Characterisation of older patients that require, but do not undergo, emergency laparotomy: a multicentre cohort study.

BACKGROUND: Older adults (≥65 yr) account for the majority of emergency laparotomies in the UK and are well characterised with reported outcomes. In contrast, there is limited knowledge on those patients that require emergency laparotomy but do not undergo surgery (NoLaps). METHODS: A multicentre cohort study (n=64 UK surgical centres) recruited 750 consecutive NoLap patients (February 15th - November 15th 2021, inclusive of a 90-day follow up period). Each patient was admitted to hospital with a surgical condition treatable by an emergency laparotomy (defined by The National Emergency Laparotomy Audit (NELA) criteria), but a decision was made not to undergo surgery (NoLap). RESULTS: NoLap patients were predominately female (452 patients, 60%), of advanced age (median age 83.0 yr, interquartile range 77.0-88.8), frail (523 patients, 70%), and had severe comorbidity (750 patients, 100%); 99% underwent CT scanning. The commonest diagnoses were perforation (26%), small bowel obstruction (17%), and ischaemic bowel (13%). The 90-day mortality was 79% and influencing factors were >80 yr, underweight BMI, elevated serum lactate or creatinine concentration. The majority of patients died in hospital (77%), with those with ischaemic bowel dying early. For the 21% of NoLap patients that survived to 90 days, 77% returned home with increased care requirements. CONCLUSIONS: This study reports that the NoLap patient population present significant medical challenges because of their extreme levels of comorbidity, frailty, and physiology. Despite these complexities a fifth remained alive at 90 days. Further work is underway to explore this high-risk decision-making process. CLINICAL TRIAL REGISTRATION: ISRCTN14556210.

Group sequential testing of a treatment effect using a surrogate marker.

The identification of surrogate markers is motivated by their potential to make decisions sooner about a treatment effect. However, few methods have been developed to actually use a surrogate marker to test for a treatment effect in a future study. Most existing methods consider combining surrogate marker and primary outcome information to test for a treatment effect, rely on fully parametric methods where strict parametric assumptions are made about the relationship between the surrogate and the outcome, and/or assume the surrogate marker is measured at only a single time point. Recent work has proposed a nonparametric test for a treatment effect using only surrogate marker information measured at a single time point by borrowing information learned from a prior study where both the surrogate and primary outcome were measured. In this paper, we utilize this nonparametric test and propose group sequential procedures that allow for early stopping of treatment effect testing in a setting where the surrogate marker is measured repeatedly over time. We derive the properties of the correlated surrogate-based nonparametric test statistics at multiple time points and compute stopping boundaries that allow for early stopping for a significant treatment effect, or for futility. We examine the performance of our proposed test using a simulation study and illustrate the method using data from two distinct AIDS clinical trials.

Talking About Suffering in the Intensive Care Unit.

BACKGROUND: Some have hypothesized that talk about suffering can be used by clinicians to motivate difficult decisions, especially to argue for reducing treatment at the end of life. We examined how talk about suffering is related to decision-making for critically ill patients, by evaluating transcripts of conversations between clinicians and patients' families. METHODS: We conducted a secondary qualitative content analysis of audio-recorded family meetings from a multicenter trial conducted in the adult intensive care units of five hospitals from 2012-2017 to look at how the term "suffering" and its variants were used. A coding guide was developed by consensus-oriented discussion by four members of the research team. Two coders independently evaluated each transcript. We followed an inductive approach to data analysis in reviewing transcripts; findings were iteratively discussed among study authors until consensus on key themes was reached. RESULTS: Of 146 available transcripts, 34 (23%) contained the word "suffer" or "suffering" at least once, with 58 distinct uses. Clinicians contributed 62% of first uses. Among uses describing the suffering of persons, 57% (n = 24) were related to a decision, but only 42% (n = 10) of decision-relevant uses accompanied a proposal to limit treatment, and only half of treatment-limiting uses (n = 5) were initiated by clinicians. The target terms had a variety of implicit meanings, including poor prognosis, reduced functioning, pain, discomfort, low quality of life, and emotional distress. Suffering was frequently attributed to persons who were unconscious. CONCLUSIONS: Our results did not support the claim that the term "suffering" and its variants are used primarily by clinicians to justify limiting treatment, and the terms were not commonly used in our sample when decisions were requested. Still, when these terms were used, they were often used in a decision-relevant fashion.

