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1.
BMC Pediatr ; 24(1): 418, 2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-38951759

RESUMO

PURPOSE: Metabolic bone disease of prematurity (MBDP) remains a significant cause of morbidity in extremely premature newborns. In high-risk patients, suspected diagnosis and subsequent treatment modifications, with limitations in terms of sensitivity and specificity, rely on low phosphorus levels and/or high levels of alkaline phosphatase (ALP). We investigated the potential of fibroblast growth factor-23 (FGF23) as an early marker for MBDP when measured at 3-4 weeks of life in at-risk patients. METHODS: A single-center prospective observational non-interventional study including preterm newborns of both sexes, with a gestational age of less than 32 weeks and/or a birth weight of less than 1500 g. In the standard biochemical screening for MBDP performed between 3 and 4 weeks of life within a nutritional profile, the determination of FGF23 was included along with other clinical and metabolic studies. The study was conducted at Marqués de Valdecilla University Hospital in Santander, Spain, from April 2020 to March 2021. Participants provided informed consent. Biochemical analyses were conducted using various platforms, and follow-up evaluations were performed at the discretion of neonatologists. Patients at high risk for MBDP received modifications in treatment accordingly. The sample was descriptively analyzed, presenting measures of central tendency and dispersion for continuous variables, and absolute numbers/percentages for categorical ones. Tests used included t-tests, Mann‒Whitney U tests, chi-square tests, logistic regressions, Pearson correlation, and ROC curve analysis (IBM SPSS Statistics version 19). Significance level: P < 0.05. RESULTS: In the study involving 25 at-risk premature newborns, it was found that 20% (n = 5) were diagnosed with MBDP. Three of these patients (60%) were identified as high-risk based on standard biochemical evaluation at 3-4 weeks of age, while the other two patients (40%) were diagnosed in subsequent weeks. However, in all 5 patients, measurement of FGF23 levels would allow for early identification and optimization of treatment before other markers become altered. Low levels of FGF23 at 3-4 weeks, even with normal phosphorus and ALP levels, indicate the need for modifications in nutritional supplementation. CONCLUSIONS: MBDP remains a significant concern in extremely premature newborns. Current diagnostic methods rely on limited biochemical markers. Early detection of low FGF23 levels enables timely interventions, potentially averting demineralization.


Assuntos
Biomarcadores , Doenças Ósseas Metabólicas , Fator de Crescimento de Fibroblastos 23 , Fatores de Crescimento de Fibroblastos , Humanos , Recém-Nascido , Feminino , Fatores de Crescimento de Fibroblastos/sangue , Biomarcadores/sangue , Estudos Prospectivos , Masculino , Doenças Ósseas Metabólicas/sangue , Doenças Ósseas Metabólicas/diagnóstico , Doenças Ósseas Metabólicas/etiologia , Doenças do Prematuro/diagnóstico , Doenças do Prematuro/sangue , Recém-Nascido Prematuro
2.
Sci Total Environ ; 944: 173915, 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-38871328

RESUMO

The 2021 Tajogaite eruption in La Palma (Canary Islands, Spain) emitted vast volumes of lava during 85 days, which reached the ocean in several occasions at the western flank of the island. Most of these flows merged to create a primary lava delta, covering an area of 48 ha, with an additional 30 ha underwater. Here we characterize the effects of the lava-seawater interaction on the surrounding marine environment. The area was sampled during two multidisciplinary oceanographic cruises: the first one comprised the days before the lava reached the ocean and after the first contact; and the second took place a month later, when the lava delta was already formed but still receiving lava inputs. Physical-chemical anomalies were found in the whole water column at different depths up to 300 m in all measured parameters, such as turbidity (+9 NTU), dissolved oxygen concentration (-17.17 µmol kg-1), pHT25 (-0.1), and chlorophyll-a concentration (-0.33 mg m-3). Surface temperature increased up to +2.3 °C (28.5 °C) and surface salinity showed increases and decreases of -1.01 and +0.70, respectively, in a radius of 4 km around the lava delta. In the water column, the heated waters experimented a lava-induced upwelling, bringing deeper, nutrient-rich waters to shallower depths; however, this feature did not trigger any phytoplankton bloom. In fact, integrated chlorophyll-a showed an abrupt decrease of -41 % in just two days and -69 % a month later, compared to prior conditions. The chlorophyll-a depletion reached a distance larger than 2.5 km (not delimited).


