Advanced practice in radiotherapy across Europe: stakeholders' perceptions of implementation and evolution.

INTRODUCTION: Adapting radiotherapy services with workforce innovation using skills-mix or task-shifting optimises resources, supporting current and future demands. Advanced practitioners (APs) work at a different level of practice (beyond initial registration) across four pillars: clinical practice, leadership and management, education, and research. There is limited cross-country research on the advanced therapeutic radiographers/radiation therapists (TR/RTTs), particularly in Europe. This study aimed to investigate European radiotherapy stakeholders' perceptions regarding current and future advanced practice (AP). METHODS: From June to September 2022, one-to-one online semi-structured interviews were conducted in English, and audio and video were recorded. Full verbatim audio files were independently transcribed and checked by interviewer and interviewees. Braun and Clarke's seven steps guided the thematic analysis (using NVivo). RESULTS: Thirty-three interviewees working or studying in 16 European countries represented practitioners (n=14), managers (n=6), educators (n=4), professional bodies (n=4), students (n=3), and regulators (n=2). Four overarching themes emerged: "AP drivers and outcomes", "AP challenges vs enablers", "Current vs future AP", "Becoming and being advanced practitioner". Participants identified research as the neglected AP pillar due to a lack of protected time, limited staff skills, no research culture, no funding, workload, and clinical priorities. Interviewees highlighted the importance of consistency in job titles, harmonisation of education models and curricula, definition of AP requirements, and support for all AP pillars through job plans and workforce planning. CONCLUSION: Neither the profession nor education of TR/RTTs are harmonised across Europe, which is highly reflected in advanced-level practice. Advanced TR/RTTs should work across all pillars, including research, and these should be embedded in master's programmes, including leadership. IMPLICATIONS FOR PRACTICE: This study highlights a policy gap in the education and practice of APs in radiotherapy.

Sublinear drag regime at mesoscopic scales in viscoelastic materials.

Stressed soft materials commonly present viscoelastic signatures in the form of power-law or exponential decay. Although exponential responses are the most common, power-law time dependencies arise peculiarly in complex soft materials such as living cells. Understanding the microscale mechanisms that drive rheologic behaviors at the macroscale shall be transformative in fields such as material design and bioengineering. Using an elastic network model of macromolecules immersed in a viscous fluid, we numerically reproduce those characteristic viscoelastic relaxations and show how the microscopic interactions determine the rheologic response. The macromolecules, represented by particles in the network, interact with neighbors through a spring constant k and with fluid through a non-linear drag regime. The dissipative force is given by γvα, where v is the particle's velocity, and γ and α are mesoscopic parameters. Physically, the sublinear regime of the drag forces is related to micro-deformations of the macromolecules, while α ≥ 1 represents rigid cases. We obtain exponential or power-law relaxations or a transitional behavior between them by changing k, γ, and α. We find that exponential decays are indeed the most common behavior. However, power laws may arise when forces between the macromolecules and the fluid are sublinear. Our findings show that in materials not too soft not too elastic, the rheological responses are entirely controlled by α in the sublinear regime. More specifically, power-law responses arise for 0.3 ⪅ α ⪅ 0.45, while exponential responses for small and large values of α, namely, 0.0 ⪅ α ⪅ 0.2 and 0.55 ⪅ α ⪅ 1.0.

Botulinum toxin and conservative treatment strategies in people with cervical dystonia: an online survey.

Isolated cervical dystonia is a focal, idiopathic dystonia affecting the neck muscles. Treatment usually consists of botulinum neurotoxin (BoNT) injections into the dystonic muscles. Our aim is to investigate the use of BoNT treatment and conservative treatments by people living with cervical dystonia. An online survey in English was conducted between June and August 2022. Participants were eligible to participate if they were living with cervical dystonia, were over 18 years old and could read and understand English. The survey consisted of demographic questions, characteristics of dystonia, questions relating to BoNT use and the perceived utility of conservative treatments. The data were analysed descriptively, and open-ended questions were grouped into similar topics represented by direct quotes. We received 128 responses from people with cervical dystonia, with an average age of 59 years and 77% women. Most participants (52%) described their cervical dystonia as mild to moderate with an average pain score of 5/10. Eighty-two (64%) participants were having regular BoNT injections, with overall positive perceived effects. Common activities reported to improve the symptoms were the use of heat packs, massage, relaxation, physiotherapy and participation in general exercise. Common coping strategies reported were getting sufficient rest, having the support of friends and family, and remaining engaged in enjoyable hobbies. We found that most participants received regular BoNT injections and that heat packs, exercise, massage, physiotherapy and relaxation were mostly perceived as effective in reducing the symptoms of cervical dystonia.

