Microvascular complications in South African patients with long duration diabetes mellitus

Objective. To determine the prevalence of microvascular complications in South African black and Indian patients with long-duration diabetes mellitus (DM).Design. A retrospective analysis was undertaken of clinical records of 219 OM patients (132 black, 87 Indian) with longduration OM (over 10 years) attending a diabetes clinic in Durban. Data recorded on each subject included demographic details (age, gender, ethnic group, type of diabetes, age of onset and duration of diabetes), presence of retinopathy, markers of nephropathy and biochemical variables. The prevalence of complications and the clinical and biochemical parameters were evaluated for type 1 and type 2 diabetes and for each ethnic group.Results. Of the 219 patients, 47 had type 1 OM (36 blacks, 11 Indians) and 172 were classified as type 2 OM (96 blacks, 76 Indians). The mean age of onset of OM wa later in blacks than Indians, both for type 1 (P < 0.05) and type 2 OM (P < 0.01). In patients with type 1 OM, the prevalence of retinopathy was 53.2% (blacks 55.6%, Indians 45.5%), persistent proteinuria was found in 23.4% (blacks 25%, Indians 18.2%) and hypertension in 34%. 0 ethnic difference was found except for the prevalence of hyperten ion which was higher in blacks than Indians (41.7% v. 9.1%, P < 0.5). Onset of retinopathy from time of diabetes diagno is occurred earlier in blacks than Indians (13.0 ± 4.6 yrs v. 18.0 ± 4.6 yrs, P < 0.05). For the type 2 DM group, retinopathy was found in 64.5% (black v. Indian 68.8 v. 59.2%) and per istent proteinuria in 25% (black v. Indian 30.2 v. 1 .4%). Hypertension wa observed in 68% and wa more prevalent in blacks (84.4 v. 47.,*%, P < 0.01) There was an earlier onset of retinopathy (P < 0,05) and hypertension (P < 0.01) from time of diabetes diagnosis in blacks than Indians. In the type 1 OM group retinopathy was a sociated with a ignificantly longer duration of diabetes (P < 0.05) and higher glycated haemoglobin (HbA1) (P < 0.05). For type 2 DM subjects there was a significant association between retinopathy and longer duration of diabetes (P < 0.05) and higher systolic blood pressure (P < 0.05).Conclusion. 1his study has shown that there is a high prevalence of microvascular complications in South African patients with long-duration diabetes mellitus

Type and timing of menopausal hormone therapy and breast cancer risk: individual participant meta-analysis of the worldwide epidemiological evidence

B Background Published findings on breast cancer risk associated with different types of menopausal hormone therapy (MHT) are inconsistent, with limited information on long-term effects. We bring together the epidemiological evidence, published and unpublished, on these associations, and review the relevant randomised evidence. Methods Principal analyses used individual participant data from all eligible prospective studies that had sought information on the type and timing of MHT use; the main analyses are of individuals with complete information on this. Studies were identified by searching many formal and informal sources regularly from Jan 1, 1992, to Jan 1, 2018. Current users were included up to 5 years (mean 1·4 years) after last-reported MHT use. Logistic regression yielded adjusted risk ratios (RRs) comparing particular groups of MHT users versus never users. Findings During prospective follow-up, 108 647 postmenopausal women developed breast cancer at mean age 65 years (SD 7); 55 575 (51%) had used MHT. Among women with complete information, mean MHT duration was 10 years (SD 6) in current users and 7 years (SD 6) in past users, and mean age was 50 years (SD 5) at menopause and 50 years (SD 6) at starting MHT. Every MHT type, except vaginal oestrogens, was associated with excess breast cancer risks, which increased steadily with duration of use and were greater for oestrogen-progestagen than oestrogen-only preparations. Among current users, these excess risks were definite even during years 1–4 (oestrogen-progestagen RR 1·60, 95% CI 1·52–1·69; oestrogen-only RR 1·17, 1·10–1·26), and were twice as great during years 5–14 (oestrogen-progestagen RR 2·08, 2·02–2·15; oestrogen-only RR 1·33, 1·28–1·37). The oestrogen-progestagen risks during years 5–14 were greater with daily than with less frequent progestagen use (RR 2·30, 2·21–2·40 vs 1·93, 1·84–2·01; heterogeneity p<0·0001). For a given preparation, the RRs during years 5–14 of current use were much greater for oestrogen-receptor-positive tumours than for oestrogen-receptor-negative tumours, were similar for women starting MHT at ages 40–44, 45–49, 50–54, and 55–59 years, and were attenuated by starting after age 60 years or by adiposity (with little risk from oestrogen-only MHT in women who were obese). After ceasing MHT, some excess risk persisted for more than 10 years; its magnitude depended on the duration of previous use, with little excess following less than 1 year of MHT use. Interpretation If these associations are largely causal, then for women of average weight in developed countries, 5 years of MHT, starting at age 50 years, would increase breast cancer incidence at ages 50–69 years by about one in every 50 users of oestrogen plus daily progestagen preparations; one in every 70 users of oestrogen plus intermittent progestagen preparations; and one in every 200 users of oestrogen-only preparations. The corresponding excesses from 10 years of MHT would be about twice as great.Central data collection, checking, analysis, and manuscript preparation was supported by the core funding of the Cancer Epidemiology Unit by CR-UK (C570/A16491) and the MRC (MR/K02700X/1)