Assuntos
Clorofila , Água do Mar , Água do Mar/química , Espanha , Clorofila/análise , Monitoramento Ambiental , Erupções Vulcânicas , Clorofila A , Salinidade , Fitoplâncton
3.
Talanta ; 277: 126350, 2024 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-38843772

RESUMO

This work reports the development and application of a disposable amperometric sensor built on magnetic microcarriers coupled to an Express PCR strategy to amplify a specific DNA fragment of the chloroplast trnH-psbA. The procedure involves the selective capture of a 68-mer synthetic target DNA (or unmodified PCR products) through sandwich hybridization with RNA capture probe-modified streptavidin MBs and RNA signaling probes, labeled using antibodies specific to the heteroduplexes and secondary antibodies tagged with horseradish peroxidase. Amperometric measurements were performed on screen-printed electrodes using the H2O2/hydroquinone system. Achieving a LOD of 3 pM for the synthetic target, it was possible to detect 2.5 pg of peanut DNA and around 10 mg kg-1 of peanut in binary mixtures (defatted peanut flours prepared in spelt wheat). However, the detectability decreased between 10 and 1000 times in processed samples depending on the treatment. The Express PCR-bioplatform was applied to the detection of peanut traces in foodstuff.

4.
Artigo em Inglês | MEDLINE | ID: mdl-38896382

RESUMO

INTRODUCION: The concept of a window of opportunity in hidradenitis suppurativa (HS) management suggests that early initiation of biological therapy leads to better outcomes, though its timing remains uncertain. METHODS: We conducted a retrospective observational multicenter study, including consecutive patients with moderate to severe HS who initiated secukinumab treatment following prior failure with systemic antibiotics or adalimumab. Therapeutic burden was defined as the sum of previous systemic treatment cycles and previous major surgical interventions for HS. Patients were followed up for 24 weeks. Main outcomes were safety and effectiveness, assessed through the proportion of patients achieving HS Clinical Response (HiSCR) and a 55% reduction in International HS Severity Score System (IHS4-55). Additionally, potential predictors of response to secukinumab were studied. Analysis was performed on an intention-to-treat basis. RESULTS: A total of 67 patients (33 men, 34 women) were included, with a mean age of 41.55 (11.94) years and a mean baseline IHS4 of 17.88 (11.13). The mean therapeutic burden was 6.06 (3.49). At week 24, 10.45% (7/67) of patients experienced adverse events, with three leading to treatment discontinuation. At week 24, 41.79% (28/67) of patients achieved HiSCR, and 44.78% (30/67) of patients achieved IHS4-55. HiSCR could not be calculated in 12 patients with a baseline AN count < 3. A lower therapeutic burden was significantly associated with a higher likelihood of achieving HiSCR and IHS4-55 at week 24. CONCLUSIONS: Secukinumab showed safety and efficacy in real-world patients with HS, and the inverse correlation found between therapeutic burden and treatment response supports the concept of a window of opportunity, offering insights into its timing.

5.
Chemosphere ; 362: 142541, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38851497

RESUMO

Glyphosate is the most widely utilized herbicide worldwide due to its effectiveness in controlling agricultural weeds. However, its persistence in aquatic ecosystems has raised concerns about the well-being of non-target organisms such as fish. This study aimed to evaluate the effects of chronic exposure (21 days) to glyphosate or its formulated product Roundup Transorb R®, at an environmentally relevant concentration permitted by regulations in certain countries (65 µg/L of glyphosate), on the locomotor activity and reproductive success of the fish Jenynsia lineata, as well as on the morphology/development and locomotor activity of its offspring, as intergenerational effects. Neither the pure nor formulated herbicide altered the distance traveled and velocity of adult fish exposed to the herbicide (F0), but they negatively affected reproductive success, decreasing the percentage of positive response to the presence of the female, reducing the number of gravid females, causing abortions, and lowering offspring survival (F1). In the F1 generation, a decrease in weight and length was noted along with developmental abnormalities in both treatment groups (pure or formulated glyphosate), with the formulation causing more harm. Observed developmental abnormalities included muscle atrophy, ascites, pigmentary disorders, vertebral agenesis, spinal deviation, and exophthalmia. Furthermore, parental exposure to pure glyphosate led to an increase in the distance traveled and velocity of F1 (hyperlocomotion), whereas exposure to the formulated product resulted in a decrease in these behaviors (hypolocomotion) of F1. These findings highlight the toxic effects of glyphosate at very low concentrations, although varying between pure and formulated, and demonstrate the intergenerational consequences of herbicide exposure, underscoring the risk to the survival of fish offspring in glyphosate-contaminated environments.

