To investigate if a prospective feedback loop that flags older patients at risk of death can reduce non-beneficial treatment at end of life.
Prospective stepped-wedge cluster randomised trial with usual care and intervention phases.
Three large tertiary public hospitals in south-east Queensland, Australia.
14 clinical teams were recruited across the three hospitals. Teams were recruited based on a consistent history of admitting patients aged 75+ years, and needed a nominated lead specialist consultant. Under the care of these teams, there were 4,268 patients (median age 84 years) who were potentially near the end of life and flagged at risk of non-beneficial treatment.
The intervention notified clinicians of patients under their care determined as at-risk of non-beneficial treatment. There were two notification flags: a real-time notification and an email sent to clinicians about the at-risk patients at the end of each screening day. The nudge intervention ran for 16-35 weeks across the three hospitals.
The primary outcome was the proportion of patients with one or more intensive care unit (ICU) admissions. The secondary outcomes examined times from patients being flagged at-risk.
There was no improvement in the primary outcome of reduced ICU admissions (mean probability difference [intervention minus usual care] = -0.01, 95% confidence interval -0.08 to 0.01). There were no differences for the times to death, discharge, or medical emergency call. There was a reduction in the probability of re-admission to hospital during the intervention phase (mean probability difference -0.08, 95% confidence interval -0.13 to -0.03).
This nudge intervention was not sufficient to reduce the trial\'s non-beneficial treatment outcomes in older hospital patients.
Australia New Zealand Clinical Trial Registry, ACTRN12619000675123 (registered 6 May 2019).

BACKGROUND: Advance Directive documents allow citizens to choose the treatments they want for end-of-life care without considering therapeutic futility.
OBJECTIVE: To analyze patients\' and caregivers\' answers to Advance Directives and understand their expectations regarding their decisions.
METHODS: This study analyzed participants\' answers to a previously published trial, conceived to test the document\'s efficacy as a communication tool.
METHODS: Sixty palliative patients and 60 caregivers (n = 120) registered their preferences in the Advance Directive document and expressed their expectations regarding whether to receive the chosen treatments.
RESULTS: In the patient and caregiver groups, 30% and 23.3% wanted to receive cardiorespiratory resuscitation; 23.3% and 25% wanted to receive artificial organ support; and 40% and 35% chose to receive artificial feeding and hydration, respectively. The participants ignored the concept of therapeutic futility and expected to receive invasive treatments. The concept of therapeutic futility should be addressed and discussed with both the patients and caregivers. Legal Advanced Directive documents should be made clear to reduce misinterpretations and potential legal conflicts.
CONCLUSIONS: The authors suggest that all citizens should be clarified regarding the futility concept before filling out the Advance Directives and propose a grammatical change in the document, replacing the phrase \"Health Care to Receive / Not to Receive\" with the sentence \"Health Care to Accept / Refuse\" so that patients cannot demand treatments, but instead accept or refuse the proposed therapeutic plans.
BACKGROUND: ClinicalTrials.gov ID NCT05090072.
UNASSIGNED: https://clinicaltrials.gov/ct2/show/NCT05090072.

BACKGROUND: Life-sustaining treatment limitation (LSV) is the medical act of withdrawing or not initiating measures that are considered futile in a patient\'s specific situation. LSV in critically ill patients remains a difficult topic to study, due to the multitude of factors that condition it.
OBJECTIVE: To determine factors related to LSV in ICU in cases of post-ICU in-hospital mortality, as well as factors associated with survival after discharge from ICU.
METHODS: Retrospective longitudinal study.
UNASSIGNED: Intensive care unit of a tertiary hospital.
METHODS: People who died in the hospitalization ward after ICU treatment between January 2014 and December 2019.
METHODS: None. This is an observational study.
METHODS: Age, sex, probability of death, type of admission, LSV in ICU, oncological disease, dependence, invasive mechanical ventilation, emergency hemodialysis, transfusion of blood products, nosocomial infection (NI), pre-ICU, intra-ICU and post-ICU stays.
RESULTS: Of 114 patients who died outside the ICU, 49 had LSV registered in the ICU (42.98%). Age and stay prior to ICU admission were positively associated with LSV (OR 1,03 and 1,08, respectively). Patients without LSV had a higher post-ICU stay, while it was lower for male patients.
CONCLUSIONS: Our results support that LSV established within the ICU can avoid complications commonly associated with unnecessary prolongation of stay, such as NI.

