A hub-and-spoke model to deliver effective access to chimeric antigen receptor T-cell therapy in a public health network: the Catalan Blood and Tissue Bank experience.

BACKGROUND AIMS: To describe and analyze whether a hub-and-spoke organizational model could efficiently provide access to chimeric antigen receptor (CAR) T-cell therapy within a network of academic hospitals and address the growing demands of this complex and specialized activity. METHODS: The authors performed a retrospective evaluation of activity within the Catalan Blood and Tissue Bank network, which was established for hematopoietic stem cell transplantation to serve six CAR T-cell programs in academic hospitals of the Catalan Health Service. Procedures at six hospitals were followed from 2016 to 2021. Collection shipments of starting materials, CAR T-cell returns for storage and infusions for either clinical trials or commercial use were evaluated. RESULTS: A total of 348 leukocytapheresis procedures were performed, 39% of which were delivered fresh and 61% of which were cryopreserved. The network was linked to seven advanced therapy medicinal product manufacturers. After production, 313 CAR T-cell products were shipped back to the central cryogenic medicine warehouse located in the hub. Of the units received, 90% were eventually administered to patients. A total of 281 patients were treated during this period, 45% in clinical trials and the rest with commercially available CAR T-cell therapies. CONCLUSIONS: A hub-and-spoke organizational model based on an existing hematopoietic stem cell transplantation program is efficient in incorporating CAR T-cell therapy into a public health hospital network. Rapid access and support of growing activity enabled 281 patients to receive CAR T cells during the study period.

Leukocytapheresis variables and transit time for allogeneic cryopreserved hpc: better safe than sorry.

Cryopreservation was recommended to ensure continuity in allogeneic hematopoietic progenitor cells (HPC) transplantation during the COVID-19 pandemic. Several groups have shown no impact on clinical outcomes for patients who underwent HPC transplantation with cryopreserved products during the first months of this pandemic. However, concerns about quality control attributes after cryopreservation have been raised. We investigated, in 155 allogeneic peripheral blood cryopreserved HPC, leukocytapheresis characteristics influencing viable CD34+ and CD3+ cells, and CFU-GM recoveries after thawing. Collection characteristics such as volume, nucleated cells (NC)/mL and hematocrit correlated with viable CD34+ and CD3+ cells recoveries after thawing in univariate analysis but only CD3+ cells remained statistically significant in multivariate analysis (r2 = 0.376; P = < 0.001). Additionally, transit time also showed correlation with viable CD34+ (r2 = 0.186), CD3+ (r2 = 0.376) and CFU-GM recoveries (r2 = 0.212) in multivariate analysis. Thus, diluting leukocytapheresis below 200 × 106 NC/mL, avoiding red cells contamination above 2%, cryopreserving below 250 × 106 NC/mL and minimizing transit time below 36 h, prevented poor viable CD34+ and CD3+ cells, and CFU-GM recoveries. In summary, optimizing leukocytapheresis practices and minimizing transportation time may better preserve the quality attributes of HPC when cryopreservation is indicated.

Dietary Calcium Intake and Adherence to the Mediterranean Diet in Spanish Children: The ANIVA Study.

The aim of this study was to evaluate the relationship of dietary calcium intake with anthropometric measures, physical activity and adherence to the Mediterranean diet (MedDiet) in 1176 Spanish children aged 6-9 years. Data were obtained from "Antropometría y Nutrición Infantil de Valencia" (ANIVA), a cross-sectional study of a representative sample. Dietary calcium intake assessed from three-day food records was compared to recommended daily intakes in Spain. Anthropometric measures (weight and height) were measured according to international standards and adherence to the MedDiet was evaluated using the Mediterranean Diet Quality Index (KIDMED) test. For the total sample of children, 25.8% had inadequate calcium intake, a significantly higher prevalence in girls (p = 0.006) and inadequate calcium intake was associated with lower height z-score (p = 0.001) for both sexes. In girls, there was an inverse relationship between calcium intake and body mass index (p = 0.001) and waist/hip ratio (p = 0.018). Boys presented a polarization in physical activity, reporting a greater level of both physical and sedentary activity in comparison with girls (p = 0.001). Children with poor adherence to MedDiet, even if they consume two yogurts or cheese (40 g) daily, adjusted by gender, age, total energy intake, physical activity and father's level of education, are at risk of inadequate total calcium intake (odds ratio adjusted [ORa]: 3.36, 95% confidence interval [CI]: 1.13-9.94, p = 0.001). The intake of these dairy products was insufficient to cover calcium intake recommendations in this age group (6-9 years). It is important to prioritize health strategies that promote the MedDiet and to increase calcium intake in this age group.

