Health economic implications of irbesartan plus conventional antihypertensive medications versus conventional blood pressure control alone in patients with type 2 diabetes, hypertension, and renal disease in Switzerland.

The aim of this health economic modelling study was to investigate the effect of irbesartan combined with conventional antihypertensive medications compared to conventional antihypertensive therapy alone on the progression of nephropathy in patients with hypertension, type 2 diabetes and microalbuminuria in a Swiss setting. In simulated patients with hypertension and type 2 diabetes, treatment of microalbuminuria with irbesartan 300 mg daily plus conventional antihypertensive medications was compared to a control regimen (conventional medications excluding angiotensin converting enzyme inhibitors, other angiotensin-2-receptor antagonist and dihydropyridine calcium channel blockers). Progression from microalbuminuria to nephropathy, doubling of serum creatinine, ESRD, and all-cause mortality was simulated over a 25-year time horizon using a published Markov model adapted to a Swiss setting. Transition probabilities were based on the Irbesartan in Reduction of Microalbuminuria-2 Study, Irbesartan in Diabetic Nephropathy Trial and other sources. Costs and clinical outcomes were discounted at 5% annually according to Swiss guidelines, and a third party payer perspective was taken. Treatment with irbesartan was projected to improve mean life expectancy by 0.57 years compared to conventional antihypertension treatment (undiscounted 1.22 years). Irbesartan treatment was associated with cost savings of CHF 21,488 per patient over the 25-year time horizon. Sensitivity analysis showed that irbesartan therapy remained dominant to conventional antihypertension treatment over a range of plausible assumptions. Addition of irbesartan to conventional antihypertension therapy was projected to improve life expectancy and reduce costs in hypertensive patients with type 2 diabetes and microalbuminuria in a Swiss setting

Bronchopulmonary Dysplasia

Hospitalizations for respiratory syncytial virus bronchioliti

Monitoring of ultrafine particles in French regional air quality network

Monitoring of ultrafine particles (UFP) in the ambient air is ongoing since 2012 in France. A national working group was created in 2014, including nowadays five French regional air quality monitoring networks. The main instrument selected to monitor UFP is the particle sizer “UFP-3031” (TSI Inc.). It measures the particle number concentration between 20 and 800 nm with six size channels. Two intercomparisons were organized in 2014 and 2015, which evaluated the accuracy of this instrument through a comparison with other techniques (such as Scanning Mobility Particle Sizer, SMPS), and through uncertainty calculations. Recently, several networks have been also equipped with CPC (condensation particle counter) to be able to measure the total UFP number concentration from 7 nm. This work presents the main results of short and long-term measurement of UFP which have been carried out in various environments: urban/traffic sites, near heavy industry zones (Dunkerque and Fos-sur-Mer in northern and southern France, respectively), near harbor area (Nice)… For urban/ traffic environment, the number concentration and size distribution are compared at the national level; it appears that they vary significantly depending on the influence of road traffic around the site. The concentration levels near traffic sites are at least twice than in the urban area, especially for UFP smaller than 50 nm. Additionally, the UFP measurement also makes it possible to improve the identification of specific sources and to understand the atmospheric physicochemical phenomena. The relationship between UFP and industrial emissions, ferries, forest fires was clearly identified in different places in France. During summer, the UFP monitoring also shows the formation of new particles (between 20-30 nm or smaller) in the afternoon, due to photochemical reactions. From 2019, the French national strategy on UFP will start putting a particular emphasis on the impact of UFP on human health

Variations in patterns of care across neonatal units and their associations with outcomes in very preterm infants: the French EPIPAGE-2 cohort study

