Prediction of Renal Acid Load in Adult Patients on Parenteral Nutrition

Metabolic acidosis and metabolic bone disease are frequent complications in patients on parenteral nutrition (PN). A common contributor to these complications could be a daily high renal acid load. This study aims to find a method for predicting the potential total acid load (PTAL) and the pH of the compounded parenteral nutrition mixtures. The pH and titratable acidity (TA) of fifty compounded mixtures were measured. The potential metabolic acid load (PMAL) was calculated by considering the amount of nutrients that are acid producers and consumers. The PTAL of the TPN mixtures was calculated by adding TA to PMAL. Multiple linear regression analyses were used to develop a predictive model for the TA and pH of the compounded mixtures. The predicted TA and pH values of the analyzed mixtures agreed with those measured (Passing-Bablok analysis). The PTAL was >50 mmol/day for 82% of the mixtures, >75 mmol/day for 40% of the mixtures, and >100 mmol/day for 22% of the mixtures. The prediction of the renal acid load in patients on long-term PN could allow more appropriate acid-base balancing. Moreover, predicting the pH of such mixtures could be useful to pharmacists to assess the stability and compatibility of the components in the compounded mixtures

Subjective palatability and appetite after gluten-free pasta: A pilot study

The interest in gluten-free (GF) diet has greatly increased also in people without celiac disease (CD). This pilot study aimed to investigate the postprandial effect of GF-pasta, made by using the pasta-making process applied to artisan wheat pasta, on palatability, appetite sensation, and glucose metabolism in 8 healthy volunteers. Two iso-caloric lunch-meals consisting of: 1) gluten-free pasta (GFP) and 2) refined wheat pasta (RP) were compared in cross-over design. Both subjective appetite, assessed by visual analogue scale (VAS), and blood sample were taken before meal and at half-hour intervals for 4 hours. Palatability was evaluated immediately after the meal-test by VAS. All participants underwent pre- and postprandial energy expenditure (EE) measured by indirect calorimetry. We found that subjective palatability did not significantly differ between meals. Similarly, repeated measures ANOVA showed that GFP did not affect appetite ratings, postprandial glucose, and insulin responses compared to RP. Then, postprandial EE was affected by time (P=0.006), increasing at 60 min, but not by meals. In conclusion, artisanal GFP was as palatable as RP pasta, without affecting perceived satiety and postprandial glycaemia compared to RP in healthy subjects. Clearly, GFP results are preliminary and need to be investigated in larger studies

Clinical and genetic factors predicting Dravet syndrome in infants with SCN1A mutations

OBJECTIVE: To explore the prognostic value of initial clinical and mutational findings in infants with SCN1A mutations. METHODS: Combining sex, age/fever at first seizure, family history of epilepsy, EEG, and mutation type, we analyzed the accuracy of significant associations in predicting Dravet syndrome vs milder outcomes in 182 mutation carriers ascertained after seizure onset. To assess the diagnostic accuracy of all parameters, we calculated sensitivity, specificity, receiver operating characteristic (ROC) curves, diagnostic odds ratios, and positive and negative predictive values and the accuracy of combined information. We also included in the study demographic and mutational data of the healthy relatives of mutation carrier patients. RESULTS: Ninety-seven individuals (48.5%) had Dravet syndrome, 49 (23.8%) had generalized/genetic epilepsy with febrile seizures plus, 30 (14.8%) had febrile seizures, 6 (3.5%) had focal epilepsy, and 18 (8.9%) were healthy relatives. The association study indicated that age at first seizure and frameshift mutations were associated with Dravet syndrome. The risk of Dravet syndrome was 85% in the 0- to 6-month group, 51% in the 6- to 12-month range, and 0% after the 12th month. ROC analysis identified onset within the sixth month as the diagnostic cutoff for progression to Dravet syndrome (sensitivity = 83.3%, specificity = 76.6%). CONCLUSIONS: In individuals with SCN1A mutations, age at seizure onset appears to predict outcome better than mutation type. Because outcome is not predetermined by genetic factors only, early recognition and treatment that mitigates prolonged/repeated seizures in the first year of life might also limit the progression to epileptic encephalopathy

