergic to penicillin': association between penicillin allergy status in 2.3 million NHS general practice electronic health records, antibiotic prescribing and health outcomes.

BACKGROUND: The prevalence of reported penicillin allergy (PenA) and the impact these records have on health outcomes in the UK general population are unknown. Without such data, justifying and planning enhanced allergy services is challenging. OBJECTIVES: To determine: (i) prevalence of PenA records; (ii) patient characteristics associated with PenA records; and (iii) impact of PenA records on antibiotic prescribing/health outcomes in primary care. METHODS: We carried out cross-sectional/retrospective cohort studies using patient-level data from electronic health records. Cohort study: exact matching across confounders identified as affecting PenA records. Setting: English NHS general practices between 1 April 2013 and 31 March 2014. Participants: 2.3 million adult patients. Outcome measures: prevalence of PenA, antibiotic prescribing, mortality, MRSA infection/colonization and Clostridioides difficile infection. RESULTS: PenA prevalence was 5.9% (IQR = 3.8%-8.2%). PenA records were more common in older people, females and those with a comorbidity, and were affected by GP practice. Antibiotic prescribing varied significantly: penicillins were prescribed less frequently in those with a PenA record [relative risk (RR)  = 0.15], and macrolides (RR = 4.03), tetracyclines (RR = 1.91) nitrofurantoin (RR = 1.09), trimethoprim (RR = 1.04), cephalosporins (RR = 2.05), quinolones (RR = 2.10), clindamycin (RR = 5.47) and total number of prescriptions were increased in patients with a PenA record. Risk of re-prescription of a new antibiotic class within 28 days (RR = 1.32), MRSA infection/colonization (RR = 1.90) and death during the year subsequent to 1 April 2013 (RR = 1.08) increased in those with PenA records. CONCLUSIONS: PenA records are common in the general population and associated with increased/altered antibiotic prescribing and worse health outcomes. We estimate that incorrect PenA records affect 2.7 million people in England. Establishing true PenA status (e.g. oral challenge testing) would allow more people to be prescribed first-line antibiotics, potentially improving health outcomes.

What the public think about participation in medical research during an influenza pandemic: an international cross-sectional survey.

OBJECTIVES: The public and patients are primary contributors and beneficiaries of pandemic-relevant clinical research. However, their views on research participation during a pandemic have not been systematically studied. We aimed to understand public views regarding participation in clinical research during a hypothetical influenza pandemic. STUDY DESIGN: This is an international cross-sectional survey. METHODS: We surveyed the views of nationally representative samples of people in Belgium, Poland, Spain, Ireland, the United Kingdom, Canada, Australia and New Zealand, using a scenario-based instrument during the 2017 regional influenza season. Descriptive and regression analyses were conducted. RESULTS: Of the 6804 respondents, 5572 (81.8%) thought pandemic-relevant research was important, and 5089 (74.8%) thought 'special rules' should be applied to make this research feasible. The respondents indicated willingness to take part in lower risk (4715, 69.3%) and higher risk (3585, 52.7%) primary care and lower risk (4780, 70.3%) and higher risk (4113, 60.4%) intensive care unit (ICU) study scenarios. For primary care studies, most (3972, 58.4%) participants preferred standard enrolment procedures such as prospective written informed consent, but 2327 (34.2%) thought simplified procedures would be acceptable. For ICU studies, 2800 (41.2%) preferred deferred consent, and 2623 (38.6%) preferred prospective third-party consent. Greater knowledge about pandemics, trust in a health professional, trust in the government, therapeutic misconception and having had ICU experience as a patient or carer predicted increased willingness to participate in pandemic-relevant research. CONCLUSIONS: Our study indicates current public support for pandemic-relevant clinical research. Tailored information and initiatives to advance research literacy and maintain trust are required to support pandemic-relevant research participation and engagement.

