Cross sectional study of childhood obesity and prevalence of risk factors for cardiovascular disease and diabetes in children aged 11–13

Background

European and Developing Countries Clinical Trials Partnership (EDCTP) was founded in 2003 by the European Parliament and Council. It is a partnership of 14 European Union (EU) member states, Norway, Switzerland, and Developing Countries, formed to fund acceleration of new clinical trial interventions to fight the human immunodeficiency virus and acquired immune deficiency syndrome (HIV/AIDS), malaria and tuberculosis (TB) in the sub-Saharan African region. EDCTP seeks to be synergistic with other funding bodies supporting research on these diseases.

Methods

EDCTP promotes collaborative research supported by multiple funding agencies and harnesses networking expertise across different African and European countries. EDCTP is different from other similar initiatives. The organisation of EDCTP blends important aspects of partnership that includes ownership, sustainability and responds to demand-driven research. The Developing Countries Coordinating Committee (DCCC); a team of independent scientists and representatives of regional health bodies from sub-Saharan Africa provides advice to the partnership. Thus EDCTP reflects a true partnership and the active involvement and contribution of these African scientists ensures joint ownership of the EDCTP programme with European counterparts.

Results

The following have been the major achievements of the EDCTP initiative since its formation in 2003; i) increase in the number of participating African countries from two to 26 in 2008 ii) the cumulative amount of funds spent on EDCTP projects has reached € 150 m, iii) the cumulative number of clinical trials approved has reached 40 and iv) there has been a significant increase number and diversity in capacity building activities.

Conclusion

While we recognise that EDCTP faced enormous challenges in its first few years of existence, the strong involvement of African scientists and its new initiatives such as unconditional funding to regional networks of excellence in sub-Saharan Africa is envisaged to lead to a sustainable programme. Current data shows that the number of projects supported by EDCTP is increasing. DCCC proposes that this success story of true partnership should be used as model by partners involved in the fight against other infectious diseases of public health importance in the region.     

Genetic profile of ischemic cerebrovascular disease and carotid stenosis

Objectives –  Carotid artery stenosis (CS) is a major risk factor for ischemic cerebrovascular disease (ICVD) and is therefore of interest in genetic investigating. Here we report the distribution of 100 polymorphisms in 47 suspected susceptibility genes for ICVD and its risk factors.
Materials and methods –  Previously published markers in suspected susceptibility genes were genotyped in ICVD patients and controls (928/602). Genotyping was performed using multiplex polymerase chain reaction (PCR) and linear immobilized probe array assays. ICVD cases were subtyped according to Trial of Org 10172 in Acute Stroke Treatment (TOAST) or subdivided into CS and non-CS patients by ultrasonography in a separate analysis.
Results –  Three polymorphisms located in the lipoprotein lipase (LPL), angiotensinogen (AGT) and guanine nucleotide-binding protein beta-3 (GNB3) genes were significantly associated with ICVD after correction for age and gender. The strongest association was found for the protective LPL Ser447Term polymorphism. All the significant markers showed varying frequencies in different subphenotypes of ICVD. Factor VII, apolipoprotein E and two renin polymorphisms were differentially frequent in patients with evidence of CS compared with non-CS patients.
Conclusions –  We have found that some previously described susceptibility polymorphisms are weakly associated with ICVD and that subdivision of patients into CS and non-CS groups may help to identify new candidate polymorphisms.     

Screening for abdominal aortic aneurysms in men: a Canadian perspective using Monte Carlo–based estimates

Objective

Recently generated randomized screening trial data have provided good evidence in favour of routine screening for abdominal aortic aneurysm (AAA) to reduce AAA-related deaths in men aged 65 years and older. We developed an economic model that assessed the incremental cost–utility of AAA screening to help decision makers judge the relevance of a national screening program in Canada.

Methods

We constructed a 14 health state Markov model comparing 2 cohorts of 65-year-old men, where the first cohort was invited to attend screening for AAA using ultrasonography (US) and the second cohort followed the current practice of opportunistic detection. Lifetime outcomes included the life-years gained, AAA rupture avoided, AAA-related mortality, quality-adjusted life years (QALYs) and costs. Transition probabilities were derived from a systematic review of the literature, and a probabilistic sensitivity analysis was carried out to examine the effect of joint uncertainty in the variables of our analysis. The perspective adopted was that of the health care provider.

