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Heterozygous de novo or inherited gain-of-function mutations in the MTOR gene cause Smith-Kingsmore syndrome (SKS). SKS is a rare autosomal dominant condition, and individuals with SKS display macrocephaly/megalencephaly, developmental delay, intellectual disability, and seizures. A few dozen individuals are reported in the literature. Here, we report a cohort of 28 individuals with SKS that represent nine MTOR pathogenic variants. We conducted a detailed natural history study and found pathophysiological deficits among individuals with SKS in addition to the common neurodevelopmental symptoms. These symptoms include sleep-wake disturbance, hyperphagia, and hyperactivity, indicative of homeostatic imbalance. To characterize these variants, we developed cell models and characterized their functional consequences. We showed that these SKS variants display a range of mechanistic target of rapamycin (mTOR) activities and respond to the mTOR inhibitor, rapamycin, differently. For example, the R1480_C1483del variant we identified here and the previously known C1483F are more active than wild-type controls and less responsive to rapamycin. Further, we showed that SKS mutations dampened circadian rhythms and low-dose rapamycin improved the rhythm amplitude, suggesting that optimal mTOR activity is required for normal circadian function. As SKS is caused by gain-of-function mutations in MTOR, rapamycin was used to treat several patients. While higher doses of rapamycin caused delayed sleep-wake phase disorder in a subset of patients, optimized lower doses improved sleep. Our study expands the clinical and molecular spectrum of SKS and supports further studies for mechanism-guided treatment options to improve sleep-wake behavior and overall health.
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INTRODUCTION AND OBJECTIVES: In recent years, there has been an increase in the number of children with tracheostomies. The objective was to describe the characteristics of paediatric patients with a tracheostomy followed up by the Department of Palliative Care and Chronic Medically Complex Illness (DPCCMCI) of a tertiary care hospital. METHODS: Single-centre retrospective observational study in patients aged less than 18 years with a tracheostomy followed up by the PCCCPS of a tertiary care hospital (November 2020-June 2022). We analysed epidemiological, clinical, microbiological and social data by reviewing the health records. RESULTS: The sample included 44 tracheostomized patients. The most frequent underlying disease was acquired upper airway disease (20.5%). The most common indication for tracheostomy was upper airway obstruction (66%). Bacterial isolates were detected in 84% of the tracheal aspirates, among which P. aeruginosa was the most frequent (56.8%). The most frequently prescribed antibiotic was ciprofloxacin (84%). In addition, 18.1% of the patients received at least 1 course of intravenous antibiotherapy and 29.5% received more than 3 systemic antibiotic regimens in the past 20 months. Fifty-nine percent of the children were schooled: 38.6% attended a regular school, 15.9% a special needs school and 4.5% were home-schooled. We identified social difficulties in 53.7%. Also, 22.7% of the families received financial support to care for a child with severe illness. CONCLUSIONS: Because of the complexity of caring for tracheostomized children, integral and coordinated management is essential. Schooling is possible and safe if caregivers are trained.
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Cuidados Paliativos , Traqueostomia , Humanos , Estudos Retrospectivos , Masculino , Feminino , Criança , Cuidados Paliativos/métodos , Traqueostomia/estatística & dados numéricos , Adolescente , Pré-Escolar , Doença Crônica , Lactente , Antibacterianos/uso terapêutico , Antibacterianos/administração & dosagem , Centros de Atenção TerciáriaRESUMO
Cancer survival is becoming more common which means that there is now a growing population of cancer survivors, in whom pain may be common. However, its prevalence has hardly been addressed systematically. We aimed to assess the prevalence and explore the pathophysiology and impact of pain on health outcomes in cancer survivors. We conducted a retrospective-prospective cohort study in cancer-free patients diagnosed with cancer at least five years before the study start date. We used multivariable regression to establish the association of patients' cancer characteristics with pain, and then the association of patients' pain features with health outcomes and related symptoms. Between March and July 2021, 278 long-term cancer survivors were evaluated. Almost half of them (130/278, 46.8%) had pain, of whom 58.9% had a probable neuropathic component, but only 18 (13.8%) were taking specific drugs for neuropathic pain. A history of surgery-related pain syndrome in breast cancer patients was more than twice as frequent in the pain cohort. Post-chemotherapy and post-radiotherapy pain syndromes were uncommon. Pain was associated with lower QoL, emotional functioning, professional performance, and disability scores. Pain is a frequent health determinant in cancer survivors. Referral to specialised pain services may be a reasonable move in some cases.
