Objectives: To establish a reproducible method to estimate he point prevalence of smoking and second-hand smoke (SHS) exposure in cars, and to compare this prevalence between two areas of contrasting ...socioeconomic status. Method: A method involving two teams of observers was developed and evaluated. It involved observing 16 055 cars in Wellington, New Zealand. Two of the observation sites represented a high and a low area of deprivation (based on a neighbourhood deprivation index) and three were in the central city. Results: A 4.1% point prevalence of smoking in cars was observed (95% confidence interval (CI) 3.8% to 4.4%). There was a higher prevalence of smoking in cars in the high deprivation area relative to the other sites, and particularly compared to the low deprivation area (rate ratio relative to the latter 3.2, 95% CI 2.6 to 4.0). Of cars with smoking, 23.7% had other occupants being exposed to SHS. Cars with smoking and other occupants were significantly more likely to have a window open (especially if the smoker was not the driver). The observation method developed was practical, and inter-observer agreement was high (κ value for the “smoking seen in car” category 0.95). Conclusions: Observational studies can be an effective way of investigating smoking in cars. The data from this survey suggest that smoking in cars occurs at a higher rate in relatively deprived populations and hence may contribute to health inequalities. Fortunately, there are a number of policy options for reducing SHS exposure in cars including mass media campaigns and laws for smoke-free cars.
Recent work has highlighted a possible role for altered epigenetic modifications, including differential DNA methylation, in susceptibility to psychiatric illness. Here, we investigate blood-based ...DNA methylation in a large family where a balanced translocation between chromosomes 1 and 11 shows genome-wide significant linkage to psychiatric illness. Genome-wide DNA methylation was profiled in whole-blood-derived DNA from 41 individuals using the Infinium HumanMethylation450 BeadChip (Illumina Inc., San Diego, CA). We found significant differences in DNA methylation when translocation carriers (n = 17) were compared to related non-carriers (n = 24) at 13 loci. All but one of the 13 significant differentially methylated positions (DMPs) mapped to the regions surrounding the translocation breakpoints. Methylation levels of five DMPs were associated with genotype at SNPs in linkage disequilibrium with the translocation. Two of the five genes harbouring significant DMPs, DISC1 and DUSP10, have been previously shown to be differentially methylated in schizophrenia. Gene Ontology analysis revealed enrichment for terms relating to neuronal function and neurodevelopment among the genes harbouring the most significant DMPs. Differentially methylated region (DMR) analysis highlighted a number of genes from the MHC region, which has been implicated in psychiatric illness previously through genetic studies. We show that inheritance of a translocation linked to major mental illness is associated with differential DNA methylation at loci implicated in neuronal development/function and in psychiatric illness. As genomic rearrangements are over-represented in individuals with psychiatric illness, such analyses may be valuable more widely in the study of these conditions.
Background Emergency abdominal surgery is associated with poor patient outcomes. We studied the effectiveness of a national quality improvement (QI) programme to implement a care pathway to improve ...survival for these patients. Objectives The objectives were to assess whether or not the QI programme improves 90-day survival after emergency abdominal surgery; to assess effects on 180-day survival, hospital stay and hospital readmission; and to better understand these findings through an integrated process evaluation, ethnographic study and cost-effectiveness analysis. Design This was a stepped-wedge cluster randomised trial. Hospitals were organised into 15 geographical clusters, and commenced the QI programme in random order over 85 weeks. Analyses were performed on an intention-to-treat basis. The primary outcome was analysed using a mixed-effects parametric survival model, adjusting for time-related effects. Ethnographic and economics data were collected in six hospitals. The process evaluation included all hospitals. Setting The trial was set in acute surgical services of 93 NHS hospitals. Participants Patients aged ≥ 40 years who were undergoing emergency abdominal surgery were eligible. Intervention The intervention was a QI programme to implement an evidence-based care pathway. Main outcome measures The primary outcome measure was mortality within 90 days of surgery. Secondary outcomes were mortality within 180 days, length of hospital stay and hospital readmission within 180 days. The main economic measure was the quality-adjusted life-years. Data sources Data were obtained from the National Emergency Laparotomy Audit database; qualitative interviews and ethnographic observations; quality-of-life and NHS resource use data were collected via questionnaires. Results Of 15,873 eligible patients from 93 NHS hospitals, primary outcome data were analysed for 8482 participants in the usual care group and 7374 in the QI group. The primary outcome occurred in 1393 participants in the usual care group (16%), compared with 1210 patients