Differential presentation of hypersensitivity reactions to carboplatin and oxaliplatin: Phenotypes, endotypes, and management with desensitization.

BACKGROUND: Drug hypersensitivity reactions (DHRs) to platinum-based drugs are heterogenous and restrict their access, and drug desensitization (DD) has provided a ground-breaking procedure for their re-introduction, although the response is heterogeneous. We aimed to identify the phenotypes, endotypes, and biomarkers of reactions to carboplatin and oxaliplatin and their response to DD. METHODS: Seventy-nine patients presenting with DHRs to oxaliplatin (N = 46) and carboplatin (N = 33) were evaluated at the Allergy Departments of two tertiary care hospitals in Spain. Patient symptoms, skin testing, biomarkers, and outcomes of 267 DDs were retrospectively analyzed. RESULTS: Oxaliplatin-reactive patients presented with type I (74%), cytokine release reaction (CRR) (11%), and mixed (Mx) (15%) phenotypes. In contrast, carboplatin reactive patients presented with predominantly type I (85%) and Mx (15%) but no CRRs. Out of 267 DDs, breakthrough reactions (BTRs) to oxaliplatin occurred twice as frequently as carboplatin (32% vs. 15%; p < .05). Phenotype switching from type I to another phenotype was observed in 46% of oxaliplatin DDs compared to 21% of carboplatin DDs. Tryptase was elevated in type I and Mx reactions, and IL-6 in CRR and Mx, indicating different mechanisms and endotypes. CONCLUSION: Carboplatin and oxaliplatin induced three different types of reactions with defined phenotypes and endotypes amendable to DD. Although most of the initial reactions for both were type I, oxaliplatin presented with unique CRR reactions. During DD, carboplatin reactive patients presented mostly type I BTR, while oxaliplatin-reactive patients frequently switched from type I to CRR, providing a critical difference and the need for personalized DD protocols.

Individualised Care Scale-Nurse: Construct validity and internal consistency of the Spanish version.

BACKGROUND: Individualising the provided care is mandatory in nursing and is essential in clinical practice. Therefore, there is a need to develop accurate instruments to evaluate the quality of care. Moreover, there is no validated instrument to assess nurses' views of individualised care in Spanish-speaking countries. AIM: To assess the construct validity and internal consistency of the Spanish version of the Individualised Care Scale-Nurse. METHODS: A cross-sectional study including 108 nursing professionals (40.84 ± 9.51 years old, 86.1% female) was used to validate the Spanish Individualised Care Scale-Nurse version. A forward-back translation method with an expert panel and a cross-sectional study was used for transcultural adaptation and psychometric validation purposes. Psychometric properties of feasibility, reliability and validity were assessed. Construct validity was examined through a confirmatory factor analysis and fit indices of the overall model were computed. Internal consistency was explored through McDonald's omega and Cronbach's alpha coefficients among other correlation measures. RESULTS: The back-translation concluded both Spanish and English Individualised Care Scale-Nurse versions to be equivalent. The original structure of the Individualised Care Scale-Nurse was verified in the Spanish version through the confirmatory factor analysis (factor loadings >0.3; acceptable fit indices: SRMR ≈ 0.08, CFI ≈ 0.9, RMSEA ≈ 0.09 after posteriori modifications). McDonald's omega exceeded 0.7 for both subscales and complete scales revealing an adequate internal consistency. CONCLUSIONS: The Spanish version of the Individualised Care Scale-Nurse has exhibited good properties of homogeneity and construct validity for its use in practice and research in health care systems.

Wildfire response to changing daily temperature extremes in California's Sierra Nevada.

