Precision medicine and artificial intelligence : a pilot study on deep learning for hypoglycemic events detection based on ECG

Tracking the fluctuations in blood glucose levels is important for healthy subjects and crucial diabetic patients. Tight glucose monitoring reduces the risk of hypoglycemia, which can result in a series of complications, especially in diabetic patients, such as confusion, irritability, seizure and can even be fatal in specific conditions. Hypoglycemia affects the electrophysiology of the heart. However, due to strong inter-subject heterogeneity, previous studies based on a cohort of subjects failed to deploy electrocardiogram (ECG)-based hypoglycemic detection systems reliably. The current study used personalised medicine approach and Artificial Intelligence (AI) to automatically detect nocturnal hypoglycemia using a few heartbeats of raw ECG signal recorded with non-invasive, wearable devices, in healthy individuals, monitored 24 hours for 14 consecutive days. Additionally, we present a visualisation method enabling clinicians to visualise which part of the ECG signal (e.g., T-wave, ST-interval) is significantly associated with the hypoglycemic event in each subject, overcoming the intelligibility problem of deep-learning methods. These results advance the feasibility of a real-time, non-invasive hypoglycemia alarming system using short excerpts of ECG signal

Precision medicine and artificial intelligence : a pilot study on deep learning for hypoglycemic events detection based on ECG

Tracking the fluctuations in blood glucose levels is important for healthy subjects and crucial diabetic patients. Tight glucose monitoring reduces the risk of hypoglycemia, which can result in a series of complications, especially in diabetic patients, such as confusion, irritability, seizure and can even be fatal in specific conditions. Hypoglycemia affects the electrophysiology of the heart. However, due to strong inter-subject heterogeneity, previous studies based on a cohort of subjects failed to deploy electrocardiogram (ECG)-based hypoglycemic detection systems reliably. The current study used personalised medicine approach and Artificial Intelligence (AI) to automatically detect nocturnal hypoglycemia using a few heartbeats of raw ECG signal recorded with non-invasive, wearable devices, in healthy individuals, monitored 24 hours for 14 consecutive days. Additionally, we present a visualisation method enabling clinicians to visualise which part of the ECG signal (e.g., T-wave, ST-interval) is significantly associated with the hypoglycemic event in each subject, overcoming the intelligibility problem of deep-learning methods. These results advance the feasibility of a real-time, non-invasive hypoglycemia alarming system using short excerpts of ECG signal

Spatial analysis of risk factors for childhood morbidity in Nigeria

Recent Demographic and Health Surveys (DHS) from Sub-Saharan Africa (SSA) indicate a decline in childhood vaccination coverage but a high prevalence of childhood diarrhea, cough, and fever. We used Nigerian DHS data to investigate the impact of geographical factors and other important risk factors on diarrhea, cough, and fever using geoadditive Bayesian semiparametric models. A higher prevalence of childhood diarrhea, cough, and fever is observed in the northern and eastern states, while lower disease prevalence is observed in the western and southern states. In addition, children from mothers with higher levels of education and those from poor households had a significantly lower association with diarrhea; children delivered in hospitals, living in urban areas, or from mothers having received prenatal visits had a significantly lower association with fever. Our maps are a novel and relevant tool to help local governments to improve health-care interventions and achieve Millennium Development Goals (MDG4)

Elevated cystatin-C concentration is associated with progression to prediabetes: the Western New York Study

