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Objectives: Despite the discrepancy between demand and availability of organs for transplantation, controlled circulatory death donation has not been implemented in Portugal. This study aimed to estimate the potential increase in organ donation from implementing such a program. Material and Methods: All deceased patients within the intensive care medicine department at Centro Hospitalar Universitário de São João, throughout the year 2019, were subjected to retrospective analysis. Potential gain was estimated comparing the results with the number of donors and organs collected during the same period at this hospital center. Differences in variables between groups were assessed using t tests for independent samples or Mann-Whitney U tests for continuous variables, and chi-squared tests were used for categorical variables. Results: During 2019, 152 deaths occurred after withdrawal of life-sustaining therapies, 10 of which would have been potentially eligible for donation after controlled circulatory death. We can anticipate a potential increase of 10 prospective donors, a maximum 21% growth in yearly transplantation activity, with a greater impact on kidney transplantation. For most patients, the time between withdrawal of organ support and death surpassed 120 minutes, an outcome explained by variations in withdrawal of life-sustaining measures and insufficient clinical records, underestimating the potential for controlled circulatory arrest donation. Conclusion: This study effectively highlights public health benefits of controlled circulatory arrest donation. Legislation allowing donation through this method represents a social gain and enables patients who will never meet brain death criteria to donate organs as part of the end-of-life process in intensive care medicine, within a framework of complete ethical alignment.

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BACKGROUND: Despite medical advancements in neonatal survival rates, many children have poor neurological outcomes. Because the law in Korea restricts the withdrawal of life-sustaining treatment to only cases of imminent death, treatment discontinuation may not be an option, even in patients with poor neurological prognosis. This study investigated the opinions of the general population and clinicians regarding life-sustaining treatment withdrawal in such cases using hypothetical scenarios. METHODS: We conducted a cross-sectional study on the general population and clinicians using a web-based questionnaire. The sample of the general population from an online panel comprised 500 individuals aged 20-69 years selected by quota sampling. The clinician sample comprised 200 clinicians from a tertiary university hospital. We created hypothetical vignettes and questionnaire items to assess attitudes regarding mechanical ventilation withdrawal for an infant at risk of poor neurological prognosis due to birth asphyxia at 2 months and 3 years after the incidence. RESULTS: Overall, 73% of the general population and 74% of clinicians had positive attitudes toward mechanical ventilator withdrawal at 2 months after birth asphyxia. The proportion of positive attitudes toward mechanical ventilator withdrawal was increased in the general population (84%, P < 0.001) and clinicians (80.5%, P = 0.02) at 3 years after birth asphyxia. Religion, spirituality, the presence of a person with a disability in the household, and household income were associated with the attitudes of the general population. In the multivariable logistic regression analysis of the general population, respondents living with a person with a disability or having a disability were more likely to find the withdrawal of the ventilator at 2 months and 3 years after birth asphyxia not permissible. Regarding religion, respondents who identified as Christians were more likely to find the ventilator withdrawal at 2 months after birth asphyxia unacceptable. CONCLUSION: The general population and clinicians shared the perspective that the decision to withdraw life-sustaining treatment in infants with a poor neurological prognosis should be considered before the end of life. A societal discussion about making decisions centered around the best interest of pediatric patients is warranted.

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Respiración Artificial , Privación de Tratamiento , Humanos , Masculino , Femenino , Adulto , Pronóstico , Encuestas y Cuestionarios , Privación de Tratamiento/legislación & jurisprudencia , Persona de Mediana Edad , Estudios Transversales , Lactante , Anciano , Adulto Joven , Recién Nacido , Asfixia Neonatal/terapia , República de Corea , Actitud del Personal de Salud

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Background: Chronic Spontaneous Urticaria (CSU) is an immune-mediated skin disease that may require prolonged treatments. Currently, there are no recommendations for treatment discontinuation once CSU symptoms are controlled, particularly among patients primarily diagnosed with severe CSU. Objective: In this real-life study we aimed to describe our experience of omalizumab (Oma) treatment withdrawal in CSU and define biomarkers related to these outcomes. Methods: CSU patients followed at our allergy clinic from January 2016 to December 2022 were included. Response to Oma therapy, and Oma-withdrawal outcomes among patients who reached complete remission for >6 months were analyzed. Results: During the study period 192/335(%) CSU patients were categorized as severe-CSU and entitled to receive Oma according to our country's regulations. Of them, 131/192(68%) were considered "Oma-responders", and 95/131(72.5%) patients underwent gradual treatment withdrawal. Successful Oma-withdrawal was documented in 47/95(49.5%) whereas 48/95(50.5%) patients experienced flare and were defined as unsuccessful OMA-withdrawal. The first was associated with shorter disease duration 7.1 ± 7.4 years vs. 10.7 ± 9.4 (P = 0.042), lower baseline-IgE 81.6 ± 84.1IU/ml vs. 324.7 ± 555.9 (P = 0.005), and lower baseline-eosinophils count 131.4 ± 110.5 vs. 195.6 ± 98.4 (P = 0.043) in comparison to failure of Oma-withdrawal group. Conclusion: OMA may be successfully withdrawn in up to 50% of severe CSU patients following complete remission of disease symptoms, utilizing a gradual withdrawal protocol. Oma-withdrawal failure was linked with longer duration of disease as well as high IgE and eosinophil counts prior to initiation of Oma therapy. These parameters may enable the design of a treatment withdrawal algorithm.

