Successful Heart-Lung Transplant for a Patient on Continuous-Flow Left Ventricular Assist Device Support Complicated With Amiodarone-Induced Pulmonary Fibrosis.

In this case report, we present a successful case of en bloc heart-lung transplant in a patient with advanced cardiopulmonary respiratory failure from amiodarone-associated pulmonary fibrosis that occurred post-left ventricular assist device implantation.

Testing the impact of local alcohol licencing policies on reported crime rates in England.

BACKGROUND: Excessive alcohol use contributes to public nuisance, antisocial behaviour, and domestic, interpersonal and sexual violence. We test whether licencing policies aimed at restricting its spatial and/or temporal availability, including cumulative impact zones, are associated with reductions in alcohol-related crime. METHODS: Reported crimes at English lower tier local authority (LTLA) level were used to calculate the rates of reported crimes including alcohol-attributable rates of sexual offences and violence against a person, and public order offences. Financial fraud was included as a control crime not directly associated with alcohol abuse. Each area was classified as to its cumulative licensing policy intensity for 2009-2015 and categorised as 'passive', low, medium or high. Crime rates adjusted for area deprivation, outlet density, alcohol-related hospital admissions and population size at baseline were analysed using hierarchical (log-rate) growth modelling. RESULTS: 284 of 326 LTLAs could be linked and had complete data. From 2009 to 2013 alcohol-related violent and sexual crimes and public order offences rates declined faster in areas with more 'intense' policies (about 1.2, 0.10 and 1.7 per 1000 people compared with 0.6, 0.01 and 1.0 per 1000 people in 'passive' areas, respectively). Post-2013, the recorded rates increased again. No trends were observed for financial fraud. CONCLUSIONS: Local areas in England with more intense alcohol licensing policies had a stronger decline in rates of violent crimes, sexual crimes and public order offences in the period up to 2013 of the order of 4-6% greater compared with areas where these policies were not in place, but not thereafter.

EULAR/ERA-EDTA recommendations for the management of ANCA-associated vasculitis.

In this article, the 2009 European League Against Rheumatism (EULAR) recommendations for the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) have been updated. The 2009 recommendations were on the management of primary small and medium vessel vasculitis. The 2015 update has been developed by an international task force representing EULAR, the European Renal Association and the European Vasculitis Society (EUVAS). The recommendations are based upon evidence from systematic literature reviews, as well as expert opinion where appropriate. The evidence presented was discussed and summarised by the experts in the course of a consensus-finding and voting process. Levels of evidence and grades of recommendations were derived and levels of agreement (strengths of recommendations) determined. In addition to the voting by the task force members, the relevance of the recommendations was assessed by an online voting survey among members of EUVAS. Fifteen recommendations were developed, covering general aspects, such as attaining remission and the need for shared decision making between clinicians and patients. More specific items relate to starting immunosuppressive therapy in combination with glucocorticoids to induce remission, followed by a period of remission maintenance; for remission induction in life-threatening or organ-threatening AAV, cyclophosphamide and rituximab are considered to have similar efficacy; plasma exchange which is recommended, where licensed, in the setting of rapidly progressive renal failure or severe diffuse pulmonary haemorrhage. These recommendations are intended for use by healthcare professionals, doctors in specialist training, medical students, pharmaceutical industries and drug regulatory organisations.

Cardiac assessment prior to non-cardiac surgery.

BACKGROUND: Increasingly, patients undergoing non-cardiac surgery are older and have more comorbidities yet preoperative cardiac assessment appears haphazard and unsystematic. We hypothesised that patients at high cardiac risk were not receiving adequate cardiac assessment, and patients with low-cardiac risk were being over-investigated. AIMS: To compare in a representative sample of patients undergoing non-cardiac surgery the use of cardiac investigations in patients at high and low preoperative cardiac risk. METHODS: We examined cardiac assessment patterns prior to elective non-cardiac surgery in a representative sample of patients. Cardiac risk was calculated using the Revised Cardiac Risk Index. RESULTS: Of 671 patients, 589 (88%) were low risk and 82 (12%) were high risk. We found that nearly 14% of low-risk and 45% of high-risk patients had investigations for coronary ischaemia prior to surgery. Vascular surgery had the highest rate of investigation (38%) and thoracic patients the lowest rate (14%). Whilst 78% of high-risk patients had coronary disease, only 46% were on beta-blockers, 49% on aspirin and 77% on statins. For current smokers (17.3% of cohort, n = 98), 60% were advised to quit pre-op. CONCLUSIONS: Practice patterns varied across surgical sub-types with low-risk patients tending to be over-investigated and high-risk patients under-investigated. A more systemised approach to this large group of patients could improve clinical outcomes, and more judicious use of investigations could lower healthcare costs and increase efficiency in managing this cohort.

