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.

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.

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.

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.

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.

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.

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.

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.

Stereological analysis of hepatic fine structure in the Fischer 344 rat. Influence of sublobular location and animal age.

Stereological analysis of hepatic fine structure in Fischer 344 male rats at 1, 6, 10, 16, 20, 25, and 30 mo of age revealed differences in the amounts and distributions of hepatocellular organelles as a function of sublobular location or animal age. Between 1 and 16 mo of age, both the centrolobular and periportal hepatocytes increased in volume by 65 and 35%, respectively. Subsequently, the cell volumes declined until the hepatocytes of 30-mo-old rats approached the size of those found in the youngest animals. Regardless of animal age, the centrolobular cells were consistently larger than the corresponding periportal hepatocytes. The cytoplasmic and ground substance compartments reflected similar changes in their volumes, although there was no significant alteration in the nuclear volume. The volumes of the mitochondrial and microbody compartments increased and decreased concomitant with the changes in average hepatocyte size. Both lobular zones in the 30-mo-old rats contained significantly smaller relative volumes of mitochondria than similar parenchyma in 16-mo-old animals. The volume density of the dense bodies (lysosomes) increased markedly in both lobular zones between 1 and 30 mo of age, confirming reports of an age-dependent increase in this organelle. The surface area of the endoplasmic reticulum in the centrolobular and periportal hepatocytes reached its maximum level in the 10-mo-old rats and subsequently declined to amounts which approximated those measured in the 1-mo-old animals. This age-related loss of intracellular membrane is attributable to a significant reduction in the surface area of the smooth-surfaced endoplasmic reticulum (SER) in animals beyond 16 mo of age. The amount of rough-surfaced endoplasmic reticulum (RER) in the periportal parenchymal cells was unaffected by aging, but the centrolobular hepatocytes of 30-mo-old animals contained 90% more RER than similar cells in the youngest rats. The centrolobular parenchyma contained more SER and the portal zones more RER throughout the age span studied. These quantitative data suggest that (a) certain hepatic fine structural parameters undergo marked changes as a function of animal age, (b) there exists a gradient in hepatocellular fine structure across the entire liver lobule, and (c) there are remarkable similarities in hepatocyte ultrastructure between very young and senescent animals, including cell size and the amount of SER.

Age-related changes in the hepatic endoplasmic reticulum: a quantitative analysis.

Morphometric analysis demonstrated a twofold increase in the surface area of the hepatic endoplasmic reticulum in Fischer 344 rats between 1 and 20 months of age, followed by a significant decrease in this parameter between 20 and 30 months. These changes are attributed to the smooth-surfaced endoplasmic reticulum, since neither the rough-surfaced variety nor the Golgi membranes underwent any significant change in surface area as a function of the age of the animal.

Entry of insulin into human cultured lymphocytes: electron microscope autoradiographic analysis.

Electron microscope autoradiographs were prepared of IM-9 human cultured lymphocytes incubated with iodine-125-labeled insulin. With the use of [125I]insulin and Ilford L-4 emulsion, the technique had a resolution half-distance of approximately 0.085 micrometer. Autoradiographs revealed a time-dependent entry of insulin into the cell interior that was maximal after 30 minutes of incubation. At this time point nearly 40 percent of the [125I]insulin was in the interior of the cell at a distance 1 micrometer or greater from the plasma membrane. Grain distribution and volume density analyses revealed that the intracellular insulin was concentrated in the endoplasmic reticulum and nuclear membrane.

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.

Study on the prevalence of Toxoplasma gondii and Neospora caninum and molecular evidence of Encephalitozoon cuniculi and Encephalitozoon (Septata) intestinalis infections in red foxes (Vulpes vulpes) in rural Ireland.

Thoracic fluid (pleural fluid and clotted blood) from 206 foxes were examined for antibodies to Toxoplasma gondii and 220 thoracic fluid samples were tested for Neospora caninum antibodies using indirect immunofluorescent antibody tests (IFAT). A total of 115 (56%) and six (3%) foxes had antibodies to T. gondii and N. caninum, respectively. The brains from 148 foxes were examined for histological lesions and pathological changes suggestive of parasitic encephalitis were observed in 33 (22%). Two thirds of these foxes had antibodies to T. gondii and one fox had antibodies to both T. gondii and N. caninum. PCR assays carried out on DNA extracted from the 33 brains with histological lesions were negative for N. caninum but one of the brains was positive for T. gondii. Microsporidian DNA was also amplified from the brains of two of these foxes. Sequencing these amplicons revealed 100% homology with Encephalitozoon (Septata) intestinalis in one fox and Encephalitozoon cuniculi in the second fox. This is the first report of Encephalitozoon infections in wildlife in Ireland.