6.
Biomolecules ; 14(5)2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38785966

RESUMO

INTRODUCTION: Urine free cortisol measurements are routinely performed to evaluate hypercortisolism. Despite their analytical inaccuracy, immunoassay-based methods are frequently used. Advances in liquid chromatography-high-resolution mass spectrometry (LC-HRMS) facilitate the incorporation of powerful diagnostic tools into clinical laboratories. In addition to its high analytical specificity and simultaneous analysis of different metabolites, accurate mass measurement allows for untargeted compound identification, which may help to identify clinically relevant metabolites or drugs. METHODS: The present study aimed to validate a simple routine LC-HRMS method to quantify cortisol, cortisone, 6ß-hydroxycortisol, and 18-hydroxycortisol simultaneously in human urine. Additionally, the study also validated a GC-MS method for the same steroids, evaluated their cross-reactivity with commercial cortisol immunoassays, and quantified the 24 h urine excretion in patients under clinical suspicion or follow-up for hypercortisolism. RESULTS: The LC-HRMS method involved liquid-liquid extraction using dichloromethane, micro-LC for chromatographic separation and detection using the accurate masses of the steroids, and simultaneous high-resolution full scan acquisition. The method presented acceptable linearity, precision, and accuracy. Significant interference from 6ß-hydroxycortisol and cortisone was demonstrated in the cortisol immunoassays, which impacted their reliability in the follow-up of patients with hypercortisolism and significant changes in these cortisol metabolites (i.e., due to drug-induced changes in CYP3A4 activity). CONCLUSION: A rapid and accurate routine LC-HRMS method was validated, which is useful for the evaluation of hypercortisolism and other disorders of glucocorticoid and mineralocorticoid metabolism.


Assuntos
Cortisona , Cromatografia Gasosa-Espectrometria de Massas , Hidrocortisona , Humanos , Hidrocortisona/urina , Hidrocortisona/análogos & derivados , Cortisona/urina , Cromatografia Gasosa-Espectrometria de Massas/métodos , Cromatografia Líquida/métodos , Glucocorticoides/urina , Síndrome de Cushing/urina , Síndrome de Cushing/diagnóstico , Masculino , Feminino
7.
Am J Transplant ; 24(2): 213-221, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37739346

RESUMO

One concern about the use of normothermic regional perfusion (NRP) in controlled donation after the circulatory determination of death (cDCD) is that the brain may be perfused. We aimed to demonstrate that certain technical maneuvers preclude such brain perfusion. A nonrandomized trial was performed on cDCD donors. In abdominal normothermic regional perfusion (A-NRP), the thoracic aorta was blocked with an intra-aortic occlusion balloon. In thoracoabdominal normothermic regional perfusion (TA-NRP), the arch vessels were clamped and the cephalad ends vented to the atmosphere. The mean intracranial arterial blood pressure (ICBP) was invasively measured at the circle of Willis. Ten cDCD donors subject to A-NRP or TA-NRP were included. Mean ICBP and mean blood pressure at the thoracic and the abdominal aorta during the circulatory arrest were 17 (standard deviation [SD], 3), 17 (SD, 3), and 18 (SD, 4) mmHg, respectively. When A-NRP started, pressure at the abdominal aorta increased to 50 (SD, 13) mmHg, while the ICBP remained unchanged. When TA-NRP was initiated, thoracic aorta pressure increased to 71 (SD, 18) mmHg, but the ICBP remained unmodified. Recorded values of ICBP during NRP were 10 mmHg. In conclusion, appropriate technical measures applied during NRP preclude perfusion of the brain in cDCD. This study might help to expand NRP and increase the number of organs available for transplantation.