Lung Quality and Utilization in Controlled Donation After Circulatory Determination of Death Within the United States.

Although controlled donation after circulatory determination of death (cDCDD) could increase the supply of donor lungs within the United States, the yield of lungs from cDCDD donors remains low compared with donation after neurologic determination of death (DNDD). To explore the reason for low lung yield from cDCDD donors, Scientific Registry of Transplant Recipient data were used to assess the impact of donor lung quality on cDCDD lung utilization by fitting a logistic regression model. The relationship between center volume and cDCDD use was assessed, and the distance between center and donor hospital was calculated by cDCDD status. Recipient survival was compared using a multivariable Cox regression model. Lung utilization was 2.1% for cDCDD donors and 21.4% for DNDD donors. Being a cDCDD donor decreased lung donation (adjusted odds ratio 0.101, 95% confidence interval [CI] 0.085-0.120). A minority of centers have performed cDCDD transplant, with higher volume centers generally performing more cDCDD transplants. There was no difference in center-to-donor distance or recipient survival (adjusted hazard ratio 1.03, 95% CI 0.78-1.37) between cDCDD and DNDD transplants. cDCDD lungs are underutilized compared with DNDD lungs after adjusting for lung quality. Increasing transplant center expertise and commitment to cDCDD lung procurement is needed to improve utilization.

Propensity score matching for selection of local areas as controls for evaluation of effects of alcohol policies in case series and quasi case-control designs.

OBJECTIVES: Area-level public health interventions can be difficult to evaluate using natural experiments. We describe the use of propensity score matching (PSM) to select control local authority areas (LAU) to evaluate the public health impact of alcohol policies for (1) prospective evaluation of alcohol policies using area-level data, and (2) a novel two-stage quasi case-control design. STUDY DESIGN: Ecological. METHODS: Alcohol-related indicator data (Local Alcohol Profiles for England, PHE Health Profiles and ONS data) were linked at LAU level. Six LAUs (Blackpool, Bradford, Bristol, Ipswich, Islington, and Newcastle-upon-Tyne) as sample intervention or case areas were matched to two control LAUs each using PSM. For the quasi case-control study a second stage was added aimed at obtaining maximum contrast in outcomes based on propensity scores. Matching was evaluated based on average standardized absolute mean differences (ASAM) and variable-specific P-values after matching. RESULTS: The six LAUs were matched to suitable control areas (with ASAM < 0.20, P-values >0.05 indicating good matching) for a prospective evaluation study that sought areas that were similar at baseline in order to assess whether a change in intervention exposure led to a change in the outcome (alcohol related harm). PSM also generated appropriate matches for a quasi case-control study--whereby the contrast in health outcomes between cases and control areas needed to be optimized in order to assess retrospectively whether differences in intervention exposure were associated with the outcome. CONCLUSIONS: The use of PSM for area-level alcohol policy evaluation, but also for other public health interventions, will improve the value of these evaluations by objective and quantitative selection of the most appropriate control areas.

Lessons learnt from a feasibility study on price incentivised healthy eating promotions in workplace catering establishments.

BACKGROUND: It is recognised that the worksite catering sector is likely to play a pivotal role in influencing dietary intake in adults of working age. The present study aimed to assess the feasibility of engaging worksites in a healthy eating intervention, implementing a price incentivised main meal intervention and measuring indicative intervention responses to inform the design of a future trial. METHODS: Workplaces registered with the Scottish Healthy Living Award were invited to participate. The EatSMART intervention (a reduced price, healthy meal combination plus promotions) was implemented over 10 weeks in two worksites. Implementation was assessed by observational and sales data. Indicative effects on food habits were measured using online pre- and post-intervention questionnaires. Focus group discussions and interviews were used to determine catering staff and consumer acceptability. RESULTS: Thirty-seven worksites were invited to participate and four worksites responded positively. Two sites (with 1600 and 500 employees, respectively) participated. Both required significant implementation support. Estimated sales data indicated that the uptake of promoted items varied by week (range 60-187 items) and by site. A poor response rate from questionnaires limited the evaluation of intervention impact. Consumers reported improved value for money and quality. Both sites reported an intention to continue the intervention delivery. CONCLUSIONS: Significant efforts are required to engage worksite catering teams and implement healthy eating interventions. Evaluation methods require further development to improve data collection. Responses from consumers and catering staff suggest that further work in this area would be welcomed.

Finding the fifth intercostal space for chest drain insertion: guidelines and ultrasound.