Futile therapeutic nursing interventions in adult intensive care: A descriptive study.

Background: Despite the progress made in recent decades on the phenomenon of futility in adult intensive care, recognizing it during clinical care practice remains a complex and sensitive process, during which questions are often raised for which concrete answers are difficult to find. Aims: To analyze the frequency with which futile nursing interventions are implemented in critically ill patients admitted to adult intensive care in specific situations and how often futile autonomous and interdependent nursing interventions are implemented in the same population, as perceived by adult intensive care nurses. Research design: Cross-sectional, quantitative, and descriptive study, which employed a questionnaire constructed specifically for this research to assess the perception of therapeutic futility in nursing in adult intensive care. Following an evaluation of the psychometric properties, the questionnaire was made available in an electronic format on the EUSurvey platform between August and October 2024. The data was analyzed between November 2023 and March 2024 using the statistical software packages SPSS and R. Participants and research context: A simple random sample of nurses working in level II and level III intensive care units in Portugal. Ethical considerations: Research ethical approvals were obtained, and the participants provided informed consent. Findings/results: Four hundred and fourteen valid questionnaires were obtained. The results allow the identification of thirty-three statistically significant associations, the inference of intervals for the mean and median for the perception of futility of nursing interventions with a 95% confidence interval, and enable the hierarchization of nursing interventions implemented in critically ill patients admitted to adult intensive care units according to the nurses' perception of their futility. Conclusion: There is a balance in nurses' perception of the futility of their interventions in the specific situations analyzed. There is statistically significant evidence that interdependent nursing interventions are, in general, more frequently perceived as futile when compared to autonomous nursing interventions.

Withdrawal/Withholding of Life-Sustaining Therapies: Limitation of Therapeutic Effort in the Intensive Care Unit.

Background/Objectives: The change in critically ill patients makes limitation of therapeutic effort (LTE) a widespread practice when therapeutic goals cannot be achieved. We aimed to describe the application of LTE in a post-surgical Intensive Care Unit (ICU), analyze the measures used, the characteristics of the patients, and their evolution. Methods: Retrospective observational study, including all patients to whom LTE was applied in a postsurgical ICU between January 2021 and December 2022. The LTE defined were brain death, withdrawal of measures, and withholding. Withholding limitations included orders for no cardiopulmonary resuscitation, no orotracheal intubation, no reintubation, no tracheostomy, no renal replacement therapies, and no vasoactive support. Patient and ICU admission data were related to the applied LTE. Results: Of the 2056 admitted, LTE protocols were applied to 106 patients. The prevalence of LTE in the ICU was 5.1%. Data were analyzed in 80 patients. A total of 91.2% of patients had been admitted in an emergency situation, and 56.2% had been admitted after surgery. The most widespread limitation was treatment withholding (83.8%) compared to withdrawal (13.8%). No differences were found regarding who made the decision and the type of limitation employed. However, patients with the limitation of no intubation had a longer stay (p = 0.025). Additionally, the order of not starting or increasing vasopressor support resulted in a longer hospital stay (p = 0.007) and a significantly longer stay until death (p = 0.044). Conclusions: LTE is a frequent measure in critically ill patient management and is less common in the postoperative setting. The most widespread measure was withholding, with the do-not-resuscitate order being the most common. The decision was made mainly by the medical team and the family, respecting the wishes of the patients. A joint patient-centered approach should be made in these decisions to avoid futile treatment and ensure end-of-life comfort.

[Ethical boundary decisions in intensive care medicine]. / Ethische Grenzentscheidungen in der Intensivmedizin.

BACKGROUND: Ethical decision-making is a cornerstone of intensive care and emergency medicine. In acute scenarios, clinicians often face rapid, high-stakes decisions concerning life and death, made more challenging by time constraints and incomplete information. These decisions are further complicated by economic constraints, limited resources, and evolving technological capabilities. QUESTION: What decision-making aids and factors can be employed in ethical borderline cases within intensive care medicine? RESULTS: Fundamental ethical principles such as patient autonomy, beneficence, non-maleficence, and justice form the basis for medical treatment decisions. Evaluating the patient's will through advanced directives or proxy consensus is crucial, although advanced directives can be ambiguous. Assessing quality of life is increasingly important, with instruments such as the Clinical Frailty Scale (CFS) being utilized. For older patients, a holistic approach is recommended, focusing on overall health rather than chronological age. In patients with advanced underlying diseases, a multidisciplinary dialogue is essential. DISCUSSION: Decision-making in intensive care medicine requires careful consideration of medical, ethical, and individual factors. Despite advances in artificial intelligence and prognostic models, human judgment remains crucial. During periods of resource scarcity, ethically sound triage protocols are required. The challenge lies in applying these principles and factors in clinical practice while respecting the individuality of each patient.

