77 research outputs found
Treatment and long term follow-up of children and young adults with familial hypercholesterolemia
No full textFamilial hypercholesterolemia (FH) is a common, genetic, autosomal dominant condition, resulting in reduced capacity to clear low density lipoprotein (LDL) from the circulation and increased risk of cardiovascular disease. Typically LDL-cholesterol (LDL-C) levels are doubled from birth on. Development of atherosclerosis can be prevented by treatment with cholesterol lowering drugs, usually statins. Guidelines recommend initiating statin therapy from 8-10 years of age.
In the thesis, Treatment and long term follow-up of children and young adults with familial hypercholesterolemia, Gisle Langslet and co-workers investigated open-label treatment with rosuvastatin for 2 years and atorvastatin for 3 years, in children with FH, aged 6 to 17 years. LDL-C was reduced by approximately 40 % in both studies. There were no serious safety issues and the treatment had no evident effect on growth or pubertal development.
Increased thickness of the arterial wall in the carotid arteries, carotid intima-media-thickness (cIMT), is an early sign of atherosclerosis. In the rosuvastatin study, already before 8 years of age, cIMT was higher in untreated children with FH, compared with siblings without FH. After 2 years of rosuvastatin treatment in the children with FH, the difference in cIMT was no longer significant.
Paper IV reports adherence and effect of treatment in 67 young adults with FH, having started with lipid lowering therapy (LLT) around 15 years of age. At mean age 25 years, 25 % had stopped using LLT and only 6 % attained their LDL-C goal.
Paper V reports lipid lowering treatment in 302 children at the Lipid Clinic in 2014-2016. Mean age at start of statins was 12.5 years, 59 % were treated at their last visit and 71% of those on stable LLT attained their LDL-C goal.
In conclusion, early start of statins in children with FH is safe and can slow down the arteriosclerotic process. Regular follow-up is important to obtain satisfactory adherence and attain treatment goals
Efficacy and Safety of Pitavastatin in Children and Adolescents at High Future Cardiovascular Risk
No full textAbstract: Objectives: Elevated low-density lipoprotein cholesterol (LDL-C) is a risk factor for coronary heart disease (CHD) in adults, but the underlying atherogenesis begins in childhood. Therefore guidelines recommend consideration of statin therapy in children at high future CVD risk. The aim of the study was to assess the safety and efficacy of pitavastatin in children and adolescents with hyperlipidemia. Study design: A total of 106 hyperlipidemic children and adolescents, ages 6 to 17 years, were enrolled in a 12 week randomized, double blind, placebo controlled study and randomly assigned to pitavastatin 1 mg, 2 mg, 4 mg or placebo. During a 52 week extension period, subjects were up-titrated from 1 mg pitavastatin to a maximum dose of 4 mg in an effort to achieve an optimum LDL-C treatment target of 110mg/dL (2.8 mmol/L). Safety was assessed in terms of adverse event rates, including abnormal clinical laboratory variables, vital signs and physical examination.Results: Compared with placebo, pitavastatin 1, 2 and 4 mg significantly reduced LDL-C from baseline by 23.5%, 30.1% and 39.3%, respectively and in the open label study 20.5% of the subjects reached the LDL-C goal < 110 mg/dL (2.8 mmol/L). No safety issues became evident.Conclusion: Pitavastatin at doses up to 4 mg is well tolerated and efficacious in children and adolescents aged 6-17 years
EFFICACY OF ALIROCUMAB IN 1,191 PATIENTS WITH A WIDE SPECTRUM OF MUTATIONS IN GENES CAUSATIVE FOR FAMILIAL HYPERCHOLESTEROLEMIA
No full textBackground: Next Generation Sequencing was performed to examine treatment response with alirocumab in patients carrying one or
more causative mutation(s) in five familial hypercholesterolemia (FH) genes.
Methods: From 6 clinical trials of alirocumab (one Phase 2, five Phase 3), 1191 patients with elevated LDL-C and phenotypic FH (including
758 treated with alirocumab) were sequenced for mutations using the SEQPRO LIPO platform in LDL receptor (LDLR), apolipoprotein B
(APOB), PCSK9 (PCSK9), LDL receptor adaptor protein 1 (LDLRAP1), and signal-transducing adaptor protein 1 (STAP1) genes. New
mutations were confirmed by Sanger sequencing and MLPA analysis in case of large gene rearrangements in the original DNA samples.