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BACKGROUND: Neoadjuvant endocrine therapy (NET) in oestrogen receptor-positive (ER+) /HER2-negative (HER2-) breast cancer allows real-time evaluation of drug efficacy as well as investigation of the biological and molecular changes that occur after estrogenic deprivation. Clinical and pathological evaluation after NET may be used to obtain prognostic and predictive information of tumour response to decide adjuvant treatment. In this setting, clinical scales developed to evaluate response after neoadjuvant chemotherapy are not useful and there are not validated biomarkers to assess response to NET beyond Ki67 levels and preoperative endocrine prognostic index score (mPEPI). METHODS: In this prospective study, we extensively analysed radiological (by ultrasound scan (USS) and magnetic resonance imaging (MRI)) and pathological tumour response of 104 postmenopausal patients with ER+ /HER2- resectable breast cancer, treated with NET for a mean of 7 months prior to surgery. We defined a new score, tumour cellularity size (TCS), calculated as the product of the residual tumour cellularity in the surgical specimen and the tumour pathological size. RESULTS: Our results show that radiological evaluation of response to NET by both USS and MRI underestimates pathological tumour size (path-TS). Tumour size [mean (range); mm] was: path-TS 20 (0-80); radiological-TS by USS 9 (0-31); by MRI: 12 (0-60). Nevertheless, they support the use of MRI over USS to clinically assess radiological tumour response (rad-TR) due to the statistically significant association of rad-TR by MRI, but not USS, with Ki67 decrease (p = 0.002 and p = 0.3, respectively) and mPEPI score (p = 0.002 and p = 0.6, respectively). In addition, we propose that TCS could become a new tool to standardize response assessment to NET given its simplicity, reproducibility and its good correlation with existing biomarkers (such as ΔKi67, p = 0.001) and potential added value. CONCLUSION: Our findings shed light on the dynamics of tumour response to NET, challenge the paradigm of the ability of NET to decrease surgical volume and point to the utility of the TCS to quantify the scattered tumour response usually produced by endocrine therapy. In the future, these results should be validated in independent cohorts with associated survival data.
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Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Terapia Neoadjuvante/métodos , Estudos Prospectivos , Antígeno Ki-67 , Reprodutibilidade dos Testes , Receptores de Estrogênio/análise , Receptor ErbB-2RESUMO
This paper investigates the effects of the fungicide azoxystrobin, a compound widely used in rice farming, on aquatic communities representative of two habitats characteristic of Mediterranean wetland ecosystems: water springs and eutrophic lake waters. The long-term effects of azoxystrobin were evaluated on several structural (phytoplankton, zooplankton, macroinvertebrate populations and communities) and functional (microbial decomposition, macrophyte and periphyton growth) parameters making use of freshwater mesocosms. Azoxystrobin was applied in two pulses of 2, 20, 200 µg/L separated by 14 d using the commercial product ORTIVA (23 % azoxystrobin w/w). The results show that these two habitats responded differently to the fungicide application due to their distinct physico-chemical, functional, and structural characteristics. Although overall sensitivity was found to be similar between the two (lowest NOEC < 2 µg/L), the taxa and processes that were affected differed substantially. In general, the most sensitive species to the fungicide were found in the water spring mesocosms, with some species of phytoplankton (Nitzschia sp.) or macrocrustaceans (Echinogammarus sp. and Dugastella valentina) being significantly affected at 2 µg/L. In the eutrophic lake mesocosms, effects were found on phytoplankton taxa (Desmodesmus sp. and Coelastrum sp.), on numerous zooplankton taxa, on chironomids and on the beetle Colymbetes fuscus, although at higher concentrations. The hemipteran Micronecta scholtzi was affected in both treatments. In addition, functional parameters such as organic matter decomposition or macrophyte growth were also affected at relatively low concentrations (NOEC 2 µg/L). Structural Equation Modelling was used to shed light on the indirect effects caused by azoxystrobin on the ecosystem. These results show that azoxystrobin is likely to pose structural and functional effects on Mediterranean wetland ecosystems at environmentally relevant concentrations. Moreover, it highlights the need to consider habitat-specific features when conducting ecotoxicological research at the population and community levels.
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Fungicidas Industriais , Pirimidinas , Estrobilurinas , Poluentes Químicos da Água , Animais , Ecossistema , Fungicidas Industriais/toxicidade , Áreas Alagadas , Poluentes Químicos da Água/toxicidade , Fitoplâncton , Zooplâncton , Lagos , Água/farmacologiaRESUMO
OBJECTIVES: Hospital at home (HAH) replaces acute inpatient hospital care for selected patients by providing care in their homes. We sought to describe the characteristics, management, and complications of patients with osteoarticular infections (OAIs) treated in an HAH program and its economic impact. METHODS: We conducted a retrospective observational study evaluating an HAH program in a pediatric hospital in Spain, describing the characteristics of patients with confirmed OAIs requiring intravenous antibiotic therapy admitted to this program between January 2019 and December 2022. The program operates as a virtual ward with possible daily visits by physicians and nurses and 24/7 telephone contact. RESULTS: A total of 88 patients (median age, 4.1 years; interquartile range [IQR], 1.7-10.6) with OIAs were admitted to the HAH program. Osteomyelitis (57%) and septic arthritis (29%) were the most frequent infections. Cefuroxime (42%) and cefazolin (39%) were the most frequently prescribed antibiotics. Caregiver self-administration was performed in 99%, allowing multiple daily doses of antimicrobial therapy, 80% by peripheral line. Thirteen patients (15%) had drug-related adverse events, only 3 requiring drug modification. Two patients (2%) were readmitted during HAH, and 1 was readmitted within 30 days of HAH discharge. The median HAH stay was 7 days (IQR, 4-8.75). For osteomyelitis, hospital days lowered from 8.5 days (IQR, 4.5-12) to 4 days (IQR, 3-7) after HAH implementation (P = .005) with 68% per-patient estimated cost savings. CONCLUSIONS: HAH treatment of OAIs is effective and cost-efficient. Patient support by medical and nursing staff, adequate family training, and regular communication are essential to ensure safe home admission.