in the QI group (16%) QI vs. usual care hazard ratio (HR) 1.11, 95% confidence interval (CI) 0.96 to 1.28. No differences were found in mortality at 180 days or hospital readmission; there was a small increase in hospital stay in the QI group (HR for discharge 0.90, 95% CI 0.83 to 0.97). There were only modest improvements in care processes following QI implementation. The ethnographic study revealed good QI engagement, but limited time and resources to implement change, affecting which processes teams addressed, the rate of change and eventual success. In some sites, there were challenges around prioritising the intervention in busy environments and in obtaining senior engagement. The intervention is unlikely to be cost-effective at standard cost-effectiveness thresholds, but may be cost-effective over the lifetime horizon. Limitations Substantial delays were encountered in securing data access to national registries. Fewer patients than expected underwent surgery and the mortality rate was lower than anticipated. Conclusions There was no survival benefit from a QI programme to implement a care pathway for patients undergoing emergency abdominal surgery. The modest impact of the intervention on process measures, despite good clinician engagement, may have been limited by the time and resources needed to improve patient care. Future work Future QI programmes must balance intervention complexity with the practical realities of NHS services to ensure that such programmes can be delivered with the resources available. Trial registration Current Controlled Trials ISRCTN80682973 and The Lancet protocol 13PRT/7655. Funding This project was funded by the National Institute for Health Research (NIHR) Health Services and Delivery Research programme and will be published in full in Health Services and Delivery Research ; Vol. 7, No. 32. See the NIHR Journals Library website for further project information.
Established pharmaceutical products often have complex supply chains and regulatory histories. In Europe the European Directorate for the Quality of Medicine (EDQM) (information from European ...Pharmacopoeia website, http://www.pheur.org/) have promoted the use of certificates of suitability of the European Pharmacopoeia to ensure the quality of medicines by a commonly recognised set of standards, allowing the free movement of medicinal products in member states. This contribution describes the analytical and synthetic chemistry required to synthesise the impurities of manufacture of clobetasone butyrate.
ABSTRACT
Non‐allogeneic factors such as increased nephron “workload” may contribute to chronic renal allograft rejection. Reducing dietary protein from 20 % to 8 % was tested in a model of chronic ...rejection: Dark Agouti kidney to Albinc Surgery recipient, “tolerised” by previous donor blood transfusions. Survival, weight gain, serum creatinine concentration and creatinine clearance were similar for both groups at all times. Urinary protein was significantly (P < 0.05) lower in the low‐protein (LP) group 1 montl after transplantation. After 3 and 6 months, both groups demonstrated mild chronic rejection. After 6 months, tubular atrophy was significantly (P < 0.05) less in the LP group and interstitial fibrosis was marginally reduced. Glomerular hypertrophy, glomerular sclerosis, tubular dilatation, leucocyte infiltration, adhesion molecule expression and TGF‐β1 mRNA expression were similarly increased in both groups. Thus, reducing dietary protein to 8 % lowered urinary protein, but did not significantly affect the development of chronic rejection in renal allografts beyond affording a degree of protection from tubulointerstitial damage.
A model of chronic renal rejection in the Dark-Agouti to Albino-Surgery rat combination is described. In a number of cases, the original allograft was replaced by a second Dark-Agouti allograft. ...Seventy-five percent of rats experienced early episodes of rejection that subsided spontaneously. Second allografts had better initial renal function. Variable degrees of tubular atrophy, interstitial fibrosis, vascular damage, glomerulosclerosis, deposition of humoral mediators, and mononuclear leukocyte infiltrate were observed in all long-term allografts. Chronic damage increased with time, and was less severe in second allografts. At 5 days, total interstitial infiltrate was similar to that seen in unmodified rejection, but there was a significant increase in CD4+ cells and a decrease in ED2 and IL-2R expression. Subsequently, the total interstitial infiltrate decreased with time, although it remained significantly higher than in isografts and residual kidneys from uninephrectomized rats. No significant decrease over time was seen in numbers of CD4+ and CD45RC+ cells. The latter had a marked focal distribution after 100 days. Total leukocyte infiltrate was similar in original and second allografts, but there were changes in the proportions of leukocyte subpopulations, including significantly lower numbers of CD45RC+ cells in the latter. The persistence of CD45RC+ cells throughout the course of chronic rejection and their lower numbers in the second allografts favors a role for these cells in the development of chronic injury. The model of chronic renal allograft rejection characterized in this study will be valuable in further studies of the mechanisms of injury in this pathology.
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