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OBJECTIVE: To investigate real-world retention and remission rates in PsA patients initiating a 2nd or 3rd TNFi and the association with reason for discontinuation from the previous TNFi-treatment. METHODS: Prospectively collected routine care data from 12 European registries were pooled. Retention rates (Kaplan-Meier estimation) and crude/LUNDEX-adjusted rates of Disease Activity Score 28 and Disease Activity index for PSoriatic Arthritis (DAS28 and DAPSA28) remission were calculated and compared with adjusted Cox regression analyses and Chi-squared test, respectively). RESULTS: We included 5233 (2nd TNFi) and 1906 (3rd TNFi) patients. Twelve-month retention rates for the 2nd and 3rd TNFi were 68% (95%CI: 67-70%) and 66% (64-68%), respectively. Patients who stopped the previous TNFi due to AE/LOE had 12-month retention rates of 66%/65% (2nd TNFi), and 65%/63% (3rd TNFi), respectively. Patients who stopped the previous TNFi due to LOE after less vs more than 24 weeks had 12-month retention rates of 54%/69% (2nd TNFi), and 58%/65% (3rd TNFi). Six-month crude/LUNDEX-adjusted DAS28 remission rates were 48%/35% and 38%/27%, and DAPSA28 remission rates were 19%/14% and 14%/10%, for the 2nd and 3rd TNFi. CONCLUSION: Two-thirds of patients remained on TNFi at 12months for both the 2nd and 3rd TNFi, while one-third and one-quarter of patients were in DAS28 remission after 6months on the 2nd and 3rd TNFi. While drug effectiveness was similar in patients who stopped the previous TNFi due to AE compared to overall LOE, drug effectiveness was better in patients who had stopped the previous TNF due to secondary LOE compared to primary LOE.

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Artritis Psoriásica , Sistema de Registros , Inducción de Remisión , Índice de Severidad de la Enfermedad , Humanos , Artritis Psoriásica/tratamiento farmacológico , Masculino , Femenino , Persona de Mediana Edad , Resultado del Tratamiento , Estudios Prospectivos , Inducción de Remisión/métodos , Adulto , Antirreumáticos/uso terapéutico , Europa (Continente) , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Anciano , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores

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INTRODUCTION: Patients with pediatric low-grade gliomas (pLGGs), the most common primary brain tumors in children, can often benefit from MAPK inhibitor (MAPKi) treatment. However, rapid tumor regrowth, also referred to as rebound growth, may occur once treatment is stopped, constituting a significant clinical challenge. METHODS: Four patient-derived pediatric glioma models were investigated to model rebound growth in vitro based on viable cell counts in response to MAPKi treatment and withdrawal. A multi-omics dataset (RNA sequencing and LC-MS/MS based phospho-/proteomics) was generated to investigate possible rebound-driving mechanisms. Following in vitro validation, putative rebound-driving mechanisms were validated in vivo using the BT-40 orthotopic xenograft model. RESULTS: Of the tested models, only a BRAFV600E-driven model (BT-40, with additional CDKN2A/Bdel) showed rebound growth upon MAPKi withdrawal. Using this model, we identified a rapid reactivation of the MAPK pathway upon MAPKi withdrawal in vitro, also confirmed in vivo. Furthermore, transient overactivation of key MAPK molecules at transcriptional (e.g. FOS) and phosphorylation (e.g. pMEK) levels, was observed in vitro. Additionally, we detected increased expression and secretion of cytokines (CCL2, CX3CL1, CXCL10 and CCL7) upon MAPKi treatment, maintained during early withdrawal. While increased cytokine expression did not have tumor cell intrinsic effects, presence of these cytokines in conditioned media led to increased attraction of microglia cells in vitro. CONCLUSION: Taken together, these data indicate rapid MAPK reactivation upon MAPKi withdrawal as a tumor cell intrinsic rebound-driving mechanism. Furthermore, increased secretion of microglia-recruiting cytokines may play a role in treatment response and rebound growth upon withdrawal, warranting further evaluation.