暂无摘要。

The desire to deliver appropriate care after trauma creates challenges when deciding to proceed if care appears futile. This study aimed to analyze survival rates for trauma patients who undergo closed chest compressions by decade of life.
A multicenter retrospective review of trauma patients with an Injury Severity Score ≥16 who underwent closed chest compressions from 2015 to 2020 at four large, urban, academic Level I trauma centers was conducted. Those with intraoperative arrest were excluded. The primary endpoint was survival to discharge.
Of the 247 patients meeting inclusion criteria, 18% were 70 years or older, 78% were male, and 24% presented due to a penetrating mechanism of injury. Compressions occurred in the prehospital setting (56%), emergency department (21%), intensive care unit (19%), and on the floor (3%). On average, patients arrested on hospital day 2, and survived 1 day after arrest if return of spontaneous circulation was achieved. Overall mortality was 92%. Average hospital length of stay was lower in patients 70 years or older (3 days vs. 6 days, p < 0.01). Survival was highest in patients 60 years to 69 years (24%), and although patients 70 years or older presented with lower Injury Severity Scores (28 vs. 32, p = 0.04), no patient 70 years or older survived to hospital discharge (0% v 9%, p = 0.03).
Closed chest compressions are associated with a high mortality rate after moderate to severe trauma with 100% mortality in patients older than 70 years. This information may assist with the decision to withhold chest compression, especially in older adults.
Prognostic and Epidemiological; Level IV.

BACKGROUND: In Colombia, cancer incidence is increasing, as is the demand for end-of-life care. Understanding how patients who die from cancer experience this phase will allow the identification of factors associated with greater suffering and actions to improve end-of-life care. We aimed to explore associations between the level of suffering of patients who died from cancer and were cared for in three Colombian hospitals with patient, tumor, treatment, and care characteristics and provided information.
METHODS: Data on the last week of life and level of suffering were collected through proxies: Bereaved caregivers of patients who died from cancer in three participating Colombian hospitals. Bereaved caregivers participated in a phone interview and answered a series of questions regarding the last week of the patient\'s life. An ordinal logistic regression model explored the relationship between the level of suffering reported by bereaved caregivers with the patient\'s demographic and clinical characteristics, the bereaved caregivers, and the care received. Multivariate analyses were adjusted for place of death, treatments to prolong of life, prolongation of life during the dying process, suffering due to prolongation of life, type of cancer, age, if patient had partner, rural/urban residence of patient, importance of religion for the caregiver, caregivers´ relationship with the patient, and co-living with the patient.
RESULTS: A total of 174 interviews were included. Median age of the deceased patients was 64 years (IQR 52-72 years), and 93 patients were women (53.4%). Most caregivers had rated the level of suffering of their relative as \"moderately to extremely\" (n = 139, 80%). In multivariate analyses, factors associated with a higher level of suffering were: unclear information about the treatment and the process before death Odds Ratio (OR) 2.26 (90% CI 1.21-4.19), outpatient palliative care versus home care OR 3.05 (90% CI 1.05-8.88), procedures inconsistent with the patient\'s wishes OR 2.92 (90% CI 1.28-6.70), and a younger age (18-44 years) at death versus the oldest age group (75-93 years) OR 3.80 (90% CI 1.33-10.84, p = 0.04).
CONCLUSIONS: End-of-life care for cancer patients should be aligned as much as possible with patients´ wishes, needs, and capacities. A better dialogue between doctors, family members, and patients is necessary to achieve this.

Cancer immunotherapy trials are frequently characterized by delayed treatment effects such that the proportional hazards assumption is violated and the log-rank test suffers a substantial loss of statistical power. To increase the efficacy of the trial design, a variety of weighted log-rank tests have been proposed for fixed sample and group sequential trial designs. However, in such a group sequential design, it is often not recommended for futility interim monitoring due to possible delayed treatment effect which could result a high false-negative rate. To resolve this problem, we propose a group sequential design using a piecewise weighted log-rank test which provides an event-driven approach based on number of events after the delayed time. That is, the interim looks will not be conducted until the planned number of events observed after the delay time. Thus, it avoids the possibility of false-negative rate due to the delayed treatment effect. Furthermore, with an event-driven approach, the proposed group sequential design is robust against the underlying survival, accrual and censoring distributions. The group sequential designs using Fleming-Harrington-(ρ,γ) weighted log-rank test and a new weighted log-rank test are also discussed.