Results: In total, 387 patients (32%) and 438 (37%) had single receptor defective and receptor negative mutations in LDLR, respectively;
46 (4%) had single mutations in APOB; 8 (0.7%) had single gain-of-function mutations in PCSK9; 2 (0.17%) were homozygous
for mutations in LDRAP1; 6 (0.5%) were double heterozygotes for mutations in both APOB and LDLR; 10 (0.8%) were compound
heterozygotes in LDLR; 1 (0.08%) was a double heterozygote for mutations in LDLR and PCSK9; 293 (25%) had no identifiable causative
mutation in any of the genes investigated. LDL-C reduction with alirocumab at week 12 was generally similar across background FH
mutations: LDLR defective heterozygotes -51.8% (N=231), LDLR negative heterozygotes -50.2% (N=289); APOB heterozygotes -45.5%
(N=26); PCSK9 heterozygotes -53.3% (N=5); subjects with no identifiable mutation -51.0% (N=171). A similar large decrease in LDL-C
was also seen in the 3 double heterozygotes (LDLR, APOB, -49.2%) and 6 potentially compound heterozygous (LDLR, -48.0%) patients.
Overall rates of TEAEs were similar for alirocumab vs controls, with a higher rate of injection site reactions with alirocumab.
Conclusions: In this large cohort of FH patients, individuals with a wide spectrum of mutations in genes causative for FH responded
substantially to alirocumab treatment. LDL-C-lowering activity by alirocumab in compound heterozygotes and double heterozygotes is likely
attributable to the presence of at least one partially functional allele
A 3-year study of atorvastatin in children and adolescents with heterozygous familial hypercholesterolemia
No full textBACKGROUND: The efficacy and safety of atorvastatin in children/adolescents aged 10-17 years with heterozygous familial hypercholesterolemia (HeFH) have been demonstrated in trials of up to 1 year in duration. However, the efficacy/safety of >1 year use of atorvastatin in children/adolescents with HeFH, including children from 6 years of age, has not been assessed. OBJECTIVE: To characterize the efficacy and safety of atorvastatin over 3 years and to assess the impact on growth and development in children aged 6-15 years with HeFH. METHODS: A total of 272 subjects aged 6-15 years with HeFH and low-density lipoprotein cholesterol (LDL-C) mmol/L (154 mg/dL) were enrolled in a 3-year study (NCT00827606). Subjects were initiated on atorvastatin (5 mg or 10 mg) with doses increased to up to 80 mg based on LDL-C levels. RESULTS: Mean percentage reductions from baseline in LDL-C at 36 months/early termination were 43.8% for subjects at Tanner stage (TS) 1 and 39.9% for TS There was no evidence of variations in the lipid-lowering efficacy of atorvastatin between the TS groups analyzed (1 vs >= 2) or in subjects aged <10 vs years, and the treatment had no adverse effect on growth or maturation. Atorvastatin had a favorable safety and tolerability profile, and only 6 (2.2%) subjects discontinued because of adverse events. CONCLUSIONS: Atorvastatin over 3 years was efficacious, had no impact on growth/maturation, and was well tolerated in children and adolescents with HeFH aged 6-15 years. (C) 2016 National Lipid Association. Published by Elsevier Inc
A 3-year study of atorvastatin in children and adolescents with heterozygous familial hypercholesterolemia
No full textBackgroundThe efficacy and safety of atorvastatin in children/adolescents aged 10–17 years with heterozygous familial hypercholesterolemia (HeFH) have been demonstrated in trials of up to 1 year in duration. However, the efficacy/safety of >1 year use of atorvastatin in children/adolescents with HeFH, including children from 6 years of age, has not been assessed.ObjectiveTo characterize the efficacy and safety of atorvastatin over 3 years and to assess the impact on growth and development in children aged 6–15 years with HeFH.MethodsA total of 272 subjects aged 6–15 years with HeFH and low-density lipoprotein cholesterol (LDL-C) ≥4.0 mmol/L (154 mg/dL) were enrolled in a 3-year study (NCT00827606). Subjects were initiated on atorvastatin (5 mg or 10 mg) with doses increased to up to 80 mg based on LDL-C levels.ResultsMean percentage reductions from baseline in LDL-C at 36 months/early termination were 43.8% for subjects at Tanner stage (TS) 1 and 39.9% for TS ≥2. There was no evidence of variations in the lipid-lowering efficacy of atorvastatin between the TS groups analyzed (1 vs ≥2) or in subjects aged <10 vs ≥10 years, and the treatment had no adverse effect on growth or maturation. Atorvastatin had a favorable safety and tolerability profile, and only 6 (2.2%) subjects discontinued because of adverse events.ConclusionsAtorvastatin over 3 years was efficacious, had no impact on growth/maturation, and was well tolerated in children and adolescents with HeFH aged 6–15 years