Pseudorapidity Dependence of Particle Production and Elliptic Flow in Asymmetric Nuclear Collisions of p+Al, p+Au, d+Au, and

Asymmetric nuclear collisions of p+Al, p+Au, d+Au, and ^{3}He+Au at sqrt[s_{NN}]=200 GeV provide an excellent laboratory for understanding particle production, as well as exploring interactions among these particles after their initial creation in the collision. We present measurements of charged hadron production dN_{ch}/dη in all such collision systems over a broad pseudorapidity range and as a function of collision multiplicity. A simple wounded quark model is remarkably successful at describing the full data set. We also measure the elliptic flow v_{2} over a similarly broad pseudorapidity range. These measurements provide key constraints on models of particle emission and their translation into flow.

Nuclear Dependence of the Transverse-Single-Spin Asymmetry for Forward Neutron Production in Polarized p+A Collisions at sqrt[s_{NN}]=200 GeV.

During 2015, the Relativistic Heavy Ion Collider (RHIC) provided collisions of transversely polarized protons with Au and Al nuclei for the first time, enabling the exploration of transverse-single-spin asymmetries with heavy nuclei. Large single-spin asymmetries in very forward neutron production have been previously observed in transversely polarized p+p collisions at RHIC, and the existing theoretical framework that was successful in describing the single-spin asymmetry in p+p collisions predicts only a moderate atomic-mass-number (A) dependence. In contrast, the asymmetries observed at RHIC in p+A collisions showed a surprisingly strong A dependence in inclusive forward neutron production. The observed asymmetry in p+Al collisions is much smaller, while the asymmetry in p+Au collisions is a factor of 3 larger in absolute value and of opposite sign. The interplay of different neutron production mechanisms is discussed as a possible explanation of the observed A dependence.

Measurements of Multiparticle Correlations in d+Au Collisions at 200, 62.4, 39, and 19.6 GeV and p+Au Collisions at 200 GeV and Implications for Collective Behavior.

Recently, multiparticle-correlation measurements of relativistic p/d/^{3}He+Au, p+Pb, and even p+p collisions show surprising collective signatures. Here, we present beam-energy-scan measurements of two-, four-, and six-particle angular correlations in d+Au collisions at sqrt[s_{NN}]=200, 62.4, 39, and 19.6 GeV. We also present measurements of two- and four-particle angular correlations in p+Au collisions at sqrt[s_{NN}]=200 GeV. We find the four-particle cumulant to be real valued for d+Au collisions at all four energies. We also find that the four-particle cumulant in p+Au has the opposite sign as that in d+Au. Further, we find that the six-particle cumulant agrees with the four-particle cumulant in d+Au collisions at 200 GeV, indicating that nonflow effects are subdominant. These observations provide strong evidence that the correlations originate from the initial geometric configuration, which is then translated into the momentum distribution for all particles, commonly referred to as collectivity.

Risk factors for influenza-related complications in children during the 2009/10 pandemic: a UK primary care cohort study using linked routinely collected data.

Primary care clinicians have a central role in managing influenza/influenza-like illness (ILI) during influenza pandemics. This study identifies risk factors for influenza-related complications in children presenting with influenza/ILI in primary care. We conducted a cohort study using routinely collected linked data from the Clinical Practice Research Datalink on children aged 17 years and younger who presented with influenza/ILI during the 2009/10 pandemic. We calculated odds ratios (ORs) for potential risk factors in relation to influenza-related complications, complications requiring intervention, pneumonia, all-cause hospitalisation and hospitalisation due to influenza-related complications within 30 days of presentation. Analyses were adjusted for potential confounders including age, vaccination and socio-economic deprivation. Asthma was a risk factor for influenza-related complications (adjusted OR 1.48, 95% confidence interval (CI) 1.21-1.80, P < 0.001), complications requiring intervention (adjusted OR 1.44, 95% CI 1.11-1.88; P = 0.007), pneumonia (adjusted OR 1.64, 95% CI 1.07-2.51, P = 0.024) and hospitalisation due to influenza-related complications (adjusted OR 2.46, 95% CI 1.09-5.56, P = 0.031). Neurological conditions were risk factors for all-cause hospitalisation (adjusted OR 4.25, 95% CI 1.50-12.07, P = 0.007) but not influenza-related complications (adjusted OR 1.46, 95% CI 0.83-2.56, P = 0.189). Community-based early interventions to prevent influenza-related clinical deterioration should therefore be primarily targeted at children with asthma and neurological conditions.

