Treatment adherence in tyrosinemia type 1 patients

Background: While therapeutic advances have signifcantly improved the prognosis of patients with hereditary tyrosinemia type 1 (HT1), adherence to dietary and pharmacological treatments is essential for an optimal clinical outcome. Poor treatment adherence is well documented among patients with chronic diseases, but data from HT1 patients are scarce. This study evaluated pharmacological and dietary adherence in HT1 patients both directly, by quantifying blood levels nitisinone (NTBC) levels and metabolic biomarkers of HT1 [tyrosine (Tyr), phenylalanine (Phe), and succinylacetone]; and indirectly, by analyzing NTBC prescriptions from hospital pharmacies and via clinical inter views including the Haynes-Sackett (or self-compliance) test and the adapted Battle test of patient knowledge of the disease. Results: This observational study analyzed data collected over 4 years from 69 HT1 patients (7 adults and 62 children; age range, 7months-35 years) who were treated with NTBC and a low-Tyr, low-Phe diet. Adherence to both pharmacological and, in particular, dietary treatment was poor. Annual data showed that NTBC levels were lower than recommended in more than one third of patients, and that initial Tyr levels were high (>400µM) in 54.2-64.4% of patients and exceeded 750µM in 25.8% of them. Remarkably, annual normalization of NTBC levels was observed in 29.4-57.9% of patients for whom serial NTBC determinations were performed. Poor adherence to dietary treatment was more refractory to positive reinforcement: 36.2% of patients in the group who underwent multiple analyses per year maintained high Tyr levels during the entire study period, and, when considering each of the years individually this percentage ranged from 75 to 100% of them. Indirect methods revealed percentages of non-adherent patients of 7.3 and 15.9% (adapted Battle and Haynes tests, respectively). Conclusions: Despite initially poor adherence to pharmacological and especially dietary treatment among HT1 patients, positive reinforcement at medical consultations resulted in a marked improvement in NTBC levels, indicating the importance of systematic positive reinforcement at medical visits.Funding. NTBC determination was funded by SOBI. Acknowledgements. The authors thank all participating centers, as well as the patients and their families

Non-alcoholic fatty liver in hereditary fructose intolerance

Background: Non-alcoholic fatty liver disease (NAFLD) is characterized by fat accumulation affecting >5% of the liver volume that is not explained by alcohol abuse. It is known that fructose gives rise to NAFLD and it has been recently described that the ingestion of fructose in low amounts in aldolase B deficient mice is associated with the development of fatty liver. Therefore, it is reasonable that patients with HFI (Hereditary Fructose Intolerance) present fatty liver at diagnosis, but its prevalence in patients treated and with adequate follow-up is not well documented in the literature. The aim of this study is to analyze the association between HFI and NAFLD in treated patients. Methods: A cross-sectional observational study was conducted. The population comprised 16 genetically diagnosed HFI patients aged from 3 years to 48 and in dietary treatment of fructose, sorbitol and sacarose exclusion at least for two years. Blood samples were obtained for analytical studies and anthropometric measurements of each patient were performed. Results: Patients presented a Body Mass Index (BMI) of 17.9 ± 2.9 kg/m 2 . The HOMA index and Quick index were in normal range for our population. The S-adenosyl-methionine (SAM)/S-adenosyl-L-homocysteine (SAH) ratio was increased in the patients in whom this analysis was performed. By imaging techniques it was observed that 9 of the 16 patients presented fatty liver (7 by hepatic MRI). Of these 9 patients, only 3 presented hepatomegaly. 7 of 9 patients affected by the c.448G > C mutation had fatty infiltration, of which three of them presented in addition hepatomegaly. Conclusions: There is a high prevalence of fatty liver in HFI patients and it is not related to obesity and insulin resistance. The diagnosis of fatty liver in HFI patients and, above all, the identification of new therapeutic approaches, can positively impact the quality of life of these patients

Phenylketonuria in Portugal: Genotype-Phenotype Correlations Using Molecular, Biochemical, and Haplotypic Analyses

The impairment of the hepatic enzyme phenylalanine hydroxylase (PAH) causes elevation of phenylalanine levels in blood and other body fluids resulting in the most common inborn error of amino acid metabolism (phenylketonuria). Persistently high levels of phenylalanine lead to irreversible damage to the nervous system. Therefore, early diagnosis of the affected individuals is important, as it can prevent clinical manifestations of the disease.info:eu-repo/semantics/publishedVersio