Assuntos
Preservação de Órgãos , Obtenção de Tecidos e Órgãos , Humanos , Morte , Sobrevivência de Enxerto , Preservação de Órgãos/métodos , Perfusão/métodos , Estudos Prospectivos , Doadores de Tecidos
8.
Nat Biomed Eng ; 2023 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-37749309

RESUMO

The threat of spillovers of coronaviruses associated with the severe acute respiratory syndrome (SARS) from animals to humans necessitates vaccines that offer broader protection from sarbecoviruses. By leveraging a viral-genome-informed computational method for selecting immune-optimized and structurally engineered antigens, here we show that a single antigen based on the receptor binding domain of the spike protein of sarbecoviruses elicits broad humoral responses against SARS-CoV-1, SARS-CoV-2, WIV16 and RaTG13 in mice, rabbits and guinea pigs. When administered as a DNA immunogen or by a vector based on a modified vaccinia virus Ankara, the optimized antigen induced vaccine protection from the Delta variant of SARS-CoV-2 in mice genetically engineered to express angiotensin-converting enzyme 2 and primed by a viral-vector vaccine (AZD1222) against SARS-CoV-2. A vaccine formulation incorporating mRNA coding for the optimized antigen further validated its broad immunogenicity. Vaccines that elicit broad immune responses across subgroups of coronaviruses may counteract the threat of zoonotic spillovers of betacoronaviruses.

9.
Int J Dermatol ; 62(10): 1300-1303, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37548251

RESUMO

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory disease that negatively impacts the quality of life of patients. It presents as deep-seated nodules, abscesses, fistulae, sinus tracts, and scars in the axilla, inguinal area, submammary folds, and perianal area. Recently, two phenotypes have been described: a follicular phenotype and an inflammatory phenotype. Numerous medical treatments are available for hidradenitis suppurativa, with particular importance of antitumor necrosis factor antibodies. Due to the association of HS with other conditions with a pro-inflammatory state, particularly Crohn's disease, it has been suggested that azathioprine may have a role in the treatment of HS. OBJECTIVE: To assess the effectiveness of azathioprine monotherapy in patients with moderate-severe HS. METHODS: We retrospectively studied patients with HS treated with azathioprine in monotherapy. We performed both clinical and ultrasound evaluation at baseline as well as in the follow-up visits. Their baseline score on the iHS4 and DLQI scales and 12-16 weeks after starting the treatment were compared. We also registered the number of patients who achieved HiSCR. RESULTS: Six patients presented significant improvement, reducing their score in iHS4 and DLQI scales and achieving HiSCR. Another patient had clinical improvement, meaning reduction in iHS4 and DLQI, but without achieving HiSCR. Two patients stopped the treatment before week 12 because of adverse events. The remaining two patients presented no improvement. The median (Q3-Q1) baseline iHS4 score was 6 (12-6), and follow-up iHS4 score, 4 (6-2), being these differences statistically significant (P = 0.006). Median (Q3-Q1) baseline DLQI scores and 12-16 weeks after treatment were 17 (23-11) and 14 (18-9) although statistically nonsignificant (P = 0.099). CONCLUSION: We present a case series of 11 patients treated with azathioprine with good clinical and ultrasonographic response. We suggest that azathioprine may benefit a certain patient profile with the inflammatory phenotype.


