RESUMEN
BACKGROUND: Chronic malnutrition is a condition associated with negative impacts on physical and cognitive development. It is multi-causal and can start very early in life, already in utero, thus it is especially challenging to find appropriate interventions to tackle it. The government of Angola is implementing a standard of care program with potential to prevent it, and the provision of cash transfers and the supplementation with small quantity lipid-based nutrients (SQ-LNS) are also promising interventions. We aimed to evaluate the impact of the standard of care program alone and of the standard of care plus a cash transfer intervention in the lineal growth of children less than 2 years old and compare it to the effectiveness of a nutrition supplementation plus standard of care program in Southern Angola. METHODS/DESIGN: The three-arm parallel cluster randomised controlled trial is set in four communes of Huila and Cunene provinces. Clusters are villages or neighbourhoods with a population around 1075 people. A total of twelve clusters were selected per arm and forty pregnant women are expected to be recruited in each cluster. Pregnant women receive the standard of care alone, or the standard of care plus unconditional cash transfer or plus nutritional supplementation during the first 1000 days, from pregnancy to the child reaching 24 months. The primary outcome is the prevalence of stunting measured as height-for-age Z-score (HAZ) < -2 in children below 2 years. Impact will be assessed at 3, 6, 12, 18 and 24 months of children's age. Secondary outcomes include mortality, morbidity, caring, hygiene and nutrition behaviours and practices, and women and children's dietary diversity. Quantitative data are also collected on women's empowerment, household food security, expenditure and relevant clinical and social events at baseline, endline and intermediate time points. DISCUSSION: The results will provide valuable information on the impact of the standard of care intervention alone as well as combined with an unconditional cash transfer intervention compared to a nutrition supplementation plus standard of care intervention, carried out during the first 1000 days, in the children´s growth up to 2 years and related outcomes in Southern Angola. TRIAL REGISTRATION: Clinical Trials NCT05571280. Registered 7 October 2022.
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Desnutrición , Nivel de Atención , Niño , Humanos , Femenino , Embarazo , Lactante , Preescolar , Angola , Estado Nutricional , Suplementos Dietéticos , Desnutrición/prevención & control , Desnutrición/epidemiología , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Rapid diagnostic tests (RDTs) for point-of-care (POC) testing of infectious diseases are popular because they are easy to use. However, RDTs have limitations such as low sensitivity and qualitative responses that rely on subjective visual interpretation. Additionally, RDTs are made using paper-bound reagents, which leads to batch-to-batch variability, limited storage stability and detection of only the analytes they were designed for. This work presents the development of a versatile technology, based on short magneto-assays and inexpensive paper-based microfluidic electro-analytical devices (PMEDs). PMEDs were produced locally using low-cost equipment, they were stable at room temperature, easy to use, and provided quantitative and objective results. The devices served to detect alternatively a variety of magneto-assays, granting quantitation of streptavidin-HRP, biotinylated HRP and Pasmodium falciparum lactate dehydrogenase (Pf-LDH) in less than 25 min, using either commercial or customized screen-printed electrodes and measurement equipment. Furthermore, Pf-LDH detection in diluted lysed whole blood displayed a linear response between 3 and 25 ng mL-1, detection and quantification limits ranging between 1 and 3 ng mL-1 and 6-12 ng mL-1, respectively, and provided results that correlated with those of the reference ELISA. In short, this technology is versatile, simple, and highly cost-effective, making it perfect for POC testing.
