Phenotypic expansion of the BPTF-related neurodevelopmental disorder with dysmorphic facies and distal limb anomalies

Neurodevelopmental disorder with dysmorphic facies and distal limb anomalies (NEDDFL), defined primarily by developmental delay/intellectual disability, speech delay, postnatal microcephaly, and dysmorphic features, is a syndrome resulting from heterozygous variants in the dosage-sensitive bromodomain PHD finger chromatin remodeler transcription factor BPTF gene. To date, only 11 individuals with NEDDFL due to de novo BPTF variants have been described. To expand the NEDDFL phenotypic spectrum, we describe the clinical features in 25 novel individuals with 20 distinct, clinically relevant variants in BPTF, including four individuals with inherited changes in BPTF. In addition to the previously described features, individuals in this cohort exhibited mild brain abnormalities, seizures, scoliosis, and a variety of ophthalmologic complications. These results further support the broad and multi-faceted complications due to haploinsufficiency of BPTF.Genetics of disease, diagnosis and treatmen

Ekonomiczne sposoby zwiększenie efektywności planowania budowy dróg

The formation of the road-building program with the use of traffic flows logistics can achieve rational use of the limited financial resources and to provide current and long-term interests of the road users. In order to evaluate the effectiveness of conducting the road repair and reconstruction, the factors reflecting their importance for the national economy are used: road organizations, which are the main subjects of the implementation of the formed program; enterprises of motor transport complex, which are the main consumers of the road facilities and the state, who is the main investor in the road branch. The integral criterion characterizing the efficiency of using the logistical approach to the formation of the optimal scheme of repairing and reconstructing the road network, both for the users and for the contractors, is calculated. Its size makes it possible to assess the effectiveness of fulfilling the overhaul and reconstruction on a definite site and at the formed optimal scheme of distributing the overhaul and reconstruction of the road network. The article presents the methodological fundamentals of the economic evaluation logistical systems of roads facilities.Powstawanie programu budowy dróg z wykorzystaniem informacji na temat natężenia ruchu drogowego może przyczynić się do racjonalnego wykorzystania ograniczonych często zasobów finansowych. Do oceny skutecznośi przebudowy i remontu dróg angażuje się organizacje zajmujące się implementacją programu budowy dróg, przedsiębiorstwa transportu drogowego, będące głównym konsumentem infrastruktury drogowej, jak również państwo, które jest głównym inwestorem takiego przedsięwzięcia. Zaleca się wykorzystanie wskaźnika, określającego skuteczność wykorzystania logistycznego podejścia w procesie tworzenia programu naprawy i odbudowy sieci drogowej, zarówno dla jej użytkowników, jak i wykonawców

Relative cost-effectiveness of using an extensively hydrolyzed casein formula containing the probiotic Lactobacillus rhamnosus GG in managing infants with cow's milk allergy in Poland

Julian F Guest,1,2 Diana Weidlich,1 Maciej Kaczmarski,3 Elzbieta Jarocka-Cyrta,4 Natalia Kobelska-Dubiel,5 Agnieszka Krauze,6 Iwona Sakowska-Maliszewska,7 Anna Zawadzka-Krajewska8 1Catalyst Health Economics Consultants, Northwood, Middlesex, 2Faculty of Life Sciences and Medicine, King’s College, London, UK; 3Department of Pediatrics, Gastroenterology, and Allergology, Medical University of Bialystok, Białystok, 4Uniwersytet Warmińsko‑Mazurski, Wydział Nauk Medycznych, Katedra Pediatrii Klinicznej, Olsztyn, 5Department of Pediatric Gastroenterology and Metabolic Diseases, Poznań University of Medical Sciences, Poznań, 6Klinika Pneumonologii i Alergologii Wieku Dziecięcego, Warsaw, 7Poradnia Gastroenterologiczna Centrum Pediatrii, Sosnowiec, 8Department of Pediatric Pneumonology and Allergology, Medical University of Warsaw, Warsaw, Poland Objective: To estimate the cost-effectiveness of using an extensively hydrolyzed casein formula (eHCF) containing the probiotic Lactobacillus rhamnosus GG (eHCF + LGG; Nutramigen LGG) as an initial treatment for cow’s milk allergy compared with eHCF alone and amino acid formulas (AAF) in Poland from the perspective of the Polish National Health Fund (Narodowy Fundusz Zdrowia [NFZ]) and parents. Methods: Decision modeling was used to estimate the probability of cow’s milk allergic infants developing tolerance to cow’s milk by 18 months. The model also estimated the cost to the NFZ and parents (Polish Zloty [PLN] at 2013–2014 prices) for managing infants over 18 months after starting one of the formulas as well as the relative cost-effectiveness of each of the formulas. Results: The probability of developing tolerance to cow’s milk by 18 months was higher among infants who were fed eHCF + LGG (0.82) compared with those fed eHCF alone (0.53) or an AAF (0.22). An infant who is initially managed with eHCF + LGG is expected to consume fewer health care resources than infants managed with the other formulas. Hence, the estimated total health care cost incurred by the NFZ for initially feeding infants with eHCF + LGG (PLN 5,693) was less than that of feeding infants with eHCF alone (PLN 7,749) or an AAF (PLN 24,333). However, the total cost incurred by parents for initially feeding infants with an AAF (PLN 815) was marginally less than that of feeding with eHCF + LGG (PLN 993), which was less than that of feeding with eHCF alone (PLN 1,226). Conclusion: Using eHCF + LGG instead of eHCF alone or an AAF for first-line management of newly diagnosed infants with cow’s milk allergy affords a cost-effective use of NFZ-funded resources, since it improves outcome for less cost. Whether eHCF + LGG would be viewed as being cost-effective by parents is dependent on their willingness to pay an additional cost for additional tolerance acquisition to cow’s milk. Keywords: amino acid formula, cost-effectiveness, cow’s milk allergy, extensively hydrolyzed formula, Lactobacillus Rhamnosus GG, Polan