Calcium Intake and Nutritional Adequacy in Spanish Children: The ANIVA Study.

Calcium is an important nutrient for child development. The main objective of this study was to assess calcium intake and its adequacy with dietary reference intake (DRI) in Spanish children. The ANIVA (Antropometría y Nutrición Infantil de Valencia) study is a descriptive cross-sectional study. During two academic years 2013-2014 and 2014-2015, 1176 schoolchildren aged 6-9 years were selected from 14 primary schools in Valencia (Spain). Three-day food records were used to assess dietary intake, completed by parents/guardian. Anthropometric data (weight and height) were evaluated in all subjects. Nutritional intake was compared to estimated average requirements (EARs) and adequate intake (AI) values to determine nutritional adequacy. A percentage of 25.77% had inadequate calcium intake, and a significantly higher prevalence was observed in girls (p = 0.006). Adequate calcium intake showed a positive association with the height z-score (p = 0.032). When assessing dietary patterns, schoolchildren with adequate calcium intakes had better nutritional adequacy in all nutrients, except cholesterol (p = 0.086) and fluorine (p = 0.503). These results suggest a public health problem that must be addressed through nutrition education programs to increase intake of calcium-rich food and to correct the associated dietary pattern.

Economic Evaluation of Health Services Costs During Pandemic Influenza A (H1N1) Pdm09 Infection in Pregnant and Non-Pregnant Women in Spain.

BACKGROUND: The healthcare and socio-economic burden resulting from influenza A (H1N1) pdm09 in Spain was considerable. Our aim was to estimate and compare the management (resource utilization) and economic healthcare impact in an at-risk group of unvaccinated pregnant women with an unvaccinated group of non-pregnant woman of childbearing age (15-44 yr old). METHODS: We addressed this question with a longitudinal, observational, multicentre study. Inputs were the requirements in managing both groups of women. Outcome measures were healthcare costs. Direct healthcare (including medical utilisation, prescriptions of antivirals, medication, diagnostic tests, and hospitalisation) costs and indirect (productivity loss) costs were considered. Unit of cost was attributed to the frequency of health service resources utilisation. The mean cost per patient was calculated in this group of women. RESULTS: We found that the influenza clinical pattern was worse in non-pregnant women as they had a high medical risk of 20.4% versus 6.1% of pregnant women. Non-pregnant required more antipyretics and antibiotics, and needed more health service resource utilisation (338 medical visits in non-pregnant women vs. 42 in pregnant women). The total cost of non-pregnant women was higher (€4,689.4/non-pregnant and €2,945.07/pregnant). CONCLUSIONS: Cost per (H1N1) pdm09 was lower for pregnant women, probably due to more preventive measures adopted for their protection in Spain. The highest costs were incurred by hospitalisations/day and work absenteeism for non-pregnant than for pregnant women. These data will allow better future pandemic influenza planning.

Nutrient Intake and Depression Symptoms in Spanish Children: The ANIVA Study.

The aim of this study was to examine the relationship between nutritional intake and depressive symptoms in Valencian schoolchildren. The ANIVA (Antropometria y Nutricion Infantil de Valencia) study is a descriptive cross-sectional study. During academic year 2013-2014, 710 schoolchildren aged 6-9 years were selected from eleven primary schools in Valencia (Spain). Children's dietary intake was measured on three-day food records, completed by parents/guardians; children completed the 20-item Center for Epidemiologic Studies Depression Scale for Children (CES-DC) Questionnaire to measure depressive symptoms. Weight, height, and body mass index (BMI), and z-scores were evaluated in all subjects. Nutrient adequacy was assessed using Spanish dietary recommended intakes (DRIs); 20.70% of the sample presented depressive symptoms. We identified a positive association between children with depressive symptoms and non-depressive symptoms for thiamin, vitamin K, and bromine (p < 0.05), and a negative association for protein, carbohydrates, pantothenic acid, biotin, vitamin B12 and E, zinc, manganese, cobalt, and aluminum (p < 0.05). Statistically significant differences were found between both groups according to the DRIs for intakes of total energy (p = 0.026), fiber (p < 0.001), vitamin C (p < 0.001), vitamin E (p = 0.004), magnesium (p = 0.018), and iron (p = 0.013). Our results demonstrated that carbohydrates were the most closely associated factor with depressive symptoms, and highlight the potential significant public health implications of inadequate nutritional intake on schoolchildren's mental health.