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Hospitalização , Osteomielite , Humanos , Criança , Pré-Escolar , Tempo de Internação , Alta do Paciente , Osteomielite/tratamento farmacológico , HospitaisRESUMO
BACKGROUND: Value-based healthcare (VBHC) is a conceptual framework to improve the value of healthcare by health, care-process and economic outcomes. Benchmarking should provide useful information to identify best practices and therefore a good instrument to improve quality across healthcare organizations. This paper aims to provide a proof-of-concept of the feasibility of an international VBHC benchmarking in breast cancer, with the ultimate aim of being used to share best practices with a data-driven approach among healthcare organizations from different health systems. METHODS: In the VOICE community-a European healthcare centre cluster intending to address VBHC from theory to practice-information on patient-reported, clinical-related, care-process-related and economic-related outcomes were collected. Patient archetypes were identified using clustering techniques and an indicator set following a modified Delphi was defined. Benchmarking was performed using regression models controlling for patient archetypes and socio-demographic characteristics. RESULTS: Six hundred and ninety patients from six healthcare centres were included. A set of 50 health, care-process and economic indicators was distilled for benchmarking. Statistically significant differences across sites have been found in most health outcomes, half of the care-process indicators, and all economic indicators, allowing for identifying the best and worst performers. CONCLUSIONS: To the best of our knowledge, this is the first international experience providing evidence to be used with VBHC benchmarking intention. Differences in indicators across healthcare centres should be used to identify best practices and improve healthcare quality following further research. Applied methods might help to move forward with VBHC benchmarking in other medical conditions.
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Benchmarking , Qualidade da Assistência à Saúde , Humanos , Benchmarking/métodos , Atenção à SaúdeRESUMO
OBJECTIVES: To validate and test the reliability of the 10-Item Unilateral Vocal Fold Paralysis-Voice Handicap Index (UVFP-HI-10) quality of life (QoL) questionnaire for patients with UVFP. DESIGN: Prospective describe study based on perceptive surveys. PARTICIPANTS: We recruited 61 patients with UVFP and 53 healthy individuals comprised the control group. MAIN OUTCOME MEASURES: Both the patients and controls completed the UVFP-HI-10 questionnaire. A statistical analysis was performed to assess the internal consistency and validity of the survey. In addition, maximum phonation time (MPT) was used to objectively measure patient QoL. RESULTS: Internal consistency was high (α = .914) and the correlation with MPT was significant (rs = -0.722). The estimated marginal mean in the discriminant validity study was around seven times higher in the UVFP group compared to the controls. The UVFP-HI-10 cut-off value was more than 0.9 and the sensitivity and specificity were more than 0.8. CONCLUSIONS: The UVFP-HI-10 is a self-administered patient-reported outcome questionnaire with a high reliability and excellent criterion-based validity. This questionnaire can be used to evaluate specific clinical complaints (e.g., vocalisation, swallowing, and breathing) in terms of their impact on QoL in patients with UVFP. Thus, its use is appropriate as a basic assessment tool as part of a specific UVFP treatment protocol.
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Paralisia das Pregas Vocais , Prega Vocal , Humanos , Qualidade de Vida , Estudos Prospectivos , Reprodutibilidade dos Testes , Paralisia das Pregas Vocais/cirurgia , Inquéritos e QuestionáriosRESUMO
Introduction: Background: patients with cancer are one of the main group of patients on home parenteral nutrition (HPN). Patients with malignant bowel obstruction (MBO) represent a challenging group when considering HPN. At the Ethics Working Group of SENPE ethical considerations on this subject were reviewed and a guidelines proposal was made. Methods: a literature search was done and a full set of questions arose: When, if ever, is HPN indicated for patients with MBO? How should the training program be? When withdrawal of HPN should be considered? Other questions should be also taken into consideration. May any Oncologist send home a patient with HPN? The educational program could be shortened? When considering to withdraw parenteral nutrition? Results: HPN in MBO has better outcomes when patients have a good functional status (Karnofsky ≥ 50 or ECOG ≤ 2), expected survival > 2-3 months, and low inflammatory markers. Very few data have been reported on quality of life, but HPN allows a valuable time at home albeit with a considerable burden for both patients and their families. Proposal: once a patient is considered for HPN, there is a need for a deep talk on the benefits, complications and risks. In this initial talk, when HNP should be stopped needs to be included. The palliative care team with the help of the nutrition support team should follow the patient, whose clinical status must be assessed regularly. HPN should be withdrawn when no additional benefits are achieved. Conclusion: HPN may be considered an option in patients with MBO when they have a fair or good functional status and a desire to spend their last days at home.
