Diabetes management during cardiac surgery in the UK: A survey.

AIM: To determine current practice regarding the diabetes management of people undergoing cardiac surgery in the UK. METHODS: We conducted an online survey of UK cardiothoracic surgeons. All cardiothoracic surgeons listed in the Society of Cardiothoracic Surgery membership directory were invited to participate. The survey, compiled using SurveyMonkey software, comprised 15 closed and open-ended questions about the management of people with diabetes pre- and peri-operatively. RESULTS: Sixty-two cardiothoracic surgeons from all 33 UK cardiac centres completed the survey. Of these, 44% responded that they routinely measure HbA1c preoperatively for all patients, 19% had an HbA1c threshold above which they would not operate and 21% currently undertake a point-of-care HbA1c measurement during the cardiothoracic outpatient visit. A total of 74% of respondents reported that it was 'easy' or 'very easy' to obtain a diabetes team review; diabetes nurse specialists were the members of the diabetes team working most closely with cardiac surgeons. Up to a third of the surgeons did not provide physical activity recommendations prior to admission and over 80% did not have a different preoperative or surgical diabetes protocol. Inconsistency in the responses within centres suggests that differences in practice may depend on individual surgeons rather than local policy. CONCLUSIONS: The study demonstrates there is only limited peri-operative management of diabetes in people undergoing cardiac surgery in the UK. There is an opportunity for greater involvement of the diabetes specialist team both before and during admission for surgery to improve outcomes. (Trial registration: ISRCTN10170306).

A Systematic Review and Meta-analysis of Paediatric Inflammatory Bowel Disease Incidence and Prevalence Across Europe.

BACKGROUND AND AIMS: Inflammatory bowel disease [IBD] is often one of the most devastating and debilitating chronic gastrointestinal disorders in children and adolescents. The main objectives here were to systematically review the incidence and prevalence of paediatric IBD across all 51 European states. METHODS: We undertook a systematic review and meta-analysis based on PubMed, CINAHL, the Cochrane Library, searches of reference lists, grey literature and websites, covering the period from 1970 to 2018. RESULTS: Incidence rates for both paediatric Crohn's disease [CD] and ulcerative colitis [UC] were higher in northern Europe than in other European regions. There have been large increases in the incidence of both paediatric CD and UC over the last 50 years, which appear widespread across Europe. The largest increases for CD have been reported from Sweden, Wales, England, the Czech Republic, Denmark and Hungary, and for UC from the Czech Republic, Ireland, Sweden and Hungary. Incidence rates for paediatric CD have increased up to 9 or 10 per 100 000 population in parts of Europe, including Scandinavia, while rates for paediatric UC are often slightly lower than for CD. Prevalence reported for CD ranged from 8.2 per 100 000 to approximately 60 and, for UC, from 8.3 to approximately 30. CONCLUSIONS: The incidence of paediatric IBD continues to increase throughout Europe. There is stronger evidence of a north-south than an east-west gradient in incidence across Europe. Further prospective studies are needed, preferably multinational and based on IBD registries, using standardized definitions, methodology and timescales.

Weekend admission and mortality for gastrointestinal disorders across England and Wales.

BACKGROUND: Little has been reported on mortality following admissions at weekends for many gastrointestinal (GI) disorders. The aim was to establish whether GI disorders are susceptible to increased mortality following unscheduled admission on weekends compared with weekdays. METHODS: Record linkage was undertaken of national administrative inpatient and mortality data for people in England and Wales who were hospitalized as an emergency for one of 19 major GI disorders. RESULTS: The study included 2 254 701 people in England and 155 464 in Wales. For 11 general surgical and medical GI disorders there were little, or no, significant weekend effects on mortality at 30 days in either country. There were large consistent weekend effects in both countries for severe liver disease (England: 26·2 (95 per cent c.i. 21·1 to 31·6) per cent; Wales: 32·0 (12·4 to 55·1 per cent) and GI cancer (England: 21·8 (19·1 to 24·5) per cent; Wales: 25·0 (15·0 to 35·9) per cent), which were lower in patients managed by surgeons. Admission rates were lower at weekends than on weekdays, most strongly for severe liver disease (by 43·3 per cent in England and 51·4 per cent in Wales) and GI cancer (by 44·6 and 52·8 per cent respectively). Both mortality and the weekend mortality effect for GI cancer were lower for patients managed by surgeons. DISCUSSION: There is little, or no, evidence of a weekend mortality effect for most major general surgical or medical GI disorders, but large weekend effects for GI cancer and severe liver disease. Lower admission rates at weekends indicate more severe cases. The findings for severe liver disease may suggest a lack of specialist hepatological resources. For cancers, reduced availability of end-of-life care in the community at weekends may be the cause.

The impact of social deprivation on mortality following hip fracture in England and Wales: a record linkage study.

