A pooled subgroup analysis of glucarpidase treatment in 86 pediatric, adolescent, and young adult patients receiving high-dose methotrexate therapy in open-label trials.

BACKGROUND: Delayed methotrexate elimination can occur in patients undergoing high-dose methotrexate cancer treatment. Effectiveness of glucarpidase for rapidly reducing methotrexate concentrations was shown in compassionate-use trials in patients aged 0-84 years. METHODS: We performed post hoc analyses of infants (≥28 days to <2 years), children (≥2 to <12 years), adolescents (≥12 to <15 years), and young adults (≥15 to <25 years) from four multicenter, open-label, single-arm, glucarpidase compassionate-use trials. Patients had toxic methotrexate levels due to delayed methotrexate elimination and/or renal dysfunction, and received glucarpidase (50 U/kg). The primary endpoint was clinically important reduction (CIR) in plasma methotrexate (methotrexate ≤1 µmol/L at all post-glucarpidase measurements) based on high-performance liquid chromatography. RESULTS: Among 86 patients included in efficacy analyses, CIR was achieved by zero of one infant (0.0%), five of 16 children (31.3%), seven of 24 adolescents (29.2%), and 26/45 young adults (57.8%). Median methotrexate reduction was 98.7% or higher in each group 15 minutes post-glucarpidase. Patients with pre-glucarpidase methotrexate less than 50 µmol/L (35/42, 83.3%) were more likely to achieve CIR than those with methotrexate 50 µmol/L or higher (1/37, 2.7%). The most common treatment-related adverse event was paresthesia, occurring in three adolescents (4.5%) and six young adults (5.2%). No other treatment-related adverse event occurred in 5% or higher of any age group. CONCLUSION: After accounting for pre-glucarpidase methotrexate levels, glucarpidase efficacy at inducing CIR in pediatric/young adult patients was consistent, with efficacy observed in the overall study population (i.e., patients aged 0-84), and no unexpected safety findings were observed. These findings demonstrate glucarpidase (50 U/kg) is an effective and well-tolerated dose for pediatric, adolescent, and young adult patients.

Incidence and management of patients with methotrexate delayed elimination in the clinical practice: A Delphi study.

INTRODUCTION: High-dose methotrexate (HDMTX) is administered for the treatment of some cancers. HDMTX is usually safe but may crystallize in renal tubules causing acute kidney injury (AKI). Consequently, MTX elimination is delayed, resulting in a severe and life-threatening condition. No studies have been published about the impact of MTX toxicity in Spain. This study aims to estimate the incidence and management of MTX delayed elimination and toxicity. METHODS: A two-round Delphi study was performed to reach consensus between 10 medical experts on haemato-oncology and paediatric oncology with experience in the management of HDMTX treated patients from leading Spanish hospitals. An online questionnaire was developed based on national and international guidelines and previous evidence regarding HDMTX-related toxicity. Consensus was established at 80% agreement. Median and interquartile ranges were calculated, and incidence data were extrapolated to the Spanish general population. RESULTS: Out of 1.475 patients estimated to receive HDMTX treatment annually in Spain, 27.5% present MTX delayed elimination and 11.6% develop HDMTX-induced AKI (35.4% with severe systemic toxicities (>grade 3) and 18.8% develop chronic renal disease). Mortality is estimated in 4.2%. Immuno-enzymatic assay is used in most of the hospitals (90%) for MTX serum level monitoring. All experts use increased supportive care and high leucovorin as first-line treatment. Available treatments in experts' hospitals in case toxicity persists are haemodialysis (90% of hospitals), glucarpidase (60%) and hemofiltration (50%). Most prevalent non-renal systemic toxicities are haematologic and mucositis (21-40% of patients). Patients with HDMTX-induced AKI require from intensive care (5% of patients), more than 3 sessions and 4 days of dialysis, and about 8.5 days of hospitalization (non-ICU patients) and 12 days in case of patients requiring ICU. CONCLUSIONS: These results are the first evidence regarding HDMTX-induced AKI in Spain. Incidence and mortality results are in line with previous studies. Clinical management is based on preventive measures and the treatment depend on the availability in the hospital. The need for effective, safe and rapid treatment for the reduction of MTX toxic levels and the improvement of monitoring methods were noted by experts as urgent needs. Further observational studies to validate these results would be needed.

Beyond the consultation room: Proposals to approach health promotion in primary care according to health-care users, key community informants and primary care centre workers.