Epidemiological trends of HIV/HCV coinfection in Spain, 2015-2019

Altres ajuts: Spanish AIDS Research Network; European Funding for Regional Development (FEDER).Objectives: We assessed the prevalence of anti-hepatitis C virus (HCV) antibodies and active HCV infection (HCV-RNA-positive) in people living with HIV (PLWH) in Spain in 2019 and compared the results with those of four similar studies performed during 2015-2018. Methods: The study was performed in 41 centres. Sample size was estimated for an accuracy of 1%. Patients were selected by random sampling with proportional allocation. Results: The reference population comprised 41 973 PLWH, and the sample size was 1325. HCV serostatus was known in 1316 PLWH (99.3%), of whom 376 (28.6%) were HCV antibody (Ab)-positive (78.7% were prior injection drug users); 29 were HCV-RNA-positive (2.2%). Of the 29 HCV-RNA-positive PLWH, infection was chronic in 24, it was acute/recent in one, and it was of unknown duration in four. Cirrhosis was present in 71 (5.4%) PLWH overall, three (10.3%) HCV-RNA-positive patients and 68 (23.4%) of those who cleared HCV after anti-HCV therapy (p = 0.04). The prevalence of anti-HCV antibodies decreased steadily from 37.7% in 2015 to 28.6% in 2019 (p < 0.001); the prevalence of active HCV infection decreased from 22.1% in 2015 to 2.2% in 2019 (p < 0.001). Uptake of anti-HCV treatment increased from 53.9% in 2015 to 95.0% in 2019 (p < 0.001). Conclusions: In Spain, the prevalence of active HCV infection among PLWH at the end of 2019 was 2.2%, i.e. 90.0% lower than in 2015. Increased exposure to DAAs was probably the main reason for this sharp reduction. Despite the high coverage of treatment with direct-acting antiviral agents, HCV-related cirrhosis remains significant in this population

Hospitalización a Domicilio en hospitales públicos gallegos

Objetivo: Mostrar en qué consisten y la actividad que realizan las Unidades de Hospitalización a Domicilio (HADO) en los hospitales públicos gallegos. La finalidad es obtener una visión de la organización y actividad que se realiza en nuestra Comunidad Autónoma. Material y métodos: Hemos realizado una encuesta con diferentes ítems sobre la actividad, organización, docencia, relación con atención primaria…, basándonos en los datos de la actividad del 2013, a cada una de las unidades del Sistema Público. Se realizó un estudio descriptivo de las variables expresando las medidas de centralización y dispersión de las variables cuantitativas y, en caso de las cualitativas, en valor absoluto y porcentaje. Resultados: Participaron las 10 unidades de Hospitalización a Domicilio, de la red pública de Galicia, en activo durante el año 2013, lo que representa el 78% de los centros hospitalarios. El 5.92% de las camas hospitalarias pertenecen a estas unidades, con una media de 12 camas por facultativo. Hay 38 médicos trabajando en esta modalidad de los que el 50% son Médicos de Familia y el 31.7% Internistas. Se realiza un 17.13% de ingresos directamente desde Atención Primaria. Del total de ingresos anuales, 5514, el 27% eran pacientes paliativos oncológicos Conclusiones: HADO es un modelo de asistencia alternativo a la hospitalización convencional, con una gran heterogeneidad entre cada una de las Unidades pero con una clara vocación en el cuidado en casa de pacientes paliativos oncológicos y no oncológicos, así como en exacerbación de patología crónica y patología infecciosa aguda. Objective: To show what they are units of Hospital at Home (HADO) and their occupation in Galician public hospitals. The aim is to get an overview of the organization and activity that performs in our region. Methods: We conducted a survey with different items on the activity, organization, teaching, relationship with primary care... on 2013 data, each of the units of the public system. A descriptive study of variables was performed, expressing the measures of central tendency and dispersion for quantitative variables and absolute value and percentage of qualitative variables. Results: Ten Hospital at Home active units of Galician public network during 2013 participated, representing 78% of the centers. 5.92% of hospital beds are in these units, with an average of 12 beds per physician. There are 38 doctors working in this type of which 50% are Family Practice and 31.7% Internists. It takes 17.13% of income directly from Primary Care. The percentage of cancer palliative respect to total income, 5514, is 27%. Conclusions: HADO is an alternative model to conventional hospital care, with a large heterogeneity between each of the units but with a clear vocation on home care patients palliative oncological and non-oncological, as well as exacerbation of chronic pathology and acute infectious phatology

Micronutrient in hyperphenylalaninemia

The data presented here are the biochemical parameters of 156 patients with hyperphenylalaninemia. PKU patients, who, in order to maintain optimal serum Phe concentrations, receive dietary treatment consisting of a diet low in natural protein supplemented with special low protein foods and a Phe-free amino acid mixture, vitamins and minerals. The obtained data reflects a high percentage of patients with prealbumin and selenium deficiencies, as well as an increased level of folic acid. This data article is related to the research article entitled, “Vitamin and mineral status in patients with hyperphenylalaninemia”, by Crujeiras et al. [1]

Molecular epidemiology and genotype-phenotype correlation in phenylketonuria patients from South Spain