OBJECTIVE – We conducted a nested case-control investigation to examine if elevated baseline concentrations of cystatin-C predicted progression from normoglycaemia to prediabetes over 6 years of follow-up from the Western New York Health Study. RESEARCH DESIGN AND METHODS – 1,455 participants from the Western New York Health Study, free of type 2 diabetes and known cardiovascular disease at baseline (1996-2001), were reexamined in 2002-2004. An incident case of prediabetes was defined as one with fasting glucose below 100 mg/dl at the baseline examination and ≥ 100 mg/dl and ≤ 125 mg/dl at the follow-up examination. All cases (n=91) were matched 1:3 to control participants based upon sex, race/ethnicity and year of study enrollment. All controls had fasting glucose levels < 100 mg/dl at both baseline and follow-up examinations. Cystatin-C concentrations and the urinary albumin to creatinine ratio were measured from frozen (-196 Cº) baseline blood and urine samples. Serum creatinine concentrations were available from the baseline examination. RESULTS –Multivariate conditional logistic regression analyses adjusted for age, baseline glucose level, HOMA-IR, body mass index, hypertension, eGFR, cigarette smoking, and alcohol use revealed a significantly increased risk of progression to prediabetes among those with elevated baseline concentrations of cystatin-C (Odds Ratio, 95% CI: 3.04, 1.34, 6.89) (upper quintile vs. the remainder). Results of secondary analyses that considered hs-CRP, IL-6, E-selectin, or sICAM did not alter these results. CONCLUSIONS - These results suggest that early renal impairment indexed with cystatin-C imparted a three-fold excess risk of progression to prediabetes in this study population. Recent evidence from randomized clinical trials (1,2) among people with prediabetes have provided convincing evidence that early intervention can significantly delay or prevent the progression to type 2 diabetes. The identification of those with prediabetes is assuming greater importance (3) especially in light of the fact that approximately 35 million adults aged 40-74 years old in the United States have prediabetes defined as impaired fasting glucose (4). Microalbuminuria occurs frequently in nondiabetic subjects and places them at increased risk for cardiovascular disease (5-7). The mechanisms behind this observation are poorly understood, however. Albuminuria may reflect underlying vascular damage (8), hypertension (9, 10) endothelial dysfunction (11, 12) and/or low-grade inflammation (13). A large percentage of type 2 individuals pass through a period of prediabetes (14) and may experience early renal dysfunction e.g., a glomerular filtration rate (GFR) above 60 ml/minute per 1.73m2. Currently used estimating equations are poor at identifying early renal impairment and better indices are of great interest (15, 16). Recently, several studies have suggested that cystatin-C levels may be a more sensitive marker of early renal impairment than either albuminuria or serum creatinine concentration (17-20). Therefore, a better understanding of a putative role for cystatin-C in the etiology of prediabetes could shed light on the renal/heart disease connection (21). Given the reported superiority of cystatin C over conventional measures of renal function, we hypothesized that cystatin-C would predict progression to prediabetes independent of serum creatinine or estimated GFR. We also investigated the role of intervening mechanisms including hypertension, insulin resistance, endothelial dysfunction and inflammation

'Mediterranean' dietary pattern for the primary prevention of cardiovascular disease

It is well established that diet plays a major role in cardiovascular disease risk. The traditional Mediterranean dietary pattern is of particular interest because of observations from the 1960s that populations in countries of the Mediterranean region, such as Greece and Italy, had lower mortality from cardiovascular disease compared with northern European populations or the US, probably as a result of different eating habits. This review assessed the effects of providing dietary advice to follow a Mediterranean-style dietary pattern to healthy adults or people at increased risk of cardiovascular disease in order to prevent the occurrence of cardiovascular disease and reduce the risk factors associated with it. Definitions of a Mediterranean dietary pattern vary and we included only randomised controlled trials (RCTs) of interventions that reported at least two of the following components: (1) high monounsaturated/saturated fat ratio, (2) low to moderate red wine consumption, (3) high consumption of legumes, (4) high consumption of grains and cereals, (5) high consumption of fruits and vegetables, (6) low consumption of meat and meat products and increased consumption of fish, and (7) moderate consumption of milk and dairy products. The control group was no intervention or minimal intervention. We found 11 RCTs (15 papers) that met these criteria. The trials varied enormously in the participants recruited and the different dietary interventions. Four trials were conducted in women only, two trials were in men only and the remaining five were in both men and women. Five trials were conducted in healthy individuals and six trials were in people at increased risk of cardiovascular disease or cancer. The number of components relevant to a Mediterranean dietary pattern ranged from two to five and only seven trials described the intervention as a Mediterranean diet. The largest trial, which recruited only postmenopausal women and was not described as a Mediterranean diet meeting only two of the criteria described above, reported no difference in the occurrence of cardiovascular disease between the dietary advice group and the control group. The other trials measured risk factors for cardiovascular disease. As the studies were so different, it was not possible to combine studies for most of the outcomes. Where it was possible to combine studies, we found small reductions in total cholesterol levels as well as in the harmful low-density lipoprotein (LDL) cholesterol concentrations. The reductions in total cholesterol were greater in the studies that described themselves as providing a Mediterranean diet. None of the trials reported side effects. The review concludes that, from the limited evidence to date, a Mediterranean dietary pattern reduces some cardiovascular risk factors. However, more trials are needed to look at the effects of the different participants recruited and the different dietary interventions to see which interventions might work best in different populations

