Acute-on-chronic liver failure (ACLF), which was described relatively recently (2013), is a severe form of acutely decompensated cirrhosis characterised by the existence of organ system failure(s) and a high risk of short-term mortality. ACLF is caused by an excessive systemic inflammatory response triggered by precipitants that are clinically apparent (e.g., proven microbial infection with sepsis, severe alcohol-related hepatitis) or not. Since the description of ACLF, some important studies have suggested that patients with ACLF may benefit from liver transplantation and because of this, should be urgently stabilised for transplantation by receiving appropriate treatment of identified precipitants, and full general management, including support of organ systems in the intensive care unit (ICU). The objective of the present Clinical Practice Guidelines is to provide recommendations to help clinicians recognise ACLF, make triage decisions (ICU vs. no ICU), identify and manage acute precipitants, identify organ systems that require support or replacement, define potential criteria for futility of intensive care, and identify potential indications for liver transplantation. Based on an in-depth review of the relevant literature, we provide recommendations to navigate clinical dilemmas followed by supporting text. The recommendations are graded according to the Oxford Centre for Evidence-Based Medicine system and categorised as \'weak\' or \'strong\'. We aim to provide the best available evidence to aid the clinical decision-making process in the management of patients with ACLF.

In Poland, guidelines for the management of ineffective treatment of children in neonatal and paediatric departments developed by the Polish Neonatal Society and the Polish Paediatric Society, have been published. The specific problems of futile therapy in paediatric anaesthesiology and intensive care units should be defined and solved separately. For this purpose, the guidelines presented below were prepared. They present the principles for managing children for whom therapeutic options available in paedia-tric anaesthesiology and intensive care units have been exhausted and ineffectiveness of maintaining organ functions, i.e. futile therapy, has been suspected. The decision to withdraw futile therapy of a child is undoubtedly one of the most difficult for both doctors and parents, and for this reason, it should be made collectively, respecting the dignity of the child and his/her parents or legal representatives, and continuing the management aimed at relieving the child\'s pain and suffering, as well as minimising anxiety and fear. Due to the small amount of reliable evidence-based data, the guidelines constitute the consensus of the Group of Experts and are dedicated to minor patients treated in paediatric anaesthesiology and intensive care units.

The pandemic caused by COVID19 is associated with an increase in the number of cases of cardiorespiratory arrest, which has resulted in ethical concerns regarding the enforceability of cardiopulmonary resuscitation, as well as the conditions to carry it out. The risk of aerosol transmission and the clinical uncertainties about the efficacy, the potential sequelae, and the circumstances that could justify limiting this procedure during the pandemic have multiplied the ethical doubts on how to proceed in these cases. Based on ethical and legal grounds, this paper offers a practical guide on how to proceed in the clinical setting in cases of cardiopulmonary arrest during the pandemic. The criteria of justice, benefit, no harm, respect for autonomy, precaution, integrity, and transparency are asserted in an organized and practical framework for decision-making regarding cardiopulmonary resuscitation.
La pandemia de COVID-19 se ha asociado con un incremento en el número de casos de paro cardiorrespiratorio y con ello han aumentado las inquietudes éticas en torno a la exigencia de la reanimación cardiopulmonar, así como sobre las condiciones para realizarla. El riesgo de contagio por aerosoles y las incertidumbres clínicas sobre la eficacia, las potenciales secuelas y las circunstancias que podrían justificar la limitación del procedimiento durante la pandemia, han multiplicado las dudas éticas sobre cómo proceder en estos casos. Con base en fundamentos éticos y jurídicos, en el presente artículo se ofrece una guía práctica sobre cómo proceder en los casos de paro cardiopulmonar en el contexto de la pandemia. Los criterios de justicia, beneficio, no daño, respeto a la autonomía, precaución, integridad y transparencia, se presentan de forma organizada y práctica para la adopción de decisiones en materia de reanimación cardiopulmonar.

Objectives To identify the probability of survival and severe neurodevelopmental impairment (sNDI) at which perinatal physicians would or would not offer or recommend resuscitation at birth for extremely preterm infants. Methods A Delphi process consisting of five rounds was implemented to seek consensus (>80% agreement) amongst British Columbia perinatal physicians. The first-round consisted of neonatal and maternal-fetal-medicine Focus Groups. Rounds two to five surveyed perinatal physicians, building upon previous rounds. Draft guidelines were developed and agreement sought. Results Based on 401 responses across all rounds, consensus was obtained that resuscitation should not be offered if survival probability <5%, not recommended if survival probability 5 to <10%, resuscitation recommended if survival without sNDI probability >70 to 90% and resuscitation standard care if survival without sNDI >90%. Conclusions This physician consensus-based, objective framework for the management of an anticipated extremely preterm infant is a transparent alternative to existing guidelines, minimizing gestational-ageism and allowing for individualized management utilizing up-to-date data. Further input from other key stakeholders will be required prior to guideline implementation.

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BACKGROUND: Futility (inefficacy) interim monitoring is an important component in the conduct of phase III clinical trials, especially in life-threatening diseases. Desirable futility monitoring guidelines allow timely stopping if the new therapy is harmful or if it is unlikely to demonstrate to be sufficiently effective if the trial were to continue to its final analysis. There are a number of analytical approaches that are used to construct futility monitoring boundaries. The most common approaches are based on conditional power, sequential testing of the alternative hypothesis, or sequential confidence intervals. The resulting futility boundaries vary considerably with respect to the level of evidence required for recommending stopping the study.
OBJECTIVE: We evaluate the performance of commonly used methods using event histories from completed phase III clinical trials of the Radiation Therapy Oncology Group, Cancer and Leukemia Group B, and North Central Cancer Treatment Group.
METHODS: We considered published superiority phase III trials with survival endpoints initiated after 1990. There are 52 studies available for this analysis from different disease sites. Total sample size and maximum number of events (statistical information) for each study were calculated using protocol-specified effect size, type I and type II error rates. In addition to the common futility approaches, we considered a recently proposed linear inefficacy boundary approach with an early harm look followed by several lack-of-efficacy analyses. For each futility approach, interim test statistics were generated for three schedules with different analysis frequency, and early stopping was recommended if the interim result crossed a futility stopping boundary. For trials not demonstrating superiority, the impact of each rule is summarized as savings on sample size, study duration, and information time scales.
RESULTS: For negative studies, our results show that the futility approaches based on testing the alternative hypothesis and repeated confidence interval rules yielded less savings (compared to the other two rules). These boundaries are too conservative, especially during the first half of the study (<50% of information). The conditional power rules are too aggressive during the second half of the study (>50% of information) and may stop a trial even when there is a clinically meaningful treatment effect. The linear inefficacy boundary with three or more interim analyses provided the best results. For positive studies, we demonstrated that none of the futility rules would have stopped the trials.
CONCLUSIONS: The linear inefficacy boundary futility approach is attractive from statistical, clinical, and logistical standpoints in clinical trials evaluating new anti-cancer agents.