OBJECTIVES: To describe patterns of care for very preterm (VP) babies across neonatal intensive care units (NICUs) and associations with outcomes. DESIGN: Prospective cohort study, EPIPAGE-2. SETTING: France, 2011. PARTICIPANTS: 53 (NICUs); 2135 VP neonates born at 27 to 31 weeks. OUTCOME MEASURES: Clusters of units, defined by the association of practices in five neonatal care domains - respiratory, cardiovascular, nutrition, pain management and neurodevelopmental care. Mortality at 2 years corrected age (CA) or severe/moderate neuro-motor or sensory disabilities and proportion of children with scores below threshold on the neurodevelopmental Ages and Stages Questionnaire (ASQ). METHODS: Hierarchical cluster analysis to identify clusters of units. Comparison of outcomes between clusters, after adjustment for potential cofounders. RESULTS: Three clusters were identified: Cluster 1 with higher proportions of neonates free of mechanical ventilation at 24 hours of life, receiving early enteral feeding, and neurodevelopmental care practices (26 units; n=1118 babies); Cluster 2 with higher levels of patent ductus arteriosus and pain screening (11 units; n=398 babies); Cluster 3 with higher use of respiratory, cardiovascular and pain treatments (16 units; n=619 babies). No difference was observed between clusters for the baseline maternal and babies' characteristics. No differences in outcomes were observed between Clusters 1 and 3. Compared with Cluster 1, mortality at 2 years CA or severe/moderate neuro-motor or sensory disabilities was lower in Cluster 2 (adjusted OR 0.46, 95% CI 0.25 to 0.84) but with higher proportion of children with an ASQ below threshold (adjusted OR 1.49, 95% CI 1.07 to 2.08). CONCLUSION: In French NICUs, care practices for VP babies were non-randomly associated. Differences between clusters were poorly explained by unit or population differences, but were associated with mortality and development at 2 years. Better understanding these variations may help to improve outcomes for VPT babies, as it is likely that some of these discrepancies are unwarranted

Continuous subcutaneous insulin infusion therapy is associated with reduced retinopathy progression compared with multiple daily injections of insulin

AIMS/HYPOTHESIS: We aimed to compare diabetic retinopathy outcomes in people with type 1 diabetes following introduction of continuous subcutaneous insulin infusion (CSII) therapy with outcomes in people receiving continuing therapy with multiple daily insulin injections (MDI). METHODS: This is a retrospective cohort study using the Scottish Care Information – Diabetes database for retinal screening outcomes and HbA(1c) changes in 204 adults commenced on CSII therapy between 2013 and 2016, and 211 adults eligible for CSII during the same period but who continued on MDI therapy. Diabetic retinopathy progression (time to minimum one-grade worsening in diabetic retinopathy from baseline grading) was plotted for CSII and MDI cohorts using Kaplan–Meier curves, and outcomes were compared using multivariate Cox regression analysis adjusting for age, sex, baseline HbA(1c), blood pressure, cholesterol, smoking status and socioeconomic quintile. Impact of baseline HbA(1c) and change in HbA(1c) on diabetic retinopathy progression was assessed within CSII and MDI cohorts. RESULTS: CSII participants were significantly younger, were from less socially deprived areas, and had lower HbA(1c) and higher diastolic BP at baseline. There was a larger reduction in HbA(1c) at 1 year in those on CSII vs MDI (−6 mmol/mol [−0.6%] vs −2 mmol/mol [−0.2%], p < 0.01). Diabetic retinopathy progression occurred in a smaller proportion of adults following commencement of CSII vs continued MDI therapy over mean 2.3 year follow-up (26.5% vs 18.6%, p = 0.0097). High baseline HbA(1c) (75 mmol/mol [9%]) was associated with diabetic retinopathy progression in the MDI group (p = 0.0049) but not the CSII group (p = 0.93). Change in HbA(1c) at follow-up, irrespective of baseline glycaemic status, did not significantly affect diabetic retinopathy progression in either group. CONCLUSIONS/INTERPRETATION: CSII was associated with reduced diabetic retinopathy progression compared with continued MDI therapy, and may be protective against diabetic retinopathy progression for those with high baseline HbA(1c). Progression of diabetic retinopathy over 3 years was not associated with a change in HbA(1c). GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains peer-reviewed but unedited supplementary material available at 10.1007/s00125-021-05456-w

Altruism can proliferate through group/kin selection despite high random gene flow

The ways in which natural selection can allow the proliferation of cooperative behavior have long been seen as a central problem in evolutionary biology. Most of the literature has focused on interactions between pairs of individuals and on linear public goods games. This emphasis led to the conclusion that even modest levels of migration would pose a serious problem to the spread of altruism in group structured populations. Here we challenge this conclusion, by analyzing evolution in a framework which allows for complex group interactions and random migration among groups. We conclude that contingent forms of strong altruism can spread when rare under realistic group sizes and levels of migration. Our analysis combines group-centric and gene-centric perspectives, allows for arbitrary strength of selection, and leads to extensions of Hamilton's rule for the spread of altruistic alleles, applicable under broad conditions.Comment: 5 pages, 2 figures. Supplementary material with 50 pages and 26 figure

Tandem quadruplication of HMA4 in the zinc (Zn) and cadmium (Cd) hyperaccumulator noccaea caerulescens