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Técnicas Biosensibles , Sistemas de Atención de Punto , Microfluídica , Pruebas en el Punto de Atención , AutomatizaciónRESUMEN
OBJECTIVES: The objective of this study was to identify Brazil's most critical garbage codes (GCs) reclassified to Chagas disease (ChD) in mortality data and their proportions. We also estimated the potential impact of misclassification on the number of deaths attributed to ChD. STUDY DESIGN: Population-based descriptive study. METHODS: We used the Mortality Information System (SIM; in Portuguese) data before and after routine GC investigation in 2015-2019 to evaluate ChD deaths detected among them. We identified priority GCs, which contributed more than 0.1 % to the percentage of total ChD deaths registered. Spearman's correlation was used to evaluate the association between the reclassification of priority GCs and ChD prevalence. Then, we applied the GC correction factors to estimate the number of deaths attributed to ChD. RESULTS: 22,154 deaths were reported as ChD in the study period. Among them, 1004 deaths originally listed as priority GCs were deaths reclassified to ChD after an investigation in the SIM final database. Unspecific cardiomyopathy (10.2 %), unspecific heart diseases (4.7 %), and heart failure (2.8 %) were GCs with the highest proportions of reclassification to ChD in Brazil. Higher ChD prevalence at the state level was associated with a higher proportion of GC deaths reclassified as ChD. When applying correction factors identified after investigation, we estimated an increase of 26.4 % in registered ChD deaths, mostly in states with higher endemicity. CONCLUSIONS: GCs might conceal deaths due to ChD, particularly in Brazil's states with higher endemicity. The approach suggested in this study may offer an alternative method for estimating ChD-related deaths in endemic countries.
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Enfermedad de Chagas , Cardiopatías , Insuficiencia Cardíaca , Humanos , Causas de Muerte , Brasil/epidemiologíaRESUMEN
The implantation of percutaneous balloon expandable valves in native or patched right ventricular outflow tracts (nRVOT) is a challenging technique due to the diversity of anatomies and shapes, the large sizes, and the distensibility of the nRVOT, for which specific techniques have been developed. We present a single center experience with balloon expandable percutaneous pulmonary valves in nRVOT, describing the techniques used, complications observed, and a short-mid term follow-up.. This is a single center descriptive study of patients who underwent a percutaneous pulmonary valve implantation in a nRVOT with a balloon expandable pulmonary valve in our center between September 2012 and June 2022.. We implanted successfully 45 valves in 46 patients (20 Sapien and 25 Melody). Tetralogy of Fallot or pulmonary atresia with VSD were the main congenital heart disease (n = 32). All were pre-stented, 18 in a one step procedure. We used a Dryseal sheath in 13/21 Sapien. In 6 patients we used the anchoring technique, 5 with a very large nRVOT and one pyramidal nRVOT. In the 3.5 year follow-up 7 patients developed endocarditis and 3 required a valve redilation, no fractures were observed. PPVI of native RVOT with balloon expandable valves is feasible in a number of selected anatomies, including large or pyramidal nRVOT, using specific techniques, (presenting, LPA anchoring).
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Cardiopatías Congénitas , Implantación de Prótesis de Válvulas Cardíacas , Prótesis Valvulares Cardíacas , Insuficiencia de la Válvula Pulmonar , Válvula Pulmonar , Humanos , Válvula Pulmonar/cirugía , Implantación de Prótesis de Válvulas Cardíacas/métodos , Prótesis Valvulares Cardíacas/efectos adversos , Resultado del Tratamiento , Cardiopatías Congénitas/cirugía , Cateterismo Cardíaco/métodos , Diseño de Prótesis , Estudios RetrospectivosRESUMEN
BACKGROUND: The impact of COVID-19 on the diagnosis and management of tuberculosis (TB) patients is unknown. METHODS: Participating centres completed a structured web-based survey regarding changes to TB patient management during the COVID-19 pandemic. The study also included data from participating centres on patients aged ≥18 diagnosed with TB in 2 periods: March 15 to June 30, 2020 and March 15 to June 30, 2019. Clinical variables and information about patient household contacts were retrospectively collected. RESULTS: A total of 7 (70%) TB units reported changes in their usual TB team operations. Across both periods of study, 169 patients were diagnosed with active TB (90 in 2019, 79 in 2020). Patients diagnosed in 2020 showed more frequent bilateral lesions in chest X-ray than patients diagnosed in 2019 (P = 0.004). There was a higher percentage of latent TB infection and active TB among children in households of patients diagnosed in 2020, compared with 2019 (P = 0.001). CONCLUSIONS: The COVID-19 pandemic has caused substantial changes in TB care. TB patients diagnosed during the COVID-19 pandemic showed more extended pulmonary forms. The increase in latent TB infection and active TB in children of patient households could reflect increased household transmission due to anti-COVID-19 measures.