Dynapenic Abdominal Obesity as a Risk Factor for Metabolic Syndrome in Individual 50 Years of Age or Older: English Longitudinal Study of Ageing.

OBJECTIVES: To analyse whether dynapenic abdominal obesity is a risk factor for Metabolic syndrome (MetS) and its components in individuals 50 years of age or older. DESIGN: A longitudinal study was conducted with an eight-year follow-up. SETTING: Representative sample of community-dwelling participants of the English Longitudinal Study of Ageing (ELSA). PARTICIPANTS: 3,952 individuals free of MetS at baseline. MEASUREMENTS: Dynapenic abdominal obesity was defined based on waist circumference (> 102 cm for men and > 88 cm for women) and grip strength (< 26 kg for men and < 16 kg for women). The participants were classified as non-abdominally obese/non-dynapenic (NAO/ND - reference group), abdominally obese/non-dynapenic (AO/ND), non-abdominally obese/dynapenic (NAO/D) and abdominally obese/dynapenic (AO/D). The outcome was the incidence of MetS based on the presence of three or more of the following criteria: hypertriglyceridemia, hyperglycaemia, low HDL cholesterol, arterial hypertension or body mass index ≥ 30 kg/m2 throughout eight-year follow-up. Additionally, the incidence of each component of MetS was also analyzed. Poisson regression models were run and controlled for sociodemographic, behavioural and clinical variables. RESULTS: The mean age of the participants was 65 years and 55% were women. The prevalence of AO/ND, NAO/D and AO/D were 35.3, 4.3 and 2.2%, respectively. At the end of follow-up 558 incident cases of MetS were recorded. The adjusted model demonstrated that although abdominal obesity was a risk factor for MetS (IRR: 2.26; 95% CI: 1.87 - 2.73), the IRR was greater in AO/D individuals (IRR: 3.34; 95% CI: 2.03 - 5.50) compared with ND/NAO group. Furthermore, ND/AO was a risk factor for incidence of hypertriglyceridemia (IRR: 1.27; 95% CI: 1.06 - 1.52), hyperglycaemia (IRR: 1.41; 95% CI: 1.18 - 1.69), low HDL cholesterol (IRR: 1.70; 95% CI: 1.32 - 2.19) and BMI ≥ 30 kg/m2 (IRR: 2.58; 95% CI: 2.04 - 3.26) while D/AO was a risk factor for hyperglycaemia (IRR: 1.78; 95% CI: 1.02 - 3.10), low HDL cholesterol (IRR: 2.36; 95% CI: 1.10 - 5.08), and BMI ≥ 30 kg/m2 (IRR: 2.79; 95% CI: 1.38 - 5.62). CONCLUSIONS: Dynapenic abdominal obesity increases the risk of MetS, with a higher IRR compared to obesity alone. The understanding of this synergic action could guide specific clinical strategies, enabling the prevention of metabolic changes that can lead to cardiovascular disease, disability and death.

Dysphagia and pulmonary complications in acute cerebrovascular disease: A retrospective observational study / Disfagia y complicaciones pulmonares en la enfermedad cerebrovascular aguda: estudio observacional retrospectivo

Introduction: Dysphagia is a common post-stroke complication, which may result in serious pulmonary sequelae. Early detection of dysphagia and aspiration risk can reduce morbidity, mortality and length of hospitalization. Objectives: This study aims to identify association between dysphagia and acute cerebrovascular disease, and evaluate the prevalence and impact of pulmonary complications on readmissions and mortality. Material and methods: Retrospective observational study based on 250 clinical records of patients with acute cerebrovascular disease: clinical history, neurological examination, imaging and Gugging Swallowing Screen in the first 48h. Patients were followed for 3 months via medical records to estimate 3-month mortality and readmissions. Results: Out of 250 clinical records analyzed, 102 (40.8%) were evaluated for dysphagia. The prevalence of dysphagia was 32.4%. The risk was higher in older patients (p<0.001), in severe stroke (p<0.001) and in the hemorrhagic subtype (p=0.008). An association was found with dysarthria and aphasia (p=0.003; p=0.017). Respiratory tract infections occurred in 14.4% of all patients (GUSS group 11.8% versus no GUSS group 16.2%), and in 75% of those with severe dysphagia (p<0.001). Mortality at 3 months was 24.2% in dysphagic patients, especially high in the severe dysphagia group (75%, p<0.001). Conclusions: The type of cerebrovascular disease, NIHSS and GCS scores, age, dysarthria, and aphasia were significant associated factors to dysphagia. The prevalence of respiratory tract infections was higher in patients with no GUSS record, and no statistical significance was observed in related readmissions. Mortality at 3 months was superior in the severe dysphagia group.(AU)