Development and Validation of Futility of Resuscitation Measure in Older Adult Trauma Patients.

INTRODUCTION: This study aimed to develop and validate Futility of Resuscitation Measure (FoRM) for predicting the futility of resuscitation among older adult trauma patients. METHODS: This is a retrospective analysis of the American College of Surgeons-Trauma Quality Improvement Program database (2017-2018) (derivation cohort) and American College of Surgeons level I trauma center database (2017-2022) (validation cohort). We included all severely injured (injury severity score >15) older adult (aged ≥60 y) trauma patients. Patients were stratified into decades of age. Injury characteristics (severe traumatic brain injury [Glasgow Coma Scale ≤ 8], traumatic brain injury midline shift), physiologic parameters (lowest in-hospital systolic blood pressure [≤1 h], prehospital cardiac arrest), and interventions employed (4-h packed red blood cell transfusions, emergency department resuscitative thoracotomy, resuscitative endovascular balloon occlusion of the aorta, emergency laparotomy [≤2 h], early vasopressor requirement [≤6 h], and craniectomy) were identified. Regression coefficient-based weighted scoring system was developed using the Schneeweiss method and subsequently validated using institutional database. RESULTS: A total of 5562 patients in derivation cohort and 873 in validation cohort were identified. Mortality was 31% in the derivation cohort and FoRM had excellent discriminative power to predict mortality (area under the receiver operator characteristic = 0.860; 95% confidence interval [0.847-0.872], P < 0.001). Patients with a FoRM score of >16 had a less than 10% chance of survival, while those with a FoRM score of >20 had a less than 5% chance of survival. In validation cohort, mortality rate was 17% and FoRM had good discriminative power (area under the receiver operator characteristic = 0.76; 95% confidence interval [0.71-0.80], P < 0.001). CONCLUSIONS: FoRM can reliably identify the risk of futile resuscitation among older adult patients admitted to our level I trauma center.

Markers of Futile Resuscitation in Traumatic Hemorrhage: A Review of the Evidence and a Proposal for Futility Time-Outs during Massive Transfusion.

The reduction in the blood supply following the 2019 coronavirus pandemic has been exacerbated by the increased use of balanced resuscitation with blood components including whole blood in urban trauma centers. This reduction of the blood supply has diminished the ability of blood banks to maintain a constant supply to meet the demands associated with periodic surges of urban trauma resuscitation. This scarcity has highlighted the need for increased vigilance through blood product stewardship, particularly among severely bleeding trauma patients (SBTPs). This stewardship can be enhanced by the identification of reliable clinical and laboratory parameters which accurately indicate when massive transfusion is futile. Consequently, there has been a recent attempt to develop scoring systems in the prehospital and emergency department settings which include clinical, laboratory, and physiologic parameters and blood products per hour transfused as predictors of futile resuscitation. Defining futility in SBTPs, however, remains unclear, and there is only nascent literature which defines those criteria which reliably predict futility in SBTPs. The purpose of this review is to provide a focused examination of the literature in order to define reliable parameters of futility in SBTPs. The knowledge of these reliable parameters of futility may help define a foundation for drawing conclusions which will provide a clear roadmap for traumatologists when confronted with SBTPs who are candidates for the declaration of futility. Therefore, we systematically reviewed the literature regarding the definition of futile resuscitation for patients with trauma-induced hemorrhagic shock, and we propose a concise roadmap for clinicians to help them use well-defined clinical, laboratory, and viscoelastic parameters which can define futility.

Liver transplantation for acute liver failure and acute-on-chronic liver failure.

