Effectiveness of cardiac resynchronization therapy in heart failure patients with valvular heart disease: comparison with patients affected by ischaemic heart disease or dilated cardiomyopathy. The InSync/InSync ICD Italian Registry

AimsTo analyse the effectiveness of cardiac resynchronization therapy (CRT) in patients with valvular heart disease (a subset not specifically investigated in randomized controlled trials) in comparison with ischaemic heart disease or dilated cardiomyopathy patients.Methods and resultsPatients enrolled in a national registry were evaluated during a median follow-up of 16 months after CRT implant. Patients with valvular heart disease treated with CRT (n = 108) in comparison with ischaemic heart disease (n = 737) and dilated cardiomyopathy (n = 635) patients presented: (i) a higher prevalence of chronic atrial fibrillation, with atrioventricular node ablation performed in around half of the cases; (ii) a similar clinical and echocardiographic profile at baseline; (iii) a similar improvement of LVEF and a similar reduction in ventricular volumes at 6-12 months; (iv) a favourable clinical response at 12 months with an improvement of the clinical composite score similar to that occurring in patients with dilated cardiomyopathy and more pronounced than that observed in patients with ischaemic heart disease; (v) a long-term outcome, in term of freedom from death or heart transplantation, similar to patients affected by ischaemic heart disease and basically more severe than that of patients affected by dilated cardiomyopathy.ConclusionIn 'real world' clinical practice, CRT appears to be effective also in patients with valvular heart disease. However, in this group of patients the outcome after CRT does not precisely overlap any of the two other groups of patients, for which much more data are currently available

Global variation in diabetes diagnosis and prevalence based on fasting glucose and hemoglobin A1c

Fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) are both used to diagnose diabetes, but these measurements can identify different people as having diabetes. We used data from 117 population-based studies and quantified, in different world regions, the prevalence of diagnosed diabetes, and whether those who were previously undiagnosed and detected as having diabetes in survey screening, had elevated FPG, HbA1c or both. We developed prediction equations for estimating the probability that a person without previously diagnosed diabetes, and at a specific level of FPG, had elevated HbA1c, and vice versa. The age-standardized proportion of diabetes that was previously undiagnosed and detected in survey screening ranged from 30% in the high-income western region to 66% in south Asia. Among those with screen-detected diabetes with either test, the age-standardized proportion who had elevated levels of both FPG and HbA1c was 29-39% across regions; the remainder had discordant elevation of FPG or HbA1c. In most low- and middle-income regions, isolated elevated HbA1c was more common than isolated elevated FPG. In these regions, the use of FPG alone may delay diabetes diagnosis and underestimate diabetes prevalence. Our prediction equations help allocate finite resources for measuring HbA1c to reduce the global shortfall in diabetes diagnosis and surveillance

Worldwide trends in underweight and obesity from 1990 to 2022: a pooled analysis of 3663 population-representative studies with 222 million children, adolescents, and adults

Background Underweight and obesity are associated with adverse health outcomes throughout the life course. We estimated the individual and combined prevalence of underweight or thinness and obesity, and their changes, from 1990 to 2022 for adults and school-aged children and adolescents in 200 countries and territories. Methods We used data from 3663 population-based studies with 222 million participants that measured height and weight in representative samples of the general population. We used a Bayesian hierarchical model to estimate trends in the prevalence of different BMI categories, separately for adults (age ≥20 years) and school-aged children and adolescents (age 5–19 years), from 1990 to 2022 for 200 countries and territories. For adults, we report the individual and combined prevalence of underweight (BMI <18·5 kg/m2) and obesity (BMI ≥30 kg/m2). For schoolaged children and adolescents, we report thinness (BMI <2 SD below the median of the WHO growth reference) and obesity (BMI >2 SD above the median). Findings From 1990 to 2022, the combined prevalence of underweight and obesity in adults decreased in 11 countries (6%) for women and 17 (9%) for men with a posterior probability of at least 0·80 that the observed changes were true decreases. The combined prevalence increased in 162 countries (81%) for women and 140 countries (70%) for men with a posterior probability of at least 0·80. In 2022, the combined prevalence of underweight and obesity was highest in island nations in the Caribbean and Polynesia and Micronesia, and countries in the Middle East and north Africa. Obesity prevalence was higher than underweight with posterior probability of at least 0·80 in 177 countries (89%) for women and 145 (73%) for men in 2022, whereas the converse was true in 16 countries (8%) for women, and 39 (20%) for men. From 1990 to 2022, the combined prevalence of thinness and obesity decreased among girls in five countries (3%) and among boys in 15 countries (8%) with a posterior probability of at least 0·80, and increased among girls in 140 countries (70%) and boys in 137 countries (69%) with a posterior probability of at least 0·80. The countries with highest combined prevalence of thinness and obesity in school-aged children and adolescents in 2022 were in Polynesia and Micronesia and the Caribbean for both sexes, and Chile and Qatar for boys. Combined prevalence was also high in some countries in south Asia, such as India and Pakistan, where thinness remained prevalent despite having declined. In 2022, obesity in school-aged children and adolescents was more prevalent than thinness with a posterior probability of at least 0·80 among girls in 133 countries (67%) and boys in 125 countries (63%), whereas the converse was true in 35 countries (18%) and 42 countries (21%), respectively. In almost all countries for both adults and school-aged children and adolescents, the increases in double burden were driven by increases in obesity, and decreases in double burden by declining underweight or thinness. Interpretation The combined burden of underweight and obesity has increased in most countries, driven by an increase in obesity, while underweight and thinness remain prevalent in south Asia and parts of Africa. A healthy nutrition transition that enhances access to nutritious foods is needed to address the remaining burden of underweight while curbing and reversing the increase in obesit

