Impact of malaria related messages on insecticide-treated net (ITN) use for malaria prevention in Ghana

Background: Media messages have been used in Ghana to promote insecticide-treated net (ITN)/bed net usage in an effort to impact on malaria prevention. The aim of this study was to assess the effect of such malaria-related messages delivered through electronic/print media and by volunteers/health workers on the use of ITNs by children living in a household. Methods: Data was collected from September to November of 2008 using a structured, interviewer-administered questionnaire by the Ghana Statistical Service as part of a national demographic and health survey (DHS). Secondary data analysis was performed on the collected data using multivariate logistic regression for both individual messages and a composite (any of) message variable. Results: From the 11,788 households surveyed, 45% had at least one net. Households with male heads were more likely to have a child sleeping under a bed net the previous night (p = 0.0001). Individual Messages delivered by a health worker or a dedicated radio programme, had the highest effect for one or more children sleeping under a net the night before (OR adjusted = 1.65; 95% CI = 1.44 to 1.88 and OR adjusted = 1.26; 95% CI =1.12 to 1.42 respectively) while hearing any of the eight messages (composite score) resulted in the highest odds for one or more children (OR adjusted = 3.06; 95% CI = 2.27 to 4.12) sleeping under a bed net. Conclusion: Efforts to relate ITN messages to the public are very useful in increasing use of bed nets and having multiple ways of reaching the public increases their effect, with the biggest effect seen when health workers and volunteers were used to deliver malaria-related messages to the public

Ethical issues concerning the use of commercially available wearables in children

Wearable and mobile technology has advanced in leaps and bounds in the last decade with technological advances creating a role from enhancing healthy living to monitoring and treating disease. However, the discussion about the ethical use of such commercial technology in the community, especially in minors, is lacking behind. In this paper, we first summarize the major ethical concerns that arise from the usage of commercially available wearable technology in children, with a focus on smart watches, highlighting issues around the consent process, mitigation of risk and potential confidentiality and privacy issues, as well as the potential for therapeutic misconceptions when used without medical advice. Then through a relevant thought experiment we move on to outline some further ethical concerns that are connected to the use of wearables by minors, to wit the issue of informed consent in the case of minors, forcing them to live in the spotlight, and compromising their right to an open future. We conclude with the view that mitigating potential pitfalls and enhancing the benefits of wearable technology especially for minors requires brave and comprehensive moral debates

Etički problemi vezani uz korištenje komercijalno dostupnih nosivih uređaja kod djece: Informirani pristanak, život u centru pažnje i pravo na otvorenu budućnost

Wearable and mobile technology has advanced in leaps and bounds in the last decade with technological advances creating a role from enhancing healthy living to monitoring and treating disease. However, the discussion about the ethical use of such commercial technology in the community, especially in minors, is lacking behind. In this paper, we first summarize the major ethical concerns that arise from the usage of commercially available wearable technology in children, with a focus on smart watches, highlighting issues around the consent process, mitigation of risk and potential confidentiality and privacy issues, as well as the potential for therapeutic misconceptions when used without medical advice. Then through a relevant thought experiment we move on to outline some further ethical concerns that are connected to the use of wearables by minors, to wit the issue of informed consent in the case of minors, forcing them to live in the spotlight, and compromising their right to an open future. We conclude with the view that mitigating potential pitfalls and enhancing the benefits of wearable technology especially for minors requires brave and comprehensive moral debates.Nosiva i mobilna tehnologija značajno su napredovale tijekom proteklog desetljeća i dobile su novu ulogu - više ne unaprjeđuju zdrave životne navike, već nadgledavaju i liječe bolesti.S druge strane, rasprava o etičkom korištenju takvih komercijalnih tehnologija međupopulacijom, posebice maloljetnicima, značajno kaska. U ovom ćemo radu najprije sažeti glavna etička pitanja koja se pojavljuju kad djeca koriste komercijalno dostupnu nosivu tehnologiju s naglaskom na pametne satove. Istaknut ćemo probleme vezane uz proces davanjapristanka, smanjivanje rizika te moguće probleme vezane uz povjerljivost i privatnost, kao imoguće terapeutske zablude kad se uređaji koriste bez liječničkog savjetovanja. Zatim ćemokroz značajan misaoni pokus navesti daljnja etička pitanja vezana uz maloljetničko korištenje nosivih uređaja. Primarno se to odnosi na pitanje informiranog pristanka kod maloljetnika, toga da ih se prisiljava da žive u centru pažnje, i ugrožavanje njihova prava na otvorenu budućnost. Zaključit ćemo rad mišljenjem da ublažavanje mogućih zamki i unaprjeđivanje prednosti nosive tehnologije, posebno za maloljetnike, zahtijeva hrabre i iscrpne moralne rasprave

Ethical issues concerning the use of commercially available wearables in children: Informed consent, living in the spotlight, and the right to an open future

Wearable and mobile technology has advanced in leaps and bounds in the last decade with technological advances creating a role from enhancing healthy living to monitoring and treating disease. However, the discussion about the ethical use of such commercial technology in the community, especially in minors, is lacking behind. In this paper, we first summarize the major ethical concerns that arise from the usage of commercially available wearable technology in children, with a focus on smart watches, highlighting issues around the consent process, mitigation of risk and potential confidentiality and privacy issues, as well as the potential for therapeutic misconceptions when used without medical advice. Then through a relevant thought experiment we move on to outline some further ethical concerns that are connected to the use of wearables by minors, to wit the issue of informed consent in the case of minors, forcing them to live in the spotlight, and compromising their right to an open future. We conclude with the view that mitigating potential pitfalls and enhancing the benefits of wearable technology especially for minors requires brave and comprehensive moral debates

Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD

Phenome-wide association analysis of LDL-cholesterol lowering genetic variants in PCSK9

Abstract: Background: We characterised the phenotypic consequence of genetic variation at the PCSK9 locus and compared findings with recent trials of pharmacological inhibitors of PCSK9. Methods: Published and individual participant level data (300,000+ participants) were combined to construct a weighted PCSK9 gene-centric score (GS). Seventeen randomized placebo controlled PCSK9 inhibitor trials were included, providing data on 79,578 participants. Results were scaled to a one mmol/L lower LDL-C concentration. Results: The PCSK9 GS (comprising 4 SNPs) associations with plasma lipid and apolipoprotein levels were consistent in direction with treatment effects. The GS odds ratio (OR) for myocardial infarction (MI) was 0.53 (95% CI 0.42; 0.68), compared to a PCSK9 inhibitor effect of 0.90 (95% CI 0.86; 0.93). For ischemic stroke ORs were 0.84 (95% CI 0.57; 1.22) for the GS, compared to 0.85 (95% CI 0.78; 0.93) in the drug trials. ORs with type 2 diabetes mellitus (T2DM) were 1.29 (95% CI 1.11; 1.50) for the GS, as compared to 1.00 (95% CI 0.96; 1.04) for incident T2DM in PCSK9 inhibitor trials. No genetic associations were observed for cancer, heart failure, atrial fibrillation, chronic obstructive pulmonary disease, or Alzheimer’s disease – outcomes for which large-scale trial data were unavailable. Conclusions: Genetic variation at the PCSK9 locus recapitulates the effects of therapeutic inhibition of PCSK9 on major blood lipid fractions and MI. While indicating an increased risk of T2DM, no other possible safety concerns were shown; although precision was moderate

Association between alcohol and cardiovascular disease: Mendelian randomisation analysis based on individual participant data.

OBJECTIVE: To use the rs1229984 variant in the alcohol dehydrogenase 1B gene (ADH1B) as an instrument to investigate the causal role of alcohol in cardiovascular disease. DESIGN: Mendelian randomisation meta-analysis of 56 epidemiological studies. PARTICIPANTS: 261 991 individuals of European descent, including 20 259 coronary heart disease cases and 10 164 stroke events. Data were available on ADH1B rs1229984 variant, alcohol phenotypes, and cardiovascular biomarkers. MAIN OUTCOME MEASURES: Odds ratio for coronary heart disease and stroke associated with the ADH1B variant in all individuals and by categories of alcohol consumption. RESULTS: Carriers of the A-allele of ADH1B rs1229984 consumed 17.2% fewer units of alcohol per week (95% confidence interval 15.6% to 18.9%), had a lower prevalence of binge drinking (odds ratio 0.78 (95% CI 0.73 to 0.84)), and had higher abstention (odds ratio 1.27 (1.21 to 1.34)) than non-carriers. Rs1229984 A-allele carriers had lower systolic blood pressure (-0.88 (-1.19 to -0.56) mm Hg), interleukin-6 levels (-5.2% (-7.8 to -2.4%)), waist circumference (-0.3 (-0.6 to -0.1) cm), and body mass index (-0.17 (-0.24 to -0.10) kg/m(2)). Rs1229984 A-allele carriers had lower odds of coronary heart disease (odds ratio 0.90 (0.84 to 0.96)). The protective association of the ADH1B rs1229984 A-allele variant remained the same across all categories of alcohol consumption (P=0.83 for heterogeneity). Although no association of rs1229984 was identified with the combined subtypes of stroke, carriers of the A-allele had lower odds of ischaemic stroke (odds ratio 0.83 (0.72 to 0.95)). CONCLUSIONS: Individuals with a genetic variant associated with non-drinking and lower alcohol consumption had a more favourable cardiovascular profile and a reduced risk of coronary heart disease than those without the genetic variant. This suggests that reduction of alcohol consumption, even for light to moderate drinkers, is beneficial for cardiovascular health

Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background: Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods: For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings: Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8-13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05-6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50-75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation: Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life

Familial hypercholesterolaemia in children and adolescents from 48 countries : a cross-sectional study

Background: Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods: For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings: Of 63093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11848 individuals. Median age at registry entry was 9·6 years (IQR 5·8–13·2). 10 099 (89·9%) of 11235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05–6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50–75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation: Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life.peer-reviewe

Matrix Metalloproteinases and Subclinical Atherosclerosis in Chronic Kidney Disease: A Systematic Review

Background. Cardiovascular disease (CVD) remains a significant problem in Chronic Kidney Disease (CKD). Subclinical atherosclerosis identified by noninvasive methods could improve CVD risk prediction in CKD but these methods are often unavailable. We therefore systematically reviewed whether circulating levels of Matrix Metalloproteinases (MMPs) and tissue inhibitors (TIMPs) are associated with subclinical atherosclerosis in CKD, as this would support their use as biomarkers or pharmacologic targets. Methods. All major electronic databases were systematically searched from inception until May 2015 using appropriate terms. Studies involving CKD patients with data on circulating MMPs levels and atherosclerosis were considered and subjected to quality assessment. Results. Overall, 16 studies were identified for qualitative synthesis and 9 studies were included in quantitative synthesis. MMP-2 and TIMP-1 were most frequently studied while most studies assessed carotid Intima-Media Thickness (cIMT) as a measure of subclinical atherosclerosis. Only MMP-2 demonstrated a consistent positive association with cIMT. Considerable variability in cIMT measurement methodology and poor plaque assessment was found. Conclusions. Although MMPs demonstrate great potential as biomarkers of subclinical atherosclerosis, they are understudied in CKD and not enough data existed for meta-analysis. Larger studies involving several MMPs, with more homogenized approaches in determining the atherosclerotic burden in CKD, are needed