Morbidity from diarrhoea, cough and fever among young children in Nigeria

Diarrhoea, cough and fever are the leading causes of childhood morbidity and mortality in sub-Saharan Africa. Despite it being a determinant of mortality in many developing countries, geographical location has seldom been considered as an explanatory factor for the large regional variations seen in the childhood morbidity attributed to these causes in this area. The relevant data collected in two Nigerian Demographic and Health Surveys, one in 1999 and the other in 2003, have now therefore been analysed and compared. The aim was to reveal and explore inequalities in the health of Nigerian children by mapping the spatial distribution of childhood morbidity associated with recent diarrhoea, cough and fever and accounting for important risk factors, using a Bayesian geo-additive model based on Markov-chain–Monte-Carlo techniques. Although the overall prevalences of recent diarrhoea, cough and fever recorded in 1999 (among children aged ,3 years) were similar to those seen in 2003 (among children aged ,5 years), the mapping of residual spatial effects indicated that, in each survey, the morbidity attributable to each of these causes varied, differently, at state level. Place of birth (hospital v. other), type of feeding (breastfed only v. other), parental education, maternal visits to antenatal clinics, household economic status, marital status of mother and place of residence were each significantly associated with the childhood morbidity investigated. In both surveys, children from urban areas were found to have a significantly lower risk of fever than their rural counterparts. Most other factors affecting diarrhoea, cough and fever differed in the two surveys. The risk of developing each of these three conditions increased in the first 6–8 months after birth but then gradually declined. The analysis explained a significant share of the pronounced residual spatial effects. Maps showing the prevalences of diarrhoea, cough and fever in young children across Nigeria were generated during this study. Such maps should facilitate the development of policies to fulfil the Millennium Development Goals in Nigeria and throughout sub-Saharan Africa

Selenium supplementation for the primary prevention of cardiovascular disease

Background: Selenium is a key component of a number of selenoproteins which protect against oxidative stress and have the potential to prevent chronic diseases including cardiovascular disease (CVD). However, observational studies have shown inconsistent associations between selenium intake and CVD risk; in addition, there is concern around a possible increased risk of type 2 diabetes with high selenium exposure. Objectives: To determine the effectiveness of selenium only supplementation for the primary prevention of CVD and examine the potential adverse effect of type 2 diabetes. Search methods: The following electronic databases were searched: the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 10 of 12, October 2012) on The Cochrane Library; MEDLINE (Ovid) (1946 to week 2 October 2012); EMBASE Classic + EMBASE (Ovid) (1947 to 2012 Week 42); CINAHL (EBSCO) (to 24 October 2012); ISI Web of Science (1970 to 24 October 2012); PsycINFO (Ovid) (1806 to week 3 October 2012); Database of Abstracts of Reviews of Effects (DARE), Health Technology Assessment Database and Health Economics Evaluations Database (Issue 4 of 4, October 2012) on The Cochrane Library. Trial registers and reference lists of reviews and articles were searched and experts in the field were approached. No language restrictions were applied. Selection criteria: Randomised controlled trials on the effects of selenium only supplementation on major CVD end-points, mortality, changes in CVD risk factors, and type 2 diabetes were included both in adults of all ages from the general population and in those at high risk of CVD. Trials were only considered where the comparison group was placebo or no intervention. Only studies with at least three months follow-up were included in the meta-analyses, shorter term studies were dealt with descriptively. Data collection and analysis: Two review authors independently assessed trial quality and extracted data. Study authors were contacted for additional information. Main results: Twelve trials (seven with duration of at least three months) met the inclusion criteria, with 19,715 participants randomised. The two largest trials that were conducted in the USA (SELECT and NPC) reported clinical events. There were no statistically significant effects of selenium supplementation on all cause mortality (RR 0.97, 95% CI 0.88 to 1.08), CVD mortality (RR 0.97, 95% CI 0.79 to 1.2), non-fatal CVD events (RR 0.96, 95% CI 0.89 to 1.04) or all CVD events (fatal and non-fatal) (RR 1.03, 95% CI 0.95 to 1.11). There was a small increased risk of type 2 diabetes with selenium supplementation but this did not reach statistical significance (RR 1.06, 95% CI 0.97 to 1.15). Other adverse effects that increased with selenium supplementation, as reported in the SELECT trial, included alopecia (RR 1.28, 95% CI 1.01 to 1.62) and dermatitis grade 1 to 2 (RR 1.17, 95% CI 1.0 to 1.35). Selenium supplementation reduced total cholesterol but this did not reach statistical significance (WMD - 0.11 mmol/L, 95% CI - 0.3 to 0.07). Mean high density lipoprotein (HDL) levels were unchanged. There was a statistically significant reduction in non-HDL cholesterol (WMD - 0.2 mmol/ L, 95% CI - 0.41 to 0.00) in one trial of varying selenium dosage. None of the longer term trials examined effects on blood pressure. Overall, the included studies were regarded as at low risk of bias. Authors’ conclusions: The limited trial evidence that is available to date does not support the use of selenium supplements in the primary prevention of CVD