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COVID-19 , Tuberculosis , Niño , Trazado de Contacto , Humanos , Pandemias , Estudios Retrospectivos , SARS-CoV-2 , España/epidemiología , Tuberculosis/diagnóstico , Tuberculosis/tratamiento farmacológico , Tuberculosis/epidemiologíaRESUMEN
OBJECTIVE: Information from critically ill coronavirus disease 2019 (COVID-19) patients is limited and in many cases coming from health systems approaches different from the national public systems existing in most countries in Europe. Besides, patient follow-up remains incomplete in many publications. Our aim is to characterize acute respiratory distress syndrome (ARDS) patients admitted to a medical critical care unit (MCCU) in a referral hospital in Spain. DESIGN: Retrospective case series of consecutive ARDS COVID-19 patients admitted and treated in our MCCU. SETTING: 36-bed MCCU in referral tertiary hospital. PATIENTS AND PARTICIPANTS: SARS-CoV-2 infection confirmed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay of nasal/pharyngeal swabs. INTERVENTIONS: None MAIN VARIABLES OF INTEREST: Demographic and clinical data were collected, including data on clinical management, respiratory failure, and patient mortality. RESULTS: Forty-four ARDS COVID-19 patients were included in the study. Median age was 61.50 (53.25 - 67) years and most of the patients were male (72.7%). Hypertension and dyslipidemia were the most frequent co-morbidities (52.3 and 36.4% respectively). Steroids (1mg/Kg/day) and tocilizumab were administered in almost all patients (95.5%). 77.3% of the patients needed invasive mechanical ventilation for a median of 16 days [11-28]. Prone position ventilation was performed in 33 patients (97%) for a median of 3 sessions [2-5] per patient. Nosocomial infection was diagnosed in 13 patients (29.5%). Tracheostomy was performed in ten patients (29.4%). At study closing all patients had been discharged from the CCU and only two (4.5%) remained in hospital ward. MCCU length of stay was 18 days [10-27]. Mortality at study closing was 20.5% (n 9); 26.5% among ventilated patients. CONCLUSIONS: The seven-week period in which our MCCU was exclusively dedicated to COVID-19 patients has been challenging. Despite the severity of the patients and the high need for invasive mechanical ventilation, mortality was 20.5%.
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COVID-19/complicaciones , Síndrome de Dificultad Respiratoria/etiología , SARS-CoV-2 , Anciano , Anticuerpos Monoclonales Humanizados/uso terapéutico , COVID-19/epidemiología , COVID-19/mortalidad , COVID-19/terapia , Comorbilidad , Enfermedad Crítica , Infección Hospitalaria/epidemiología , Diabetes Mellitus/epidemiología , Dislipidemias/epidemiología , Femenino , Humanos , Hipertensión/epidemiología , Tiempo de Internación , Masculino , Persona de Mediana Edad , Pronóstico , Posición Prona , Respiración Artificial/métodos , Respiración Artificial/estadística & datos numéricos , Síndrome de Dificultad Respiratoria/mortalidad , Estudios Retrospectivos , España/epidemiología , Esteroides/uso terapéutico , Traqueostomía/estadística & datos numéricosRESUMEN
OBJECTIVES: During the last decade, some changes in the epidemiology of invasive infections have been reported; however, specific studies with patient-level data are scarce. The aim of this study was to describe and evaluate the epidemiologic changes in bloodstream infections (BSI) during the last decade in Andalucía, Spain. METHODS: Data from two prospective cohorts of BSI in adults with the same methodology performed 10 years apart in 11 hospitals (eight tertiary and three community) in Andalucía, Spain, were compared; the 2006-7 cohort study was performed between October 2006 and March 2007, and the 2016-17 cohort study was performed between October 2016 and March 2017. Population-based incidence rates were calculated and extrapolated for 1 year. Relative risk ratios were calculated between the 2 periods. Multivariate analyses were performed by logistic regression. RESULTS: Overall, 1262 episodes of BSI were included, 563 (44.6%) in 2006-7 and 699 (55.3%) in 2016-17. Multivariate models selected the following changes in patients' features in 2016-17, after controlling for type of acquisition: higher age (odds ratio (OR) = 1.02; 95% confidence interval [CI] 1.01-1.03), lower urinary catheter (OR = 0.37; 95% CI, 0.26-0.48) and lower Pitt score (OR = 0.76; 95% CI, 0.71-0.82). Adjusted estimations considering patients' features and exposure to procedures showed a reduction in coagulase-negative staphylococci (OR = 0.47; 95% CI, 0.32-0.69), and an increase in Proteus spp. (OR = 3.12; 95% CI, 1.18-8.23) and Candida spp. (OR = 3.01; 95% CI, 1.03-8.86). CONCLUSIONS: We found relevant epidemiologic changes in BSI in our area, including rates, frequency of acquisition types, changes in patient's profiles and aetiologic agents.