BACKGROUND: Primary health care (PHC) is the ideal setting to provide integrated services centred on the person and to implement health promotion (HP) activities. OBJECTIVE: To identify proposals to approach HP in the context of primary care according to health-care users aged 45-75 years, key community informants and primary care centre (PCC) workers. METHODS: Descriptive-interpretive qualitative research with 276 participants from 14 PCC of seven Spanish regions. A theoretical sampling was used for selection. A total of 25 discussion groups, two triangular groups and 30 semi-structured interviews were carried out. A thematic interpretive contents analysis was carried out. RESULTS: Participants consider that HP is not solely a matter for the health sector and they emphasize intersectoral collaboration. They believe that it is important to strengthen community initiatives and to create a healthy social environment that encourages greater responsibility and participation of health-care users in decisions regarding their own health and better management of public services and resources. HP, care in the community and demedicalization should be priorities for PHC. Participants propose organizational changes in the PCC to improve HP. PCC workers are aware that HP falls within the scope of their responsibilities and propose to increase their training, motivation, competences and knowledge of the social environment. Informants emphasize that HP should be person-centred approach and empathic communication. HP activities should be appealing, ludic and of proven effectiveness. CONCLUSIONS: According to a socio-ecological and intersectoral model, PHC services must get actively involved in HP together with community and through outreach interventions.

Investigation of III-V nanowires by plan-view transmission electron microscopy: InN case study.

We discuss observations of InN nanowires (NWs) by plan-view high-resolution transmission electron microscopy (TEM). The main difficulties arise from suitable methods available for plan-view specimen preparation. We explore different approaches and find that the best results are obtained using a refined preparation method based on the conventional procedure for plan-view TEM of thin films, specifically modified for the NW morphology. The fundamental aspects of such a preparation are the initial mechanical stabilization of the NWs and the minimization of the ion-milling process after dimpling the samples until perforation. The combined analysis by plan-view and cross-sectional TEM of the NWs allows determination of the degree of strain relaxation and reveals the formation of an unintentional shell layer (2-3-nm thick) around the InN NWs. The shell layer is composed of bcc In2O3 nanocrystals with a preferred orientation with respect to the wurtzite InN: In2O3 [111] || InN [0001] and In2O3<110>||InN<1120>.

Royal jelly extracellular vesicles promote wound healing by modulating underlying cellular responses.

Apis mellifera royal jelly (RJ) is a well-known remedy in traditional medicine around the world and its versatile effects range from antibacterial to anti-inflammatory properties and pro-regenerative properties. As a glandular product, RJ has been shown to contain a substantial number of extracellular vesicles (EVs), and, in this study, we aimed to investigate the extent of involvement of RJEVs in wound healing-associated effects. Molecular analysis of RJEVs verified the presence of exosomal markers such as CD63 and syntenin, and cargo molecules MRJP1, defensin-1, and jellein-3. Furthermore, RJEVs were demonstrated to modulate mesenchymal stem cell (MSC) differentiation and secretome, as well as decrease LPS-induced inflammation in macrophages by blocking the mitogen-activated protein kinase (MAPK) pathway. In vivo studies confirmed antibacterial effects of RJEVs and demonstrated an acceleration of wound healing in a splinted mouse model. This study suggests that RJEVs play a crucial role in the known effects of RJ by modulating the inflammatory phase and cellular response in wound healing. Transfer of RJ into the clinics has been impeded by the high complexity of the raw material. Isolating EVs from the raw RJ decreases the complexity while allowing standardization and quality control, bringing a natural nano-therapy one step closer to the clinics.

Gender and Leadership Positions in Spanish Dentistry.

Dentists in Spain reached equal gender representation in 2012 and the number of female dentists has continued to grow (until 57.3% in 2020). This study aims to increase evidence about the gender distribution on the high responsibility positions and opinion leaders of the dental profession and academia. Composition of the executive comities of the main dental institutions of Spain (regional professional associations, national dental association, and scientific societies), members of the Faculty of Dentistry of the University of Granada in 2020 and speakers of the main dental congresses of 2019 (due to the lack of congress in 2020) were recorded and analyzed by genders using chi-squared test (P < .05). Mean representation of female dentists in executive committees of professional associations was 35.6%. More than 70% of presidents and vice-presidents of professional colleges and more than 60% of these positions in scientific societies were occupied by male dentists. None of dental congresses of 2019 reached equal gender participation, being 81.3% of lecturers presenting on main auditoriums male dentists. Although dental workforce in Spain is slightly overrepresented by females, leadership positions and figures among Spanish dentists doesn't seem to reflect the gender distribution of the collective. There is a lack of women occupying high-level positions in dentistry that proves the existence of the so-called "glass ceiling effect" on the profession. Further studies about sociodemographic aspects of dental workforce are needed to develop evidence-based policies for the collective.

Effect of Two Immediate Dentin Sealing Approaches on Bond Strength of Lava™ CAD/CAM Indirect Restoration.