Introducción: La disfagia es una complicación frecuente posterior a un evento cerebrovascular, que puede provocar graves secuelas pulmonares. La detección temprana de la disfagia y el riesgo de aspiración puede reducir la morbilidad, la mortalidad y la duración de la hospitalización. Objetivos: Este estudio pretende identificar asociaciones entre la disfagia y la enfermedad cerebrovascular aguda, y evaluar la prevalencia y el impacto de las complicaciones pulmonares en los reingresos y en la mortalidad. Material y método: Estudio observacional retrospectivo basado en 250 historias clínicas de pacientes con enfermedad cerebrovascular aguda: historia clínica, examen neurológico, pruebas de imagen y Gugging Swallowing Screen (GUSS) en las primeras 48h. Los pacientes fueron seguidos durante 3 meses a través de las historias clínicas para estimar la mortalidad a los 3 meses y los reingresos. Resultados: De las 250 historias clínicas analizadas, 102 (40,8%) fueron evaluados por disfagia. La prevalencia de disfagia fue del 32,4%. El riesgo fue mayor en los pacientes de mayor edad (p<0,001), en el ictus grave (p<0,001) y en el subtipo hemorrágico (p=0,008). Se encontró asociación con la disartria y la afasia (p=0,003; p=0,017). Las infecciones del tracto respiratorio se produjeron en el 14,4% de todos los pacientes (grupo GUSS 11,8% vs. grupo sin GUSS 16,2%), y en el 75% de los que tenían disfagia grave (p<0,001). La mortalidad a los 3 meses fue del 24,2% en pacientes disfágicos, especialmente alta en el grupo de disfagia grave (75%; p<0,001). Conclusiones: El tipo de enfermedad cerebrovascular, las puntuaciones NIHSS y GCS, edad, disartria y afasia fueron factores asociados de forma significativa a la disfagia. La prevalencia de infecciones del tracto respiratorio fue mayor en los pacientes sin registro GUSS, y no se observó significación estadística en los reingresos relacionados. La mortalidad a los 3 meses fue superior en el grupo de disfagia grave.(AU)

Growth and production of cowpea beans under potassium doses in soil of cerrado in Amapá, Brazil.

The cowpea bean [Vigna unguiculata (L.) Walp.], a legume of great socioeconomic importance, it was previously cultivated exclusively for subsistence and commercial purposes, especially in the North and Northeast regions. This crop has a low production cost and high nutritional value, in addition to a high potential for productivity growth and expansion to other regions. The objective of this work was to evaluate parameters of growth and production in cowpea culture, as a function of potassium fertilization in soil of the cerrado of Amapá. The parameters of growth and production of the cowpea culture were evaluated, as a function of potassium fertilization in the soil of the cerrado of Amapá. The experiment was conducted in a greenhouse, using a completely randomized experimental design, with four replications, in a 5x2 factorial scheme, totaling 40 experimental units, which were composed of plastic pots containing 7 dm3 of soil collected from the arable layer (0-20 cm ) of a typical Hyperdystrophic Yellow Argisol, with a sandy clay loam texture, in a cerrado area in the municipality of Porto Grande-AP. The factors consisted of the control treatment (without K), four doses of K (45, 90, 135 and 180 kg ha-1) in the form of potassium chloride, and two cowpea cultivars (Pretinho and BRS Tumucumaque). The cultivar BRS Tumucumaque shows better growth and production of cowpea plants. Doses of 90 kg ha-1 provided greater height (98.75 cm) and stem diameter (10.0 mm). As for production, the dose of 135 kg ha-1 caused greater grain weight gain (5.25 g) and dry mass of pods (13.92 g), and the doses of 90 and 180 kg ha-1 induced greater number and length of pods (3.16 pods) respectively. These results show better responsiveness of the BRS Tumucumaque cultivar at doses of 90, 135 and 180 kg ha-1 in the type of soil where the study was conducted.