Fortune Telling, Gambling and Decision-Making at Stora Kopparberget in the Early 17th Century
No full textIn the early 17th century, when the city of Falun was among the largest cities in Sweden due to its important copper mine, Gisle Jacobson, a local mining clerk, became the author of a small book which was published in Stockholm in 1613, entitled Ett litet Tidh- fördriff/ Der medh man kan fördröye Tidhen (A small pastime, wherewith one can delay time). A small pastime is a moral-didactic oracle book intended to be used while playing dice, and is based on the so-called “dobbel”, a game of dice the miners in Falun used to play on New Year’s Day to settle the mining order and to sha- re the ore among them. Reports suggest that this ritual was con- ducted annually at the Copper mine ever since the Middle Ages. Besides moral advice and various rules for how the miners should conduct their lives, Gisle Jacobson’s book also includes a short section where the senior miners’ special way of playing the game of “dobbel” is described. In my paper I will describe the miners’ way of using and playing the game of “dobble”, its function in relation to Gisle Jacobson’s book and give an insight into how this game was used to make important decision concerning the inner organization of the mine.</p
Simultaneous Reduction in Both HbA1c and Body Weight with Canagliflozin Versus Glimepiride in Patients with Type 2 Diabetes on Metformin
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Response by Kusters et al to Letter Regarding Article, "Effect of Rosuvastatin on Carotid Intima-Media Thickness in Children With Heterozygous Familial Hypercholesterolemia: The CHARON Study (Hypercholesterolemia in Children and Adolescents Taking Rosuvastatin Open Label)"
No full textsponsorship: Dr Langslet has received advisory board fees from Amgen, Sanofi, Boehringer Ingelheim, and Janssen Pharmaceuticals. Dr McCrindle has received consulting fees from Eli Lilly, Medpace, Merck, and Bristol Myers Squibb and research support from AstraZeneca. Dr Cassiman serves as a clinical investigator for the Fund for Scientific Research-Flanders. Dr Francis has been a member of the speakers board or an advisor to Aegerion, Alexion, Amgen, Sanofi, and Valeant. Dr Gagne has participated in studies sponsored by Amgen, AstraZeneca, Genzyme, Isis, Merck/Schering-Plow, Pfizer, Regeneron, and Sanofi. Dr Gaudet has served as a consultant or advisor for AstraZeneca, Regeneron, Amgen, Novartis, Isis, Uniqure, and Catabasis. Dr Morrison has received research support from AstraZeneca. Dr Stein has received consultant and expert witness fees from AstraZeneca regarding statins. Dr Kastelein has received grant support from AstraZeneca, Pfizer, Roche, Novartis, Merck, Merck/Schering-Plow, Isis, Genzyme, and Sanofi-Aventis; lecture fees from AstraZeneca, GlaxoSmithKline, Pfizer, Novartis, Merck/Schering-Plow, Roche, Isis, and Boehringer Ingelheim; and consulting fees from AstraZeneca, Abbott, Pfizer, Isis, Genzyme, Roche, Novartis, Merck, Merck/Schering-Plow, and Sanofi-Aventis. Dr Hutten has received an independent grant for learning and change from Pfizer. Drs Miller, Raichlen, and Martin are employees of AstraZeneca. The other authors report no conflicts. (Amgen, Sanofi, Boehringer Ingelheim, Janssen Pharmaceuticals, Eli Lilly, Medpace, Merck, Bristol Myers Squibb, AstraZeneca, Genzyme, Isis, Merck/Schering-Plow, Pfizer, Regeneron, Roche, Novartis, Sanofi-Aventis, GlaxoSmithKline, Abbott)status: Publishe
Smeknamn i vardagslag och i skrift : Bruket av hypokorismer i det medeltida Jämtland
No full textIn this article, the question is raised whether the personal names used in medieval documents differed from the names used in oral communication within the local communities of that time. The author concludes that in Jämtland, a province in Mid-Scandinavia with a rather good source material for investigating this question, there was a difference. In everyday life, a lot of men were apparently called by their hypocorisms (nicknames), i.e. weak forms of their given names, e.g. Pale, Gumme, Gisle instead of Pavel, Gudhmund, Ødhgisl. In written, official documents, the given names were preferred. These conclusions are drawn from analyses of male names occurring in medieval place names (which are expected to reflect a naming custom close to everyday life) and in the extant documents from c. 1300-1550. Some comparisons with other areas are made. Female names are not dealt with in this study.</p
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