Fighting autoinflammation in FIRES: The role of interleukins and early immunomodulation

Febrile infection-related epilepsy syndrome (FIRES) is a challenging condition with unfavorable outcome in most cases. Preliminary evidence suggests that some interleukins, in particular IL-1 Receptor Antagonist (IL-1RA), could be elevated due to a functional deficiency of anti-inflammatory pathways. Therefore, treatment strategies acting on innate immunity could represent a targeted treatment. We describe the case of an 11-year-old child with super-refractory status epilepticus (SE), lasting more than two months. After being treated aggressively with antiseizure medications, anesthetics and empiric treatment for autoimmune encephalitis without success, she responded to anakinra and ketogenic diet. Escalation of the therapy was supported by the finding of a very high serum level of IL-1RA. This immunomodulatory approach allowed to discharge the child from intensive care 48 days after the SE onset. After more than one year follow-up the patient has moderate intellectual disability but with good language skills; she is seizure free and without motor deficits. This case suggests that serum IL-1RA serum levels may help to support treatment escalation. Moreover, anakinra and ketogenic diet represent encouraging immunomodulatory strategies which deserve further studies and could potentially have a synergistic effect. Finally, structured neuropsychological testing is an important outcome measure that will help to define the effectiveness of different treatment strategies

Covid-19 infection in children, infants and pregnant subjects: An overview of recent insights and therapies

Background: The SARS-CoV-2 pandemic has involved a severe increase of cases worldwide in a wide range of populations. The aim of the present investigation was to evaluate recent insights about COVID-19 infection in children, infants and pregnant subjects. Methods: a literature overview was performed including clinical trials, in vitro studies, reviews and published guidelines regarding the present paper topic. A descriptive synthesis was performed to evaluate recent insights and the effectiveness of therapies for SARS-CoV-2 infection in children, infants and pregnant subjects. Results: Insufficient data are available regarding the relationship between COVID-19 and the clinical risk of spontaneous abortion and premature foetus death. A decrease in the incidence of COVID-19 could be correlated to a minor expression of ACE2 in childrens’ lungs. At present, a modulation of the dose-effect posology for children and infants is necessary. Conclusions: Pregnant vertical transmission has been hypothesised for SARS-CoV-2 infection. Vaccines are necessary to achieve mass immunity for children and also pregnant subjects

Economic consequences of investing in anti-HCV antiviral treatment from the Italian NHS perspective : a real-world-based analysis of PITER data

OBJECTIVE: We estimated the cost consequence of Italian National Health System (NHS) investment in direct-acting antiviral (DAA) therapy according to hepatitis C virus (HCV) treatment access policies in Italy. METHODS: A multistate, 20-year time horizon Markov model of HCV liver disease progression was developed. Fibrosis stage, age and genotype distributions were derived from the Italian Platform for the Study of Viral Hepatitis Therapies (PITER) cohort. The treatment efficacy, disease progression probabilities and direct costs in each health state were obtained from the literature. The break-even point in time (BPT) was defined as the period of time required for the cumulative costs saved to recover the Italian NHS investment in DAA treatment. Three different PITER enrolment periods, which covered the full DAA access evolution in Italy, were considered. RESULTS: The disease stages of 2657 patients who consecutively underwent DAA therapy from January 2015 to December 2017 at 30 PITER clinical centres were standardized for 1000 patients. The investment in DAAs was considered to equal €25 million, €15 million, and €9 million in 2015, 2016, and 2017, respectively. For patients treated in 2015, the BPT was not achieved, because of the disease severity of the treated patients and high DAA prices. For 2016 and 2017, the estimated BPTs were 6.6 and 6.2 years, respectively. The total cost savings after 20 years were €50.13 and €55.50 million for 1000 patients treated in 2016 and 2017, respectively. CONCLUSIONS: This study may be a useful tool for public decision makers to understand how HCV clinical and epidemiological profiles influence the economic burden of HCV