OBJECTIVES: International guidelines exist for chest drain insertion and recommend identifying the fifth intercostal space or above, around the midaxillary line. In a recent study, applying these guidelines in cadavers risked insertion in the 6th intercostal space or below in 80% of cases. However, there are limitations of cadaveric studies and this investigation uses ultrasound to determine the intercostal space identified when applying these guidelines in healthy adult volunteers. METHODS: On each side of the chest wall in 31 volunteers, the position for drain insertion was identified using the European Trauma Course method, Advanced Trauma Life Support (ATLS) method, British Thoracic Society's 'safe triangle' and the 'traditional' method of palpation. Ultrasound imaging was used to determine the relationship of the skin marks with the underlying intercostal spaces. RESULTS: Five methods were assessed on 60 sides. In contrast to the cadaveric study, 94% of skin marks lay over a safe intercostal space. However, the range of intercostal spaces found spanned the second to the seventh space. In 44% of women, the inferior boundary of the 'safe triangle' and the ATLS guidelines located the sixth intercostal space or below. CONCLUSIONS: Current guidelines often identify a safe site for chest drain insertion, although the same site is not reproducibly found. In addition, women appear to be at risk of subdiaphragmatic drain insertion when the nipple is used to identify the fifth intercostal space. Real-time ultrasonography can be used to confirm the intercostal space during this procedure, although a safe guideline is still needed for circumstances in which ultrasound is not possible.

Invasive mold infections in lung and heart-lung transplant recipients: Stanford University experience.

BACKGROUND: Recipients of lung transplantation (LT) and heart-lung transplantation (HLT) are at increased risk of infection, including invasive mold infections (IMIs). The clinical presentation, radiographic correlates, and outcomes of Aspergillus and non-AspergillusIMIs in this population have not been well documented. METHODS: LT and HLT recipients diagnosed with IMIs between 1990 and 2012 were identified using the Stanford Translational Research Integrated Database Environment and Stanford LT and HLT clinical database. Recipient clinical and radiographic characteristics were obtained via retrospective review of medical records and compared between Aspergillus and non-Aspergillus mold recipients. Risk factors for mortality were identified using multivariate logistic regression analysis. RESULTS: During the study period, 87 (14%) transplant recipients were diagnosed with IMIs. Aspergillus species were isolated in 63 (72%) and non-Aspergillus molds in 24 (28%) recipients. No significant difference was seen in presenting symptoms or radiographic findings between Aspergillus and non-Aspergillus mold recipients. Median time to diagnosis was 363 days in the Aspergillus group and 419 days in the non-Aspergillus group, with dissemination occurring only within the non-Aspergillus group (12.5%). Overall 90-day and 1-year mortality following IMI was 24% and 44%. One-year mortality was increased in the non-Aspergillus group (39.5% vs. 60.5%, P = 0.03). CONCLUSIONS: There is significant overlap in risk factors, presentation, and radiographic patterns in IMI in LT or HLT recipients. Non-Aspergillus molds were more likely to present late, with disseminated disease, and portend increased 1-year mortality.

Guidelines for chest drain insertion may not prevent damage to abdominal viscera.

OBJECTIVES: Guidelines to improve the ease and safety of chest drain insertion recommend using the fifth intercostal space, around the midaxillary line (MAL). This study aimed to assess whether compliance with published guidelines reliably ensured such placement and avoided the potentially serious complications of subdiaphragmatic insertion and peripheral nerve injury. METHODS: Three international guidelines were assessed by identifying the intercostal space for chest drain insertion using 16 cadavers (32 sides) at a point 1 cm anterior to MAL. The European Trauma Course method was compared with the British Thoracic Society's 'safe triangle' and the ATLS course technique. RESULTS: The level most commonly found was the sixth intercostal space (43%; 41 of 96 sides). Overall the sixth space or below was found in 83% of insertions (80 of 96 sides). In the fifth intercostal space, the long thoracic nerve ran posterior to the marker placed in all cases and the lateral cutaneous branches of intercostal nerves arose anteriorly to the marker in all but one case. CONCLUSIONS: The results suggest these guidelines may result in insertion of chest drains below the fifth intercostal space, potentially risking injury to subdiaphragmatic structures. Peripheral nerves of the lateral thoracic wall appear safe from incisions 1 cm anterior to MAL.

Impact of the lung allocation score on survival beyond 1 year.