Acute liver failure (ALF) and acute-on-chronic liver (ACLF) are distinct phenotypes of liver failure and, thus, need to be compared and contrasted for appropriate management. There has been a significant improvement in the outcomes of these patients undergoing liver transplantation (LT). Survival post-LT for ALF and ACLF ranges between 90% and 95% and 80% and 90% at 1 year, futility criteria have been described in both ALF and ACLF where organ failures define survival. Plasma exchange and continuous renal replacement therapy may serve as bridging therapies. Identifying the futility of LT is as necessary as the utility of LT in patients with ALF and ACLF. The role of regenerative therapies such as granulocyte colony-stimulating factors in ACLF and hepatocyte and xenotransplantation in both conditions remains uncertain. Measures to increase the donor pool through increasing deceased donor transplants in Asian countries, living donations in Western countries, auxiliary liver transplants, and ABO-incompatible liver transplants are necessary to improve the survival of these patients. In this review, we discuss the similarities and differences in clinical characteristics and the timing and outcomes of LT for ALF and ACLF, briefly highlighting the role of bridging therapies and providing an overview of recent advances in the management of ALF and ACLF.

First do no harm: Predicting futility of intervention in geriatric emergency general surgery.

BACKGROUND: Emergent surgical conditions are common in geriatric patients, often necessitating major operative procedures on frail patients. Understanding risk profiles is crucial for decision-making and establishing goals of care. METHODS: We queried NSQIP 2015-2019 for patients ≥65 years undergoing open abdominal surgery for emergency general surgery conditions. Logistic regression was used to identify 30-day mortality predictors. RESULTS: Of 41,029 patients, 5589 (13.6 â€‹%) died within 30 days of admission. The highest predictors of mortality were ASA status 5 (aOR 9.7, 95 â€‹% CI,3.5-26.8, p â€‹< â€‹0.001), septic shock (aOR 4.9, 95 â€‹% CI,4.5-5.4, p â€‹< â€‹0.001), and dialysis (aOR 2.1, 95 â€‹% CI,1.8-2.4, p â€‹< â€‹0.001). Without risk factors, mortality rates were 11.9 â€‹% after colectomy and 10.2 â€‹% after small bowel resection. Patients with all three risk factors had a mortality rate of 79.4 â€‹% and 100 â€‹% following colectomy and small bowel resection, respectively. CONCLUSIONS: In older adults undergoing emergent open abdominal surgery, septic shock, ASA status, and dialysis were strongly associated with futility of surgical intervention. These findings can inform goals of care and informed decision-making.

Group sequential design for time-to-event outcome with non-proportional hazards using the concept of relative time utilizing two different Weibull distributions.

A group sequential design allows investigators to sequentially monitor efficacy and safety as part of interim testing in phase III trials. Literature is well developed in the case of continuous and binary outcomes, however, in case of trials with a time-to-event outcome, popular methods of sample size calculation often assume proportional hazards. In situations where the proportional hazards assumption is inappropriate as indicated by historical data, these popular methods are very restrictive. In this paper, a novel simulation-based group sequential design is proposed for a two-arm randomized phase III clinical trial with a survival endpoint for the non-proportional hazards scenario. By assuming that the survival times for each treatment arm follow two different Weibull distributions, the proposed method utilizes the concept of Relative Time to calculate the efficacy and safety boundaries at selected interim testing points. The test statistic used to generate these boundaries is asymptotically normal, allowing p-value calculation at each boundary. Many design features specific to time-to-event data can be incorporated with ease. Additionally, the proposed method allows the flexibility of having the accelerated failure time model and the proportional hazards model as constrained special cases. Real life applications are discussed demonstrating the practicality of the proposed method.

Traumatic Brain Injury as an Independent Predictor of Futility in the Early Resuscitation of Patients in Hemorrhagic Shock.

This review explores the concept of futility timeouts and the use of traumatic brain injury (TBI) as an independent predictor of the futility of resuscitation efforts in severely bleeding trauma patients. The national blood supply shortage has been exacerbated by the lingering influence of the COVID-19 pandemic on the number of blood donors available, as well as by the adoption of balanced hemostatic resuscitation protocols (such as the increasing use of 1:1:1 packed red blood cells, plasma, and platelets) with and without early whole blood resuscitation. This has underscored the urgent need for reliable predictors of futile resuscitation (FR). As a result, clinical, radiologic, and laboratory bedside markers have emerged which can accurately predict FR in patients with severe trauma-induced hemorrhage, such as the Suspension of Transfusion and Other Procedures (STOP) criteria. However, the STOP criteria do not include markers for TBI severity or transfusion cut points despite these patients requiring large quantities of blood components in the STOP criteria validation cohort. Yet, guidelines for neuroprognosticating patients with TBI can require up to 72 h, which makes them less useful in the minutes and hours following initial presentation. We examine the impact of TBI on bleeding trauma patients, with a focus on those with coagulopathies associated with TBI. This review categorizes TBI into isolated TBI (iTBI), hemorrhagic isolated TBI (hiTBI), and polytraumatic TBI (ptTBI). Through an analysis of bedside parameters (such as the proposed STOP criteria), coagulation assays, markers for TBI severity, and transfusion cut points as markers of futilty, we suggest amendments to current guidelines and the development of more precise algorithms that incorporate prognostic indicators of severe TBI as an independent parameter for the early prediction of FR so as to optimize blood product allocation.