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Infecciones Bacterianas/epidemiología , Micosis/epidemiología , Sepsis/microbiología , Anciano , Infecciones Bacterianas/mortalidad , Femenino , Humanos , Incidencia , Modelos Logísticos , Masculino , Persona de Mediana Edad , Mortalidad , Micosis/mortalidad , Estudios Prospectivos , Factores de Riesgo , Sepsis/epidemiología , Sepsis/mortalidad , España/epidemiologíaRESUMEN
Objective: Information from critically ill coronavirus disease 2019 (COVID-19) patients is limited and in many cases coming from health systems approaches different from the national public systems existing in most countries in Europe. Besides, patient follow-up remains incomplete in many publications. Our aim is to characterize acute respiratory distress syndrome (ARDS) patients admitted to a medical critical care unit (MCCU) in a referral hospital in Spain. Design: Retrospective case series of consecutive ARDS COVID-19 patients admitted and treated in our MCCU. Setting: 36-bed MCCU in referral tertiary hospital. Patients and participants: SARS-CoV-2 infection confirmed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay of nasal/pharyngeal swabs. Interventions: None. Main variables of interest: Demographic and clinical data were collected, including data on clinical management, respiratory failure, and patient mortality. Results: Forty-four ARDS COVID-19 patients were included in the study. Median age was 61.50 (53.25 - 67) years and most of the patients were male (72.7%). Hypertension and dyslipidemia were the most frequent co-morbidities (52.3 and 36.4% respectively). Steroids (1mg/Kg/day) and tocilizumab were administered in almost all patients (95.5%). 77.3% of the patients needed invasive mechanical ventilation for a median of 16 days [11-28]. Prone position ventilation was performed in 33 patients (97%) for a median of 3 sessions [2-5] per patient. Nosocomial infection was diagnosed in 13 patients (29.5%). Tracheostomy was performed in ten patients (29.4%). At study closing all patients had been discharged from the CCU and only two (4.5%) remained in hospital ward. MCCU length of stay was 18 days [10-27]. Mortality at study closing was 20.5% (n 9); 26.5% among ventilated patients. Conclusions: The seven-week period in which our MCCU was exclusively dedicated to COVID-19 patients has been challenging. Despite the severity of the patients and the high need for invasive mechanical ventilation, mortality was 20.5%.
Objetivo: La información de pacientes críticos con enfermedad por coronavirus 2019 (COVID-19) es limitada y, en muchos casos, proviene de sistemas de salud diferentes a la organización pública de la mayoría de los países de Europa. Además, el seguimiento del paciente sigue siendo incompleto en muchas publicaciones. Nuestro objetivo es caracterizar a los pacientes con síndrome de distres respiratorio agudo (SDRA) ingresados en una unidad de cuidados críticos médicos (MCCU) en un hospital de referencia en España. Diseño: Serie retrospectiva de casos de pacientes consecutivos con SDRA por COVID-19 ingresados y tratados en nuestra MCCU. Lugar: UCC de 36 camas en un hospital terciario de referencia. Pacientes y participantes: Infección por SARS-CoV-2 confirmada por ensayo en tiempo real de la transcriptasa inversa-reacción en cadena de la polimerasa (RT-PCR) de hisopos nasales/faríngeos. Intervenciones: Ninguna. Principales variables de interés: Se recopilaron datos demográficos y clínicos, incluidos datos sobre manejo clínico, insuficiencia respiratoria y mortalidad del paciente. Resultados: Cuarenta y cuatro pacientes con SDRA por COVID-19 fueron incluidos en el estudio. La mediana de edad fue de 61.50 (53.25 - 67) años y la mayoría de los pacientes eran hombres (72.7%). La hipertensión y la dislipidemia fueron las comorbilidades más frecuentes (52,3 y 36,4%, respectivamente). Se administraron esteroides (1mg/kg/día) y tocilizumab en casi todos los pacientes (95,5%). El 77,3% de los pacientes necesitaron ventilación mecánica invasiva durante una mediana de 