Results

Invitations to attend screening produced an undiscounted gain in life expectancy of 0.049 years and a gain in discounted QALY of 0.019 for an estimated incremental lifetime cost of CAN$118. The estimated incremental cost–utility ratio was CAN$6194 per QALY gained (95% confidence interval [CI] 1892–10 837). The numbers needed to invite to attend screening, and the numbers needed to screen to prevent 1 AAA-related death were 187 (95% CI 130–292) and 137 (95% CI 85–213), respectively. The acceptability curve showed a greater than 95% probability of the program''s being cost-effective, and the model was robust to changes in the values of key parameters within plausible ranges.

Conclusion

Our results support the economic viability of a national screening program for men reaching 65 years of age in Canada. More clinical studies are needed to define the role of screening in subgroups at high risk, especially in the female population.     

Prescribing patterns of antiretroviral treatments during pregnancy for women living with HIV in Canada 2004–2020: A surveillance study

Background

While treatment guidelines for HIV in adults have evolved rapidly with the advent of new antiretroviral (ARV) treatment, those for the prevention of vertical HIV transmission in pregnancy have evolved more slowly due to safety and efficacy concerns. Here we describe Canadian prescribing patterns for ARV treatments during pregnancy and compare them to perinatal HIV prescribing guidelines of the United States Department of Health and Human Services (HHS), that are commonly used in Canada and include recommendations for newly commercialized therapies.

Methods

The Canadian Perinatal HIV Surveillance Program (CPHSP) captures annual medical data on mothers living with HIV and their infants from 23 sites across Canada. Women from this cohort who received an ARV treatment during pregnancy and who gave birth between 2004 and 2020 were included in the study. ARV treatments were designated as ‘preferred/alternative’ as per HHS HIV perinatal guidelines, or ‘other than preferred/alternative’.

Results

We identified 3673 pregnancies from 2720 women. The proportion of women that conceived while on ARV treatment increased from 29% in 2003 to 90% in 2020. Other than preferred/alternative ARV treatments were received in 1112 (30%) of pregnancies and this was significantly associated with having initiated ARV treatment before conception.

Conclusion

In Canada during the study period, a high number of women were prescribed an other than preferred/alternative ARV treatment during pregnancy. Further optimization of ARV treatment in women of childbearing age living with HIV is warranted.     

Review of Areas/ A Keu to Diagnosis

A new technic for history taking magnifies and organizes the established model and adds a review of areas covering total behavior. Deficient, excessive or maladaptive behavior in one or several areas critically affects diagnosis and treatment. The technic is a simple means for quick, thorough assessment of shifts in homeostatic equilibrium.     

Membrane fluidization increases low-affinity muscarinic receptor binding in brain: changes with aging

Specific cholinergic muscarinic receptor binding was determined with L-[3H]quinuclidinyl benzilate ([3H]QNB) in homogenates from crude synaptosomal pellets prepared from mouse whole-brain homogenates. Specific total (high- and low-affinity) binding was determined in the absence of the agonist carbachol and low-affinity binding in its presence. These membrane preparations were fluidized by adding in vitro aliphatic alcohols ranging from ethanol to hexanol and by increasing the incubation temperatures. At 23 degrees C hexanol (14.7 mM) nearly doubled the low-affinity binding in the presence of carbachol (0.32 mM) and decreased high-affinity binding by the same amount. This suggested a change of muscarinic receptors from high- to low-affinity conformation. Increase of incubation temperature from 24 degrees C to 37 degrees C nearly tripled low-affinity binding. Brain homogenates from female C57BL/6J mice, ages 6, 12, 18, and 30 months, showed a progressively lower stimulation by hexanol of low-affinity [3H]QNB binding in the presence of carbachol. We postulate that this diminished change with age of [3H]QNB-receptor binding in response to alcohols may be a result of increasing membrane rigidity with advancing age. Rigidity of membranes may link aging at the membrane level, synaptic receptors, and impaired learning behavior.