Potential methane reservoirs beneath Antarctica.

Once thought to be devoid of life, the ice-covered parts of Antarctica are now known to be a reservoir of metabolically active microbial cells and organic carbon. The potential for methanogenic archaea to support the degradation of organic carbon to methane beneath the ice, however, has not yet been evaluated. Large sedimentary basins containing marine sequences up to 14 kilometres thick and an estimated 21,000 petagrams (1 Pg equals 10(15) g) of organic carbon are buried beneath the Antarctic Ice Sheet. No data exist for rates of methanogenesis in sub-Antarctic marine sediments. Here we present experimental data from other subglacial environments that demonstrate the potential for overridden organic matter beneath glacial systems to produce methane. We also numerically simulate the accumulation of methane in Antarctic sedimentary basins using an established one-dimensional hydrate model and show that pressure/temperature conditions favour methane hydrate formation down to sediment depths of about 300 metres in West Antarctica and 700 metres in East Antarctica. Our results demonstrate the potential for methane hydrate accumulation in Antarctic sedimentary basins, where the total inventory depends on rates of organic carbon degradation and conditions at the ice-sheet bed. We calculate that the sub-Antarctic hydrate inventory could be of the same order of magnitude as that of recent estimates made for Arctic permafrost. Our findings suggest that the Antarctic Ice Sheet may be a neglected but important component of the global methane budget, with the potential to act as a positive feedback on climate warming during ice-sheet wastage.

The management of acne vulgaris in primary care: a cohort study of consulting and prescribing patterns using the Clinical Practice Research Datalink.

BACKGROUND: Effective management of acne vulgaris in primary care involves support (usually provided over a number of consultations) and prescription of effective treatments. However, consulting and prescribing patterns for acne in primary care are not well described. OBJECTIVES: To describe the rate of primary-care consultations and follow-up consultations; prescribing patterns, including overall use of acne-related medications (ARMs); and initial and follow-up prescription for acne vulgaris in the U.K. METHODS: U.K. primary-care acne consultations and prescriptions for ARMs were identified in the Clinical Practice Research Datalink. Annual consultation rates (between 2004 and 2013) by age and sex, new consultations and consultations in the subsequent year were calculated, along with prescribing trends - during a new consultation and over the subsequent 90 days and year - using the number of registered patients as the denominator. RESULTS: Two-thirds (66·1%) of patients who had a new acne consultation had no further acne consultations in the subsequent year. Overall 26·7%, 24·9%, and 23·6% and 2·8% of patients were prescribed no ARM, an oral antibiotic, a topical antibiotic or an oral plus topical antibiotic, respectively, during a new acne consultation. In total 60·1% and 38·6% of patients prescribed an ARM received no further ARM prescriptions in the following 90 days and 1 year, respectively, despite most prescriptions being for 2 months or less. Prescribing rates for lymecycline and topical combined clindamycin and benzoyl peroxide increased substantially between 2004 and 2013. There were no important changes in consultation rates between 2004 and 2013. CONCLUSIONS: These data suggest that patients with acne are receiving a suboptimal initial choice of ARMs, longitudinal care and prescribing.

Validation of the Airway-Dyspnoea-Voice-Swallow (ADVS) scale and Patient-Reported Outcome Measure (PROM) as disease-specific instruments in paediatric laryngotracheal stenosis.