16 días [11-28]. La ventilación en posición prono se realizó en 33 pacientes (97%) con una mediana de 3 sesiones [2-5] por paciente. Se diagnosticó una infección nosocomial en 13 pacientes (29,5%). La traqueotomía se realizó en diez pacientes (29,4%). Al cierre del estudio, todos los pacientes habían sido dados de alta de la MCCU y solo dos permanecían hospitalizados. La estancia en MCCU fue de 18 días [10-27]. La mortalidad al cierre del estudio fue del 20,5% (n 9); 26.5% para pacientes ventilados. Conclusiones: El período de siete semanas en el que nuestra MCCU se dedicó exclusivamente a pacientes con COVID-19 ha sido un gran desafío. A pesar de la gravedad de los pacientes y la elevada necesidad de ventilación mecánica invasiva, la mortalidad fue del 20,5%.
RESUMEN
Over the last decades, significant improvements in the clini- cal management of patients with cirrhosis have increased their life expectancy. Thus, indications for surgical procedures other than liver transplantation are becoming more frequent. However, patients with advanced liver disease are at high risk of perioperative morbidity and mortality. This is the consequence of multiple factors that include the presence of portal hypertension, alterations on hemostasis and coagulation, the immune dysfunction that entails an increased risk of infections, and the impaired synthesis of proteins that impacts on the nutritional status and the wound healing. Surgical outcomes are not only determined by the severity of the liver disease, but also by the type of surgery and the presence of other comorbidities. Different models to predict mortality have been proposed, including the MELD score, the Child-Pugh classification, the hepatic venous pressure gradient, and the Mayo postoperative mortality risk calculator, among others. Multidisciplinary committees including surgeons, anesthesiologists, hepatologists, critical care physicians and other specialties involved in each case, should assess individually the risk-benefit of the surgical procedure, also considering patient`s expectations and will.
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Hipertensión Portal , Cirrosis Hepática , Trasplante de Hígado , Medición de Riesgo , Humanos , Cirrosis Hepática/complicaciones , Presión Portal , Periodo PreoperatorioRESUMEN
BACKGROUND: Chagas disease (CD) continues to be a neglected infectious disease with one of the largest burdens globally. Despite the modest cure rates in adult chronic patients and its safety profile, benznidazole (BNZ) is still the drug of choice. Its current recommended dose is based on nonrandomized studies, and efficacy and safety of the optimal dose of BNZ have been scarcely analyzed in clinical trials. METHODS/DESIGN: MULTIBENZ is a phase II, randomized, noninferiority, double-blind, multicenter international clinical trial. A total of 240 patients with Trypanosoma CD in the chronic phase will be recruited in four different countries (Argentina, Brazil, Colombia, and Spain). Patients will be randomized to receive BNZ 150 mg/day for 60 days, 400 mg/day for 15 days, or 300 mg/day for 60 days (comparator arm). The primary outcome is the efficacy of three different BNZ therapeutic schemes in terms of dose and duration. Efficacy will be assessed according to the proportion of patients with sustained parasitic load suppression in peripheral blood measured by polymerase chain reaction. The secondary outcomes are related to pharmacokinetics and drug tolerability. The follow-up will be 12 months from randomization to end of study participation. Recruitment was started in April 2018. CONCLUSION: This is a clinical trial conducted for the assessment of different dose schemes of BNZ compared with the standard treatment regimen for the treatment of CD in the chronic phase. MULTIBENZ may help to clarify which is the most adequate BNZ regimen in terms of efficacy and safety, predicated on sustained parasitic load suppression in peripheral blood. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03191162. Registered on 19 June 2017.