Evidence on the prevalence and geographic distribution of major cardiovascular risk factors in Italy

Objective: To assess the prevalence and geographic distribution of major cardiovascular risk factors in a large community-wide sample of the Italian population. Design: A cross-sectional survey. Standardized methods were used to collect and measure cardiovascular risk factors. Data were adjusted for survey weightings. Qualitative and quantitative variables were compared with parametric and non-parametric tests, as appropriate. Setting: Towns (n 193) across different Italian regions. Subjects: Unselected adults (n 24 213; 12 626 men; 11 587 women) aged 18–98 years (mean age 56·9 (sd 15·3) years), who volunteered to participate in a community-wide screening programme over a 2 d period in 2007. Results: Overall, the prevalence of major cardiovascular risk factors was: obesity, 22·7 % (women 18·9 %, men 26·1 %); overweight, 44·7 % (women 31·6 %, men 56·7 %); hypertension, 59·6 % (women 48·3 %, men 70·0 %); dyslipidaemia, 59·1 % (women 57·7 %, men 60·3 %); diabetes, 15·3 % (women 11·2 %, men 19·0 %) and smoking, 19·8 % (women 14·0 %, men 25·2 %). We found a high prevalence of unhealthy eating habits; fruit and vegetable consumption was below the recommended range in 60 % of the study population. Ninety per cent of the study population had more than one cardiovascular risk factor and 84 % had between two and five cardiovascular risk factors. There were differences among Italian macro-areas mainly for obesity, hypertension, dyslipidaemia and diabetes. Conclusions: The study provides alarming evidence on current prevalence data for major cardiovascular risk factors in a large sample of the Italian population. Particularly, obesity and hypertension represent a relevant public health problem. There is a pressing need for effective preventive health measures which must also take into account the differences among Italian macro-areas

A randomized trial of selenium supplementation and risk of type-2 diabetes, as assessed by plasma adiponectin

Background: Evidence that selenium affects the risk of type-2 diabetes is conflicting, with observational studies and a few randomized trials showing both lower and higher risk linked to the level of selenium intake and status. We investigated the effect of selenium supplementation on the risk of type-2 diabetes in a population of relatively low selenium status as part of the UK PRECISE (PREvention of Cancer by Intervention with SElenium) pilot study. Plasma adiponectin concentration, a recognised independent predictor of type-2 diabetes risk and known to be correlated with circulating selenoprotein P, was the biomarker chosen. Methods: In a randomized, double-blind, placebo-controlled trial, five hundred and one elderly volunteers were randomly assigned to a six-month intervention with 100, 200 or 300 μg selenium/d as high-selenium or placebo yeast. Adiponectin concentration was measured by ELISA at baseline and after six months of treatment in 473 participants with one or both plasma samples available. Results: Mean (SD) plasma selenium concentration was 88.5 ng/g (19.1) at baseline and increased significantly in the selenium-treatment groups. In baseline cross-sectional analyses, the fully adjusted geometric mean of plasma adiponectin was 14% lower (95% CI, 0-27%) in the highest than in the lowest quartile of plasma selenium (P for linear trend = 0.04). In analyses across randomized groups, however, selenium supplementation had no effect on adiponectin levels after six months of treatment (P = 0.96). Conclusions: These findings are reassuring as they did not show a diabetogenic effect of a six-month supplementation with selenium in this sample of elderly individuals of relatively low selenium status