OBJECTIVE: To validate the Airway-Dyspnoea-Voice-Swallow (ADVS) instrument as a disease-specific Patient-Reported Outcome Measure in paediatric laryngotracheal stenosis. DESIGN: Prospective observational study. SETTING: A quaternary referral centre for complex airway disease. PARTICIPANTS: Forty-eight patients (30 males) with a mean age of 49 ± 49 months who underwent laryngotracheal surgery or microlaryngoscopy and bronchoscopy (MLB) following laryngotracheal surgery. MAIN OUTCOME MEASURES: Airway-Dyspnoea-Voice-Swallow summary scale and Patient-Reported Outcome Measure (PROM), Paediatric Quality of Life (PedsQL) scale, Paediatric Voice Handicap Index (pVHI) and Lansky performance scale were administered to patients before and 6-8 weeks following airway examination/surgery. RESULTS: Most patients (73%) had intubation-related subglottic stenosis, and 60% of patients had prior airway treatments. The majority of patients (77%) had more than one major chronic morbidity, and the commonest procedures were diagnostic MLB (49%), followed by airway dilation (29%). Cronbach-α value for the ADVS PROM was 0.71 overall and 0.85, 0.86 and 0.64 for the dyspnoea, voice and swallow domains, respectively. Rank correlations between Dyspnoea, Voice and Swallow summary scale and PROM scores were 0.83, 0.71 and 0.81, respectively (P < 0.0001). For those patients undergoing diagnostic MLB, pre- and post-examination scores were highly correlated (intraclass correlations >0.75). There was a significant rank correlation between ADVS PROM score and Lansky performance score (r = -0.68; P < 0.0001). There were significant correlations between PROM score and PedsQL (r = -0.57; P < 0.0001) and between voice domain of the PROM and pVHI (r = 0.78; P < 0.0001). There were strong correlations between Myer-Cotton stenosis severity and dyspnoea scale and PROM score (r = 0.68; P < 0.0001). There were significant differences in voice and swallow ADVS scales and PROM scores between patients with and without concomitant laryngeal/oesophageal pathology. Patient age and presence of high dyspnoea and swallowing PROM scores were independently associated with poorer quality of life and performance status. CONCLUSIONS: These series of observations validate the ADVS instrument as a disease-specific outcome measure for paediatric laryngotracheal stenosis. Dyspnoea and swallowing dysfunction appear to have the greatest impact on quality of life. More widespread adoption of the ADVS instrument could help create a shared language for outcomes communication and benchmarking for children with this complex condition.

Advancing the framework for considering the effects of climate change on worker safety and health.

In 2009, a preliminary framework for how climate change could affect worker safety and health was described. That framework was based on a literature search from 1988-2008 that supported seven categories of climate-related occupational hazards: (1) increased ambient temperature; (2) air pollution; (3) ultraviolet radiation exposure; (4) extreme weather; (5) vector-borne diseases and expanded habitats; (6) industrial transitions and emerging industries; and (7) changes in the built environment. This article reviews the published literature from 2008-2014 in each of the seven categories. Additionally, three new topics related to occupational safety and health are considered: mental health effects, economic burden, and potential worker safety and health impacts associated with the nascent field of climate intervention (geoengineering). Beyond updating the literature, this article also identifies key priorities for action to better characterize and understand how occupational safety and health may be associated with climate change events and ensure that worker health and safety issues are anticipated, recognized, evaluated, and mitigated. These key priorities include research, surveillance, risk assessment, risk management, and policy development. Strong evidence indicates that climate change will continue to present occupational safety and health hazards, and this framework may be a useful tool for preventing adverse effects to workers.

Tissue-Engineered Tracheal Replacement in a Child: A 4-Year Follow-Up Study.

In 2010, a tissue-engineered trachea was transplanted into a 10-year-old child using a decellularized deceased donor trachea repopulated with the recipient's respiratory epithelium and mesenchymal stromal cells. We report the child's clinical progress, tracheal epithelialization and costs over the 4 years. A chronology of events was derived from clinical notes and costs determined using reference costs per procedure. Serial tracheoscopy images, lung function tests and anti-HLA blood samples were compared. Epithelial morphology and T cell, Ki67 and cleaved caspase 3 activity were examined. Computational fluid dynamic simulations determined flow, velocity and airway pressure drops. After the first year following transplantation, the number of interventions fell and the child is currently clinically well and continues in education. Endoscopy demonstrated a complete mucosal lining at 15 months, despite retention of a stent. Histocytology indicates a differentiated respiratory layer and no abnormal immune activity. Computational fluid dynamic analysis demonstrated increased velocity and pressure drops around a distal tracheal narrowing. Cross-sectional area analysis showed restriction of growth within an area of in-stent stenosis. This report demonstrates the long-term viability of a decellularized tissue-engineered trachea within a child. Further research is needed to develop bioengineered pediatric tracheal replacements with lower morbidity, better biomechanics and lower costs.

Analytic laboratory performance of a point of care urine culture kit for diagnosis and antibiotic susceptibility testing.