The objective of this work was to compare the micro-tensile bond strength (µTBS) of CAD/CAM (Computer-Aided Design/ Computer-Aided Manufacturing) specimens cemented with different pairing of adhesives and resin-cements using two Immediate Dentin Dealing (IDS) approaches in comparison with Delay Dentin Sealing (DDS). Coronal dentin from 108 molars were divided into nine groups (n = 12) depending on the adhesive/resin-cement (A-C) assigned. Lava™ Ultimate (4 × 10 × 10 mm) was cemented according to different strategies: IDS1(cementation after dentin sealing), DDS (dentin sealing and cementation at 2-weeks), IDS2 (immediate dentin sealing and cementation at 2-weeks). Samples were sectioned and tested until failure to determine the µTBS. Failure mode was categorized as dentin/cement (DC), at Lava™ Ultimate/cement (LC) and hybrid (H). Kruskal-Wallis and Mann-Whitney U tests and influence of the type of failure on the µTBS by survival analysis with competing risk was explored. Mostly, µTBS values were equal or higher in IDS2 than DDS. In general, A-Cs that showed higher µTBS, have high percentages of LC failure. Survival analysis with competing risk between DC + H and LC values showed that some A-Cs would significantly increase the µTBS values for IDS2. A-Cs with the highest adhesion values showed a high percentage of fractures at the LC interface, suggesting that the adhesion at the adhesive/dentin interface would be higher.

Adaptation and validation for Spain of the Child-Oral Impact on Daily Performance (C-OIDP) for use with adolescents.

OBJECTIVES: To linguistically and culturally adapt the Child-OIDP, an Oral Health-Related Quality of Life (OHRQoL) index, into Spanish for use among adolescents, and to validate it by evaluating the psychometric properties of the self-administered version. STUDY DESIGN: Following a forward - backward translation procedure, the English version of the questionnaire was translated by independent translators and the reconciled version was then sent to three experts for assessment. A pilot study was conducted on a sub-sample of 30 adolescents aged between 11 - 12 years to assess their understanding of the questionnaire and its wording. The participants in the main study comprised 425 school children aged from 11 to 14 and pertaining to the oral health survey on school children in Navarre; these children were given a clinical examination and answered a structured questionnaire on oral health self-perception, satisfaction and perceived dental treatment needs. We evaluated the content validity, face validity, criterion validity, internal consistency and reliability. RESULTS: With regard to the face validity, the experts' opinion was that the version was adequate. The pilot study indicated minor changes to the wording to better adapt it for the target population. Regarding criterion and construct validity, the association of the C-OIDP with the self-perception variables gave statistically significant results (p<0.01) in all cases. For the internal consistency analysis, no negative correlations were present in the correlations matrix nor were any of the values too high to become redundant; the majority were statistically significant (p<0.05). Cronbach's alpha value was 0.68, with corrected item-total values of between 0.20 and 0.56 and with no alpha if-item-deleted values greater than 0.68. The test-retest analysis gave an intraclass correlation coefficient (ICC)=0.98. CONCLUSION: The Spanish version of the self-administered questionnaire for the C-OIDP for adolescents adequately demonstrated successful psychometric properties and, therefore, is a valid and reliable instrument for measuring the OHRQoL of adolescents.

Validation the Oral Health Impact Profile (OHIP-14sp) for adults in Spain.

OBJECTIVES: The oral health-related quality of life indicators are increasingly used to measure the impact of oral conditions on quality of life to complement clinical data in cross-sectional and longitudinal studies. One of the most internationally spread indicators is the Oral Health Impact Profile (OHIP-14), but it has still never been applied in Spain. The aim of this study was to validate the OHIP-14 for use among adults in Spain. STUDY DESIGN: A cross-sectional study was performed in Granada (Spain). A consecutive sample (n=270) of the Regional Government staff visiting the Employment Risk Prevention Centre for a routine medical check-up participated in this study. All participants self-completed the piloted OHIP-14sp and were examined according to World Health Organization methodology for caries, periodontal disease and prosthesis. Reliability analyses and validity tests were carried out to evaluate the psychometric properties of the OHIP-14sp by using two different methods of total scoring (i.e. the Additive and the Simple Count). RESULTS: The reliability coefficient (Cronbach's alpha) of the OHIP-14sp was above the recommended 0.7 threshold and considered excellent (alpha: 0.89). Some subjective factors (perceived dental treatment need, complaints about mouth and self-rated oral satisfaction) were strongly associated with both total scoring methods of the OHIP-14sp, supporting the criterion, construct and convergent validity. Moreover the impact levels were mainly influenced by caries data, e.g., number of teeth requiring extraction (r = 0.21; p<0.01) and number of decayed visible teeth (between premolars) (r = 0.17; p<0.01). The prevalence of impacts was 80.7% using the occasional or more frequently threshold. The most prevalently affected OHIP domains were "psychological discomfort" (53.7%), "functional limitation" (51.1%) and "physical pain" (42.2%). CONCLUSIONS: The OHIP-14sp is a precise, valid and reliable instrument for assessing oral health-related quality of life among adult population in Spain.