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Neoplasias Encefálicas , Citocinas , Glioma , Microglía , Mutación , Inhibidores de Proteínas Quinasas , Proteínas Proto-Oncogénicas B-raf , Humanos , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas Proto-Oncogénicas B-raf/metabolismo , Microglía/metabolismo , Microglía/efectos de los fármacos , Glioma/metabolismo , Glioma/tratamiento farmacológico , Glioma/patología , Glioma/genética , Citocinas/metabolismo , Animales , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/genética , Inhibidores de Proteínas Quinasas/farmacología , Ensayos Antitumor por Modelo de Xenoinjerto , Niño , Ratones , Proliferación Celular/efectos de los fármacos , Línea Celular Tumoral , Sistema de Señalización de MAP Quinasas/efectos de los fármacos

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AIM: To obtain an in-depth understanding of the lived experiences, values, and beliefs of Taiwanese women with breast cancer who withdrew from cancer treatment. BACKGROUND: Fear of side effects, negative experiences and personal beliefs were identified as reasons for withdrawing from cancer treatments. Body-mind consciousness and body autonomy play a crucial role in cancer treatment decisions. DESIGN: Descriptive phenomenological approach. METHODS: We conducted semi-structured, face-to-face and in-depth interviews with 16 women diagnosed with breast cancer. Participants were purposefully selected from the Cancer Registry database. Employing a phenomenological approach, our aim was to explore the lived experiences of these individuals. Data analysis followed Giorgi's five-step process. To ensure a comprehensive report the COREQ checklist was applied. FINDINGS: 'The Determination to Preserve Me' is the essence of treatment withdrawal, identified by three themes and seven sub-themes. 'Raising Body-Mind Consciousness' was generated using body autonomy and preventing repeated psychological trauma from the participant's view. Their lifestyles, maintaining the family role, and returning to a normal trajectory help develop 'Maintaining Stability for Being a Patient and a Family Carer'. 'Self-Defending Against the Body Harm' was generated by concerns about maintaining health and preventing harm. CONCLUSION: Women's behaviours became transformed by suffering. Actions were influenced by physical and psychological distress, misconceptions about treatments, and appearance changes by self-determination through self-protection. RELEVANCE TO CLINICAL PRACTICE: Healthcare professionals should respect women's autonomy and work collaboratively to ensure their decision-making with accurate information and awareness of the potential risks and benefits of treatment withdrawal need to concern.

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Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/psicología , Persona de Mediana Edad , Adulto , Taiwán , Privación de Tratamiento , Investigación Cualitativa , Anciano

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BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common endocrinopathy associated with infertility and metabolic disorder in women of reproductive age. Animal models have been developed and used as tools to unravel the pathogenesis of PCOS, among which most postnatal models employ continuing experimental manipulations. However, the persistence and stability of these animals after modeling is unknown. Dehydroepiandrosterone (DHEA)-induced PCOS mouse model is commonly used in PCOS studies. Thus the aim of the present study was to investigate the reproductive features of DHEA-induced PCOS mice fed a normal chow or an high-fat diet (HFD) with treatment withdrawal or consecutive treatments after PCOS mouse models were established. METHODS: Prepubertal C57BL/6 J mice (age 25 days) were injected (s.c.) daily with DHEA on a normal chow or a 60% HFD for 20 consecutive days to induce PCOS mouse models. Mice injected with the vehicle sesame oil were used as controls. After 20 days, mice were divided into 2 groups, namely "Continue dosing group" and "Stop dosing group". The animals were consecutively treated with DHEA or DHEA + HFD, or housed without any treatment for 2 or 4 weeks. Estrous cycles were evaluated during this period. At the end of the experiment, serum testosterone (T) levels were measured and the morphology of ovaries was evaluated. RESULTS: The mice in Continue dosing groups maintained reproductive phenotypes of PCOS mouse models. In contrast, 2 or 4 weeks after PCOS models were established, the mice with treatment withdrawal in Stop dosing groups exhibited normal serum testosterone levels, regular estrous cycle, and relatively normal ovarian morphology. In addition, even with consecutive treatments, there was no marked difference in body weight between DHEA mice on the normal chow or an HFD in Continue dosing groups and the control animals 3 weeks after modeling. CONCLUSIONS: After PCOS mice were induced with DHEA or DHEA + HFD, the mice still need consecutive treatments to maintain reproductive phenotypes to be regarded as PCOS mice that meet the diagnostic criteria of PCOS defined by the 2003 Rotterdam criteria.

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Síndrome del Ovario Poliquístico , Humanos , Femenino , Ratones , Animales , Recién Nacido , Síndrome del Ovario Poliquístico/inducido químicamente , Síndrome del Ovario Poliquístico/tratamiento farmacológico , Ratones Endogámicos C57BL , Fenotipo , Modelos Animales de Enfermedad , Testosterona , Deshidroepiandrosterona/efectos adversos

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OBJECTIVE: Approximately one third of children with JIA receive biologic therapy, but evidence on biologic therapy withdrawal is lacking. This study aims to increase our understanding of whether and when pediatric rheumatologists postpone a decision to withdraw biologic therapy in children with clinically inactive non-systemic JIA. METHODS: A survey containing questions about background characteristics, treatment patterns, minimum treatment time with biologic therapy, and 16 different patient vignettes, was distributed among 83 pediatric rheumatologists in Canada and the Netherlands. For each vignette, respondents were asked whether they would withdraw biologic therapy at their minimum treatment time, and if not, how long they would continue biologic therapy. Statistical analysis included descriptive statistics, logistic and interval regression analysis. RESULTS: Thirty-three pediatric rheumatologists completed the survey (40% response rate). Pediatric rheumatologists are most likely to postpone the decision to withdraw biologic therapy when the child and/or parents express a preference for continuation (OR 6.3; p < 0.001), in case of a flare in the current treatment period (OR 3.9; p = 0.001), and in case of uveitis in the current treatment period (OR 3.9; p < 0.001). On average, biologic therapy withdrawal is initiated 6.7 months later when the child or parent prefer to continue treatment. CONCLUSION: Patient's and parents' preferences were the strongest driver of a decision to postpone biologic therapy withdrawal in children with clinically inactive non-systemic JIA and prolongs treatment duration. These findings highlight the potential benefit of a tool to support pediatric rheumatologists, patients and parents in decision making, and can help inform its design.