Currently available point-of-care (POC) diagnostic tests for managing urinary tract infections (UTIs) in general practice are limited by poor performance characteristics, and laboratory culture generally provides results only after a few days. This laboratory evaluation compared the analytic performance of the POC UK Flexicult(™) (Statens Serum Institut) (SSI) urinary kit for quantification, identification and antibiotic susceptibility testing and routine UK National Health Service (NHS) urine processing to an advanced urine culture method. Two hundred urine samples routinely submitted to the Public Health Wales Microbiology Laboratory were divided and: (1) analysed by routine NHS microbiological tests as per local laboratory standard operating procedures, (2) inoculated onto the UK Flexicult(™) SSI urinary kit and (3) spiral plated onto Colorex Orientation UTI medium (E&O Laboratories Ltd). The results were evaluated between the NHS and Flexicult(™ )methods, and discordant results were compared to the spiral plating method. The UK Flexicult(™) SSI urinary kit was compared to routine NHS culture for identification of a pure or predominant uropathogen at ≥ 10(5) cfu/mL, with a positive discordancy rate of 13.5% and a negative discordancy rate of 3%. The sensitivity and specificity were 86.7% [95% confidence interval (CI) 73.8-93.7] and 82.6% (95% CI 75.8-87.7), respectively. The UK Flexicult(™) SSI urinary kit was comparable to routine NHS urine processing in identifying microbiologically positive UTIs in this laboratory evaluation. However, the number of false-positive samples could lead to over-prescribing of antibiotics in clinical practice. The Flexicult(™) SSI kit could be useful as a POC test for UTIs in primary care but further pragmatic evaluations are necessary.

Climate change, food systems and population health risks in their eco-social context.

The establishment of ecological public health as crucial to modern public health is overdue. While the basic concepts have been gestating for decades, receptivity within broader public health has been limited. This position is changing, not least as the population-level impacts of climate change and, more broadly, of limits to growth are emerging from theory and forecasting into daily reality. This paper describes several key elements of ecological public health thinking. These include the 'environmental' risks to human health (often systemic and disruptive, rather than local and toxic) posed by climate change and other forms of adverse global environmental change. Closer recognition of the links between social and environmental factors has been urged--an 'eco-social' approach--and, relatedly, for greater co-operation between social and natural sciences. The authors revisit critics of capitalism who foresaw the global capture and transformation of ecosystems for material human ends, and their resultant despoliation. The perennial call within public health to reduce vulnerability by lessening poverty is more important than ever, given the multifactored threat to the health of the poor which is anticipated, assuming no radical strategies to alleviate these pressures. But enhanced health security for the poor requires more than the reconfiguring of social determinants; it also requires, as the overarching frame, ecological public health.

Atlantic bluefin tuna Thunnus thynnus feeding ecology in the northern Gulf of Mexico: a preliminary description of diet from the western Atlantic spawning grounds.

A combination of stomach contents, nitrogen stable-isotope and tissue C:N values are presented to demonstrate feeding activity of Atlantic bluefin tuna Thunnus thynnus on the Gulf of Mexico (GOMEX) spawning grounds. Diets include teleosts, cephalopods, crustaceans and a pelagic tunicate (Pyrosoma atlanticum). Results reveal the need to classify the GOMEX as a T. thynnus feeding ground.

Cardiovascular MRI predicts 5-year adverse clinical outcome in heart transplant recipients.

Imaging recommendations for the follow-up of heart transplant recipients (HTRs) lack evidence justifying their prognostic value. Cardiovascular magnetic resonance imaging (CMRI) can characterize heart structure and function and has prognostic value in many myocardial diseases. We hypothesized that CMRI evaluation of cardiac allografts would predict adverse events. We performed CMRI on 60 HTRs evaluating biventricular size, function and myocardial scar. We performed survival analysis to identify independent predictors of cardiovascular (CV) death or hospitalization. Participants had a mean age of 51 ± 14 years, mean graft age of 3.5 years (±4) and 75% are male. Median follow-up time was 4.9 years with 22 CV hospitalizations and 7 CV deaths. A multivariable survival analysis of imaging and clinical variables identified myocardial scar (hazard ratio [HR] of 10.7, p = 0.005), right ventricular end- diastolic volume index (RVEDVI; 1.1/mL/m(2) , p = 0.001), graft age (HR = 1.2/year, p = 0.004) and previous allograft rejection (HR = 4.4, p = 0.006) as predictive of time to CV death or hospitalization. CMRI-derived myocardial scar and RVEDVI are independently associated with CV outcomes in HTRs.