Introducción: Introducción: los pacientes con cáncer constituyen uno de los principales grupos de pacientes dentro de los programas de nutrición parenteral domiciliaria (NPD). Existe un grupo de pacientes con obstrucción intestinal maligna (OIM) en quienes el uso de la NPD es controvertido. Desde el Grupo de Ética de la SENPE se revisan las cuestiones éticas detrás de la decisión de iniciar la NPD en un paciente con OIM y se propone una propuesta de acción. Método: se procedió a hacer una revisión crítica de la literatura, tras la cual se diseñaron las preguntas que este documento pretendía responder: ¿Está indicado el uso de la NPD en pacientes con OIM? ¿En qué situaciones? Quedarían otros aspectos que también merecen una reflexión: ¿Cualquier oncólogo puede enviar a un paciente a su domicilio con NPD? ¿Debe ser el programa de formación de los cuidados en la NPD igual que el referente a los pacientes con fracaso intestinal de causa benigna? ¿Se debe suspender la NPD en algún momento? Resultados: la NPD en pacientes con OIM consigue mejores resultados en aquellos con una buena situación funcional (índice de Karnofsky ≥ 50 o ECOG ≤ 2), con un pronóstico vital superior a 2-3 meses e, idealmente, con niveles de marcadores inflamatorios bajos. En los escasos trabajos publicados en los que se valoran las ventajas sobre la calidad de vida, se concluye que la NPD permite a los pacientes disponer de un tiempo valioso en su domicilio pero a costa de una carga significativa para ellos mismos y sus familias. Propuesta de acción: una vez considerado como candidato a la NPD, se debe tener una conversación abierta con el paciente y sus familiares en la que se aborden los beneficios potenciales, las implicaciones prácticas y los riesgos. En esa conversación inicial debe también plantearse en qué momento considerar la retirada de la NPD. El responsable de la NPD es el equipo de soporte domiciliario en colaboración con el de nutrición clínica. La situación clínica debe evaluarse de forma periódica de manera que, cuando la NPD no proporcione ningún beneficio adicional, se plantee su retirada, manteniendo el resto de medidas de tratamiento sintomático paliativo. Conclusión: la NPD puede constituir una opción de tratamiento paliativo en pacientes con OIM con buena capacidad funcional y un deseo manifiesto de disponer de más tiempo en su domicilio en los últimos estadios de su enfermedad.
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Neoplasias , Nutrição Parenteral no Domicílio , Humanos , Qualidade de Vida , Nutrição Parenteral no Domicílio/efeitos adversos , Avaliação de Estado de Karnofsky , Neoplasias/complicações , Neoplasias/terapiaRESUMO
OBJECTIVE: The main objective of this study was to compare the demographic and clinical characteristics of patients with laryngeal dystonia (LD), dystonic tremor (DT), and vocal tremor (VT). STUDY DESIGN: This was a retrospective longitudinal study. METHODS: Data analysis from every patient diagnosed with LD, DT, or VT from January 1, 2010, to September 30, 2022, at a tertiary hospital center. Differential diagnosis between these entities was clinical (clinical history, voice assessment, and endoscopy) and confirmed by laryngeal electromyography. RESULTS: A total of 87 patients were included in this study: 50 patients with LD, 23 with DT, and 14 with VT. Age at diagnosis was significantly lower in patients with LD, with a mean age of 56.2 years when compared to DT (67.6 years; P = 0.002) and VT (70.5 years; P = 0.009). Furthermore, VT had a higher female prevalence (92.9%) when compared with LD (52%; P = 0.011). LD was mainly adductor, with only two patients diagnosed with abductor LD, and DT was adductor in every case. Tremor direction in patients with VT was horizontal in 50% and mixed (horizontal + vertical) in 50%, while in DT was mixed in 65.2% and horizontal in 34.8%. LD was more commonly an isolated laryngeal movement disorder (78%) when compared to DT (47.8%; P = 0.015) or VT (28.5%; P < 0.001), which were more often secondary to generalized neurological disorders. There were no differences between groups on Voice Handicap Index-10, self-reported grade of dysphonia on a visual analogic scale (0-10), maximum phonation time, and G, R, B, A, and I in the GRBAS-I scale at diagnosis (P > 0.05). S was significantly higher in LD when compared to VT (P < 0.001) and nonsignificantly higher than in DT (P = 0.075). CONCLUSIONS: LD, DT, and VT seem to be different entities with different demographics and clinical characteristics.