Burned area has increased across California, especially in the Sierra Nevada range. Recent fires there have had devasting social, economic, and ecosystem impacts. To understand the consequences of new extremes in fire weather, here we quantify the sensitivity of wildfire occurrence and burned area in the Sierra Nevada to daily meteorological variables during 2001­2020. We find that the likelihood of fire occurrence increases nonlinearly with daily temperature during summer, with a 1°C increase yielding a 19 to 22% increase in risk. Area burned has a similar, nonlinear sensitivity, with 1°C of warming yielding a 22 to 25% increase in risk. Solely considering changes in summer daily temperatures from climate model projections, we estimate that by the 2040s, fire number will increase by 51 ± 32%, and burned area will increase by 59 ± 33%. These trends highlight the threat posed to fire management by hotter and drier summers.

Quality of survival and growth in children and young adults in the PNET4 European controlled trial of hyperfractionated versus conventional radiation therapy for standard-risk medulloblastoma.

PURPOSE: To compare quality of survival in "standard-risk" medulloblastoma after hyperfractionated radiation therapy of the central nervous system with that after standard radiation therapy, combined with a chemotherapy regimen common to both treatment arms, in the PNET4 randomised controlled trial. METHODS AND MATERIALS: Participants in the PNET4 trial and their parents/caregivers in 7 participating anonymized countries completed standardized questionnaires in their own language on executive function, health status, behavior, health-related quality of life, and medical, educational, employment, and social information. Pre- and postoperative neurologic status and serial heights and weights were also recorded. RESULTS: Data were provided by 151 of 244 eligible survivors (62%) at a median age at assessment of 15.2 years and median interval from diagnosis of 5.8 years. Compared with standard radiation therapy, hyperfractionated radiation therapy was associated with lower (ie, better) z-scores for executive function in all participants (mean intergroup difference 0.48 SDs, 95% confidence interval 0.16-0.81, P=.004), but health status, behavioral difficulties, and health-related quality of life z-scores were similar in the 2 treatment arms. Data on hearing impairment were equivocal. Hyperfractionated radiation therapy was also associated with greater decrement in height z-scores (mean intergroup difference 0.43 SDs, 95% confidence interval 0.10-0.76, P=.011). CONCLUSIONS: Hyperfractionated radiation therapy was associated with better executive function and worse growth but without accompanying change in health status, behavior, or quality of life.

[Differential aspects in children and adult patients with medulloblastoma]. / Meduloblastoma: aspectos diferenciales entre el tumor infantil y del adulto.

BACKGROUND AND OBJECTIVE: Medulloblastoma is the more frequent malignant cerebral tumor in childhood. PATIENTS AND METHODS: This is an observational study of a retrospective cohort in which there were included all the patients diagnosed of medulloblastoma in the last 19 years (1989-2007) in Hospital de Cruces of Baracaldo, Vizcaya, Spain. RESULTS: There were included 37 patients, 20 men and 17 women, with ages between 1 and 48 years (average age 13.7 years with standard deviation 11.4). Tumor site and mortality according to initial dissemination were variables of statistic significance. Metastases were detected at diagnosis in two patients. The surgical resection was total in 75% of the patients. A relapse was diagnosed in the follow-up in 59.5% of the patients, with a positive spinal fluid in 27%. Sequelae were detected in 100% of the survivors, mainly with cerebellar and ocular alterations. One patient developed a meningioma and a maxillary sarcoma at the long term follow-up. It is important to emphasize the aggressiveness of medulloblastoma in both children and adults, with a global mortality of 56.8% and 48,6% at 5 years. CONCLUSIONS: It is considered necessary a multidisciplinary treatment and a long term monitoring of the patients and the sequelae of the survivors, including the possibility of second tumours.

Vigilancia de la mortalidad del menor de cinco años / Monitoring of the moetality of minor than five years

Uno de los componentes del proyecto piloto que desarrolló Plan Internacional, en el departamento de Chuquisaca en 22 comunidades del área de Tarabuco, fue el de la vigilancia cualitativa de la mortalidad del menor de cinco años. En este proyecto, se estableció un sistema de notificación temprana de mortalidad basado en Agentes Comunitarios de Salud (ACS) capacitados/as, quienes tienen a su cargo un promedio de 15 a 20 familias con niños menores de cinco años, que son visitados/as y atendidos/as cada mes en sus hogares con la estrategia AIPEI comunitario