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Artritis Juvenil , Productos Biológicos , Privación de Tratamiento , Niño , Humanos , Productos Biológicos/uso terapéutico , Canadá , Duración de la Terapia , Países Bajos , Reumatólogos , Artritis Juvenil/terapia

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Prolactinomas are the most common pituitary tumor histotype, with microprolactinomas being prevalent in women and macroprolactinomas in men. Hyperprolactinemia is among the most common causes of hypogonadotropic hypogonadism in both sexes, prompting medical advice for hypogonadism (infertility, oligo-amenorrhea, impotence, osteoporosis/osteopenia) in both sexes, and for signs and symptoms of mass effects (hypopituitarism, visual loss, optic chiasm compression, cranial nerve deficits, headaches) predominantly in men. Diagnostic workup involves a single prolactin measurement and pituitary imaging, but some laboratory artifacts (ie, the "hook effect" and macroprolactin) can complicate or delay the diagnosis. The treatment of choice for prolactinomas is represented by dopamine agonists, mainly cabergoline, which are able to induce disease control, restore fertility in both sexes, and definitively cure one-third of patients, thus permitting treatment discontinuation. Pregnancy and menopause may promote spontaneous prolactin decline and anticipate cabergoline discontinuation in women. Surgery and/or radiotherapy are indicated in case of resistance to cabergoline not overcome by the increase in drug dose up to the maximally tolerated or the patient's personal choice of surgery. The evidence of resistance to cabergoline in invasive and proliferative tumors may indicate biological aggressiveness, thus requiring alternative therapeutic approaches mainly based on temozolomide use as monotherapy or combined with radiotherapy. In uncontrolled patients, new medical approaches (alternative hormonal treatments, cytotoxic drugs, peptide receptor radionuclide therapy, mTOR/Akt inhibitors, tyrosine kinase inhibitors, or immunotherapy) may be offered but the experience collected to date is still very scant. This article reviews different facets of prolactinomas and discusses approaches to the condition in more common clinical situations.

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Hipogonadismo , Neoplasias Hipofisarias , Prolactinoma , Masculino , Embarazo , Humanos , Femenino , Prolactinoma/diagnóstico , Prolactinoma/terapia , Prolactinoma/complicaciones , Cabergolina/uso terapéutico , Prolactina , Ergolinas/uso terapéutico , Neoplasias Hipofisarias/diagnóstico , Neoplasias Hipofisarias/terapia , Neoplasias Hipofisarias/complicaciones , Agonistas de Dopamina/uso terapéutico , Hipogonadismo/tratamiento farmacológico

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BACKGROUND & AIMS: In children with autoimmune hepatitis, uncertainties include outcomes associated with type 2 hepatitis, the possibility of and criteria for attempting withdrawal of treatment, and long-term outcomes. We report our experience on these issues. METHODS: From 1973 to 2002, 117 children with type 1 (n = 65) or type 2 (n = 52) hepatitis, excluding fulminant hepatitis, were treated, primarily with prednisone and azathioprine. Median follow-up was 20 years in survivors. RESULTS: Normalisation of aminotransferases and prothrombin ratio were observed in 93% and 84% of children, respectively; sustained remission after treatment withdrawal was recorded in 24% of the entire population, with a median follow-up of 7 years. Sustained treatment-free remission was obtained in 11 of 24 children with follow-ups of 4-22 years based on durable normalisation of aminotransferases (without histological assessment). Gastrointestinal bleeding from varices and the emergence of extrahepatic autoimmune disorders occurred in 10 and 22 patients, respectively. Liver transplantation was performed in 23 patients at a median age of 21 years. The 30-year probabilities of overall and native liver survival were 81% and 61%, respectively. No differences were observed between type 1 and 2 hepatitis for any of the component parts of outcome. In the multivariate analysis, a persistent abnormal prothrombin ratio was associated with worse probabilities of overall and native liver survival. CONCLUSIONS: In terms of liver outcome, type 2 hepatitis is not different from type 1. Withdrawal of treatment is possible without prior liver histology. A persistent abnormal prothrombin ratio identifies patients who will require liver transplantation in adolescence or early adulthood. IMPACT AND IMPLICATIONS: In children with autoimmune hepatitis, there are conflicting reports on the differences in outcome between type 1 and type 2 hepatitis, and on the possibility of treatment withdrawal, before which liver histology is required; data concerning >10-year overall and native liver survival rates are limited. In this study, we found no differences in outcomes between type 1 and 2 hepatitis; a durable treatment-free state was achieved in 19% of all patients throughout childhood and early adulthood, and in 45% of children for whom treatment withdrawal was attempted without prior liver histology; prothrombin was found to be predictive of 30-year overall and native liver survival. The results allow for a less-strict approach to treatment withdrawal in children, avoiding the risks of a liver biopsy, and they provide a tool to help anticipate the need for liver transplantation before complications occur.