Assuntos
Hidradenite Supurativa , Humanos , Hidradenite Supurativa/complicações , Hidradenite Supurativa/tratamento farmacológico , Azatioprina/uso terapêutico , Estudos Retrospectivos , Qualidade de Vida , Inflamação/complicações , Índice de Gravidade de Doença , Resultado do Tratamento
10.
Int J Pharm ; 642: 123194, 2023 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-37394160

RESUMO

Metabolic syndrome is a collection of abnormalities, including at least three of the following insulin resistance, hypertension, dyslipidemia, type 2 diabetes, obesity, inflammation, and non-alcoholic fatty liver disease. 3D printed solid dosage forms have emerged as a promising tool enabling the fabrication of personalized medicines and offering solutions that cannot be achieved by industrial mass production. Most attempts found in the literature to manufacture polypills for this syndrome contain just two drugs. However, most fixed-dose combination (FDC) products in clinical practice required the use of three or more drugs. In this work, Fused deposition modelling (FDM) 3D printing technology coupled with hot-melt extrusion (HME) has been successfully applied in the manufacture of polypills containing nifedipine (NFD), as an antihypertensive drug, simvastatin (SMV), as an antihyperlipidemic drug, and gliclazide (GLZ) as an antiglycemic drug. Hanssen solubility parameters (HSPs) were utilized as predictors to guide the formation of amorphous solid dispersion between drug and polymer to ensure miscibility and enhanced oral bioavailability. The HSP varied from 18.3 for NFD, 24.6 for SMV, and 7.0 for GLZ while the total solubility parameter for the excipient mixture was 27.30.5. This allowed the formation of an amorphous solid dispersion in SMV and GLZ 3D printed tablets compared to NFD which was partially crystalline. Popypill showed a dual release profile combining a faster SMV release (< 6h) with a 24 h sustained release for NDF and GLZ. This work demonstrated the transformation of FDC into dynamic dose-personalized polypills.


Assuntos
Diabetes Mellitus Tipo 2 , Síndrome Metabólica , Humanos , Liberação Controlada de Fármacos , Tecnologia Farmacêutica , Síndrome Metabólica/tratamento farmacológico , Solubilidade , Comprimidos/química , Impressão Tridimensional
11.
Transplantation ; 107(11): 2415-2423, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37389647

RESUMO

BACKGROUND: Controlled donation after circulatory death (cDCD) has increased the number of lung donors significantly. The use of abdominal normothermic regional perfusion (A-NRP) during organ procurement is a common practice in some centers due to its benefits on abdominal grafts. This study aimed to assess whether the use of A-NRP in cDCD increases the frequency of bronchial stenosis in lung transplant (LT) recipients. METHODS: A single-center, retrospective study including all LTs was performed between January 1, 2015, and August 30, 2022. Airway stenosis was defined as a stricture that leads to clinical/functional worsening requiring the use of invasive monitoring and therapeutic procedures. RESULTS: A total of 308 LT recipients were included in the study. Seventy-six LT recipients (24.7%) received lungs from cDCD donors using A-NRP during organ procurement. Forty-seven LT recipients (15.3%) developed airway stenosis, with no differences between lung recipients with grafts from cDCD (17.2%) and donation after brain death donors (13.3%; P = 0.278). A total of 48.9% of recipients showed signs of acute airway ischemia on control bronchoscopy at 2 to 3 wk posttransplant. Acute ischemia was an independent risk factor for airway stenosis development (odds ratio = 2.523 [1.311-4.855], P = 0.006). The median number of bronchoscopies per patient was 5 (2-9), and 25% of patients needed >8 dilatations. Twenty-three patients underwent endobronchial stenting (50.0%) and each patient needed a median of 1 (1-2) stent. CONCLUSIONS: Incidence of airway stenosis is not increased in LT recipients with grafts obtained from cDCD donors using A-NRP.

13.
Pharmaceutics ; 15(6)2023 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-37376057

RESUMO

Cromoglycate (SCG) is widely used for allergy processes, and inflammatory states acting as a mast cell membrane stabilizer that inhibits the histamine and mediator release. Currently, SCG topical extemporaneous compounding formulations are prepared in hospitals and community pharmacies, as no industrial fabricated medicines are available in Spain. The stability of these formulations is unknown. Additionally, there are no clear guidelines on which concentration and vehicle are more suitable to enhance permeation across the skin. In this work, the stability of commonly prescribed topical SCG formulations in clinical practice was evaluated. Different vehicles commonly employed by pharmacists daily for formulating topical SCG were investigated (Eucerinum, Acofar Creamgel, and Beeler's base) at different concentrations, ranging from 0.2 to 2%. The stability of topical extemporaneous compounded SCG formulations can be extended for up to three months at room temperature (25 °C). Creamgel 2% formulations significantly improved the topical permeation of SCG across the skin, being 4.5-fold higher than formulations prepared with Beeler's base. The reason attributed to this performance can be related to the lower droplet size formed upon dilution in aqueous media combined with a lower viscosity, which facilitates its application and extensibility on the skin. The higher the SCG concentration in Creamgel formulations, the higher the permeability across both synthetic membranes and pig skin (p-value < 0.05). These preliminary results can be used as a guide to prompt a rational prescription of topical SCG formulations.

