NICE says that patients' age should affect treatment.
Ontology highlight
ABSTRACT:
SUBMITTER: Mayor S
PROVIDER: S-EPMC557925 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description: Not available
| S-EPMC1601991 | biostudies-literature
Project description:Background: Phenylketonuria (PKU) is an inborn error of metabolism caused by phenylalanine hydroxylase (PAH) deficiency. Patients with mild or moderate PKU can be successfully treated with sapropterin dihydrochloride (SD) which since recently is registered for usage from the age of 4 months. SD is a pharmaceutical version of tetrahydrobiopterin (BH4), a cofactor of PAH. Similar BH4 concentrations to those observed in plasma have been found in CSF of patients after a single oral administration thus proving that SD crosses the BBB. Hyperactivity has recently been reported as a post-marketing observation in some PKU patients treated with SD. Methods: 60 or 120 ng/ml sepiapterin, a stable precursor of BH4, were applied to study the effects of BH4 on developing brain cells in 3D organotypic rat brain cell cultures at two developmental stages. Immunohistochemistry, western blotting, metabolomics and RNA sequencing were performed. Findings: BH4 and BH2 measurements confirmed a successful conversion of sepiapterin to the active form BH4. In the earlier developmental stage, brain cell specific markers showed swollen astrocytes and diminished astrocytic fibres, delayed differentiation of oligodendrocytes and perturbation of axonal elongation. Immunofluorescence for activated caspase-3 revealed an increased apoptosis rate. We also found signs of perturbated GABAergic neurotransmission. RNAseq analyses revealed a number of significantly affected genes. GO enrichment allowed to identify key biological processes. Interestingly, none of these effects was observed in the later developmental stage. We show deleterious effects of SD on developing brain cells in a rat in vitro model. This observation raises the question whether the use of SD can be recommended in very young PKU patients as currently licensed.
2021-03-20 | GSE112108 | GEO
Project description:The World Health Organization predicts that the proportion of the world's population over 60 will almost double from 12% to 22% between 2015 and 2050. Ageing is the biggest risk factor for cancer, which is a leading cause of deaths worldwide. Unfortunately, research describing how genetic variants affect cancer progression commonly neglects to account for the ageing process. Herein is the first systematic analysis that combines a large longitudinal data set with a targeted candidate gene approach to examine the effect of genetic variation on survival as a function of age in cancer patients. Survival was significantly decreased in individuals with heterozygote or rare homozygote (i.e. variant) genotypes compared to those with a common homozygote genotype (i.e. wild type) for two single nucleotide polymorphisms (rs11574358 and rs4147918), one gene (SIRT3) and one pathway (FoxO signalling) in an age-dependent manner. All identified genes and pathways have previously been associated with ageing and cancer. These observations demonstrate that there are ageing-related genetic elements that differentially affect mortality in cancer patients in an age-dependent manner. Understanding the genetic determinants affecting prognosis differently with age will be invaluable to develop age-specific prognostic biomarkers and personalized therapies that may improve clinical outcomes for older individuals.
| S-EPMC5680559 | biostudies-literature
Project description:BackgroundMore and more heart failure (HF) patients aged ≥ 75 years undergo cardiac resynchronization therapy (CRT) device implantation, however the data regarding the outcomes and their predictors are scant. We investigated the mid- to long-term outcomes and their predictors in CRT patients aged ≥ 75 years.MethodsPatients in the Cardiac Resynchronization Therapy Modular (CRT MORE) Registry were divided into three age-groups: <65 (group A), 65-74 (group B) and ≥75 years (group C). Mortality, hospitalization, and composite event rate were evaluated at 1 year and during long-term follow-up.ResultsPatients (n = 934) were distributed as follows: group A 242; group B 347; group C 345. On 12-month follow-up examination, 63% of patients ≥ 75 years displayed a positive clinical response. Mortality was significantly higher in patients ≥ 75 years than in the other two groups, although the rate of hospitalizations for HF worsening was similar to that of patients aged 65-74 (7 vs. 9.5%, respectively; p = 0.15). Independent predictors of death and of negative clinical response were age >80 years, chronic obstructive pulmonary disease (COPD) and chronic kidney disease (CKD). Over long-term follow-up (1020 days (IQR 680-1362)) mortality was higher in patients ≥ 75 years than in the other two groups. Hospitalization and composite event rates were similar in patients ≥ 75 years and those aged 65-74 (9 vs. 11.8%; p = 0.26, and 26.7 vs. 20.5%; p = 0.06).ConclusionPositive clinical response and hospitalization rates do not differ between CRT recipients ≥ 75 years and those aged 65-74. However, age > 80 years, COPD and CKD are predictors of worse outcomes.
| S-EPMC8036418 | biostudies-literature
Project description: Not available
| S-EPMC1557946 | biostudies-literature
Project description:Age- and lactocrine-sensitive elements of the neonatal porcine uterine developmental program are undefined. Here, effects of age and nursing for 48 h from birth (postnatal day = [PND] 0) on the uterine transcriptome at PND 2 were identified using RNA sequencing. Pig uterine tissues were obtained from neonatal gilts (n = 4/group) within 1 h of birth [postnatal day (PND) 0], or 48 h after nursing ad libitum (PND 2N), or feeding a commercial milk replacer (PND 2R).
2016-02-15 | E-GEOD-72388 | biostudies-arrayexpress
Project description: Not available
| S-EPMC8622508 | biostudies-literature
Project description: Not available
| S-EPMC1123090 | biostudies-literature
Project description:Age- and lactocrine-sensitive elements of the neonatal porcine uterine developmental program are undefined. Here, effects of age and nursing for 48 h from birth (postnatal day = [PND] 0) on the uterine transcriptome at PND 2 were identified using RNA sequencing.
2016-02-15 | GSE72388 | GEO