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Hepatitis Autoinmune , Inmunosupresores , Niño , Adolescente , Humanos , Adulto , Adulto Joven , Inmunosupresores/uso terapéutico , Hepatitis Autoinmune/diagnóstico , Hepatitis Autoinmune/tratamiento farmacológico , Hepatitis Autoinmune/patología , Protrombina , Azatioprina/efectos adversos , Transaminasas

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We previously observed that esmolol treatment for 48 h reduced vascular lesions in spontaneously hypertensive rats (SHRs). Therefore, we investigated whether this beneficial effect is persistent after withdrawal. Fourteen-month-old SHRs (SHR-Es) were treated with esmolol (300 µg/kg/min) or a vehicle for 48 h. Two separate groups were also given identical treatment, but they were then monitored for a further 1 week and 1 month after drug withdrawal. We analyzed the geometry and composition of the coronary artery, vascular reactivity and plasma redox status. Esmolol significantly decreased wall thickness (medial layer thickness and cell count), external diameter and cross-sectional area of the artery, and this effect persisted 1 month after drug withdrawal. Esmolol significantly improved endothelium-dependent relaxation by ACh (10-9-10-4 mol/L); this effect persisted 1 week (10-9-10-4 mol/L) and 1 month (10-6-10-4 mol/L) after withdrawal. Esmolol reduced the contraction induced by 5-HT (3 × 10-8-3 × 10-5 mol/L), and this effect persisted 1 week after withdrawal (10-6-3 × 10-5 mol/L). Esmolol increased nitrates and reduced glutathione, and it decreased malondialdehyde and carbonyls; this enhancement was maintained 1 month after withdrawal. This study shows that the effect of esmolol on coronary remodeling is persistent after treatment withdrawal in SHRs, and the improvement in plasma oxidative status can be implicated in this effect.

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Antecedentes y objetivos:Se ha especulado que las estatinas pueden ser de utilidad en el tratamiento de pacientes con COVID-19, pero no existen evidencias clínicas sólidas. El objetivo de este trabajo es conocer su utilidad en una cohorte de gran tamaño de pacientes hospitalizados por COVID-19, así como si su retirada se asocia con un peor pronóstico.Material y métodos:Estudio retrospectivo observacional. Se incluyeron 2.191 pacientes hospitalizados con infección confirmada con SARS-CoV-2.Resultados:La edad media fue de 68,0 ± 17,8 años y fallecieron un total de 597 (27,3%) pacientes. Un total de 827 pacientes (37,7% de la muestra) estaban tratados previamente con estatinas. Aunque precisaron con mayor frecuencia de ingreso en camas de críticos, dicho grupo terapéutico no resultó un factor predictor independiente de muerte en el seguimiento [HR 0,95 (0,72-1,25)]. Un total de 371 pacientes (16,9%) recibió al menos una dosis de estatina durante el ingreso. A pesar de ser una población con un perfil clínico más desfavorable, tanto su uso [HR 1,03 (0,78-1,35)] como la suspensión durante el ingreso en pacientes que las recibían crónicamente [HR 1,01 (0,78-1,30)] presentaron un efecto neutro en la mortalidad. No obstante, el grupo con estatinas desarrolló con mayor frecuencia datos de citolisis hepática, rabdomiolisis y más eventos trombóticos y hemorrágicos.Conclusiones:En nuestra muestra, las estatinas no se asociaron de forma independiente a una menor mortalidad en pacientes con COVID-19. En aquellos pacientes que tengan indicación de recibirlas por su patología previa es necesario monitorizar estrechamente sus potenciales efectos adversos durante el ingreso hospitalario. (AU)

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Aims and objectives:Statins have been proposed as potentially useful agents for modulating the host response in COVID-19. However, solid evidence-based recommendations are still lacking. Our aim was to study the association between statin use and clinical outcomes in a large cohort of hospitalized patients with SARS-CoV-2 infection, as well as the specific consequences of chronic treatment withdrawal during hospital admission.Material and methods:Retrospective observational study including 2191 hospitalized patients with confirmed SARS-CoV-2 infection.Results:Mean age was 68.0±17.8 years and 597 (27.3%) patients died during follow-up. A total of 827 patients (37.7% of the whole sample), received chronic treatment with statins. Even though they underwent more frequent admissions in critical care units, chronic treatment with statins was not independently associated with all-cause mortality [HR 0.95 (0.72-1.25)]. During the whole hospital admission, 371 patients (16.9%) received at least one dose of statin. Although these patients had a significantly worse clinical profile, both treatment with statins during admission [HR 1.03 (0.78-1.35)] and withdrawal of chronic statin treatment [HR 1.01 (0.78-1.30)] showed a neutral effect in mortality. However, patients treated with statins presented more frequently hepatic cytolysis, rhabdomyolysis and thrombotic/hemorrhagic events.Conclusions:In this large cohort of hospitalized COVID-19 patients, statins were not independently associated with all-cause mortality during follow-up. Clinically relevant statin-associated adverse effects should be carefully monitored during hospital admission. (AU)