14.
Dermatol Ther (Heidelb) ; 13(4): 1029-1038, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36892752

RESUMO

INTRODUCTION: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease. Biologic drugs have a key role in the long-term anti-inflammatory treatment of moderate to severe patients due to their immunomodulatory properties. The aim of this study is to evaluate the effectiveness and safety of secukinumab in patients with moderate to severe HS after 16 weeks of treatment, and to explore potential predictors of clinical response to the drug. METHODS: Multicenter observational retrospective study. Patients treated with secukinumab 300 mg every 2 or 4 weeks who had completed at least 16 weeks of follow-up from nine hospitals based in southern Spain (Andalusia) were included in this study. Treatment effectiveness was assessed using the Hidradenitis Suppurativa Clinical Response (HiSCR). Information about adverse events was collected, the therapeutic burden of the patients was calculated as the summation of systemic medical treatments and surgical interventions (excluding incision and drainage) experienced until the start of secukinumab treatment. RESULTS: Forty-seven patients with severe HS were included for analysis. At week 16, 48.9% (23/47) of patients achieved HiSCR. Adverse events were present in 6.4% (3/47) of the patients. The multivariate analysis showed that female sex and, to a lesser extent, lower body mass index (BMI) and a lower therapeutic burden were potentially associated with a higher probability of HiSCR achievement. CONCLUSIONS: Favorable short-term effectiveness and safety of secukinumab in the treatment of severe HS patients were observed. Female sex, lower BMI and a lower therapeutic burden may be associated with a higher probability of achieving HiSCR.

15.
An Pediatr (Engl Ed) ; 98(2): 136.e1-136.e11, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36774296

RESUMO

Antibiotic resistance is a major threat to global health. Optimizing the use of antibiotics is a key measure to prevent and control this problem. Antimicrobial Stewardship Programs (ASPs) are designed to improve clinical outcomes, minimize adverse effects and protect patients, and to ensure the administration of cost-effective treatments. Inappropriate use of antibiotics also occurs in pediatric clinical practice. For this reason, ASPs should include specific objectives and strategies aimed at pediatricians and families. Implementing these programs requires the involvement of institutions and policy makers, healthcare providers as well as individuals, adapting them to the characteristics of each healthcare setting. Pediatric primary care (PPC) faces specific issues such as high demand and immediacy, scarce specialized professional resources, difficulties to access regular training and to obtain feedback. This requires the design of specific policies and strategies to achieve the objectives, including structural and organizational measures, improvement of the information flow and accessibility to frequent trainings. These programs should reach all health professionals, promoting regular trainings, prescription support tools and supplying diagnostic tests, with adequate coordination between health care levels. Periodic evaluations and surveillance tools are useful to assess the impact of the actions taken and to provide feedback to health providers in order to adapt and improve their clinical practice to meet ASPs objectives.


Assuntos
Gestão de Antimicrobianos , Humanos , Criança , Antibacterianos/uso terapêutico , Atenção Primária à Saúde
16.
An. pediatr. (2003. Ed. impr.) ; 98(2): 136.e1-136.e11, feb. 2023. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-215338