Central nervous system (CNS) cancer in children and young people in the European Union and its involvements with socio-economic and environmental factors.

Malignant central nervous system (CNS) tumors are the leading cause of death by cancer in children and the second commonest pediatric cancer type. Despite several decades of epidemiologic research, the etiology of childhood CNS tumors is still largely unknown. A few genetic syndromes and therapeutic ionizing radiation are thought to account for 5-10% of childhood cancer, but the etiology of other cases remains unknown. Nongenetic causes, like environmental agents, are thought to explain them. However, as very few epidemiologic studies have been conducted, it is not surprising that nongenetic risk factors have not been detected. The biggest difference between cancers for which there are good etiologic clues and those for which there are none could be the number of relevant studies. This study, which covers the 1980-2011 period, identified links between CNS cancer evolution and the socio-economic and environmental indicators in the same space and time limits in the European Union.

Anthropometric Status and Nutritional Intake in Children (6-9 Years) in Valencia (Spain): The ANIVA Study.

The aim of our study was to assess nutritional intake and anthropometric statuses in schoolchildren to subsequently determine nutritional adequacy with Spanish Dietary Reference Intake (DRIs). The ANIVA study, a descriptive cross-sectional study, was conducted in 710 schoolchildren (6-9 years) in 2013-2014 in Valencia (Spain). Children's dietary intake was measured using 3-day food records, completed by parents. Anthropometric measures (weight and height) were measured according to international standards, and BMI-for-age was calculated and converted into z-scores by WHO-Anthro for age and sex. Nutrient adequacy was assessed using DRI based on estimated average requirement (EAR) or adequate intake (AI). Pearson's chi-square and Student's t-test were employed. Of our study group (47.61% boys, 52.39% girls), 53.1% were normoweight and the weight of 46.9% was inadequate; of these, 38.6% had excess body weight (19.6% overweight and 19.0% obesity). We found intakes were lower for biotin, fiber, fluoride, vitamin D (p < 0.016), zinc, iodine, vitamin E, folic acid, calcium and iron (p < 0.017), and higher for lipids, proteins and cholesterol. Our results identify better nutritional adequacy to Spanish recommendations in overweight children. Our findings suggest that nutritional intervention and educational strategies are needed to promote healthy eating in these children and nutritional adequacies.

Study on the Linezolid Prescription According to the Approval of Indication in a University Hospital.

Indications for linezolid use are nosocomial or community-acquired pneumonia and skin infections or soft tissue infection caused by gram-positive microorganisms, but new recommendations may emerge. It is important to balance benefits with risks because severe adverse events have been described in patients taking linezolid treatment. Accordingly, we evaluated the suitability of linezolid prescription according to approval of indication by evaluating the presence of drug-related problems (DRP) in a University hospital. DRP were identified in 36 patients (50.0%). In most cases, they were related to known or established indications (15 patients, 20.8%), to safety (5 patients, 6.9%), and to both in others (16 patients, 22.2%). No DRP were recorded, which modified linezolid efficacy. DRP were significantly higher in the patients treated by an approved indication in Spain (63.3%) than in those treated by an unapproved indication in Spain (28.6%). We concluded that new studies about extending linezolid indications may be necessary.

Hypertension and the fat-soluble vitamins A, D and E.