Implementation of the lung allocation score (LAS) in 2005 led to transplantation of older and sicker patients without altering 1-year survival. However, long-term survival has not been assessed and emphasizing the 1-year survival metric may actually sustain 1-year survival while not reflecting worsening longer-term survival. Therefore, we assessed overall and conditional 1-year survival; and the effect of crossing the 1-year threshold on hazard of death in three temporal cohorts: historical (1995-2000), pre-LAS (2001-2005) and post-LAS (2005-2010). One-year survival post-LAS remained similar to pre-LAS (83.1% vs. 82.1%) and better than historical controls (75%). Overall survival in the pre- and post-LAS cohorts was also similar. However, long-term survival among patients surviving beyond 1 year was worse than pre-LAS and similar to historical controls. Also, the hazard of death increased significantly in months 13 (1.44, 95% CI 1.10-1.87) and 14 (1.43, 95% CI 1.09-1.87) post-LAS but not in the other cohorts. While implementation of the LAS has not reduced overall survival, decreased survival among patients surviving beyond 1 year in the post-LAS cohort and the increased mortality occurring immediately after 1 year suggest a potential negative long-term effect of the LAS and an unintended consequence of increased emphasis on the 1-year survival metric.

Patterns of detection of respiratory viruses in nasal swabs from calves in Ireland: a retrospective study.

A retrospective analysis was conducted to investigate the prevalence and seasonality of bovine viral diarrhoea virus (BVDV), bovine coronavirus (BoCV), bovine herpesvirus-1 (BoHV-1), bovine respiratory syncytical virus (BRSV) and parainfluenza virus-3 (PI3V) in calves (aged three months and below) in Ireland. Results from real-time PCR testing, including cycle threshold values, conducted on nasal swabs (single or pooled) submitted from 1364 respiratory disease outbreaks between January 1, 2008 and December 31, 2012 were included in this study. One or more viruses were detected in 34.6 per cent of submissions, with BoCV detected most frequently (22.9 per cent), followed by BRSV (11.6 per cent), PI3 V (7.0 per cent), BoHV-1 (6.1 per cent) and BVDV (5.0 per cent). The detection rate of all viruses was higher when pooled multiple swabs were submitted from outbreaks rather than single swabs, with these differences being significant for all except BVDV. Two or more viruses were detected in 39.4 per cent of positive submissions, with BoCV and BRSV most commonly present as one of the two partners in detection. With the exception of BVDV, which was detected all year round, the others showed a clear seasonal pattern, being most commonly detected in winter and spring.

The mucosal inflammatory response to non-typhoidal Salmonella in the intestine is blunted by IL-10 during concurrent malaria parasite infection.

Coinfection can markedly alter the response to a pathogen, thereby changing its clinical presentation. For example, non-typhoidal Salmonella (NTS) serotypes are associated with gastroenteritis in immunocompetent individuals. In contrast, individuals with severe pediatric malaria can develop bacteremic infections with NTS, during which symptoms of gastroenteritis are commonly absent. Here we report that, in both a ligated ileal loop model and a mouse colitis model, malaria parasites caused a global suppression of gut inflammatory responses and blunted the neutrophil influx that is characteristic of NTS infection. Further, malaria parasite infection led to increased recovery of Salmonella enterica serotype Typhimurium from the draining mesenteric lymph node (MLN) of mice. In the mouse colitis model, blunted intestinal inflammation during NTS infection was independent of anemia but instead required parasite-induced synthesis of interleukin (IL)-10. Blocking of IL-10 in coinfected mice reduced dissemination of S. Typhimurium to the MLN, suggesting that induction of IL-10 contributes to development of disseminated infection. Thus IL-10 produced during the immune response to malaria in this model contributes to suppression of mucosal inflammatory responses to invasive NTS, which may contribute to differences in the clinical presentation of NTS infection in the setting of malaria.

Development of a set of mobile phone text messages designed for prevention of recurrent cardiovascular events.

BACKGROUND: Supporting lifestyle change is an effective way of preventing recurrent events in people with cardiovascular disease (CVD). However, there is a need to develop innovative strategies that increase access to programmes for individuals at high risk of CVD. This study aimed to develop a bank of text messages designed to provide advice, motivation, and support for decreasing cardiovascular risk. DESIGN: Iterative development process with mixed methods METHODS: An initial bank of 120 text messages was drafted based on behaviour change techniques, guidelines, and input from clinicians and public health experts. A questionnaire was then administered to participants (n = 53) for evaluation of message content, usefulness, and language. To test the process of delivery, a pilot study was conducted using a specifically designed computer programme that delivered messages to multiple mobile phones according to a pre-specified schedule. Data were collected regarding message timing, delivery, and usefulness. RESULTS: In the qualitative questionnaire, 92% of participants found the messages easy to understand and 86% found the messages contained useful information. Positive feedback was also obtained from the pilot study. Based on these results, together with suggestions provided, several messages were reworded and an additional 44 were written. The need for semi-personalization was also identified and a random set of 103 individualized messages was created. CONCLUSIONS: A final bank of 137 mobile telephone text messages designed to support behaviour change and decrease cardiovascular risk have been developed through a multistep iterative process. This provides a scientific approach for future developers of health-related text messages.