Transcatheter chemoembolization in the treatment of HCC in patients not eligible for curative treatments: midterm results of doxorubicin-loaded DC bead.

PURPOSE: To examine the results of segmental transcatheter arterial chemoembolization with doxorubicin-loaded DC Bead in the treatment of hepatocellular carcinoma (HCC) in non-surgical candidates. MATERIAL AND METHODS: Seventy-one patients (60% men; 11% women; mean age 63; range 46-71 years) with documented HCC of 3-10 cm in diameter (mean 6.2) were enrolled prospectively in the study. All patients had cirrhosis-related HCC that was developed on an underlying controlled hepatitis infection. Only patients with compensated cirrhosis--Child A or B--were included in this study. RESULTS: Overall complete response (CR) according to EASL on an intention to treat basis was seen in 11 patients who developed complete necrosis (15.5%). Objective response (OR) ranged from 66.2% to 85.5% across the four treatments. Survival at 12 months was 97.05%. Sustained CR was observed in 11 (16.1%), and OR in 49 (72%). Sustained partial response was seen in 49 patients (72.05%). Survival at 18 months was 94.1%. At 24 months follow-up survival was 91.1%. Sustained OR was seen in 45 patients (66.2%) while sustained CR was 16.1% (11/68). At 30 months survival was 88.2%. One patient with CR developed multifocal HCC in areas that most likely were not embolized during the previous embolization sessions. In this patient recurrence-free survival was 28 months. Alpha Fetroprotein levels decreased significantly in measurements 1 month post each procedure (p < 0.001). Bilirubin, gamma-GT, aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase (ALP) showed only transient increases observed during the study period. Severe procedure-related complications were seen in 4.2% (cholecystitis: n = 1; liver abscess: n = 1; pleural effusion: n = 1). Post Embolization Syndrome (PES) was observed in all patients. CONCLUSION: Transcatheter arterial chemoembolization with DC Bead is an effective and safe procedure in the treatment of HCC patients not eligible for curative treatments with high rates of response and high rates of mid term survival.

[Contributions to a feminist anthropology of health: the study of the menstrual cycle]. / Aportes a una antropología feminista de la salud: el estudio del ciclo menstrual.

Medical or Health Anthropology focused on the study of women continues to be a main area of anthropological study in Spain. The contributions of two referential figures in feminist health anthropology, Marcia Inhorn and Mari Luz Esteban, are applied to review the findings of a qualitative research study on the menstrual cycle carried out through 20 interviews with women between the ages of 16 and 44 years, between 2013 and 2014, in the municipality of Madrid. The analysis shows that menstruation is a clear example of the reproductive essentialization of women, of biological reductionism, of the medicalization of women's bodies and, above all, of the standardization of bodies. The visibilization and questioning of these assumptions through the voices of the women interviewed highlight the importance of this field within medical anthropology.

Aportes a una antropología feminista de la salud: el estudio del ciclo menstrual / Contributions to a feminist anthropology of health: the study of the menstrual cycle

RESUMEN La antropología médica o de la salud centrada en el estudio de las mujeres sigue constituyendo una de las áreas principales del quehacer antropológico en el Estado español. A partir de los aportes de dos referentes de la antropología feminista de la salud como Marcia Inhorn y Mari Luz Esteban, se revisan los hallazgos de una investigación cualitativa sobre del ciclo menstrual, en la que se realizaron 20 entrevistas a mujeres de 16 a 44 años, entre 2013 y 2014, en el municipio de Madrid. El análisis muestra cómo la menstruación es un claro ejemplo de la esencialización reproductiva de las mujeres, del reduccionismo biológico, de la medicalización de los cuerpos de las mujeres y, sobre todo, de su uniformización. La visibilización y cuestionamiento de estos supuestos, a través de las voces de las mujeres entrevistadas, pone de manifiesto la relevancia de este campo dentro de la antropología médica.

ABSTRACT Medical or Health Anthropology focused on the study of women continues to be a main area of anthropological study in Spain. The contributions of two referential figures in feminist health anthropology, Marcia Inhorn and Mari Luz Esteban, are applied to review the findings of a qualitative research study on the menstrual cycle carried out through 20 interviews with women between the ages of 16 and 44 years, between 2013 and 2014, in the municipality of Madrid. The analysis shows that menstruation is a clear example of the reproductive essentialization of women, of biological reductionism, of the medicalization of women's bodies and, above all, of the standardization of bodies. The visibilization and questioning of these assumptions through the voices of the women interviewed highlight the importance of this field within medical anthropology.