Growth hormone treatment in children with short stature born small for gestational age: 5-year results of a randomized, double-blind, dose-response trial

The growth-promoting effect of continuous GH treatment was evaluated over 5 yr in 79 children with short stature (height SD score, less than -1.88) born small for gestational age (SGA; birth length SD score, less than -1.88). Patients were randomly and blindly assigned to 1 of 2 GH dosage groups (3 vs. 6 IU/m2 body surface-day). GH deficiency was not an exclusion criterium. After 5 yr of GH treatment almost every child had reached a height well within the normal range for healthy Dutch children and in the range of their target height SD score. Only in children who remained prepubertal during the study period was the 5-yr increase in height SD score (HSDS) for chronological age significantly higher in the study group receiving 6 compared to 3 IU GH/m2 x day. Remarkably, the 5-yr increment in HSDS for chronological age was not related to spontaneous GH secretion, maximum GH levels after provocation, or baseline insulin-like growth factor I levels. GH treatment was associated with an acceleration of bone maturation regardless of the GH dose given. The HSDS for bone age and predicted adult height increased significantly. GH treatment was well tolerated. In conclusion, our 5-yr data show that long term continuous GH treatment at a dose of 3 or 6 IU/m2 x day in short children born SGA results in a normalization of height during childhood followed by growth along the target height percentile

Planning drinking water for airplanes

The management of the Dutch national airline company KLM intends to bring a sufficient amount of water on board of all flights to fulfill customer’s demand. On the other hand, the surplus of water after a flight should be kept to a minimum to reduce fuel costs. The service to passengers is measured with a service level. The objective of this research is to develop models, which can be used to minimize the amount of water on board of flights such that a predefined service level is met. The difficulty that has to be overcome is the fact that most of the available data of water consumption on flights are rounded off to the nearest eighth of the water tank. For wide-body aircrafts this rounding may correspond to about two hundred litres of water. Part of the problem was also to define a good service level. The use of a service level as a model parameter would give KLM a better control of the water surplus. The available data have been analyzed to examine which aspects we had to take into consideration. Next, a general framework has been developed in which the service level has been defined as a Quality of Service for each flight: The probability that a sufficient amount of water is available on a given flight leg. Three approaches will be proposed to find a probability distribution function for the total water consumption on a flight. The first approach tries to fit a distribution for the water consumption based on the available data, without any assumptions on the underlying shape of the distribution. The second approach assumes normality for the total water consumption on a flight and the third approach uses a binomial distribution. All methods are validated and numerically illustrated. We recommend KLM to use the second approach, where the first approach can be used to determine an upper bound on the water level

Genome-wide methylation patterns in Marfan syndrome

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Aortic distensibility in Marfan syndrome:a potential predictor of aortic events?

Contains fulltext : 239962.pdf (Publisher’s version ) (Open Access

Long-term clinical outcomes of losartan in patients with Marfan syndrome:follow-up of the multicentre randomized controlled COMPARE trial

AIMS: The COMPARE trial showed a small but significant beneficial effect of 3-year losartan treatment on aortic root dilatation rate in adults with Marfan syndrome (MFS). However, no significant effect was found on clinical endpoints, possibly due to a short follow-up period. The aim of the current study was therefore to investigate the long-term clinical outcomes after losartan treatment. METHODS AND RESULTS: In the original COMPARE study (inclusion 2008-2009), adult patients with MFS (n = 233) were randomly allocated to either the angiotensin-II receptor blocker losartan® on top of regular treatment (β-blockers in 71% of the patients) or no additional medication. After the COMPARE trial period of 3 years, study subjects chose to continue their losartan medication or not. In a median follow-up period of 8 years, 75 patients continued losartan medication, whereas 78 patients, originally allocated to the control group, never used losartan after inclusion. No differences existed between baseline characteristics of the two groups except for age at inclusion [losartan 34 (interquartile range, IQR 26-43) years, control 41 (IQR 30-52) years; P = 0.031], and β-blocker use (losartan 81%, control 64%; P = 0.022). A pathological FBN1 mutation was present in 76% of patients and 58% of the patients were male. Clinical endpoints, defined as all-cause mortality, aortic dissection/rupture, elective aortic root replacement, reoperation, and vascular graft implantation beyond the aortic root, were compared between the two groups. A per-patient composite endpoint was also analysed. Five deaths, 14 aortic dissections, 23 aortic root replacements, 3 reoperations, and 3 vascular graft implantations beyond the aortic root occurred during follow-up. Except for aortic root replacement, all endpoints occurred in patients with an operated aortic root. Patients who used losartan during the entire follow-up period showed a reduced number of events compared to the control group (death: 0 vs. 5, P = 0.014; aortic dissection: 3 vs. 11, P = 0.013; elective aortic root replacement: 10 vs. 13, P = 0.264; reoperation: 1 vs. 2, P = 0.463; vascular graft implantations beyond the aortic root 0 vs. 3, P = 0.071; and composite endpoint: 14 vs. 26, P = 0.019). These results remained similar when corrected for age and β-blocker use in a multivariate analysis. CONCLUSION: These results suggest a clinical benefit of combined losartan and β-blocker treatment in patients with MFS