Real life data: follow-up assessment on Spanish Gaucher disease patients treated with eliglustat. TRAZELGA project.

BACKGROUND: The availability of multiple treatments for type 1 Gaucher disease increases the need for real-life studies to evaluate treatment efficacy and safety and provide clinicians with more information to choose the best personalized therapy for their patients. AIMS: To determine whether treatment with eliglustat produces, in adult GD1 patients, ans optimal response in daily clinical practice. METHODS: We designed a real-life study with 2 years of follow-up (TRAZELGA [GEE-ELI-2017-01]) to uniformly evaluate the response and adverse events to eliglustat treatment. This study, conducted in 30 patients across Spain and previously treated with other therapies, included the evaluation of safety and efficacy by assessing visceral enlargement, bone disease (DEXA and T and Z scores), concomitant treatments and adverse events, as well as a quality of life evaluation (SF-36). In addition, the quantification of classical biomarkers (chitotriosidase activity, CCL18/PARC and glucosylsphingosine (GluSph)) and new candidates for GD biomarkers (YKL-40, cathepsin S, hepcidin and lipocalin-2 determined by immunoassay) were also assessed. Non-parametric statistical analysis was performed and p < 0.05 was considered statistically significant. MAIN RESULTS: Thirty patients were enrolled in the study. The median age was 41.5 years and the male-female ratio was 1.1:1. 84% of the patients had received ERT and 16% SRT as previous treatment. The most common symptoms at baseline were fatigue (42%) and bone pain (38%), no patient had a bone crisis during the study, and two years after switching, 37% had reduced their use of analgesics. Patient-reported outcomes showed a significant increase in physical function scores (p = 0.027) and physical pain scores (p = 0.010). None of the enrolled patients discontinued treatment due to adverse events, which were mild and transient in nature, mainly gastrointestinal and skin dryness. None of the biomarkers show a significant increase or decompensation after switching. CCL18/PARC (p = 0.0012), YKL-40 (p = 0.00004) and lipocalin-2 (p = 0.0155) improved after two years and GluSph after one year (p = 0.0008) and two years (p = 0.0245) of oral therapy. CONCLUSION: In summary, this real-life study, showed that eliglustat maintains stability and can improve quality of life with few side effects. Significant reductions in classic and other novel biomarkers were observed after two years of therapy.

Clinical Outcomes of Patients with Chronic Neuropathic Form of Gaucher Disease in the Spanish Real-World Setting: A Retrospective Study.

This was a retrospective, multicenter study that aimed to report the characteristics of type 3 Gaucher disease (GD3) patients in Spain, including the genotype, phenotype, therapeutic options, and treatment responses. A total of 19 patients with GD3 from 10 Spanish hospitals were enrolled in the study (14 men, 5 women). The median age at disease onset and diagnosis was 1 and 1.2 years, respectively, and the mean age at follow-up completion was 12.37 years (range: 1-25 years). Most patients exhibited splenomegaly (18/19) and hepatomegaly (17/19) at the time of diagnosis. The most frequent neurological abnormalities at onset were psychomotor retardation (14/19) and extrinsic muscle disorders (11/19), including oculomotor apraxia, supranuclear palsy, and strabismus. The L444P (c.1448T>C) allele was predominant, with the L444P (c.1448T>C) homozygous genotype mainly associated with visceral manifestations like hepatosplenomegaly, anemia, and thrombocytopenia. All patients received enzyme replacement therapy (ERT); other treatments included miglustat and the chaperone (ambroxol). Visceral manifestations, including hepatosplenomegaly and hematological and bone manifestations, were mostly controlled with ERT, except for kyphosis. The data from this study may help to increase the evidence base on this rare disease and contribute to improving the clinical management of GD3 patients.

Breastfeeding and Inborn Errors of Amino Acid and Protein Metabolism: A Spreadsheet to Calculate Optimal Intake of Human Milk and Disease-Specific Formulas.

Human milk (HM) offers important nutritional benefits. However, except for phenylketonuria (PKU), there are little data on optimal levels of consumption of HM and a special formula free of disease-related amino acids (SF-AA) in infants with inborn errors of metabolism of amino acids and proteins (IEM-AA-P). We designed a spreadsheet to calculate the amounts of SF-AA and HM required to cover amino acid, protein, and energy needs in patients with the nine main IEM-AA-P in infants aged under 6 months. Upon entering the infant's weight and the essential amino acid or intact protein requirements for the specific IEM, the spreadsheet calculates the corresponding required volume of HM based on the amino acid concentration in HM. Next, the theoretical daily fluid intake (typical range, 120-200 mL/kg/day) is entered, and the estimated daily fluid intake is calculated. The required daily volume of SF-AA is calculated as the difference between the total fluid intake value and the calculated volume of HM. The spreadsheet allows for the introduction of a range of requirements based on the patient's metabolic status, and includes the option to calculate the required volume of expressed HM, which may be necessary in certain conditions such as MMA/PA and UCD. In cases in which breastfeeding on demand is feasible, the spreadsheet determines the daily amount of SF-AA divided over 6-8 feeds, assuming that SF-AA is administered first, followed by HM as needed. Intake data calculated by the spreadsheet should be evaluated in conjunction with data from clinical and nutritional analyses, which provide a comprehensive understanding of the patient's nutritional status and help guide individualized dietary management for the specific IEM.