Determination of required pharmacological knowledge for clinical practice in emergency medicine using a modified Delphi technique.

AIMS: To identify the content of the national postgraduate pharmacology curriculum for trainees in UK emergency medicine. METHODS: Modified three-round iterated Delphi technique employing a participant panel of 160 randomly selected consultants in emergency medicine. Initial Delphi content was derived from objective analysis of pharmacy stock lists and patient record cards. The outcome measure was percentage agreement, among participants, to listed aspects of therapeutics as being core knowledge for autonomous clinical practice in the emergency department. A national curriculum document was derived from the study data. RESULTS: Response rates ranged from 66-76% after three Delphi rounds. From an initial overall questionnaire content of 526 discrete items, 59% was retained as core knowledge following iteration. The subsequent national curriculum document acts as a resource tool both for question setting in postgraduate examinations and for self-directed trainee learning before the sitting of these examinations. CONCLUSIONS: Application of a national consensus methodology allows determination of curricular content in pharmacology as part of the development of a robust College educational portfolio.

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.

Bidirectional crossover and late outcome after coronary angioplasty and bypass surgery: 8 to 11 year follow-up.

Between March 1978 and July 1981, 217 symptomatic patients underwent coronary angioplasty as an alternative to coronary bypass surgery. Angioplasty was successful in 143 patients (66%), unsuccessful but uncomplicated in 65 (30%) and complicated in 9 (4%) by one or more of the following criteria: Q wave myocardial infarction (2%), emergency surgery (4%) or death (0.5%). Late follow-up evaluation was obtained in 213 patients at a mean of 9 +/- 1 years. Of patients in whom angioplasty was successful, 59 (42%) of 140 required another revascularization procedure (repeat angioplasty in 26% and bypass surgery in 16%). The actuarial survival rate at 5, 9 and 10 years after successful angioplasty was 98%, 93% and 92%, respectively. Of the 65 patients with unsuccessful and uncomplicated angioplasty (usually as a result of technical factors), 58 underwent elective bypass surgery within 2 months and 56 survived. These 56 surgical patients were compared with the 140 patients with successful angioplasty. Univariate analysis of prognostic factors did not reveal significant differences between these two groups. At late follow-up study, the successful angioplasty and the successful surgical groups had similar rates of survival (93% versus 95%, p = NS) and of death or infarction, or both (11% versus 12.5%, p = NS). Repeat revascularization was required more frequently after successful angioplasty than after surgery (42% versus 18%, p less than 0.001). Crossover from angioplasty to surgery occurred slightly more often than from surgery to angioplasty (16% versus 12.5%, p = NS). The time to crossover from angioplasty to surgery occurred earlier than from surgery to angioplasty (mean 21 versus 76 months, p less than 0.001).

Genetic analysis of suppressors of the veA1 mutation in Aspergillus nidulans.

Light-dependent conidiation in the filamentous ascomycete, Aspergillus nidulans, is contingent on the allelic state of the velvet (veA) gene. Light dependence is abolished by a mutation in this gene (veA1), which allows conidiation to occur in the absence of light. We have isolated and characterized six extragenic suppressors of veA1 that restore the light-dependent conidiation phenotype. Alleles of four genes, defined by complementation tests, were subjected to extensive genetic and phenotypic analysis. The results of light-dark shifting experiments and the phenotypes of double mutant combinations are consistent with the possibility that the expression of the light-dependent phenotype is regulated by specific interactions of the suppressor gene products with the velvet gene product and with each other.

Identification of HIV-1 in semen following primary HIV-1 infection.

OBJECTIVE: To determine whether HIV could be identified in semen samples during the first few weeks after infection. DESIGN: A series of three homosexual men with symptomatic primary HIV-1 infection. METHODS: Each subject provided a series of semen samples that was examined for HIV-1 by virus culture, polymerase chain reaction (PCR) and transmission electron micrography. RESULTS: The first samples obtained for each subject (17, 22 and 24 days following onset of primary HIV-1 infection) were all positive by PCR and negative by viral culture. Of 13 samples obtained during the first 80 days after onset of primary HIV-1 infection and analysed by PCR, 10 were positive. Only one of these samples was virus culture-positive. Four semen samples obtained from two subjects during treatment with zidovudine were PCR-positive. Eight samples were examined for presence of HIV-1 by electron microscopy and one was found to be positive. CONCLUSIONS: These results indicate that men with HIV-1 infection are potentially infectious through sexual transmission during the first few weeks after infection. The findings emphasize that individuals in all stages of HIV-1 infection should practise safer sex to reduce transmission of HIV-1.