Exposure of insects and host plants to different concentrations of CO2 affects the performance of Mahanarva spectabilis (Hemiptera: Cercopidae) in successive insect generations.

The performance of three successive generations of Mahanarva spectabilis (Distant) (Hemiptera: Cercopidae) fed on four forages exposed to environments with different CO2 concentrations was evaluated. In the first bioassay, we utilized the following scenarios: A) plants and insects were kept at high and constant CO2 (700 ppm) and B) the insects were kept at CO2 700 ppm and fed on plants from the greenhouse (average of 390 ppm). In the second bioassay, we utilized the following scenarios: C) plants and insects were kept in a greenhouse and D) the insects were kept in the greenhouse and fed on plants kept at CO2 700 ppm. The survival and duration of the nymphal and adult stages and the number of eggs/female of M. spectabilis were evaluated. It was only possible to evaluate the cumulative effects of the increase of CO2 on three successive generations of M. spectabilis kept in a greenhouse, due to the reduced survival of the insects in the first generation in the laboratory. A greater direct than indirect effect of the CO2 level on the performance of M. spectabilis was observed. Furthermore, it should be considered that the effect of CO2 elevation on the survival, periods of development, and fecundity, when taken together, can significantly impact the population dynamics of M. spectabilis in future climate scenarios.

Alterations promoted by acid straightening and/or bleaching in hair microstructures.

Human hair is a biopolymer constituted mainly of keratin intermediate filaments, lipids, pigments and water. Cosmetic treatments usually interact with the hair at the molecular level, inducing changes in its components and modifying the physicochemical and mechanical properties of the fibers. Here, the effect of acid straightening on the morphology and ultrastructure of Caucasian hair was investigated by a group of complementary experimental methods: wide-, small- and ultra-small-angle X-ray scattering; high-resolution 3D X-ray microscopy; quasi-elastic neutron scattering and inelastic neutron scattering; thermogravimetry-mass spectrometry; and differential scanning calorimetry (DSC). X-ray diffraction patterns showed that acid straightening associated with a flat iron (∼180°C) changed the cortex of the fiber, shown by denaturation of the intermediate filaments (measured by DSC). The increase in the spacing of the lipid layers and the observation of the dehydration behavior of the fiber provided indications that water may be confined between these layers, while neutron spectroscopy showed alterations in the vibration mode of the CH2 groups of the lipids and an increase of the proton (H+) mobility in the hair structure. The latter may be associated with the extremely low pH of the formulation (pH ≃ 1). Additionally, this investigation showed that bleached hair (one-time bleached) is more damaged by the action of acid straightening than virgin hair, which was shown by a threefold increase in the percentage of total porosity of the tresses. The obtained results demonstrate that the investigation approach proposed here can provide very important thermodynamic and structural information on induced changes of hair structure, and certainly can be applied for the evaluation of the action mode and efficiency of cosmetic treatments.

Mansonella sp. and associated Wolbachia endosymbionts in ring-tailed coatis (Nasua nasua) in periurban areas from Midwestern Brazil.

Coatis (Nasua nasua) are wild carnivorous well adapted to anthropized environments especially important because they act as reservoirs hosts for many arthropod-borne zoonotic pathogens. Information about filarioids from coatis and associated Wolbachia spp. in Brazil is scant. To investigate the diversity of filarial nematodes, blood samples (n = 100 animals) were obtained from two urban areas in midwestern Brazil and analyzed using blood smears and buffy coats and cPCR assays based on the cox1, 12S rRNA, 18S rRNA, hsp70 and myoHC genes for nematodes and 16S rRNA for Wolbachia. When analyzing coati blood smears and buffy coats, 30% and 80% of the samples presented at least one microfilaria, respectively. Twenty-five cox1 sequences were obtained showing 89% nucleotide identity with Mansonella ozzardi. Phylogenetic analyses clustered cox1 sequences herein obtained within the Mansonella spp. clade. Sequences of both myoHC and two hsp70 genes showed 99.8% nucleotide identity with Mansonella sp. and clustered into a clade within Mansonella sp., previously detected in coatis from Brazil. Two blood samples were positive for Wolbachia, with a 99% nucleotide identity with Wolbachia previously found in Mansonella perstans, Mansonella ozzardi and Mansonella atelensis and in ectoparasites of the genus Pseudolynchia, Melophagus and Cimex. The study showed a high prevalence of Mansonella sp. in the coati population examined, suggesting that this animal species play a role as reservoirs of a novel, yet to be described, species within the Onchocercidae family.