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Humanos , Anciano de 80 o más Años , Coronavirus/efectos de los fármacos , Hospitalización , Mortalidad , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Morbilidad

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BACKGROUND: There is no cure for Crohn's disease (CD). Available treatments and treatment strategies, particularly anti-TNF, allow healing intestinal lesions and maintaining steroid-free remission in a subset of patients. Having in mind the remitting/relapsing nature of the disease, patients and health care providers often ask themselves whether the treatment could be withdrawn. Several studies have demonstrated a risk of relapse of CD after anti-TNF withdrawal, which varies from 20 to 50% at 1 year and from 50 to 80% beyond 5 years. These numbers clearly highlight that stopping therapy should not be a systematically proposed strategy in those remitting patients. SUMMARY: Nobody would argue for anti-TNF withdrawal in patients with a high risk of short-term relapse. Nevertheless, they also indicate that a minority of patients may not relapse over midterm and that those who have relapsed may have benefited from a drug-free period before being again treated for a new cycle of treatment. The most relevant question is thus whether in those patients with a low to medium risk of disease relapse, treatment withdrawal could be contemplated. In this specific setting, there may be pros and cons for anti-TNF withdrawal. Among the pros are the potential side effects and toxicity of anti-TNF, the risk of loss of response over time, the patient preference allowing the patient to regain control of one's health and investing in it, also improving adherence, the absence of a negative impact on disease evolution of a transient anti-TNF withdrawal, and finally the cost. KEY MESSAGES: Although anti-TNF withdrawal in patients with sustained clinical remission is associated with a high risk of relapse, this risk seems to be much lower in a subgroup of patients, particularly in endoscopic and biologic remission. Stopping anti-TNF in this subgroup of patients may be associated with a favorable benefit/risk ratio.

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BACKGROUNDS AND AIMS: In autoimmune hepatitis, there are uncertainties about whether to discontinue the treatment, when the treatment should be discontinued, and the risks of relapse in the cases where remission is achieved with immunosuppressive therapy. In this study, patients with AIH, whose immunosuppressive treatments were discontinued, were evaluated for the rates of remission and the risk of relapse. MATERIALS AND METHODS: A total of 119 patients, who were diagnosed with AIH based on the AIHG scoring systems between 1990 and 2015, were evaluated. Patients were receiving standard azathioprine and steroid therapy. The treatment was discontinued in patients, who had been receiving treatment for at least 2 years, who had no clinical complaints, and whose aminotransferases were normal and when an increase occurred in AST values more than two times the normal after the treatment was interrupted, the case was considered as a relapse. RESULTS: Among the patients, 83%(n = 99) were women. When the patients were diagnosed with AIH, their mean age was 36 ± 16(8-79) years; 70.6%(n = 84) were type 1, 3.4%(n = 4) type 2, and 26%(n = 31) were autoantibody-negative AIH. At the time of discontinuation, liver biopsy was performed in 8 of the patients and minimal-mild abnormalities were detected. Patients whose treatment was discontinued received treatment for an average of 101 ± 75(range: 24-280, median: 68.5) months; and, they were followed up for an average of 19 (1-110) months during the period without medication. Relapse occurred in 67%(n = 12) of the patients with drug withdrawal. Relapse occurred within the first 12 months in 67% of these patients (n = 8) and developed with an acute hepatitis attack in 42%. None of the clinical, laboratory, and histological data were found to be effective on relapse. CONCLUSION: In patients with AIH, relapse occurs in two-thirds of patients within an average of 19 month after the discontinuation of the medication. Most relapses occur at the early period and they are accompanied by an acute hepatitis attack.

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Hepatitis Autoinmune , Adulto , Azatioprina/uso terapéutico , Femenino , Hepatitis Autoinmune/complicaciones , Hepatitis Autoinmune/diagnóstico , Hepatitis Autoinmune/tratamiento farmacológico , Humanos , Inmunosupresores/efectos adversos , Persona de Mediana Edad , Recurrencia , Inducción de Remisión , Adulto Joven