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Introduction: Women deserve special attention due to the different requirements they have in comparison with men. In the same way, transgender women need individualized attention. Transgender women are at greater risk of suffering heart attacks or ischemic accidents, among other diseases, and are also at greater risk of developing eating disorders, poorer weight control and poorer perception of their image. Hormone therapy for gender reaffirmation in trans women modifies their body composition, and may also increase the risk of suffering from some pathologies. The nutritional needs of cisgender women are different from those of men, and trans women also have special needs, which may depend on whether or not they follow hormone therapy. Dietary studies, although scarce, suggest that transgender women have poor dietary habits and lifestyle. It is necessary to deepen the study of the nutritional situation of the female group, considering its diversity, and to develop standards and references appropriate to each case that allow better attention to the needs of these groups.
Introducción: El colectivo femenino merece una especial atención debido a los diferentes requerimientos que tienen en comparación con el colectivo masculino. De la misma manera, se necesita atender de manera individualizada al colectivo transgénero. En concreto, las mujeres trans tienen más riesgo de sufrir infartos o accidentes isquémicos, entre otras enfermedades, y también tienen mayor riesgo de desarrollar trastornos del comportamiento alimentario y peor control de peso y percepción de su imagen. La terapia hormonal de reafirmación de género en mujeres trans modifica su composición corporal y también puede aumentar el riesgo de padecer algunas patologías. Las necesidades nutricionales de las mujeres cisgénero son diferentes a las de los varones, y también tienen necesidades especiales las mujeres trans, que pueden depender del seguimiento o no de un tratamiento hormonal. Los estudios dietéticos, aunque escasos, sugieren que las mujeres transgénero tienen unos hábitos dietéticos y un estilo de vida menos saludables. Es necesario profundizar en el estudio de la situación nutricional del colectivo femenino, atendiendo a la diversidad del mismo, y desarrollar estándares y referencias adecuadas a cada caso que permitan una mejor atención de las necesidades de estos colectivos.
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Infarto do Miocárdio , Pessoas Transgênero , Transexualidade , Masculino , Humanos , Feminino , HormôniosRESUMO
Education is a key component of the student's transformation towards the creation of a more sustainable future. Among the methodological adaptations in teaching-learning processes, Service-Learning (SL) stands out as a meaningful academic experience to respond to social needs by developing committed citizens to transform society. The aim of the present study was to analyze the impact of this SL program on prosocial competence and satisfaction levels in university students, enhance physical fitness and analyze the reflections of the recipients. Moreover, the reflections on SL of the students and the migrants were analyzed. A mixed-methods design was performed. Forty-five students of Physical Activity and Sport Sciences provided a service to a migrant group that consisted of physical fitness training. The instruments implemented were the Prosocial and Civic Competence, the Impact of Service-Learning During Initial Training of Physical Activity and Sports and the reflective diary. The recipients participated in a physical fitness assessment and in a group discussion. The results show that SL in PAH contributes to pedagogical, communication, wellbeing and intercultural competences and also improves their prosocial and civic attitudes. Moreover, the recipients could enhance their physical fitness and their social interaction.
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Aprendizagem , Educação Física e Treinamento , Humanos , Estudantes , Competência Profissional , Exercício FísicoRESUMO
Fundamento la infección del tracto urinario es una de las enfermedades más frecuentes en edades pediátricas y se presenta con sintomatología no específica, en especial en los niños más pequeños, en los cuales el signo más importante es la fiebre. Objetivo caracterizar una serie de casos pediátricos hospitalizados a causa de infección del tracto urinario. Métodos se realizó un estudio descriptivo, de tipo serie de casos, en el Hospital Pediátrico de Camagüey, durante el periodo de enero a marzo de 2023. La muestra quedó conformada por 112 pacientes, una vez aplicados los criterios de selección. Fueron estudiadas las variables: grupo etario y sexo, área de salud, signos y síntomas clínicos, factores de riesgo y gérmenes aislados. El procesamiento de los datos se realizó mediante el paquete estadístico para las ciencias sociales y los resultados se expresaron en valores absolutos y porcentajes. Resultados predominó el grupo etario de menores de un año (31,2 %) y el sexo femenino (68,7 %). El Área de Salud Finlay fue la que más casos aportó (22,3 %), mientras que la fiebre resultó el síntoma preponderante (93,8 %), así como el abandono de la lactancia materna se comportó como el principal factor de riesgo (25,9 %). En el 32,1 % de los casos se aisló el germen Escherichia coli. Conclusiones la infección del tracto urinario es más frecuente en lactantes femeninas, y se constata la fiebre como síntoma principal, además de recogerse como factor de riesgo sustancial el abandono de la lactancia materna.