Dysphagia and pulmonary complications in acute cerebrovascular disease: A retrospective observational study.

INTRODUCTION: Dysphagia is a common post-stroke complication, which may result in serious pulmonary sequelae. Early detection of dysphagia and aspiration risk can reduce morbidity, mortality and length of hospitalization. OBJECTIVES: This study aims to identify association between dysphagia and acute cerebrovascular disease, and evaluate the prevalence and impact of pulmonary complications on readmissions and mortality. MATERIAL AND METHODS: Retrospective observational study based on 250 clinical records of patients with acute cerebrovascular disease: clinical history, neurological examination, imaging and Gugging Swallowing Screen in the first 48h. Patients were followed for 3 months via medical records to estimate 3-month mortality and readmissions. RESULTS: Out of 250 clinical records analyzed, 102 (40.8%) were evaluated for dysphagia. The prevalence of dysphagia was 32.4%. The risk was higher in older patients (p<0.001), in severe stroke (p<0.001) and in the hemorrhagic subtype (p=0.008). An association was found with dysarthria and aphasia (p=0.003; p=0.017). Respiratory tract infections occurred in 14.4% of all patients (GUSS group 11.8% versus no GUSS group 16.2%), and in 75% of those with severe dysphagia (p<0.001). Mortality at 3 months was 24.2% in dysphagic patients, especially high in the severe dysphagia group (75%, p<0.001). CONCLUSIONS: The type of cerebrovascular disease, NIHSS and GCS scores, age, dysarthria, and aphasia were significant associated factors to dysphagia. The prevalence of respiratory tract infections was higher in patients with no GUSS record, and no statistical significance was observed in related readmissions. Mortality at 3 months was superior in the severe dysphagia group.

Do national health priorities align with Global Burden of Disease estimates on disease burden? An analysis of national health plans and official governmental websites.

OBJECTIVE: To investigate the alignment of national health priorities with a country's burden of disease as measured by disability-adjusted life years (DALYs). METHODS: We identified priorities in national health plans and the 20 most burdensome conditions measured by DALYs from the 2017 Global Burden of Disease Study. We computed point-biserial correlations (rpb) between DALYs and being nominated as a health priority and the pooled proportion (95% confidence intervals [CIs]) of the 20 most burdensome conditions nominated as a priority across countries. RESULTS: We identified national health plans and official governmental websites in 145 countries. There was little to no correlation (rpb = 0.06, 95% CI: 0.02 to 0.09) between national DALY data and whether a condition was nominated as a health priority. The pooled proportion of the 20 most burdensome conditions nominated as priorities across countries was 46%. HIV/AIDS had the greatest number of nominations as a national health priority (62 countries) as well as the greatest match with the burden of disease (among the top 20 most burdensome conditions in 51 [82%] countries). Low back pain, headache disorders and congenital birth defects had the lowest proportion of nominations as health priorities in countries where they were in the top 20 most burdensome conditions (6%, 6% and 11%, respectively). CONCLUSION: Globally, there were low correlations between national health priorities and GBD estimates on disease burden. Failing to prioritise health priorities according to burden may mean that insufficient resources have been directed to improve health outcomes for people with those health conditions.

COVID-19 impedimetric biosensor based on polypyrrole nanotubes, nickel hydroxide and VHH antibody fragment: specific, sensitive, and rapid viral detection in saliva samples.