Futility Interim Analysis Based on Probability of Success Using a Surrogate Endpoint.

In clinical trials with time-to-event data, the evaluation of treatment efficacy can be a long and complex process, especially when considering long-term primary endpoints. Using surrogate endpoints to correlate the primary endpoint has become a common practice to accelerate decision-making. Moreover, the ethical need to minimize sample size and the practical need to optimize available resources have encouraged the scientific community to develop methodologies that leverage historical data. Relying on the general theory of group sequential design and using a Bayesian framework, the methodology described in this paper exploits a documented historical relationship between a clinical "final" endpoint and a surrogate endpoint to build an informative prior for the primary endpoint, using surrogate data from an early interim analysis of the clinical trial. The predictive probability of success of the trial is then used to define a futility-stopping rule. The methodology demonstrates substantial enhancements in trial operating characteristics when there is a good agreement between current and historical data. Furthermore, incorporating a robust approach that combines the surrogate prior with a vague component mitigates the impact of the minor prior-data conflicts while maintaining acceptable performance even in the presence of significant prior-data conflicts. The proposed methodology was applied to design a Phase III clinical trial in metastatic colorectal cancer, with overall survival as the primary endpoint and progression-free survival as the surrogate endpoint.

Examining ethnic identity, school climate, and academic futility among minoritized students.

The present causal-comparative study examined the relation between school climate, ethnic identity, and academic futility among racially and ethnically minoritized students. The sample included 1721 racially and ethnically minoritized students identifying as Black, Asian, Latine, and Multiracial from 11 schools in the northeastern region of the United States. Regression models indicated a direct relation between the school climate subscales including School Connectedness, Safety, Character, Peer Support, Adult Support, Cultural Acceptance, Physical Environment, and Order and Discipline and academic futility for all groups in the study. Ethnic identity moderated the relation between school climate subscales and academic futility, although the impact differed across racial and ethnic groups. The present study's results highlight the similarities and differences in the educational experiences of minoritized students. The discussion provides recommendations for cultivating educational environments that are culturally affirming and informed to meet the needs of an increasingly diverse student population. Limitations and future directions are discussed.

Student-teacher relationships and sense of academic futility: Longitudinal associations among early adolescents of immigrant and non-immigrant background.

Sense of academic futility entails feelings of having no control over ones' educational success. Although mounting evidence points to its negative consequences for students' educational outcomes, less is known about its socio-contextual antecedents. Relatedly, the current study explored how fair and supportive relationships with teachers are related to the sense of academic futility and if class belonging mediates this link in a sample of adolescents with immigrant and non-immigrant backgrounds. A total of 1065 seventh-grade students (Mage = 13.12; SD = 0.42; 45% girls) from 55 classrooms completed questionnaires at two time points 1 year apart. Results of multilevel analyses indicated that fair and supportive relationships with teachers contributed to decreases in sense of academic futility at the individual but not at the classroom level. No mediation or moderation effects emerged. These findings highlight the crucial role of democratic student-teacher relationships in supporting the positive school adjustment of all students in increasingly multicultural societies.

Discordant conceptualisations of eating disorder recovery and their influence on the construct of terminality.