Zinc (Zn) and cadmium (Cd) hyperaccumulation may have evolved twice in the Brassicaceae, in Arabidopsis halleri and in the Noccaea genus. Tandem gene duplication and deregulated expression of the Zn transporter, HMA4, has previously been linked to Zn/Cd hyperaccumulation in A. halleri. Here, we tested the hypothesis that tandem duplication and deregulation of HMA4 expression also occurs in Noccaea. A Noccaea caerulescens genomic library was generated, containing 36,864 fosmid pCC1FOSTM clones with insert sizes ~20–40 kbp, and screened with a PCR-generated HMA4 genomic probe. Gene copy number within the genome was estimated through DNA fingerprinting and pooled fosmid pyrosequencing. Gene copy numbers within individual clones was determined by PCR analyses with novel locus specific primers. Entire fosmids were then sequenced individually and reads equivalent to 20-fold coverage were assembled to generate complete whole contigs. Four tandem HMA4 repeats were identified in a contiguous sequence of 101,480 bp based on sequence overlap identities. These were flanked by regions syntenous with up and downstream regions of AtHMA4 in Arabidopsis thaliana. Promoter-reporter b-glucuronidase (GUS) fusion analysis of a NcHMA4 in A. thaliana revealed deregulated expression in roots and shoots, analogous to AhHMA4 promoters, but distinct from AtHMA4 expression which localised to the root vascular tissue. This remarkable consistency in tandem duplication and deregulated expression of metal transport genes between N. caerulescens and A. halleri, which last shared a common ancestor >40 mya, provides intriguing evidence that parallel evolutionary pathways may underlie Zn/Cd hyperaccumulation in Brassicaceae

O COTIDIANO DAS FARMÁCIAS DE MANIPULAÇÃO

As farmácias de manipulação são responsáveis por uma grande alíquota do mercado de medicamentos no Brasil. Para tanto tem-se a preocupação com a qualidade das prescrições e da manipulação propriamente dita como forma de inserir o cenário real das mesmas na formação acadêmica do farmacêutico. O referido trabalho levantou as formulações de maior demanda nas farmácias de manipulação de três municípios do estado do Paraná. O resultado demonstrou que a demanda compõe-se de: cápsulas 48%, emulsões 18%, géis 3%, soluções 15%, xaropes 3%, shampoos 9% e 4% as demais (suspensões, óvulos, supositórios, soluções parenterais, comprimidos, pomadas, papéis entre outras). Levantou-se os estrangulamentos e deficiências do sistema, bem como apontou-se as vantagens da farmácia de manipulação sobre a ótica da Atenção Farmacêutica. THE ROUTINE OF MANIPULATION PHARMACIES Abstract The manipulation pharmacies are responsible for one large fraction of the pharmaceuticals market in Brazil.Consequently, there is amajor concern about the quality of prescriptions and themanipulation itself. Both aspects should be introduced in the academic studies of the pharmacist. This work raised the most demanded formulations in the manipulation pharmacies of three municipalities of Paraná State. The results demonstrated that the demand is divided in: capsules (48%), emulsions (18%), gels (5%), solutions (15%), syrups (3%), shampoos (9%) and 4% in suspensions, vaginal suppositories, suppositories, parenteral solutions, compressed tablets, ointments, and charts among others. It was also raised the major constraints and deficiencies of the system, as well as it was pointed out the advantages of manipulation pharmacies under the viewpoint of pharmaceutical care

Complete lung agenesis caused by complex genomic rearrangements with neo-TAD formation at the SHH locus

During human organogenesis, lung development is a timely and tightly regulated developmental process under the control of a large number of signaling molecules. Understanding how genetic variants can disturb normal lung development causing different lung malformations is a major goal for dissecting molecular mechanisms during embryogenesis. Here, through exome sequencing (ES), array CGH, genome sequencing (GS) and Hi-C, we aimed at elucidating the molecular basis of bilateral isolated lung agenesis in three fetuses born to a non-consanguineous family. We detected a complex genomic rearrangement containing duplicated, triplicated and deleted fragments involving the SHH locus in fetuses presenting complete agenesis of both lungs and near-complete agenesis of the trachea, diagnosed by ultrasound screening and confirmed at autopsy following termination. The rearrangement did not include SHH itself, but several regulatory elements for lung development, such as MACS1, a major SHH lung enhancer, and the neighboring genes MNX1 and NOM1. The rearrangement incorporated parts of two topologically associating domains (TADs) including their boundaries. Hi-C of cells from one of the affected fetuses showed the formation of two novel TADs each containing SHH enhancers and the MNX1 and NOM1 genes. Hi-C together with GS indicate that the new 3D conformation is likely causative for this condition by an inappropriate activation of MNX1 included in the neo-TADs by MACS1 enhancer, further highlighting the importance of the 3D chromatin conformation in human disease