SARS-CoV-2 rapid spread required urgent, accurate, and prompt diagnosis to control the virus dissemination and pandemic management. Several sensors were developed using different biorecognition elements to obtain high specificity and sensitivity. However, the task to achieve these parameters in combination with fast detection, simplicity, and portability to identify the biorecognition element even in low concentration remains a challenge. Therefore, we developed an electrochemical biosensor based on polypyrrole nanotubes coupled via Ni(OH)2 ligation to an engineered antigen-binding fragment of heavy chain-only antibodies (VHH) termed Sb#15. Herein we report Sb#15-His6 expression, purification, and characterization of its interaction with the receptor-binding domain (RBD) of SARS-CoV-2 in addition to the construction and validation of a biosensor. The recombinant Sb#15 is correctly folded and interacts with the RBD with a dissociation constant (KD) of 27.1 ± 6.4 nmol/L. The biosensing platform was developed using polypyrrole nanotubes and Ni(OH)2, which can properly orientate the immobilization of Sb#15-His6 at the electrode surface through His-tag interaction for the sensitive SARS-CoV-2 antigen detection. The quantification limit was determined as 0.01 pg/mL using recombinant RBD, which was expressively lower than commercial monoclonal antibodies. In pre-characterized saliva, both Omicron and Delta SARS-CoV-2 were accurately detected only in positive samples, meeting all the requirements recommended by the World Health Organization for in vitro diagnostics. A low sample volume of saliva is needed to perform the detection, providing results within 15 min without further sample preparations. In summary, a new perspective allying recombinant VHHs with biosensor development and real sample detection was explored, addressing the need for accurate, rapid, and sensitive biosensors.

Culturally adapted psychosocial interventions (CaPSI) for early psychosis in a low-resource setting: study protocol for a large multi-center RCT.

BACKGROUND: Psychosis treatment guidelines recommend cognitive behaviour therapy (CBT) and family intervention (FI), for all patients with first episode psychosis (FEP), though guidance borrows heavily from literature in adults from high income countries. To our knowledge, there are few randomized controlled trials (RCTs) examining the comparative effect of these commonly endorsed psychosocial interventions in individuals with early psychosis from high-income countries and no such trials from low and middle-income countries (LMICs). The present study aims to confirm the clinical-efficacy and cost-effectiveness of delivering culturally adapted CBT (CaCBT) and culturally adapted FI (CulFI) to individuals with FEP in Pakistan. METHOD: A multi-centre, three-arm RCT of CaCBT, CulFI, and treatment as usual (TAU) for individuals with FEP (n = 390), recruited from major centres across Pakistan. Reducing overall symptoms of FEP will be the primary outcome. Additional aims will include improving patient and carer outcomes and estimating the economic impact of delivering culturally appropriate psychosocial interventions in low-resource settings. This trial will assess the clinical-efficacy and cost-effectiveness of CaCBT and CulFI compared with TAU in improving patient (positive and negative symptoms of psychosis, general psychopathology, depressive symptoms, quality of life, cognition, general functioning, and insight) and carer related outcomes (carer experience, wellbeing, illness attitudes and symptoms of depression and anxiety). CONCLUSIONS: A successful trial may inform the rapid scale up of these interventions not only in Pakistan but other low-resource settings, to improve clinical outcomes, social and occupational functioning, and quality of life in South Asian and other minority groups with FEP. TRIAL REGISTRATION: NCT05814913.

Histology and histochemistry of the accessory gland of the female reproductive tract of Rhodnius neglectus Lent, 1954 (Hemiptera: Reduviidae).

Rhodnius neglectus is a wild triatomine, vector of the protozoan Trypanosoma cruzi, which causes Chagas' disease, and feeds on the blood of small mammals, being essential for its growth and reproduction. Accessory glands of the female reproductive tract are important in insect reproduction, but their anatomy and histology in R. neglectus are poorly studied. The aim of this work was to describe the histology and histochemistry of the accessory gland of the female reproductive tract of R. neglectus. The reproductive tract of five females of R. neglectus was dissected and the accessory glands transferred to Zamboni's fixative solution, dehydrated in a crescent series of ethanol, embedded in historesin, sectioned at 2 µm thick, stained with toluidine blue for histological analysis or mercury bromophenol blue for detection of total proteins. The accessory gland R. neglectus is tubular, without branches, opening in the dorsal region of the vagina and differing along its length in proximal and distal regions. In the proximal region, the gland is lined by the cuticle with a layer of columnar cells associated with muscle fibers. In the distal region of the gland, the epithelium has spherical secretory cells with terminal apparatus and conducting canaliculi opening in the lumen through pores in the cuticle. Proteins were identified in the gland lumen, terminal apparatus, nucleus and cytoplasm of secretory cells. The histology of the R. neglectus gland is similar to that found in other species of this genus, but with variations in the shape and size of its distal region.