RESUMO

La resistencia a antibióticos supone una amenaza para la salud pública a nivel mundial. Su estrecha relación con el consumo de antibióticos hace necesaria la adopción de medidas para optimizar su uso. Los programas de optimización del uso de antibióticos (PROA) se diseñan para mejorar los resultados clínicos de los pacientes con infecciones, minimizar los efectos adversos asociados a su uso y garantizar la administración de tratamientos costo-eficientes. En la práctica clínica pediátrica el uso inadecuado de antibióticos es una realidad. Es por ello que los PROA deben incluir objetivos y estrategias específicos dirigidos a familias y pediatras. La implementación de estos programas requiere la implicación de instituciones, profesionales y población, adaptándolos a las características de cada ámbito asistencial. La atención primaria (AP) pediátrica presenta unas peculiaridades organizativas y asistenciales (hiperdemanda e inmediatez, escasos recursos profesionales especializados, dificultades en el acceso a la formación continuada y a la retroalimentación informativa) que exigen el diseño de medidas y estrategias propias para conseguir los objetivos fijados, que incluyan medidas estructurales, organizativas, de flujo de información y de formación continuada. Es necesario que estos programas alcancen a todos los profesionales, abordando la formación continuada, las herramientas de apoyo a la prescripción y el acceso a pruebas diagnósticas, con la adecuada coordinación interniveles. Se debe evaluar periódicamente el impacto de las distintas acciones en los objetivos planteados. La información generada debe revertir a los profesionales para que puedan adaptar su práctica clínica a la consecución óptima de los objetivos. (AU)


Antibiotic resistance is a major threat to global health. Optimizing the use of antibiotics is a key measure to prevent and control this problem. Antimicrobial Stewardship Programs (ASPs) are designed to improve clinical outcomes, minimize adverse effects and protect patients, and to ensure the administration of cost-effective treatments. Inappropriate use of antibiotics also occurs in pediatric clinical practice. For this reason, ASPs should include specific objectives and strategies aimed at pediatricians and families. Implementing these programs requires the involvement of institutions and policy makers, healthcare providers as well as individuals, adapting them to the characteristics of each healthcare setting. Pediatric primary care (PPC) faces specific issues such as high demand and immediacy, scarce specialized professional resources, difficulties to access regular training and to obtain feedback. This requires the design of specific policies and strategies to achieve the objectives, including structural and organizational measures, improvement of the information flow and accessibility to frequent trainings. These programs should reach all health professionals, promoting regular trainings, prescription support tools and supplying diagnostic tests, with adequate coordination between health care levels. Periodic evaluations and surveillance tools are useful to assess the impact of the actions taken and to provide feedback to health providers in order to adapt and improve their clinical practice to meet ASPs objectives. (AU)


Assuntos
Humanos , Antibacterianos/uso terapêutico , Resistência Microbiana a Medicamentos , Gestão de Antimicrobianos , Atenção Primária à Saúde , Pediatria
17.
Transplantation ; 107(3): 703-708, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36226852

RESUMO

BACKGROUND: The benefits of normothermic regional perfusion (NRP) in posttransplant outcomes after controlled donation after the determination of death by circulatory criteria (cDCD) has been shown in different international adult experiences. However, there is no information on the use of NRP in pediatric cDCD donors. METHODS: This is a multicenter, retrospective, observational cohort study describing the pediatric (<18 y) cDCD procedures performed in Spain, using either abdominal NRP or thoracoabdominal NRP and the outcomes of recipients of the obtained organs. RESULTS: Thirteen pediatric cDCD donors (age range, 2-17 y) subject to abdominal NRP or thoracoabdominal NRP were included. A total of 46 grafts (24 kidneys, 11 livers, 8 lungs, 2 hearts, and 1 pancreas) were finally transplanted (3.5 grafts per donor). The mean functional warm ischemic time was 15 min (SD 6 min)' and the median duration of NRP was 87 min (interquartile range, 69-101 min). One-year noncensored for death kidney graft survival was 91.3%. The incidence of delayed graft function was 13%. One-year' noncensored-for-death liver graft survival was 90.9%. All lung and pancreas recipients had an excellent evolution. One heart recipient died due to a septic shock. CONCLUSIONS: This is the largest experience of pediatric cDCD using NRP as graft preservation method. Although our study has several limitations, such as its retrospective nature and the small sample size, its reveals that NRP may increase the utilization of cDCD pediatric organs and offer optimal recipients' outcomes.