UNLABELLED: We used routine hospital data to investigate whether socially deprived patients had an increased risk of dying following hip fracture compared with affluent patients. We found that the most deprived patients had a significantly increased risk of dying at 30, 90 and 365 days compared with the most affluent patients. INTRODUCTION: To identify whether social deprivation has any effect on mortality risk after emergency admission with hip fracture and to determine whether any increased mortality observed among deprived groups was associated with patient and hospital-related factors. METHODS: We used routine, linked hospital inpatient and mortality data for emergency admissions with a hip fracture in both England and Wales between 2004 and 2011. Mortality rates at 30, 90 and 365 days were reported. Logistic regression was used to identify any significant increases in mortality with higher levels of social deprivation and the influence of other risk factors on any increased mortality among the most deprived group. RESULTS: Mortality rates at 30, 90 and 365 days were 9.3, 17.4 and 29.0 % in England and 8.3, 16.1 and 27.9 % in Wales. Social deprivation was significantly associated with increased mortality in the most deprived quintile compared with the least deprived quintile at 30, 90 and 365 days in England (OR = 1.187, 1.185 and 1.154, respectively) and at 90 and 365 days in Wales (1.135 and 1.203). There was a little interaction between deprivation and other risk factors influencing 30- and 365-day mortality except for patient age, pre-fracture residence and hospital size. CONCLUSIONS: We demonstrated a positive association between social deprivation and increased mortality at 30 days post-admission for hip fracture in both England and Wales that was still evident at 90 and 365 days. We found little influence of other factors on social inequalities in mortality risk at 30 and 365 days post-admission.

Review article: the prevalence of Helicobacter pylori and the incidence of gastric cancer across Europe.

BACKGROUND: There is little up-to-date review evidence on the prevalence of Helicobacter pylori across Europe. AIM: To establish regional and national patterns in H. pylori prevalence across Europe. Secondly, to establish trends over time in H. pylori prevalence and gastric cancer incidence and, thirdly, to report on the relationship between H. pylori prevalence and age group across Europe. METHODS: A review of H. pylori prevalence from unselected surveys of adult or general populations across 35 European countries and four European regions since 1990. Secondly, an analysis of trends over time in H. pylori prevalence and in gastric cancer incidence from cancer registry data. RESULTS: Helicobacter pylori prevalence was lower in northern and western Europe than in eastern and southern Europe (P < 0.001). In 11 of 12 European studies that reported on trends, there were sharp reductions in H. pylori prevalence (mean annual reduction = 3.1%). The mean annual reduction in the incidence of gastric cancer across Europe from 1993 to 2007 was 2.1% with little variation regionally across Europe (north 2.2%, west 2.3%, east 1.9% and south 2.0%). Sharp increases in age-related prevalence of H. pylori often levelled off for middle age groups of about 50 years onwards, especially in areas with high prevalence. CONCLUSIONS: This review shows that H. pylori prevalence is much higher in less affluent regions of Europe and that age-related increases in prevalence are confined to younger age groups in some areas. There were sharp reductions in both H. pylori prevalence and gastric cancer incidence throughout Europe.

Adherence and outcomes of patients prescribed dabigatran (Pradaxa) in routine clinical practice.

AIM: To explore and detail clinical experiences of dabigatran, a novel anticoagulant, after it became available in New Zealand in July 2011. METHODS: A cohort of patients was recruited from Hutt Hospital and the two largest primary care practices in the Hutt Valley region. They were included if they took at least one dose of dabigatran between July 2011 and April 2012. Participants undertook a questionnaire 3-12 months after starting dabigatran assessing adherence, perceived side-effects and complications. Those presenting due to an adverse event were analysed separately. RESULTS: Of 102 patients identified, 92 were recruited to this study. At a median of 8 months, 70% of participants were still taking dabigatran, significantly lower than in the RE-LY trial at 12 months (P = 0.0002). The commonest reason given for discontinuation was gastrointestinal (GI) side-effects. Rates of serious adverse outcomes on dabigatran therapy were relatively low. Patients expressed polarised comments, both positive and negative, regarding their experiences of dabigatran. CONCLUSIONS: A high rate of discontinuation of dabigatran, mainly due to GI symptoms, was observed. There does not appear to be any specific predictor of dabigatran tolerance. When prescribed according to guidelines, rates of serious adverse events associated with dabigatran appear to be low.

The incidence of acute pancreatitis: impact of social deprivation, alcohol consumption, seasonal and demographic factors.