Uninterested youth? Young people's attitudes towards party politics in Britain

Following the outcome of the 2001 and 2005 General Elections, when the numbers of abstainers outweighed the numbers of Labour voters on both occasions, much attention has focused upon the state of British democracy and how to enthuse the electorate, especially young people. While the government is exploring ways to make the whole process of voting easier, it may be failing to tackle the real problem - that youth appear to find the business of politics uninviting and irrelevant. This paper examines data derived from a nationwide survey of over 700 young people in order to shed light on what lies at the heart of young people's apparent disengagement from formal politics in Britain - political apathy or a sense of political alienation. The findings reveal that they support the democratic process, but are sceptical of the way the British political system is organised and led, and are turned off by politicians and the political parties. However, there is no uniform youth orientation to politics, and the data indicate that views differ according to social class, educational history, and also gender. However both ethnicity and region of the country in which young people live seem to have little influence in structuring political attitudes and behaviour

Light smoking at base-line predicts a higher mortality risk to women than to men; evidence from a cohort with long follow-up

BACKGROUND: There is conflicting evidence as to whether smoking is more harmful to women than to men. The UK Cotton Workers’ Cohort was recruited in the 1960s and contained a high proportion of men and women smokers who were well matched in terms of age, job and length of time in job. The cohort has been followed up for 42 years. METHODS: Mortality in the cohort was analysed using an individual relative survival method and Cox regression. Whether smoking, ascertained at baseline in the 1960s, was more hazardous to women than to men was examined by estimating the relative risk ratio women to men, smokers to never smoked, for light (1–14), medium (15–24), heavy (25+ cigarettes per day) and former smoking. RESULTS: For all-cause mortality relative risk ratios were 1.35 for light smoking at baseline (95% CI 1.07-1.70), 1.15 for medium smoking (95% CI 0.89-1.49) and 1.00 for heavy smoking (95% CI 0.63-1.61). Relative risk ratios for light smoking at baseline for circulatory system disease was 1.42 (95% CI 1.01 to 1.98) and for respiratory disease was 1.89 (95% CI 0.99 to 3.63). Heights of participants provided no explanation for the gender difference. CONCLUSIONS: Light smoking at baseline was shown to be significantly more hazardous to women than to men but the effect decreased as consumption increased indicating a dose response relationship. Heavy smoking was equally hazardous to both genders. This result may help explain the conflicting evidence seen elsewhere. However gender differences in smoking cessation may provide an alternative explanation

Trial Protocol: Randomised controlled trial of the effects of very low calorie diet, modest dietary restriction, and sequential behavioural programme on hunger, urges to smoke, abstinence and weight gain in overweight smokers stopping smoking