Assuntos
Transplante de Fígado , Obtenção de Tecidos e Órgãos , Adulto , Humanos , Criança , Pré-Escolar , Adolescente , Estudos Retrospectivos , Preservação de Órgãos/métodos , Perfusão/métodos , Transplante de Fígado/métodos , Doadores de Tecidos , Sobrevivência de Enxerto , Morte
18.
Acta Chir Belg ; 123(6): 618-624, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35881765

RESUMO

OBJECTIVE: To determine the prevalence, risk factors and functional results of chronic critical illness (CCI) in polytrauma patients. DESIGN: Single-center observational retrospective study. SETTING: ICU at a tertiary hospital in Santander, Spain, between 2015 and 2019. PATIENTS: Adult trauma patients who survived beyond 48 h after injury. CCI was defined as the need for mechanical ventilation for at least 14 days or tracheostomy for difficult weaning. MEASUREMENTS AND MAIN RESULTS: About 62/575 developed CCI. These patients were characterized by higher ISS score [17 (SD 10) vs. 13.8 (SD 8.2); p < 0.001] and higher NISS (26 (SD 11) vs. 19.2 (SD 10.5); p = 0.001). CCI group had greater proportion of hospital-acquired infections (100% vs. 18.1%; p < 0.001), and acute kidney failure (33.9% vs. 22.8% p < 0.001). During the first 24 h of admission, CCI group required in a greater proportion surgical intervention (50% vs. 29%; p = 0.001), and blood products (31.3% vs. 20.5%; p < 0.047). Hospital ward stay was longer in CCI patients [9.5 days (IQR 5-16.9) vs. 43.9 (IQR 30.3-53) p < 0.001]. The CCI mortality was higher (19.5% vs. 8.1%; p = 0.004). Surgical intervention in the first 24 h (OR 2.5 95% CI 1.1-4.1), age (> 55 years) (OR 2.1 95%CI 1.1-4.2), ISS score (OR 1.1 95%CI 1.02-1.3), GCS score (OR 0.8 95%CI 0.4-23.2) and multiple organ failure (OR 9.5 95%CI 3.9-23.2) were predictors of CCI in the multivariate analysis. CONCLUSIONS: CCI after severe trauma appears in a considerable proportion of patients. Early identification and implementation of specific interventions could change the evolution of this process.


Assuntos
Estado Terminal , Centros de Traumatologia , Adulto , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Estado Terminal/terapia , Estado Terminal/epidemiologia , Unidades de Terapia Intensiva , Doença Crônica
20.
Pharmaceutics ; 14(11)2022 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-36365143

RESUMO

The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH), along with the World Health Organization (WHO), has provided a set of guidelines (ICH Q1A-E, Q3A-B, Q5C, Q6A-B) intended to unify the standards for the European Union, Japan, and the United States to facilitate the mutual acceptance of stability data that are sufficient for registration by the regulatory authorities in these jurisdictions. Overall, ICH stability studies involve a drug substance tested under storage conditions and assess its thermal stability and sensitivity to moisture. The long-term testing should be performed over a minimum of 12 months at 25 °C ± 2 °C/60% RH ± 5% RH or at 30 °C ± 2 °C/65% RH ± 5% RH. The intermediate and accelerated testing should cover a minimum of 6 months at 30 °C ± 2 °C/65% RH ± 5% RH (which is not necessary if this condition was utilized as a long-term one) and 40 °C ± 2 °C/75% RH ± 5% RH, respectively. Hence, the ICH stability testing for industrially fabricated medicines is rigorous and tedious and involves a long period of time to obtain preclinical stability data. For this reason, Accelerated Predictive Stability (APS) studies, carried out over a 3-4-week period and combining extreme temperatures and RH conditions (40-90 °C)/10-90% RH, have emerged as novel approaches to predict the long-term stability of pharmaceutical products in a more efficient and less time-consuming manner. In this work, the conventional ICH stability studies versus the APS approach will be reviewed, highlighting the advantages and disadvantages of both strategies. Furthermore, a comparison of the stability requirements for the commercialization of industrially fabricated medicines versus extemporaneous compounding formulations will be discussed.

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