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Quality of life and cost-effectiveness of a 3-year trial of lifestyle intervention in primary health care

Background: Lifestyle interventions reduce cardiovascular risk and diabetes but reports on long term effects on quality of life (QOL) and health care utilization are rare. The aim was to investigate the impact of a primary health care based lifestyle intervention program on QOL and cost-effectiveness over 3 years. Methods: 151 men and women, age 18-65 yr, at moderate-to-high risk for cardiovascular disease, were randomly assigned to either lifestyle intervention with standard care or standard care alone. Intervention consisted of supervised exercise sessions and diet counseling for 3 months, followed by regular group meetings during 3years. Change in QOL was measured with EuroQol (EQ-5D, EQ VAS), the 36-item Short Form Health Survey (SF-36), and the SF-6D.  The health economic evaluation was performed from a societal view and a treatment perspective. In a cost-utility analysis the costs, gained quality-adjusted life years (QALY) and savings in health care were considered. Cost-effectiveness was also described using the Net Monetary Benefit Method. Results: Significant differences between groups over the 3-yr period were shown in EQ VAS, SF-6D and SF-36 physical component summary but not in EQ-5D or SF-36 mental component summary. There was a net saving of 47 USD per participant. Costs per gained QALY, savings not counted, were 1,668 – 4,813 USD. Probabilities of cost-effectiveness were 89 – 100 %, when 50 000 USD was used as stakeholder’s threshold of willingness to pay for a gained QALY. Conclusion: Lifestyle intervention in primary care improves QOL and is highly cost-effective in relation to standard care

A novel phenotype in N-glycosylation disorders: Gillessen-Kaesbach-Nishimura skeletal dysplasia due to pathogenic variants in ALG9.

A rare lethal autosomal recessive syndrome with skeletal dysplasia, polycystic kidneys and multiple malformations was first described by Gillessen-Kaesbach et al and subsequently by Nishimura et al. The skeletal features uniformly comprise a round pelvis, mesomelic shortening of the upper limbs and defective ossification of the cervical spine. We studied two unrelated families including three affected fetuses with Gillessen-Kaesbach-Nishimura syndrome using whole-exome and Sanger sequencing, comparative genome hybridization and homozygosity mapping. All affected patients were shown to have a novel homozygous splice variant NM_024740.2: c.1173+2T>A in the ALG9 gene, encoding alpha-1,2-mannosyltransferase, involved in the formation of the lipid-linked oligosaccharide precursor of N-glycosylation. RNA analysis demonstrated skipping of exon 10, leading to shorter RNA. Mass spectrometric analysis showed an increase in monoglycosylated transferrin as compared with control tissues, confirming that this is a congenital disorder of glycosylation (CDG). Only three liveborn children with ALG9-CDG have been previously reported, all with missense variants. All three suffered from intellectual disability, muscular hypotonia, microcephaly and renal cysts, but none had skeletal dysplasia. Our study shows that some pathogenic variants in ALG9 can present as a lethal skeletal dysplasia with visceral malformations as the most severe phenotype. The skeletal features overlap with that previously reported for ALG3- and ALG12-CDG, suggesting that this subset of glycosylation disorders constitutes a new diagnostic group of skeletal dysplasias.European Journal of Human Genetics advance online publication, 13 May 2015; doi:10.1038/ejhg.2015.91

Birth cohort effects in neurological diseases: amyotrophic lateral sclerosis, Parkinson's disease and multiple sclerosis

Background: Generational differences in disease rates are the main subject of age-period-cohort (APC) analysis, which is mostly applied in cancer and suicide research. This study applied APC analysis to selected neurological diseases: amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD) and multiple sclerosis (MS). Methods: The analyses were based on Swiss mortality data. Age-stratified data has been available for MS, PD and ALS since 1901, 1921, and 1942, respectively. APC analysis was performed within the framework of logit models. Main effect models were extended by implementing nested effects, i.e. age effects nested in subperiods, in order to account for the fact that age profiles may change for reasons other than generational influences. Results: In preliminary analyses, APC analysis yielded noteworthy birth cohort effects in all three diseases. After implementing nested effects, the birth cohort effects disappeared in ALS, and smoothed out in PD, where they were greater for the generations born before the 1920s. In MS, the birth cohort effects remained stable, and exhibited a peak in cohorts born in the 1910s and 1920s. Conclusions: APC analysis yielded some evidence for birth cohort effects, i.e. predisposing risk factors that may change in historical terms, in MS and PD, but probably not in ALS