Design and rationale of the tobacco, exercise and diet messages (TEXT ME) trial of a text message-based intervention for ongoing prevention of cardiovascular disease in people with coronary disease: a randomised controlled trial protocol.

Background Although supporting lifestyle change is an effective way of preventing further events in people with cardiovascular disease, providing access to such interventions is a major challenge. This study aims to investigate whether simple reminders about behaviour change sent via mobile phone text message decrease cardiovascular risk. Methods and analysis Randomised controlled trial with 6 months of follow-up to evaluate the feasibility, acceptability and effect on cardiovascular risk of repeated lifestyle reminders sent via mobile phone text messages compared to usual care. A total of 720 patients with coronary artery disease will be randomised to either standard care or the TEXT ME intervention. The intervention group will receive multiple weekly text messages that provide information, motivation, support to quit smoking (if relevant) and recommendations for healthy diets and exercise. The primary end point is a change in plasma low-density lipoprotein cholesterol at 6 months. Secondary end points include a change in systolic blood pressure, smoking status, quality of life, medication adherence, waist circumference, physical activity levels, nutritional status and mood at 6 months. Process outcomes related to acceptability and feasibility of TEXT ME will also be collected. Ethics and dissemination Primary ethics approval was received from Western Sydney Local Health Network Human Research Ethics Committee-Westmead. Results will be disseminated via the usual scientific forums including peer-reviewed publications and presentations at international conferences. Clinical trials registration number ACTRN12611000161921.

Emergency head injury imaging: implementing NICE 2007 in a tertiary neurosciences centre and a busy district general hospital.

BACKGROUND: Head injuries are a common emergency department (ED) presentation. The National Institute for Health and Clinical Excellence (NICE) updated its guidance in September 2007 regarding imaging required for patients with head injuries. METHODS: A two-centre observational ED study was carried out, examining imaging practice in adults and children with head injuries attending pre-guideline and post-guideline implementation. Guideline implementation occurred through a formal implementation programme at the teaching hospital, and informally at the district general hospital (DGH). Retrospective extraction took place of prospectively recorded data case records and radiology department imaging registers. Pre-implementation data were collected from Salford Royal Foundation NHS Trust (SRFT) from January and February 2008 and post-implementation data in May 2008. Post-implementation data was collated from Royal Bolton Hospital Foundation NHS Trust (RBFT) from September to November 2007. Compliance with NICE 2007 was the primary outcome assessed. RESULTS: With the implementation of NICE 2007 guidelines at SRFT, a significant increase in compliance from 94.2% (92.9-95.5) to 98.8% (98.2-99.3) was observed for adults requiring head CTs, with an overall trend to improved clinical practice in the adult patient populations. However, a significant number of children (SRFT 68.7% and RBFT 77.1%) did not receive the indicated head CT scan following a head injury, after implementation of the guidelines. CONCLUSIONS: The SRFT implementation strategy employed was successful for adults, with the overall trend to increased clinical compliance post-guideline introduction. Evidence of a reluctance to adhere to the NICE recommendations for children indicated for CT head scan after a head injury was observed.

Single-chain recombinant HLA-DQ2.5/peptide molecules block α2-gliadin-specific pathogenic CD4+ T-cell proliferation and attenuate production of inflammatory cytokines: a potential therapy for celiac disease.

Celiac disease (CD) is a disorder of the small intestine caused by intolerance to wheat gluten and related proteins in barley and rye. CD4(+) T cells have a central role in CD, recognizing and binding complexes of HLA-DQ2.5 bearing gluten peptides that have survived digestion and that are deamidated by tissue transglutaminase (TG2), propagating a cascade of inflammatory processes that damage and eventually destroy the villous tissue structures of the small intestine. In this study, we present data showing that recombinant DQ2.5-derived molecules bearing covalently tethered α2-gliadin-61-71 peptide have a remarkable ability to block antigen-specific T-cell proliferation and inhibited proinflammatory cytokine secretion in human DQ2.5-restricted α2-gliadin-specific T-cell clones obtained from patients with CD. The results from our in vitro studies suggest that HLA-DQ2.5-derived molecules could significantly inhibit and perhaps reverse the intestinal pathology caused by T-cell-mediated inflammation and the associated production of proinflammatory cytokines.