Global variations in diabetes mellitus based on fasting glucose and haemogloblin A1c

Fasting plasma glucose (FPG) and haemoglobin A1c (HbA1c) are both used to diagnose diabetes, but may identify different people as having diabetes. We used data from 117 population-based studies and quantified, in different world regions, the prevalence of diagnosed diabetes, and whether those who were previously undiagnosed and detected as having diabetes in survey screening had elevated FPG, HbA1c, or both. We developed prediction equations for estimating the probability that a person without previously diagnosed diabetes, and at a specific level of FPG, had elevated HbA1c, and vice versa. The age-standardised proportion of diabetes that was previously undiagnosed, and detected in survey screening, ranged from 30% in the high-income western region to 66% in south Asia. Among those with screen-detected diabetes with either test, the agestandardised proportion who had elevated levels of both FPG and HbA1c was 29-39% across regions; the remainder had discordant elevation of FPG or HbA1c. In most low- and middle-income regions, isolated elevated HbA1c more common than isolated elevated FPG. In these regions, the use of FPG alone may delay diabetes diagnosis and underestimate diabetes prevalence. Our prediction equations help allocate finite resources for measuring HbA1c to reduce the global gap in diabetes diagnosis and surveillance.peer-reviewe

Nanocomposite layers for spacecraft protection: from multiscale numerical model to experimental data

In space environment, the surfaces of a spacecraft interact with the surrounding charged particles. Depending on the orbit, this interaction can induce a significant absolute charge on the structures and/or a differential charge collected among components. These phenomena generate electrostatic discharges with catastrophic consequences for the satellites. In this work, we investigate the volumetric electrical properties of nanocomposites made of aerospace-grade epoxy resin (RTM6) with single wall carbon nanotubes (SWCNT) as fillers to mitigate the electrostatic discharge phenomenon. In particular, we developed a highly conductive nanocomposite layer satisfying the NASA requirements for geostationary orbit. The study is divided into two parts, an experimental and a numerical one. In the first part, we fabricated nanocomposite samples and characterized their electrical properties at various frequencies. The electrical experimental results were compared with the numerical ones, which were calculated using a multiscale approach

Managing malaria in tuberculosis patients on fluoroquinolone-containing regimens: assessing the risk of QT prolongation.

The role of fluoroquinolones (FQs) in the management of drug-susceptible and drug-resistant tuberculosis (TB) is under investigation. They are currently being used off-licence to treat TB patients who develop hepatotoxicity on standard therapy, and in patients with drug-resistant disease. Prolongation of ventricular repolarisation, recorded as lengthening of the QT interval on an electrocardiogram, is a recognised adverse effect associated with FQs. Significant prolongation of the QT interval may precipitate torsades de pointe, a potentially fatal tachyarrhythmia. Currently licensed FQs are considered safe, and there are very few reports of associated arrhythmias, but most labels contraindicate concomitant administration of other agents that prolong QT. In many high TB burden countries, malaria is also endemic. Many antimalarials, and possibly malaria infection itself, may prolong QT; under current licence, co-administration of FQs with these antimalarials is contraindicated due to potential risk of additive QT prolongation. This poses significant challenges in planning future policy on FQ use for first-line anti-tuberculosis treatment; the duration of TB treatment makes concomitant malaria treatment inevitable, and options without FQ contraindications are limited. Furthermore, malaria diagnosis is often poor and access to treatment uncontrolled, with many patients buying 'over-the-counter' and/or 'traditional' remedies; concomitant use with anti-tuberculosis treatment is thus likely to be unregulated. Drug interaction studies are urgently required to assess the safety of managing patients with TB and malaria within endemic, resource-poor settings where programmatic management and low-cost monitoring are essential for effective implementation of public health strategies