Background\ud Weight gain accompanies smoking cessation, but dieting during quitting is controversial as hunger may increase urges to smoke. This is a feasibility trial for the investigation of a very low calorie diet (VLCD), individual modest energy restriction, and usual advice on hunger, ketosis, urges to smoke, abstinence and weight gain in overweight smokers trying to quit. \ud \ud Methods\ud This is a 3 armed, unblinded, randomized controlled trial in overweight (BMI > 25 kg/$m^2$), daily smokers (CO > 10 ppm); with at least 30 participants in each group. Each group receives identical behavioural support and NRT patches (25 mg(8 weeks),15 mg(2 weeks),10 mg(2 weeks)). The VLCD group receive a 429-559 kcal/day liquid formula beginning 1 week before quitting and continuing for 4 weeks afterwards. The modest energy restricted group (termed individual dietary and activity planning(IDAP)) engage in goal-setting and receive an energy prescription based on individual basal metabolic rate(BMR) aiming for daily reduction of 600 kcal. The control group receive usual dietary advice that accompanies smoking cessation i.e. avoiding feeling hungry but eating healthy snacks. After this, the VLCD participants receive IDAP to provide support for changing eating habits in the longer term; the IDAP group continues receiving this support. The control group receive IDAP 8 weeks after quitting. This allows us to compare IDAP following a successful quit attempt with dieting concurrently during quitting. It also aims to prevent attrition in the unblinded, control group by meeting their need for weight management. Follow-up occurs at 6 and 12 months. \ud \ud Outcome measures include participant acceptability, measured qualitatively by semi-structured interviewing and quantitatively by recruitment and attrition rates. Feasibility of running the trial within primary care is measured by interview and questionnaire of the treatment providers. Adherence to the VLCD is verified by the presence of urinary ketones measured weekly. Daily urges to smoke, hunger and withdrawal are measured using the Mood and Physical Symptoms Scale-Combined (MPSS-C) and a Hunger Craving Score (HCS). 24 hour, 7 day point prevalence and 4-week prolonged abstinence (Russell Standard) is confirmed by CO < 10 ppm. Weight, waist and hip circumference and percentage body fat are measured at each visit. \ud \ud Trial Registration\ud Current controlled trials ISRCTN83865809\ud \u

Comparative transcriptome analysis of equine alveolar macrophages

Reasons for performing study: Alveolar macrophages (AMs) are the first line of defence against pathogens in the lungs of all mammalian species and thus may constitute appropriate therapeutic target cells in the treatment and prevention of opportunistic airway infections. Therefore, acquiring a better understanding of equine macrophage biology is of paramount importance in addressing this issue in relation to the horse. Objectives: To compare the transcriptome of equine AMs with that of equine peritoneal macrophages (PMs) and to investigate the effect of lipopolysaccharide (LPS) on equine AM. Study design: Gene expression study of equine AMs. Methods: Cells from both bronchoalveolar and peritoneal lavage fluid were isolated from systemically healthy horses that had been submitted to euthanasia. Cells were cryopreserved. RNA was extracted and comparative microarray analyses were performed in AMs and PMs, and in AMs treated and untreated with LPS. Comparisons with published data derived from human AM studies were made, with particular focus on LPS-induced inflammatory status. Results: The comparison between AMs and PMs revealed the differential basal expression of 451 genes. Gene expression analysis revealed an alternative (M2) macrophage polarisation profile in AMs and a hybrid macrophage activation profile in PMs, a phenomenon potentially attributable to a degree of induced endotoxin tolerance. The gene expression profile of equine AMs following LPS stimulation revealed significant changes in the expression of 240 genes, including well-known upregulated inflammatory genes. This LPS-induced gene expression profile of equine AMs more closely resembles that of human rather than murine macrophages. Conclusions: This study improves current understanding of equine macrophage biology. These data suggest that the horse may represent a suitable animal model for the study of human macrophage-associated lung inflammation and data derived from human macrophage studies may have significant relevance to the horse