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BACKGROUND: Mortality risk is high soon after dialysis initiation in patients with kidney failure, and dialysis withdrawal is a major cause of early mortality, attributed to psychosocial or medical reasons. The temporal trends and risk factors associated with cause-specific early dialysis withdrawal within 12 months of dialysis initiation remain uncertain. METHODS: Using data from the Australia and New Zealand Dialysis and Transplant Registry, we examined the temporal trends and risk factors associated with mortality attributed to early psychosocial and medical withdrawals in incident adult dialysis patients in Australia between 2005 and 2018 using adjusted competing risk analyses. RESULTS: Of 32 274 incident dialysis patients, 3390 (11%) experienced death within 12 months post-dialysis initiation. Of these, 1225 (36%) were attributed to dialysis withdrawal, with 484 (14%) psychosocial withdrawals and 741 (22%) medical withdrawals. These patterns remained unchanged over the past two decades. Factors associated with increased risk of death from early psychosocial and medical withdrawals were older age, dialysis via central venous catheter, late referral and the presence of cerebrovascular disease; obesity and Asian ethnicity were associated with decreased risk. Risk factors associated with early psychosocial withdrawals were underweight and higher socioeconomic status. Presence of peripheral vascular disease, chronic lung disease and cancers were associated with early medical withdrawals. CONCLUSIONS: Death from dialysis withdrawal accounted for >30% of early deaths in kidney failure patients initiated on dialysis and remained unchanged over the past two decades. Several shared risk factors were observed between mortality attributed to early psychosocial and medical withdrawals.

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Fallo Renal Crónico , Insuficiencia Renal , Adulto , Estudios de Cohortes , Femenino , Humanos , Fallo Renal Crónico/terapia , Masculino , Sistema de Registros , Diálisis Renal/efectos adversos , Factores de Riesgo

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AIMS AND OBJECTIVES: Statins have been proposed as potentially useful agents for modulating the host response in COVID-19. However, solid evidence-based recommendations are still lacking. Our aim was to study the association between statin use and clinical outcomes in a large cohort of hospitalized patients with SARS-CoV-2 infection, as well as the specific consequences of chronic treatment withdrawal during hospital admission. MATERIAL AND METHODS: Retrospective observational study including 2191 hospitalized patients with confirmed SARS-CoV-2 infection. RESULTS: Mean age was 68.0±17.8 years and 597 (27.3%) patients died during follow-up. A total of 827 patients (37.7% of the whole sample), received chronic treatment with statins. Even though they underwent more frequent admissions in critical care units, chronic treatment with statins was not independently associated with all-cause mortality [HR 0.95 (0.72-1.25)]. During the whole hospital admission, 371 patients (16.9%) received at least one dose of statin. Although these patients had a significantly worse clinical profile, both treatment with statins during admission [HR 1.03 (0.78-1.35)] and withdrawal of chronic statin treatment [HR 1.01 (0.78-1.30)] showed a neutral effect in mortality. However, patients treated with statins presented more frequently hepatic cytolysis, rhabdomyolysis and thrombotic/hemorrhagic events. CONCLUSIONS: In this large cohort of hospitalized COVID-19 patients, statins were not independently associated with all-cause mortality during follow-up. Clinically relevant statin-associated adverse effects should be carefully monitored during hospital admission.

Asunto(s)

Tratamiento Farmacológico de COVID-19 , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Hospitalización , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Persona de Mediana Edad , SARS-CoV-2

RESUMEN

Background and aim: Since their effectiveness was initially demonstrated, oral corticosteroids (OCS) have been routinely used to treat asthma. We now know that their usage is linked to the development of side effects such osteoporosis and adrenal insufficiency. This is an observational study based on Delphi methodology. The questionnaire was divided into 4 sections: OCS generalities, maintenance treatment, short-term treatment, and adverse events. Materials and methods: Two rounds of a 68-item questionnaire were completed by a panel of 48 allergists and pneumologists. Results: Definitions were agreed upon, as was the proper use of OCS in the treatment of severe asthma. The experts agreed that the use of OCS should be minimized as much as possible and that in the event of maintenance treatments, a slow and progressive tapering strategy should be used. They also emphasized the importance of standardizing the technique for measuring the amount of SCG delivered in both cases. Conclusions: This consensus document attempts to bring together scientifically supported suggestions from specialists in the management of asthma to reduce the use of OCS in Spain.

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Objectives:This study aimed to evaluate the predictive value of the CHA 2DS 2-VASc score for in-hospital outcomes of patients with acute myocardial infarction (AMI). Methods:Data of 23 728 patients from the China patient-centered Evaluative Assessment of cardiac Events (China PEACE)Retrospective Acute Myocardial Infarction Study were analyzed retrospectively. The patients were categorized into 3 groups according to the CHA 2DS 2-VASc scores: the low score group (score 1-3), the middle score group (score 4-6) and the high score group (score 7-9). The in-hospital outcomes included major adverse cardiovascular events (MACE), death, death or withdrawal from treatment, reinfarction, ischemic stroke,etc. The CHA 2DS 2-VASc score was incorporated into multivariate Cox regression analyses to determine its independent impact on in-hospital outcomes. Receiver operating Characteristic (ROC) curves were constructed, and the area under the curve (AUC) was used to evaluate the predictive value of the CHA 2DS 2-VASc score for in-hospital mortality and death or withdrawal from treatment, respectively. Results:The patients had a median age of 66 (56,75) years, and 30.7% of them were females. Patients with higher CHA 2DS 2-VASc scores had a higher in-hospital mortality and more in-hospital complications (all P<0.001). After adjustment of baseline covariates, the subjects in the high score group were associated with high risks of in-hospital mortality ( OR=6.13, 95% CI 4.77-7.87, P<0.001), death or treatment withdrawal ( OR=6.43, 95% CI 5.16-8.00, P<0.001) and MACE ( OR=4.94, 95% CI 4.06-6.01, P<0.001). The AUCs of the CHA 2DS 2-VASc score were comparable with those of the mini-global registry of acute coronary events(mini-GRACE)score in evaluation of in-hospital mortality (0.699 vs. 0.696, P=0.752) and the death or treatment withdrawal risk (0.708 vs. 0.713, P=0.489). Conclusions:The CHA 2DS 2-VASc score is an independent predictor of in-hospital outcomes for patients with AMI. Its predictive value was comparable with the mini-GRACE score, which could be used as a simple tool for early and rapid outcome evaluation for AMI patients.