The Burden and Impacts of Mealtime Insulin from the Perspective of People with Diabetes.

INTRODUCTION: While there have been continued advances in insulin treatment for diabetes since the discovery of insulin 100 years ago, some unmet needs still remain, including those related to mealtime insulin (MTI). The objective of this study was to explore the impacts related to MTI and the relative burden of the impacts on people with diabetes. METHODS: This study was conducted across two phases, namely, a qualitative and quantitative phase. People with type 1 and 2 diabetes using MTI in the USA and UK were recruited for the study. The qualitative phase involved 30 interviews to explore the impacts associated with MTI. Based on the results of the qualitative phase, a list of impacts was developed to evaluate the importance of MTI impacts using best-worst scaling. RESULTS: A total of 30 participants completed interviews, and 336 completed the quantitative phase. Participants described a range of impacts associated with MTI, including psychological (72.0%), social (63.0%), work/school (53.8%), and sleep (51.7%). Impacts for the quantitative phase were categorized under the following domains: diabetes distress, diabetes management, work productivity, and social. The three most burdensome impacts were related to diabetes distress, but the diabetes management domain contributed more than diabetes distress to the relative burden. There were minor differences in the relative importance of impacts by diabetes type, diabetes duration, and experience with continuous glucose monitoring. CONCLUSION: This study confirms that people with diabetes using MTI still have an array of unmet needs, including those related to the management of their diabetes and the emotional distress of having diabetes. These findings may be useful for healthcare provider (HCP)-patient interactions to ensure HCPs are allowing patients an opportunity to discuss their experiences with MTI.

Treatment with oral or topical sirolimus in complex vascular anomalies in pediatrics. Experience in a third-level hospital. / Tratamiento con sirolimus oral o tópico en anomalías vasculares complejas en pediatría. Experiencia en un hospital terciario.

OBJECTIVE: The use of sirolimus in vascular anomalies is a special indication not authorized in its data sheet. The objective of this study was to increase the evidence of oral or topical use of sirolimus for this indication in the pediatric population. MATERIALS AND METHODS: An observational, retrospective study of patients under 18 years of age treated with oral or topical sirolimus for vascular anomalies was carried out. Diagnosis and location of lesions, administration route and dosage of sirolimus, blood levels of sirolimus in patients who received oral treatment, treatment duration, response, and toxicity were collected. RESULTS: 18 patients - 7 with oral treatment and 11 with topical treatment - were included. With oral sirolimus, the overall response rate was 85.7%. Sirolimus was discontinued in 2 cases - as a result of full resolution and progression. 57.1% of patients had adverse effects, most of which were mild. Dyslipidemia was the most frequent adverse effect. Blood levels were monitored in all patients for dose adjustment purposes. With topical treatment, the overall response rate was 72.7%. Sirolimus was discontinued in 3 cases -due to progression in 2 cases and to stability in 1. 27.3% of patients had adverse effects, with itching standing out as the most frequent one. CONCLUSIONS: The favorable results of sirolimus treatment in our patients seem to confirm its effectiveness and safety in vascular anomalies, which make it stand as a therapeutic option in pediatric patients. However, further research is required to establish the optimal treatment regimen, treatment duration, and potential long-term adverse effects.

OBJETIVO: El uso de sirolimus en anomalías vasculares es una indicación especial no autorizada en ficha técnica. El objetivo de este estudio es incrementar la evidencia del empleo por vía oral o tópica de sirolimus en esta indicación en población pediátrica. METODO: Estudio observacional retrospectivo de pacientes menores de 18 años tratados con sirolimus oral o tópico para anomalías vasculares recogiendo: diagnóstico y ubicación de lesiones, forma de administración y dosificación de sirolimus, niveles sanguíneos de fármaco en los pacientes con tratamiento oral, duración del tratamiento, respuesta y toxicidad. RESULTADOS: Se incluyeron 18 pacientes (7 con tratamiento oral y 11 tópico). Con sirolimus oral, la tasa de respuesta global fue 85,7%. Se interrumpió sirolimus en 2 casos: por resolución completa y por progresión. El 57,1% experimentó algún efecto adverso, en su mayoría leves; siendo la dislipemia el efecto adverso más frecuente. La monitorización de niveles sanguíneos fue empleada en todos los pacientes para el ajuste de dosis. Con el tratamiento tópico, la tasa de respuesta global fue 72,7%. Se interrumpió sirolimus en 3 casos: progresión en 2 casos y estabilidad en 1. El 27,3% experimentó algún efecto adverso, siendo el prurito el más frecuente. CONCLUSIONES: Los resultados favorables del tratamiento con sirolimus en nuestros pacientes parecen confirmar la efectividad y seguridad del fármaco en anomalías vasculares y lo posicionan como una opción terapéutica en pacientes pediátricos. Aun así, parece necesaria mayor investigación que trate de aclarar, entre otros, el régimen óptimo del tratamiento, la duración del mismo y los potenciales efectos adversos a largo plazo.