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Enfermedad de Chagas/tratamiento farmacológico , Enfermedades Desatendidas/parasitología , Nitroimidazoles/uso terapéutico , Tripanocidas/uso terapéutico , Trypanosoma cruzi/aislamiento & purificación , Adulto , Cuidados Posteriores , Argentina/epidemiología , Brasil/epidemiología , Estudios de Casos y Controles , Enfermedad de Chagas/parasitología , Enfermedad Crónica , Colombia/epidemiología , Método Doble Ciego , Femenino , Humanos , Masculino , Nitroimidazoles/farmacocinética , Carga de Parásitos/estadística & datos numéricos , Seguridad , España/epidemiología , Resultado del Tratamiento , Tripanocidas/farmacocinética , Trypanosoma cruzi/genéticaRESUMEN
Bed bugs are now one of the most prevalent human-associated, blood-feeding pests in the urban world, but few studies of their association with human pathogens have been conducted since their resurgence. Here, we used PCR to screen samples of field-collected bed bugs (Cimex spp.) for the presence of Rickettsia bacteria and we describe the first detection of an uncharacterized Rickettsia in Cimex lectularius in nature. Rickettsia was detected in 5/39 (12.8%) of the bed bug samples tested. In particular, three pools from the USA and two individual insects from the UK were positive for Rickettsia DNA. Sequencing and analysis of a fragment of the citrate synthase gene (gltA) from positive samples from each country revealed that the Rickettsia detected in both were identical and were closely related to a Rickettsia previously detected in the rat flea Nosopsyllus laeviceps. Additional experiments indicated that the Rickettsia localizes to multiple tissues in the bed bug and reaches high titres. Attempts were made to infect mammalian cells in culture but these efforts were inconclusive. Our findings suggest that Rickettsia are secondary endosymbionts of bed bugs and have potential implications for both bed bug control and public health. However, further investigation is required to determine the pathogenicity of this Rickettsia, its transmission mechanisms, and its contributions to bed bug physiology.
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Adalimumab/efectos adversos , Erupciones por Medicamentos/etiología , Infliximab/efectos adversos , Piel/patología , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Adulto , Enfermedad de Crohn/tratamiento farmacológico , Erupciones por Medicamentos/patología , Humanos , Linfocitos , Masculino , Psoriasis/tratamiento farmacológicoAsunto(s)
Lentigo/inducido químicamente , Inhibidores de Fosfodiesterasa/efectos adversos , Psoriasis/tratamiento farmacológico , Talidomida/análogos & derivados , Humanos , Lentigo/patología , Masculino , Persona de Mediana Edad , Inhibidores de Fosfodiesterasa/uso terapéutico , Psoriasis/complicaciones , Piel/patología , Talidomida/efectos adversos , Talidomida/uso terapéuticoAsunto(s)
Alcoholismo/complicaciones , Lipomatosis Simétrica Múltiple/complicaciones , Lipomatosis Simétrica Múltiple/cirugía , Biopsia , Humanos , Lipomatosis Simétrica Múltiple/diagnóstico por imagen , Pruebas de Función Hepática , Imagen por Resonancia Magnética , Masculino , Persona de Mediana EdadRESUMEN
AIM: To explore the effect of hospital's characteristics in the proportion of obstetric interventions (OI) performed in singleton fullterm births (SFTB) in Catalonia (2010-2014), while incentives were employed to reduce C-sections. METHODS: Data about SFTB assisted at 42 public hospitals were extracted from the dataset of hospital discharges. Hospitals were classified according to the level of complexity, the volume of births attended, and the adoption of a non-medicalized delivery (NMD) strategy. The annual average change in the percentage for OI was calculated based on Poisson regression models. RESULTS: The rate of OI (35% of all SFTB) including C-sections (20.6%) remained stable through the period. Hospitals attending less complex cases had a lower average of OI, while hospitals attending lower volumes had the highest average. Higher levels of complexity increased the use of C-sections (+4% yearly) and forceps (+16%). The adoption of the NMD strategy decreased the rate of C-sections. CONCLUSIONS: The proportion of OI, including C-sections, remained stable in spite of public incentives to reduce them. The adoption of the NMD strategy could help in decreasing the rate of OI. To reduce the OI rate, new strategies should be launched as the development of low-risk pregnancies units, alignment of incentives and hospital payment, increased value of incentives and encouragement of a cultural shift towards non-medicalized births.