One Health in a world with climate change.

The One Health movement, as defined in this paper, has progressed from a focus on emerging infectious diseases to a broader set of challenges that include food security and food safety. These interact with climate change, a so-called 'wicked problem' that has links to all human activity. Climate change acts as a threat multiplier that interacts both directly and indirectly with variables, such as disease, food production, food security, food safety and poverty. A number of these interactions are briefly described in this paper before issues of complexity and interconnectedness between these variables are discussed. A common thread underpinning this current global challenge to civilisation is that the system is now dominated by the activities of humans--and many scientists label the current epoch the 'Anthropocene'. Specifically, humans have for the first time collectively overloaded the Earth's capacity to supply, absorb, replenish and stabilise. Many scientists now observe that the ecological and environmental foundations of civilisation appear to be at risk. This paper suggests that, for the One Health movement to address such challenges, the range and number of disciplines that need to be involved must be expanded. In particular, in addition to the insights provided by technical specialists, we need to engage disciplines with the capacity to advance political, economic and social reforms. This will not be easy, but it is argued that this is what is required from the One Health movement in a world with climate change.

Stop antibiotics when you feel better? Opportunities, challenges and research directions.

Shortening standard antibiotic courses and stopping antibiotics when patients feel better are two ways to reduce exposure to antibiotics in the community, and decrease the risks of antimicrobial resistance and antibiotic side effects. While evidence shows that shorter antibiotic treatments are non-inferior to longer ones for infections that benefit from antibiotics, shorter courses still represent average treatment durations that might be suboptimal for some. In contrast, stopping antibiotics based on improvement or resolution of symptoms might help personalize antibiotic treatment to individual patients and help reduce unnecessary exposure. Yet, many challenges need addressing before we can consider this approach evidence-based and implement it in practice. In this viewpoint article, we set out the main evidence gaps and avenues for future research.

Musculoskeletal injuries in US Air Force Tactical Air Control Party trainees: an 11-year longitudinal retrospective cohort study and presentation of a musculoskeletal injury classification matrix.

INTRODUCTION: Little is known of the epidemiology of musculoskeletal injuries (MSKIs) in US Air Force Special Warfare (AFSPECWAR) Tactical Air Control Party trainees. The purpose of this longitudinal retrospective cohort study was to (1) report the incidence and type of MSKI sustained by AFSPECWAR trainees during and up to 1 year following training, (2) identify factors associated with MSKI, and (3) develop and present the MSKI classification matrix used to identify and categorise injuries in this study. METHODS: Trainees in the Tactical Air Control Party Apprentice Course between fiscal years 2010-2020 were included. Diagnosis codes were classified as MSKI or non-MSKI using a classification matrix. Incidence rates and incidence proportion for injury types and regions were calculated. Measures were compared for differences between those who did and did not sustain an MSKI during training. A Cox proportional hazards model was used to identify factors associated with MSKI. RESULTS: Of the 3242 trainees, 1588 (49%) sustained an MSKI during training and the cohort sustained MSKIs at a rate of 16 MSKI per 100 person-months. Overuse/non-specific lower extremity injuries predominated. Differences were seen in some baseline measures between those who did and did not sustain an MSKI. Factors retained in the final Cox regression model were age, 1.5-mile run times and prior MSKI. CONCLUSION: Slower run times and higher age were associated with an increased likelihood of MSKI. Prior MSKI was the strongest predictor of MSKI during training. Trainees sustained MSKIs at a higher rate than graduates in their first year in the career field. The MSKI matrix was effective in identifying and categorising MSKI over a prolonged (12-year) surveillance period and could be useful for future injury surveillance efforts in the military or civilian settings. Findings from this study could inform future injury mitigation efforts in military training environments.