Tratamiento con sirolimus oral o tópico en anomalías vasculares complejas en pediatría. Experiencia en un hospital terciario / Treatment with oral or topical sirolimus in complex vascular anomalies in pediatrics. Experience in a third-level hospital

Objetivo:El uso de sirolimus en anomalías vasculares es una in-dicación especial no autorizada en ficha técnica. El objetivo de esteestudio es incrementar la evidencia del empleo por vía oral o tópica desirolimus en esta indicación en población pediátrica. Método. Estudio observacional retrospectivo de pacientes meno-res de 18 años tratados con sirolimus oral o tópico para anomalíasvasculares recogiendo: diagnóstico y ubicación de lesiones, forma deadministración y dosificación de sirolimus, niveles sanguíneos de fár-maco en los pacientes con tratamiento oral, duración del tratamiento,respuesta y toxicidad. Resultados: Se incluyeron 18 pacientes (7 con tratamiento oral y11 tópico). Con sirolimus oral, la tasa de respuesta global fue 85,7%.Se interrumpió sirolimus en 2 casos: por resolución completa y porprogresión. El 57,1% experimentó algún efecto adverso, en su mayoríaleves; siendo la dislipemia el efecto adverso más frecuente. La moni-torización de niveles sanguíneos fue empleada en todos los pacientespara el ajuste de dosis. Con el tratamiento tópico, la tasa de respuestaglobal fue 72,7%. Se interrumpió sirolimus en 3 casos: progresión en2 casos y estabilidad en 1. El 27,3% experimentó algún efecto adverso,siendo el prurito el más frecuente. Conclusiones: Los resultados favorables del tratamiento con siroli-mus en nuestros pacientes parecen confirmar la efectividad y seguridaddel fármaco en anomalías vasculares y lo posicionan como una opciónterapéutica en pacientes pediátricos. Aun así, parece necesaria mayorinvestigación que trate de aclarar, entre otros, el régimen óptimo deltratamiento, la duración del mismo y los potenciales efectos adversosa largo plazo.(AU)

Objective: The use of sirolimus in vascular anomalies is a specialindication not authorized in its data sheet. The objective of this studywas to increase the evidence of oral or topical use of sirolimus for thisindication in the pediatric population. Materials and methods: An observational, retrospective study ofpatients under 18 years of age treated with oral or topical sirolimus forvascular anomalies was carried out. Diagnosis and location of lesions,administration route and dosage of sirolimus, blood levels of sirolimusin patients who received oral treatment, treatment duration, response,and toxicity were collected. Results: 18 patients –7 with oral treatment and 11 with topicaltreatment– were included. With oral sirolimus, the overall responserate was 85.7%. Sirolimus was discontinued in 2 cases –as a result offull resolution and progression. 57.1% of patients had adverse effects,most of which were mild. Dyslipidemia was the most frequent adverseeffect. Blood levels were monitored in all patients for dose adjustmentpurposes. With topical treatment, the overall response rate was 72.7%.Sirolimus was discontinued in 3 cases –due to progression in 2 casesand to stability in 1. 27.3% of patients had adverse effects, with itchingstanding out as the most frequent one. Conclusions: The favorable results of sirolimus treatment in ourpatients seem to confirm its effectiveness and safety in vascular anom-alies, which make it stand as a therapeutic option in pediatric patients.However, further research is required to establish the optimal treatmentregimen, treatment duration, and potential long-term adverse effects.(AU)