The aim of this study was to identify the most common genotypes in the phenylketonuria (PKU) population of Andalusia, assessing the correlation with the phenotype and the usefulness in predicting the response to treatment with tetrahydrobiopterin. We conducted a retrospective observational study between January 1980 and January 2010 in 147 Andalusian PKU patients assessing phenotype, genotype and response to a 24-h BH4 loading test. Our cohort of patients exhibited 65 different mutations, 69.2% corresponding to the missense type, in a total of 123 different genotypes. IVS10nt-11g>a was the most common mutation (10.9%). Four novel missense mutations were identified: p.L258P; p.E66K, p.R155C and p.P122S. Although generally there is a good genotype-phenotype correlation, for eight of the repeated genotypes a slightly different phenotype was observed. In 96 PKU subjects BH4 challenge was carried out. Patients with previously reported unresponsive mutations on both alleles showed a negative response, while 95.5% (28/29) of the responsive patients carry at least one missense mutation previously associated to the BH4. Our data reveal a great genetic heterogeneity in the Andalusian population. Genotype is quite a good predictor of the phenotype and of the responsiveness to tetrahydrobiopterin, which is relevant for patient management and follow-up. © 2013 The Japan Society of Human Genetics All rights reserved.Peer Reviewe

Carbohydrate status in patients with phenylketonuria

Abstract Background In patients with phenylketonuria (PKU), a low-phenylalanine (Phe) diet supplemented with low-protein foods and a Phe-free amino acid mixture favors a dietary intake rich in carbohydrates, but little is known about how these molecules are metabolized in this setting. The objective of the present study was to analyze carbohydrate metabolism in patients with hyperphenylalaninemia. Methods We conducted a multicenter cross-sectional study to investigate biochemical markers of basal and postprandial carbohydrate metabolism in PKU patients according to age, Phe tolerance, waist circumference and body mass index (BMI), diet, tetrahydrobiopterin (BH4) supplementation, and adherence to treatment. Basal biomarkers and anthropometric parameters were also evaluated in patients with mild hyperphenylalaninemia (MHPA) and in healthy controls. Results A total of 83 patients aged 4–52 years were studied; 68.7% had PKU and 31.3% had MHPA. 68 healthy controls of similar sex and age were also evaluated Metabolic control was adequate in 71.9% of PKU patients. Fasting glucose levels (mean 80.77 ± 8.06 mg/dL) were high in just one patient, but fasting insulin levels, with a mean of 12.74 ± 8.4 mIU/L, were altered in 15 PKU patients (26.3%) and markedly higher than in patients with MPHA (p = 0.035). Fasting insulin levels and Homeostasis Model Assessment Insulin Resistance (HOMA-IR) were significantly higher than in healthy controls and correlated with body mass index, waist circumference, age, and also showed statistically significant differences according to diagnosis and Phe tolerance (p < 0.05). Patients under BH4 therapy had lower insulin levels and HOMA-IR. A higher mean carbohydrate intake from AA mixtures was observed in classic PKU patients. The caloric intake in the form of carbohydrates was also higher in PKU than MHPA patients (p = 0.038) and it was correlated with basal insulin (rho = 0.468, p = 0.006), HOMA-IR (rho = 0.423, p = 0.02), BMI (rho 0.533, p = 0.002), and waist circumference (rho 0.584, p = 0.0007). Conclusions This study shows that PKU patients are at risk of carbohydrate intolerance and insulin resistance, more evident in adults and overweight patients, probably related to their higher caloric intake in form carbohydrate content. A higher dependency of AA mixtures was demonstrated in PKU patients

Limited beneficial effects of piceatannol supplementation on obesity complications in the obese Zucker rat: gut microbiota, metabolic, endocrine, and cardiac aspects

International audienceResveratrol is beneficial in obese and diabetic rodents. However, its low bioavailability raises questions about its therapeutic relevance for treating or preventing obesity complications. In this context, many related natural polyphenols are being tested for their putative antidiabetic and anti-obesity effects. This prompted us to study the influence of piceatannol, a polyhydroxylated stilbene, on the prevention of obesity complications in Zucker obese rats. A 6-week supplementation was followed by the determination of various markers in plasma, liver, adipose tissue and heart, together with a large-scale analysis of gut microbiota composition. When given in doses of 15 or 45 mg/kg body weight/day, piceatannol did not reduce either hyperphagia or fat accumulation. It did not modify the profusion of the most abundant phyla in gut, though slight changes were observed in the abundance of several Lactobacillus, Clostridium, and Bacteroides species belonging to Firmicutes and Bacteroidetes. This was accompanied by a tendency to reduce plasma lipopolysaccharides by 30 %, and by a decrease of circulating non-esterified fatty acids, LDL-cholesterol, and lactate. While piceatannol tended to improve lipid handling, it did not mitigate hyperinsulinemia and cardiac hypertrophy. However, it increased cardiac expression of ephrin-B1, a membrane protein that contributes to maintaining cardiomyocyte architecture. Lastly, ascorbyl radical plasma levels and hydrogen peroxide release by adipose tissue were similar in control and treated groups. Thus, piceatannol did not exhibit strong slimming capacities but did limit several obesity complications