Patients (pts) with polycythemia vera (PV) suffer from pruritus, night sweats, and other symptoms, as well as from thromboembolic complications and progression to post-PV myelofibrosis. Ruxolitinib (RUX) is approved for second-line therapy in high-risk PV pts with hydroxyurea intolerance or resistance. The RuxoBEAT trial (NCT02577926, registered on October 1, 2015, at clinicaltrials.gov) is a multicenter, open-label, two-arm phase-IIb trial with a target population of 380 pts with PV or ET, randomized to receive RUX or best available therapy. This pre-specified futility analysis assesses the early clinical benefit and tolerability of RUX in previously untreated PV pts (6-week cytoreduction was allowed). Twenty-eight patients were randomly assigned to receive RUX. Compared to baseline, after 6 months of treatment, there was a significant reduction of median hematocrit (46 to 41%), the median number of phlebotomies per year (4.0 to 0), and median patient-reported pruritus scores (2 to 1), and a trend for reduced night sweat scores (1.5 to 0). JAK2V617F allele burden, as part of the scientific research program, also significantly decreased. One hundred nine adverse events (AEs) occurred in 24/28 patients (all grade 1 to 3), and no pt permanently discontinued treatment because of AEs. Thus, treatment with ruxolitinib in untreated PV pts is feasible, well-tolerated, and efficient regarding the above-mentioned endpoints.

BACKGROUND: Our randomized controlled clinical trial will explore the potential of bazedoxifene plus conjugated estrogen to modulate breast tissue-based risk biomarkers as a surrogate for breast cancer risk reduction. This paper investigates the statistical design features of the trial and the rationale for the final choice of its design. Group sequential designs are a popular design approach to allow a trial to stop early for success or futility, potentially saving time and money over a fixed trial design. While Bayesian adaptive designs enjoy the same properties as group sequential designs, they have the added benefit of using prior information as well as inferential interpretation conditional on the data. Whether a frequentist or Bayesian trial, most adaptive designs have interim analyses that allow for early stopping, typically utilizing only the primary endpoint. A drawback to this approach is that the study may not have enough data for adequate comparisons of a single, key secondary endpoint. This can happen, for example, if the secondary endpoint has a smaller effect than the primary endpoint.
METHODS: In this paper, we investigate a trial design called two-endpoint adaptive, which stops early only if a criterion is met for primary and secondary endpoints. The approach focuses the final analysis on the primary endpoint but ensures adequate data for the secondary analysis. Our study has two arms with a primary (change in mammographic fibroglandular volume) and secondary endpoint (change in mammary tissue Ki-67).
RESULTS: We present operating characteristics including power, trial duration, and type I error rate and discuss the value and risks of modeling Bayesian group sequential designs with primary and secondary endpoints, comparing against alternative designs. The results indicate that the two-endpoint adaptive design has better operating characteristics than competing designs if one is concerned about having adequate information for a key secondary endpoint.
CONCLUSIONS: Our approach balances trial speed and the need for information on the single, key secondary endpoint.

BACKGROUND: A resurgence of research into phase II trial design in the mid-2000s led to the use of futility designs in a wide variety of disease areas. Phase II futility studies differ from efficacy studies in that their null hypothesis is that treatment, relative to control, does not meet or exceed the level of benefit required to justify additional study. A rejection of the null hypothesis indicates that the treatment should not proceed to a larger confirmatory trial.
METHODS: Bayesian approaches to the design of phase II futility clinical trials are presented and allow for the quantification of key probabilities, such as the predictive probability of current trial success or even the predictive probability of a future trial\'s success.
RESULTS: We provide an illustration of the design and interpretation of a phase II futility study constructed in a Bayesian framework. We focus on the operating characteristics of our motivating trial based on a simulation study, as well as the general interpretation of trial outcomes, type I, and type II errors in this framework.
CONCLUSIONS: Phase II futility clinical trials, when designed under in a Bayesian framework, offer an alternative approach to the design of mid-phase studies which provide unique benefits relative to trials designed in a frequentist framework and designs which focus on treatment efficacy.