RESUMEN

BACKGROUND & AIMS: We evaluated treatment withdrawal, long-term outcomes, and safety of budesonide oral suspension (BOS) 2.0 mg twice daily in patients with eosinophilic esophagitis who completed a 12-week induction study. METHODS: Induction full responders (≤6 eosinophils per high-power field [eos/hpf] and ≥30% reduction in the Dysphagia Symptom Questionnaire score) to BOS 2.0 mg twice daily (ORBIT1/SHP621-301/NCT02605837) were randomized to continue BOS (BOS-BOS) or withdraw to placebo (BOS-PBO) for 36 weeks (ORBIT2/SHP621-302/NCT02736409). Induction partial responders and nonresponders, and patients who received induction placebo, received BOS for 36 weeks. The primary end point was the proportion of BOS-BOS and BOS-PBO patients who relapsed (≥15 eos/hpf and ≥4 days of dysphagia [Dysphagia Symptom Questionnaire] over 2 weeks) by week 36. The key secondary end point was the proportion of induction partial responders and nonresponders who fully responded after 52 weeks of total BOS therapy. Other secondary end points included the proportion of induction full responders with histologic responses (≤1, ≤6, <15 eos/hpf) at week 12 of the extension study, and safety outcomes. RESULTS: The randomized withdrawal period enrolled 48 patients (BOS-BOS, n = 25; BOS-PBO, n = 23); 106 induction partial responders and nonresponders, and 65 induction placebo patients received BOS. More BOS-PBO than BOS-BOS patients relapsed over 36 weeks (43.5% vs 24.0%; P = .131) and had histologic responses at week 12 of therapy (P < .001). Overall, 13.2% of induction partial responders and nonresponders fully responded at week 36. BOS was well tolerated; therapy duration was not associated with new safety concerns. CONCLUSIONS: For induction full responders, continuing BOS numerically improved maintenance of efficacy vs withdrawal. A longer therapy duration did not raise safety concerns. (ClinicalTrials.gov: NCT02736409.).

Asunto(s)

Trastornos de Deglución , Esofagitis Eosinofílica , Administración Oral , Antiinflamatorios , Budesonida , Método Doble Ciego , Enteritis , Eosinofilia , Esofagitis Eosinofílica/tratamiento farmacológico , Esofagitis Eosinofílica/patología , Gastritis , Humanos , Suspensiones , Resultado del Tratamiento

RESUMEN

BACKGROUND AND OBJECTIVE: Diabetes mellitus is a complex chronic disease requiring appropriate continuous medical care and delayed, or forgone care may exacerbate the severity of the disease. This study aimed to investigate the factors affecting forgone care in patients with type2 diabetes. MATERIALS AND METHODS: This was a cross-sectional study involving 1139 patients with type 2 diabetes aged> 18 years in 2019 in Tabriz, Iran. The researcher-made questionnaire was used for data collection. Data were analyzed using IBM SPSS software version 22 and IBM AMOS 22. Exploratory Factor Analysis (EFA) was performed for dimension reduction of the questionnaire, and Confirmatory Factor Analysis (CFA) used to verify the result of EFA. We applied the binary logistic regression model to assess the factors affecting forgone care. RESULTS: Of the 1139 patients, 510 patients (45%) reported forgone care during the last year. The percentage of forgoing care was higher in patients without supplementary insurance coverage (P = 0.01), those with complications (P = 0.01) and those with a history of hospitalization (P = 0.006). The majority of patients (41.5%) reported that the most important reason for forgoing care is financial barriers resulting from disease treatment costs. Of the main four factors affecting, quality of care had the highest impact on forgone care at 61.28 (of 100), followed by accessibility (37.01 of 100), awareness and attitude towards disease (18.52 of 100) and social support (17.22 of 100). CONCLUSION: The results showed that, despite the implementation of the Islamic Republic of Iran on a fast-track to beating non-communicable diseases (IraPEN), a considerable number of patients with type2 diabetes had a history of forgoing care, and the most important reasons for forgoing care were related to the financial pressure and dissatisfaction with the quality of care. Therefore, not only more financial support programs should be carried out, but the quality of care should be improved.

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Diabetes Mellitus Tipo 2 , Enfermedad Crónica , Estudios Transversales , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/terapia , Humanos , Cobertura del Seguro , Encuestas y Cuestionarios