BACKGROUND: The incidence of acute pancreatitis has increased sharply in many European countries and the USA in recent years. AIM: To establish trends in incidence and mortality for acute pancreatitis in Wales, UK, and to assess how incidence may be linked to factors including social deprivation, seasonal effects and alcohol consumption. METHODS: Use of record linked inpatient, mortality and primary care data for 10,589 hospitalised cases of acute pancreatitis between 1999 and 2010. RESULTS: The incidence of acute pancreatitis was 30.0 per 100,000 population overall, mortality was 6.4% at 60 days. Incidence increased significantly from 27.6 per 100,000 in 1999 to 36.4 in 2010 (average annual increase = 2.7% per year), there was little trend in mortality (0.2% average annual reduction). The largest increases in incidence were among women aged <35 years (7.9% per year) and men aged 35-44 (5.7%) and 45-54 (5.3%). Incidence was 1.9 times higher among the most deprived quintile of patients compared with the most affluent (3.9 times higher for alcoholic acute pancreatitis and 1.5 for gallstone acute pancreatitis). Acute pancreatitis was increased significantly during the Christmas and New Year weeks by 48% (95% CI = 24-77%) for alcoholic aetiology, but not for gallstone aetiology (9%). Alcoholic admissions were increased with higher consumption of spirits and beer, but not wine. CONCLUSIONS: The study shows an elevated rate of alcoholic acute pancreatitis during the Christmas and New Year period. Acute pancreatitis continues to rise, most rapidly for young women, while alcoholic acute pancreatitis is linked strongly with social deprivation.

Spinal cord injury rehabilitation: the experience of women.

STUDY DESIGN: Qualitative study. OBJECTIVES: To develop the knowledge base regarding women's experiences of spinal cord injury (SCI) rehabilitation. SETTING: United Kingdom. METHODS: Qualitative interviews with 10 women from four regional SCI rehabilitation centres were transcribed verbatim and analysed according to grounded theory. RESULTS: The central psychosocial problem identified for women during SCI rehabilitation was vulnerability. Vulnerability was amplified by lack of privacy within the rehabilitation centre, by negative staff interactions (associated with perceived lack of control and lack of respect) and by women's minority status in the rehabilitation setting, which at times left women feeling marginalized and inferior. Vulnerability was contained by: negotiating privacy and space; receiving support and encouragement from staff, other patients and family; and by adopting a positive attitude. CONCLUSION: The SCI rehabilitation environment and interactions within it have the potential to influence significantly, either positively or negatively, women's feelings and behaviours as they begin to negotiate a revised identity as a disabled person. There is a need for further research to be carried out in this area in order that women's needs and concerns can be better understood and clinical practice developed accordingly.

Paraoxonase 2 (PON2) polymorphisms and development of renal dysfunction in type 2 diabetes: UKPDS 76.

AIMS/HYPOTHESIS: Identification of variants predicting development of renal dysfunction would offer substantial clinical benefits. There is evidence that coding non-synonymous variants in the gene encoding paraoxonase 2 (PON2) are associated with nephropathy in both type 1 and type 2 diabetes. METHODS: We examined the relationship between variation at the C311S and A148G polymorphisms (together with PON2 intronic variant rs12704795) and indices of renal dysfunction (progression to micro- and macroalbuminuria, plasma creatinine increases) in 3,374 newly diagnosed type 2 diabetic subjects from the UK Prospective Diabetes Study followed prospectively (median 14.0 years), using proportional hazards models, adjusted for sex, ethnicity and other known or putative risk factors. RESULTS: rs12704795 genotypes were associated with differing rates of development of microalbuminuria (relative risk [RR] for CC vs AA homozygotes 0.68 [95% CI 0.54-0.87], p=0.002) but not other measures of worsening renal function. Heterozygotes for C311S were more likely to develop microalbuminuria (RR=1.31 [95% CI 1.11-1.54], p=0.001) but less likely to double creatinine levels during follow-up (RR=0.49 [95% CI 0.27-0.89], p=0.02). There was no corroboration of this latter association for related outcomes and no prior evidence supports heterosis effects at this locus. CONCLUSIONS/INTERPRETATION: We conclude that the PON2 variants typed in this study have, at best, a small effect on the risk of renal dysfunction in type 2 diabetes.

Combustion synthesis of porous materials for bone replacement.

Production of highly porous composite materials by traditional materials processing is limited by difficult processing techniques. However, combustion or self-propagating high-temperature synthesis (SHS) allows many porous ceramic, intermetallic, glass, and metallic systems to be formed with relative ease. Examination of the SHS reaction parameters that control the extent of porosity further increases the feasibility of producing novel composites for such uses as bone implant applications. Combustion Synthesis of porous Ti-TiBx and NiTi composite materials have been studied with respect to the sensitivity to the SHS reaction parameters of stoichiometry, green density, gasifying agents, and gravity. The main objective of this research program is to engineer the required porosity and mechanical properties into the composite materials to meet the requirements of a consumer, such as for the application of bone replacement materials. Biomedical results indicated strongly that there is natural bone ingrowth with no apparent immune response in the composite materials produced by this process.