Foundation urinary tract infection is one of the most common diseases in children and presents with non-specific symptoms, especially in younger children, in which the most important sign is fever. Objective to characterize a series of pediatric cases hospitalized due to urinary tract infection. Methods a descriptive study, of a case series type, was carried out at the Pediatric Hospital of Camagüey, from January to March 2023. The sample was made up of 112 patients, once the selection criteria were applied. The studied variables were: age group and sex, health area, clinical signs and symptoms, risk factors and isolated germs. Data processing was carried out using the statistical package for the social sciences and the results were expressed in absolute values and percentages. Results the age group of children under one year (31.2%) and the female sex (68.7%) predominated. The Finlay Health Area was the one that contributed the most cases (22.3%), while fever was the predominant symptom (93.8%), as well as abandoning breastfeeding as the main risk factor (25.9%). In 32.1% of the cases the Escherichia coli germ was isolated. Conclusions urinary tract infection is more frequent in female infants, and fever is confirmed as the main symptom, in addition to the abandonment of breastfeeding being collected as a substantial risk factor.
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OBJECTIVE: This study is the first part of the MEDPAIN project "Update of analgesic parenteral admixtures: studies of use, compatibility and stability", and its goal is to develop a national map about the use of analgesic parenteral admixtures in healthcare settings. METHODS: Observational study, based on a survey aimed at Spanish hospital pharmacists, during the period December 2020 - April 2021. The questionnaire was designed in the RedCap® platform and disseminated through the Spanish Society of Hospital Pharmacy distribution list. An analgesic parenteral admixture (AM) was defined as the combination of two or more drugs, with at least one of them being an analgesic. The same combination of active ingredients, at different concentration and/or administered by different routes, was considered as a unique AM in this study. Some registered endpoints were related to the characteristics of the healthcare settings participating in the study, and others were related to the AM, such as drugs, doses and concentration range, route of administration, frequency of use, indication and type of patient (adult/pediatric) and where they are prepared. RESULTS: A total of 67 valid surveys from healthcare settings of 13 Spanish Autonomous Communities were received. They reported 462â¯AM. Every healthcare center informed an average of 6â¯AM (ICR p25-p75â¯=â¯4.0-9.0). Most of the reported mixtures were used in adults (93.9%) at hospital settings (91.8%), and they were mostly protocolized and frequently used. The 21.4% of them were compounded at the Pharmacy service. The AM included 26 different drugs, with opioid analgesics being present at the 87.4% of them. Midazolam was the most usual adjuvant drug. According to the definition of AM in this study, there were finally 137 different combinations mainly with two drugs (40.6%), but also with three (37.7%), four (15.2%) and five ingredients (6.5%). CONCLUSION: In conclusion, this study reveals the wide variability in current clinical practice and shows which are the most used analgesic parenteral admixtures in our country.
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Analgésicos , Nutrição Parenteral , Adulto , Humanos , Criança , Espanha , Preparações FarmacêuticasRESUMO
BACKGROUND: Bowel obstruction due to accidental ingestion of foreign objects occurs rarely in children because 80 to 90% of the objects can pass freely through the gastrointestinal tract. CASE REPORT: We report a case of a 14-month-old infant who presented bowel obstruction caused by the ingestion of hydrogel beads (sodium polyacrylate). Hydrogel beads are used as sensory and didactic toys that can increase their initial size 200 to 400 times by liquid absorption. An abdominal X-ray was perfomed in anteroposterior supine projection, where a round filling defect at the loop of the right flank was detected; this came to our attention because hydrogel beads are usually radiolucent. The diagnosis was established by abdominal ultrasound where free intraperitoneal fluid was reported with data of small bowel pseudo-obstruction by foreign objects. Conservative treatment was prescribed, finding persistence of increased abdominal perimeter, so an enterotomy was performed for their removal; finding impacted hydrogel beads 30 centimeters from the ileocecal valve. CONCLUSIONS: Hydrogel beads are dangerous for the pediatric population. The evolution of the patient was favorable thanks to the knowledge of the foreign objects ingested. The expectant behavior that had to be executed, stands out because we had no knowledge as to the maximum size of the hydrogel in the gastrointestinal tract.