Association between medication and intestinal intussusception in children: a case-crossover study.

OBJECTIVES: This study aimed to assess the association between the appearance of intussusception in children and medication intake in the immediately preceding period (2-15 days). METHODS: A case-crossover design was used. We selected cases of children admitted with a diagnosis of intussusception (International Classification of Diseases, Ninth Revision, 860) to the major hospitals in the city of Valencia, Spain, from 2006 to 2009. We then estimated the association between the episode of intussusception and the intake of prescription medication during the preceding 2, 7, and 15 days (case period) and for the same time window 1, 2, 3, and 4 months prior (control period). Data on previous drug administration were obtained from the Pharmaceutical Service Manager System. RESULTS: A total of 95 cases (65.3% boys and 34.7% girls) were selected; 76.6% were younger than the age of 2 years. The association between intussusception and prior drug use varied depending on the exposure window: 15-day odds ratio (OR), 1.45 (95% confidence interval [95% CI], 0.86-2.43); 7-day OR, 1.46 (95% CI, 0.80-2.67); and 2-day OR, 2.26 (95% CI, 1.10-4.64). These associations were greater for children aged younger than 2 years and were usually due to the recent administration (preceding 2 days) of antibiotics (OR, 8.00; 95% CI, 1.47-43.7). CONCLUSIONS: Intussusception was more common among boys aged younger than 2 years. A positive and significant association was observed when drugs were administered 2 to 7 days before the onset of symptoms in children younger than the age of 2 years.

Influenza vaccine effectiveness in preventing influenza A(H3N2)-related hospitalizations in adults targeted for vaccination by type of vaccine: a hospital-based test-negative study, 2011-2012 A(H3N2) predominant influenza season, Valencia, Spain.

BACKGROUND: Most evidence of the effectiveness of influenza vaccines comes from studies conducted in primary care, but less is known about their effectiveness in preventing serious complications. Here, we examined the influenza vaccine effectiveness (IVE) against hospitalization with PCR-confirmed influenza in the predominant A(H3N2) 2011-2012 influenza season. METHODS: A hospital-based, test-negative study was conducted in nine hospitals in Valencia, Spain. All emergency admissions with a predefined subset of symptoms were eligible. We enrolled consenting adults age 18 and over, targeted for influenza vaccination because of comorbidity, with symptoms of influenza-like-illness within seven days of admission. We estimated IVE as (1-adjusted vaccination odds ratio)*100 after accounting for major confounders, calendar time and recruitment hospital. RESULTS: The subjects included 544 positive for influenza A(H3N2) and 1,370 negative for influenza admissions. Age was an IVE modifying factor. Regardless of vaccine administration, IVE was 72% (38 to 88%) in subjects aged under 65 and 21% (-5% to 40%) in subjects aged 65 and over. By type of vaccine, the IVE of classical intramuscular split-influenza vaccine, used in subjects 18 to 64, was 68% (12% to 88%). The IVE for intradermal and virosomal influenza vaccines, used in subjects aged 65 and over, was 39% (11% to 58%) and 16% (-39% to 49%), respectively. CONCLUSIONS: The split-influenza vaccine was effective in preventing influenza-associated hospitalizations in adults aged under 65. The intradermal vaccine was moderately effective in those aged 65 and over.

Nosocomial rotavirus gastroenteritis in Spain: a multicenter prospective study.

BACKGROUND: The objective of this study was to assess the incidence of nosocomial rotavirus gastroenteritis among children <2 years of age. METHODS: We conducted a prospective active surveillance for acute gastroenteritis (AGE) in the pediatric wards of 3 representative hospitals in Valencia (Spain) from October 2006 to March 2007, among children between 1 and 23 months of age with acute diarrhea. Children were followed up for 3 days after discharge. We obtained clinical and demographic information from participants and tested their stool specimens for rotavirus. RESULTS: A total of 1576 children were hospitalized at the 3 hospitals and 1300 (82.5%) were followed up as the study cohort. In 69 children, AGE started 48 hours after admission and were considered nosocomial infections. In 35 of the 59 cases where stool samples were obtained, rotavirus (RV) was present (59%), and in 12 of them symptoms started after discharge. The accumulated incidence of nosocomial rotavirus disease during the study period was 2.8 cases per 100 inpatients (95% CI: 1.9-3.8), and the incidence rate was 4.8 cases per 1000 hospital days (95% CI: 3.2-6.5). The most commonly found genotype in nosocomial infection was G9P[8], in 23 cases (66%), followed by G1P[8] in 4 cases (11%). The total economic cost was 883 euro per case. CONCLUSION: Active surveillance demonstrated that the burden of nosocomial rotavirus disease is substantial, and G9P [8] was the genotype found most frequently. Following up children after discharge from hospital allowed the discovery of cases of nosocomial RVAGE which are missed in most other studies.