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Cesárea/estadística & datos numéricos , Política de Salud , Nacimiento a Término , Femenino , Hospitales Públicos , Humanos , Recién Nacido , Embarazo , España , Encuestas y CuestionariosRESUMEN
Despite its toxicity and low efficacy in the chronic phase, benznidazole is the drug of choice in Chagas disease. Scarce information about pharmacokinetics and pharmacodynamics of benznidazole has been published. We performed a phase I, open-label, nonrandomized pharmacokinetic study of benznidazole (Abarax) conducted with 8 healthy adult volunteers at the Infectious Diseases Department of the Vall d'Hebron University Hospital (Barcelona, Spain). The separation and detection of benznidazole were performed on a Waters Acquity ultraperformance liquid chromatography system (UPLC) coupled with a Waters Xevo TQ MS triple quadrupole mass spectrometer. The pharmacokinetic parameters were calculated based on a noncompartmental body model using Phoenix WinNonlin version 6.3 software. Furthermore, computational simulations were calculated for the multiple-dose administration at two dose regimens: 100 mg of benznidazole administered every 8 h and 150 mg of benznidazole administered every 12 h. After benznidazole administration, the median area under the concentration-time curve from time zero to time t (AUC0-t ) and extrapolated to infinity (AUC0-∞) were about 46.4 µg · h/ml and 48.4 µg · h/ml, respectively. Plasma benznidazole concentrations peaked at 3.5 h, with maximal concentrations of 2.2 µg/ml, and benznidazole exhibited a terminal half-life of 12.1 h. The median maximum concentration (Cmax) of benznidazole was lower in men than in women (1.6 versus 2.9 µg/ml), and median volume of distribution (V) as a function of bioavailability (F) was higher in men than in women (125.9 versus 88.6 liters). In conclusion, dose regimens (150 mg/12 h or 100 mg/8 h) reached a steady-state range concentration above of the minimum experimental therapeutic dose. Sex differences in the benznidazole pharmacokinetics were observed; mainly, men had lower Cmax and higher V/F than women.
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Modelos Estadísticos , Nitroimidazoles/farmacocinética , Tripanocidas/farmacocinética , Adolescente , Adulto , Área Bajo la Curva , Disponibilidad Biológica , Índice de Masa Corporal , Enfermedad de Chagas/tratamiento farmacológico , Enfermedad de Chagas/parasitología , Esquema de Medicación , Cálculo de Dosificación de Drogas , Femenino , Semivida , Voluntarios Sanos , Humanos , Masculino , Nitroimidazoles/sangre , Tripanocidas/sangreAsunto(s)
Carnívoros/microbiología , Carnívoros/virología , Conservación de los Recursos Naturales , Lynx , Animales , Prevalencia , EspañaRESUMEN
INTRODUCTION: Cognitive impairment (CI) affects 40-65% of patients with multiple sclerosis (MS). Few studies address telematic cognitive stimulation (TCS) in MS. The objective of this study is to evaluate the efficacy and impact of telestimulation or distance cognitive stimulation (TCS), with and without the support of face-to-face cognitive stimulation (FCS) in cognitive impairment in MS. METHODS: Multicentre, prospective, randomised, controlled study. We will include 98 MS patients with EDSS ≤ 6, symbol digit modality test (SDMT) ≤ Pc 25, and Multiple Sclerosis Neuropsychological Screening Questionnaire (MSNQ) > 26 points. Patients will be randomised into 3 groups, a TCS group, a mixed TCS/FCS group, and a control group. CS is performed 3 days a week for 3 months. Processing speed, memory, attention, and executive functions will be rehabilitated. FCS will include ecological exercises and strategies. EDSS and a cognitive evaluation (SDMT, CTMT, PASAT, and TAVEC), MSNQ, psychological impact scales (MSIS), and depression (BDI) will be carried out, baseline, postrehabilitation, and also 6 and 12 months later, to evaluate the effect of CS in the longer term. CONCLUSION: This study could help to establish the usefulness of TCS or, in its absence, TCS with face-to-face help for CI in MS. The interest lies in the clear benefits of remote rehabilitation in the daily life of patients.