INTRODUCCIÓN: La obstrucción intestinal por ingesta accidental de cuerpos extraños se presenta muy rara vez en la edad pediátrica debido a que del 80 al 90% de los objetos pueden pasar libremente por el tracto gastrointestinal. CASO CLÍNICO: Se aborda el caso de una paciente de sexo femenino de 1 año 2 meses quien presentó obstrucción intestinal debido a la ingesta de esferas de hidrogel (poliacrilato de sodio). Dichas esferas, que son utilizadas como juguetes didácticos o sensoriales, aumentan de 200 a 400 veces su tamaño inicial mediante la absorción de agua. Se realizó radiografía abdominal en proyección decúbito supino, donde llamó la atención el hallazgo de defecto de llenado redondeado en asa de flanco derecho, ya que las esferas de hidrogel son radiolúcidas. El diagnóstico se estableció mediante ultrasonido abdominal, donde se reportó líquido libre peritoneal con datos de suboclusión por cuerpos extraños a nivel intestinal. Se indicó tratamiento conservador, encontrando persistencia de aumento de perímetro abdominal. Se realizó enterotomía y se encontraron las esferas impactadas a 30 centímetros de la válvula ileocecal. CONCLUSIONES: Las esferas de hidrogel son peligrosas para la población pediátrica. La evolución de la paciente fue favorable debido al conocimiento del objeto extraño ingerido. Sobresale la conducta expectante que se tuvo que desempeñar debido a que se desconocía el crecimiento de las esferas y en qué momento no podrían continuar su paso por el tracto gastrointestinal.
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Corpos Estranhos , Obstrução Intestinal , Lactente , Humanos , Criança , Hidrogéis/efeitos adversos , Intestino Delgado , Obstrução Intestinal/etiologia , Obstrução Intestinal/cirurgia , Obstrução Intestinal/diagnóstico , Corpos Estranhos/complicações , Corpos Estranhos/diagnósticoRESUMO
PURPOSE: Selective parathyroidectomy, the treatment of choice for primary hyperparathyroidism, requires precise preoperative localization. Our purpose was to compare the accuracy and concordance of pre-surgical MIBI parathyroid scintigraphy and ultrasonography, as well as to assess the relevance of hybrid acquisition (SPECT/CT) in compromised circumstances: low-weight or ectopic adenomas, coexisting thyroid disease and re-interventions. METHODS: The study included 223 patients with primary hyperparathyroidism operated in a single Surgical Unit from August 2016 to March 2021. Preoperative ultrasonography and double-phase MIBI were performed with early SPECT/CT acquisition. A minimally invasive surgical approach was initially attempted, except in patients with concomitant thyroid surgery or multiglandular parathyroid disease. RESULTS: Selective parathyroidectomy was accomplished in 179 patients (80.2%); cervicotomy and/or thoracoscopy in 44. Removal of the parathyroid lesion was achieved in 211 patients (94.6%), corresponding 204 (96.7%) to adenomas (37 ectopic). The cure rate was 94.2%. Preoperative MIBI SPECT/CT showed higher sensitivity and accuracy (84%; 80%) compared to ultrasound (72%; 71%), being more precise in defining the exact anatomical location (75.8% vs 68.7%). These differences reached statistical significance in ectopic glands. The existence of concomitant thyroid pathology did not decrease the sensitivity of SPECT/CT (84.2%). Mean parathyroid weight was 692.2mg (95%CI: 443.5-941) in MIBI-negative cases and 1145.9mg (95%CI: 983.6-1308.3) in MIBI-positive (p=0.001). Re-intervention was successful in the 8 patients with previous surgery. CONCLUSION: MIBI SPECT/CT presents greater sensitivity, accuracy and anatomical precision than ultrasound for preoperative parathyroid localization, even in the case of ectopic glands or coexisting thyroid pathology. The weight of the pathological gland is a significantly limiting factor.
Assuntos
Adenoma , Hiperparatireoidismo Primário , Humanos , Hiperparatireoidismo Primário/diagnóstico por imagem , Hiperparatireoidismo Primário/cirurgia , Tecnécio Tc 99m Sestamibi , Glândulas Paratireoides/diagnóstico por imagem , Glândulas Paratireoides/cirurgia , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único , Adenoma/cirurgiaRESUMO
CONTEXT: The subcutaneous route is a useful alternative for drug administration in palliative care. Although there is scientific evidence on its use in adult patients, the literature in pediatric palliative care is almost nonexistent. OBJECTIVES: To describe the experience of a pediatric palliative care unit (PPCU) with in-home subcutaneous drug administration symptom control. METHODS: Prospective observational study of patients receiving home-based subcutaneous treatment administered as part of a PPCU treatment regimen over 16 months. Analysis includes demographic and clinical variables and treatment received. RESULTS: Fifty-four different subcutaneous lines were inserted in the 15 patients included, mainly in the thigh (85.2%). The median time of needle in situ was 5.5 days (range: 1-36 days). A single drug was administered in 55.7% of treatments. The most frequently used drugs were morphine chloride (82%) and midazolam (55.7%). Continuous subcutaneous infusion was the predominant administration route (96.7%), with infusion rates oscillating between 0.1 mL/h and 1.5 mL/h. A statistically significant relationship was found between the maximum infusion rate and induration onset. Of the 54 lines placed, 29 (53.7%) had an associated complication requiring line removal. The primary cause for removal was insertion-site induration (46.3%). Subcutaneous lines were mainly used to manage pain, dyspnea, and epileptic seizures. CONCLUSION: In the pediatric palliative care patients studied, the subcutaneous route is most frequently used for administering morphine and midazolam in continuous infusion. The main complication was induration, especially with longer dwell times or higher infusion rates. However, further studies are required to optimize management and prevent complications.