Low incidence of point mutations detected in the p53 tumor suppressor gene from chemically induced rat renal mesenchymal tumors.

Previous studies have shown renal mesenchymal tumors (RMTs) induced in rats by a single intrarenal injection of nickel subsulfide and iron are more pleomorphic and metastatically aggressive than RMTs induced by a single ip injection of methyl(methoxymethyl)nitrosamine (DMN-OMe). While both RMT types contain high levels of K-ras activation, the specific mutational spectra within codon 12 of K-ras are quite different. Nickel subsulfide and iron-induced tumors exhibited codon 12 GGT-->GTT transversions exclusively, while DMN-OMe RMTs showed a wide array of codon 12 mutations, as well as mutations within codons 61 and 63 [K. G. Higinbotham, J. M. Rice, B. A. Diwan, K. S. Kasprzak, C. D. Reed, and A. O. Perantoni, Cancer Res., 52: 4747-4751, 1992; K. G. Higinbotham, J. M. Rice, and A. O. Perantoni, Mol. Carcinog., 5: 136-139, 1992]. In an effort to further correlate carcinogen-specific molecular events in renal tumors, we investigated the p53 tumor suppressor gene in RMTs induced by these two carcinogens for the presence of point mutations. The evolutionarily conserved portion of the coding region of the gene, including part of exon 4 through exon 10, was surveyed for point mutations utilizing single-strand conformation polymorphism and chemical cleavage of mismatches analyses. None (0 of 10) of the nickel subsulfide and iron-induced RMTs and only 1 of 10 DMN-OMe-induced tumors that were evaluated contained point mutations within this portion of the p53 gene. Direct sequencing of the one single-strand conformation polymorphism and chemical cleavage of mismatches-"positive" DMN-OMe-induced RMT revealed a GCC-->GTC (Ala-->Val) transition in codon 345 within exon 10. These results suggest that the different tumorigenic phenotypes exhibited by these two RMTs are not the result of specific mutations or patterns of mutations within the portion of the p53 gene examined and that the mutated p53 tumorigenic pathway, whereby p53 plays a major role in many human neoplasms, does not function in RMTs induced by either agent.

The use of mouse/human chimaeric antibodies to investigate the roles of different antibody isotypes, including IgA2, in the killing of Schistosoma mansoni schistosomula by eosinophils.

We report the use of a matched set of mice/human chimaeric antibodies, directed against the 5-iodo-4-hydroxyl-3-nitrophenacetyl (NIP) hapten, to investigate the roles of different human isotypes in antibody-mediated eosinophil-dependent killing of schistosomula. The chimaeric antibodies consist of mouse VH, VL and CL regions with human gamma 1, gamma 2, gamma 3 (2 allotypes), gamma 4, alpha 2, mu or epsilon CH regions and were used in in vitro assays with human eosinophils and NIP-coated S. mansoni schistosomula. Some anti-NIP isotypes mediated high levels of killing, which was specific for NIP-coated larvae, and we suggest that these antibodies will be a valuable tool for studies on the role of antibody isotypes in anti-schistosome immune effector mechanisms. In particular, this method directly demonstrated, for the first time, that IgA is highly effective in mediating the killing of metazoan parasites by human eosinophils.

Human immunity to Schistosoma mansoni: observations on mechanisms, and implications for control.

This review summarizes the personal experiences of the authors and their colleagues during ten years of field and laboratory studies on human immunity to Schistosoma mansoni infections. There is evidence for the very slow development with age of an acquired resistance to reinfection (demonstrable after chemotherapy of the primary infection) distinguishable from a lack of reinfection due to reduced exposure. The implications of this immunity for the design of chemotherapy programs targeted at infected schoolchildren are discussed. Observational studies on the mechanisms of immunity have demonstrated a marked helminthocidal capacity of eosinophils. Subsequent correlative studies have indicated a role of IgM and IgG2 "blocking" antibodies in maintaining the continued susceptibility of young children, and of IgE antibodies in mediating protection in older individuals. Some problems in studying human immunity, and the implications for vaccine development, are also discussed.

LIGO: The Laser Interferometer Gravitational-Wave Observatory.

The goal of the Laser Interferometer Gravitational-Wave Observatory (LIGO) Project is to detect and study astrophysical gravitational waves and use data from them for research in physics and astronomy. LIGO will support studies concerning the nature and nonlinear dynamics of gravity, the structures of black holes, and the equation of state of nuclear matter. It will also measure the masses, birth rates, collisions, and distributions of black holes and neutron stars in the universe and probe the cores of supernovae and the very early universe. The technology for LIGO has been developed during the past 20 years. Construction will begin in 1992, and under the present schedule, LIGO's gravitational-wave searches will begin in 1998.