A report on the Gubbio Study thirty-eight years after its inception

The Gubbio Population Study ("Gubbio Study") is a prospective epidemiological study carried out on the resident population of the city of Gubbio, Italy. The study's objectives are both of public health nature (the control and awareness of hypertension), and experimental (the role of electrolyte handling at the cellular membrane level and its relation to hypertension). Additional objectives were addressed during the 30+ year activity of the study, in particular the role of kidney dysfunction

Sodium intake and kidney function in the general population: an observational, population-based study

Background. The relationships of sodium intake to kidney function within the population have been poorly investigated and are the objective of the study. Methods. This observational, population-based, cross-sectional and longitudinal study targeted 4595 adult participants of the Gubbio study with complete data at baseline exam. Of these participants, 3016 participated in the 15-year follow-up (mortality-corrected response rate 78.4%). Baseline measures included sodium:creatinine ratio in timed overnight urine collection, used as an index of sodium intake, together with serum creatinine, sex, age and other variables. Follow-up measures included serum creatinine and other variables. Estimated glomerular filtration rate (eGFR, mL/min/1.73 m2) was calculated using serum creatinine, sex and age and was taken as an index of kidney function. Results. The study cohort was stratified in sex- and age-controlled quintiles of baseline urine sodium:creatinine ratio. A higher quintile associated with higher baseline eGFR (P < 0.001). In multivariable analysis, the odds ratio (OR) of Stage1 kidney function (eGFR 90 mL/min/1.73 m2) was 1.98 times higher in Quintile 5 compared with Quintile 1 [95% confidence interval (CI) 1.50–2.59, P < 0.001]. The time from baseline to follow-up was 14.1 6 2.5 years. Baseline to follow-up, the eGFR change was more negative along quintiles (P < 0.001). In multivariable analysis, the OR in Quintile 5 compared with Quintile 1 was 2.21 for eGFR decline 30% (1.18–4.13, P ¼ 0.001) and 1.38 for worsened stage of kidney function (1.05–1.82, P ¼ 0.006). Findings were consistent within subgroups. Conclusions. Within the general population, an index of higher sodium intake associated cross-sectionally with higher kidney function but longitudinally with greater kidney function decline

Low protein intake in the population: low risk of kidney function decline but high risk of mortality.

OBJECTIVE: This population-based study investigated low protein intake, mortality, and kidney function decline. DESIGN: Observational longitudinal cohort study. SUBJECTS: Target cohort consisted of 4,679 adults participating in 1988-1992 and 2001-2007 examinations of the Gubbio Study (baseline and follow-up). Data collection included overnight urine urea nitrogen (UUN) and other variables at baseline, serum creatinine at baseline and follow-up, and mortality from baseline to follow-up. Three hundred seventy-two persons were excluded for missing data. UUN in the lowest 20% of the distribution was defined as low and used as index of low protein intake. Estimated glomerular filtration rate (eGFR, mL/minute × 1.73 m2) was used as kidney function index. INTERVENTION: None (observational study). MAIN OUTCOME MEASURE: Mortality and eGFR decline are the main outcome measures, and eGFR decline was defined as eGFR change from baseline to follow-up ≤ mean-1 standard deviation (Z-score ≤ -1). RESULTS: Eight hundred seventy-one deaths occurred over 15.9 ± 4.0 years of observation (417 from cardiovascular disease and 276 from neoplastic disease). Low UUN associated with mortality (hazard ratio, HR = 1.31, 95% confidence interval, CI = 1.12/1.53) due to association with mortality from neoplastic disease (HR = 1.33, 95% CI = 1.02/1.76). Mortality-corrected follow-up response rate was 79.9% (n = 2845). Baseline to follow-up eGFR change was -9.9 ± 10.1, and eGFR decline was found in 454 examinees. Low UUN associated with eGFR decline only in subgroup with baseline eGFR <90 (n = 1441, odds ratio = 0.44, 95% CI = 0.22/0.85). Low baseline eGFR interacted with the association between low UUN and eGFR decline (P = .024). CONCLUSION: Low protein intake predicted higher mortality in the whole population and lower incidence of eGFR decline only in subgroup with reduced kidney function