Assuntos
Midazolam , Cuidados Paliativos , Adulto , Humanos , Criança , Estudos Prospectivos , Morfina , Infusões SubcutâneasRESUMO
Clinical management of breast cancer (BC) metastasis remains an unmet need as it accounts for 90% of BC-associated mortality. Although the luminal subtype, which represents >70% of BC cases, is generally associated with a favorable outcome, it is susceptible to metastatic relapse as late as 15 years after treatment discontinuation. Seeking therapeutic approaches as well as screening tools to properly identify those patients with a higher risk of recurrence is therefore essential. Here, we report that the lipid-degrading enzyme fatty acid amide hydrolase (FAAH) is a predictor of long-term survival in patients with luminal BC, and that it blocks tumor progression and lung metastasis in cell and mouse models of BC. Together, our findings highlight the potential of FAAH as a biomarker with prognostic value in luminal BC and as a therapeutic target in metastatic disease.
Assuntos
Amidoidrolases , Biomarcadores Tumorais , Neoplasias Pulmonares , Animais , Camundongos , Amidoidrolases/genética , Neoplasias Pulmonares/patologia , Recidiva Local de Neoplasia/patologiaRESUMO
OBJETIVE: This study is the first part of the MEDPAIN project "Update of analgesic parenteral admixtures: studies of use, compatibility and stability", and its goal is to develop a national map about the use of analgesic parenteral admixtures in healthcare settings. METHODS: Observational study, based on a survey aimed at Spanish hospital pharmacists, during the period December 2020-April 2021. The questionnaire was designed in the RedCap® platform and disseminated through the Spanish Society of Hospital Pharmacy distribution list. An analgesic parenteral admixture (AM) was defined as the combination of two or more drugs, with at least one of them being an analgesic. The same combination of active ingredients, at different concentration and/or administered by different routes, was considered as a unique AM in this study. Some registered endpoints were related to the characteristics of the healthcare settings participating in the study, and others were related to the AM, such as drugs, doses and concentration range, route of administration, frequency of use, indication and type of patient (adult/pediatric) and where they are prepared. RESULTS: A total of 67 valid surveys from healthcare settings of 13 Spanish Autonomous Communities were received. They reported 462 AM. Every healthcare center informed an average of 6 AM (ICR p25-p75 =4.0-9.0). Most of the reported mixtures were used in adults (93.9%) at hospital settings (91.8%), and they were mostly protocolized and frequently used. The 21.4% of them were compounded at the Pharmacy service. The AM included 26 different drugs, with opioid analgesics being present at the 87.4% of them. Midazolam was the most usual adjuvant drug. According to the definition of AM in this study, there were finally 137 different combinations mainly with two drugs (40.6%), but also with three (37.7%), four (15.2%) and five ingredients (6.5%). CONCLUSION: This study reveals the wide variability in current clinical practice and shows which are the most used analgesic parenteral admixtures in our country.
Assuntos
Analgésicos , Nutrição Parenteral , Adulto , Humanos , Criança , Espanha , Preparações FarmacêuticasRESUMO
Substrate-binding proteins (SBPs) are used by organisms from the three domains of life for transport and signalling. SBPs are composed of two domains that collectively trap ligands with high affinity and selectivity. To explore the role of the domains and the integrity of the hinge region between them in the function and conformation of SBPs, here, we describe the ligand binding, conformational stability and folding kinetics of the Lysine Arginine Ornithine (LAO) binding protein from Salmonella thiphimurium and constructs corresponding to its two independent domains. LAO is a class II SBP formed by a continuous and a discontinuous domain. Contrary to the expected behaviour based on their connectivity, the discontinuous domain shows a stable native-like structure that binds l-arginine with moderate affinity, whereas the continuous domain is barely stable and shows no detectable ligand binding. Regarding folding kinetics, studies of the entire protein revealed the presence of at least two intermediates. While the unfolding and refolding of the continuous domain exhibited only a single intermediate and simpler and faster kinetics than LAO, the folding mechanism of the discontinuous domain was complex and involved multiple intermediates. These findings suggest that in the complete protein the continuous domain nucleates folding and that its presence funnels the folding of the discontinuous domain avoiding nonproductive interactions. The strong dependence of the function, stability and folding pathway of the lobes on their covalent association is most likely the result of the coevolution of both domains as a single unit.