Hypertension affects populations globally and is thus a public health and socio-economic problem. Macronutrient and micronutrient deficiencies are common in the general population, and may be even more prevalent in hypertensive patients. This study aimed to determine a possible association between hypertension and intake of fat-soluble vitamins A, D and E. Participants were from the cross-sectional Hortega nutrition study conducted with a random sample of 1514 people (50.3% women, 49.7% men) and two groups: nonhypertensive controls≥40 years old (n=429; 28.3%); unknown untreated hypertension cases≥40 years old (n=246; 16.2%). Biochemical and anthropometric measurements were taken. Data on dietary intakes, education, socio-economic status, place of residence, health habits, comorbidities, alcohol consumption and smoking were collected and assessed. A descriptive data study was done and compared by ANOVA and Chi-Square. No p value higher than 0.05 was considered significant. The results showed that vitamin A intake was higher in the hypertensive subpopulation (1732.77±962.27 µg vs. 1655.89±902.81 µg), and vitamin D and E intakes were lower (8.13±9.71 µg vs. 8.25±9.52 µg and 18.79±7.84 mg vs. 18.60±8.20 mg, respectively). No statistically significant differences were found in any adjusted model. This study did not significantly associate intake of vitamins A, D and E with hypertension in people aged over 40. Future studies on this topic and a larger sample are necessary.

Vitamin D and psoriasis pathology in the Mediterranean region, Valencia (Spain).

Vitamin D has important immunomodulatory effects on psoriasis in the Mediterranean region. To measure vitamin D intake in subjects with and without psoriasis, and to find an association with relevant clinical features, a case-control study was performed using cases (n = 50, 50% participation rate) clinically diagnosed with psoriasis and 200 healthy subjects (39.5% participation rate), leaving a final sample of 104 people. A survey was conducted using a food frequency questionnaire and clinical histories. Cases and controls were compared using univariate and multivariate analyses. We observed insufficient intake of cholecalciferol (vitamin D3) or ergocalciferol (vitamin D2) for both cases and controls. Patients with psoriasis were at greater risk of associated pathologies: dyslipidaemia (OR: 3.6, 95% CI: 0.8-15.2); metabolic syndrome (OR: 3.3, 95% CI: 0.2-53.9); hypertension (OR: 1.7, 95% CI: 0.4-7.2). Insufficient vitamin D intake in both psoriasis patients and controls in the Mediterranean population, and cardiovascular comorbility is more frequent in patients with psoriasis.

Occurrence and removal of drugs of abuse in Wastewater Treatment Plants of Valencia (Spain).

The occurrence of 8 drugs of abuse and metabolites in the influent and effluent of the 3 Wastewater Treatment Plants (WWTP) that treat wastewater from Valencia was studied in 2011, 2012 and 2013. Target drugs except 6-monoacetylmorphine (6-ACMOR) were detected in 100% of the influents. The WWTPs eliminate cocaine (COC), amphetamine (AMP), methamphetamine (MAMP) and 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THC-COOH). Benzoylecgonine (BECG) was also efficiently eliminated (93-98%), whereas 3,4-methylenedioxymethamphetamine (MDMA) presented removal rates of 32-57% and ketamine (KET) was not eliminated. The most consumed illicit drugs, according to the estimated concentrations of each compound in the studied WWTPs, were cannabis and COC followed by KET, AMP, MAMP, MDMA and heroin. Environmental risk assessment was evaluated by calculating Risk Quotient (RQ). MDMA and KET could pose a medium risk and low risk, respectively, to the aquatic organisms. Although short-term environmental risk is not worrisome, long-term effects cannot be known exactly.

Is acetaminophen use associated with atopic eczema and other allergic diseases in adolescents?

Atopic Eczema (AE) is a chronic inflammatory skin disease that affects children and adults, and alters quality of life. Previous studies have suggested several socio-demographic and environmental factors related to the prevalence of AE and other allergic diseases, including acetaminophen use. In the present study, we report the rates of isolated AE, AE associated with asthma and AE associated with rhinitis among 13- to 14-year-old Spanish adolescents and the level of association of these conditions with the use of acetaminophen. We analyzed Spanish data from a cross-sectional Phase 3 study within ISAAC. A total of 28,717 adolescents completed the Phase 3 written questionnaire by answering questions for acetaminophen use and on asthma, rhinitis and AE symptoms.We observed an association between acetaminophen use and AE among the adolescents who had used acetaminophen in the previous month. Furthermore, the prevalence rate increased with the number of allergic processes: for AE alone, the adjusted Prevalence Ratio (aPR) was 1.81 and for AE associated with rhinitis or with asthma, aPRs were 2.20 and 3.03, respectively.We conclude that acetaminophen use in childhood may be an important factor associated with development and/or maintenance of AE and other allergic diseases.