Eating disorders (EDs) are complex, multifaceted conditions that significantly impact quality-of-life, often co-occur with multiple medical and psychiatric diagnoses, and are associated with a high risk of medical sequelae and mortality. Fortunately, many people recover even after decades of illness, although there are different conceptualisations of recovery and understandings of how recovery is experienced. Differences in these conceptualisations influence categorisations of ED experiences (e.g., longstanding vs. short-duration EDs), prognoses, recommended treatment pathways, and research into treatment outcomes. Within recent years, the proposal of a 'terminal' illness stage for a subset of individuals with anorexia nervosa and arguments for the prescription of end-of-life pathways for such individuals has ignited debate. Semantic choices are influential in ED care, and it is critical to consider how conceptualisations of illness and recovery and power dynamics influence outcomes and the ED 'staging' discourse. Conceptually, 'terminality' interrelates with understandings of recovery, efficacy of available treatments, iatrogenic harm, and complex co-occurring diagnoses, as well as the functions of an individual's eating disorder, and the personal and symbolic meanings an individual may hold regarding suffering, self-starvation, death, health and life. Our authorship represents a wide range of lived and living experiences of EDs, treatment, and recovery, ranging from longstanding and severe EDs that may meet descriptors of a 'terminal' ED to a variety of definitions of 'recovery'. Our experiences have given rise to a shared motivation to analyse how existing discourses of terminality and recovery, as found in existing research literature and policy, may shape the conceptualisations, beliefs, and actions of individuals with EDs and the healthcare systems that seek to serve them.

Defining futile and potentially avoidable interhospital trauma transfers.

PURPOSE: Interhospital transfer of critically injured patients to a major trauma service reduces preventable death in major trauma. Yet some of those transferred die without intervention. These 'futile' interhospital trauma transfers (IHTs), and other potentially avoidable IHTs place enormous stress on families of trauma victims, can delay care, and incur great cost to public health resources. This study sought to characterise these IHTs using current state guidelines for interhospital transfer. METHODS: A retrospective cohort study was conducted using our institution's trauma registry from January 2016-December 2020. All adult patients transferred to our major trauma service were analysed. Futile IHTs were defined as death or transfer to hospice care without surgical, endoscopic, or radiological intervention, and without ICU admission, within 72 h of admission. Potentially avoidable IHTs were defined as all patients discharged alive without intervention or ICU care, and secondary over-triage patients are a subset of these patients who were discharged within 72 h of admission. Patient demographics, injuries, and treatments were categorised from electronic records and analysed. RESULTS: Of 2,837 IHTs, seven (0.2 %) met criteria for futility. The majority were female, median age of 80 (IQR 85-75) and had a median Injury Severity Score (ISS) of 16 (IQR 25.5-11.5). By contrast, 1391 patients (49 %) were classified as potentially avoidable and 513 (18 %) were considered secondary over-triage. The majority were male, median age of 43 (IQR 62-28), and had a median ISS of 9 (IQR 13-4). Of these potentially avoidable IHTs, 984 (70.7 %) were discharged directly home. CONCLUSION: Futile IHTs were infrequent, however over half of all trauma patients transferred from other hospitals were discharged without tertiary-level intervention. Trauma services should consider developing systems such as telehealth to support regional general and orthopaedic surgeons to co-manage lower risk trauma, particularly minor head and minor spinal trauma patients. This could be an integral part of safely reducing potentially avoidable IHTs and their associated costs while maintaining a low rate of preventable mortality in trauma.

Upstrapping to determine futility: predicting future outcomes nonparametrically from past data.

BACKGROUND: Clinical trials often involve some form of interim monitoring to determine futility before planned trial completion. While many options for interim monitoring exist (e.g., alpha-spending, conditional power), nonparametric based interim monitoring methods are also needed to account for more complex trial designs and analyses. The upstrap is one recently proposed nonparametric method that may be applied for interim monitoring. METHODS: Upstrapping is motivated by the case resampling bootstrap and involves repeatedly sampling with replacement from the interim data to simulate thousands of fully enrolled trials. The p-value is calculated for each upstrapped trial and the proportion of upstrapped trials for which the p-value criteria are met is compared with a pre-specified decision threshold. To evaluate the potential utility for upstrapping as a form of interim futility monitoring, we conducted a simulation study considering different sample sizes with several different proposed calibration strategies for the upstrap. We first compared trial rejection rates across a selection of threshold combinations to validate the upstrapping method. Then, we applied upstrapping methods to simulated clinical trial data, directly comparing their performance with more traditional alpha-spending and conditional power interim monitoring methods for futility. RESULTS: The method validation demonstrated that upstrapping is much more likely to find evidence of futility in the null scenario than the alternative across a variety of simulations settings. Our three proposed approaches for calibration of the upstrap had different strengths depending on the stopping rules used. Compared to O'Brien-Fleming group sequential methods, upstrapped approaches had type I error rates that differed by at most 1.7% and expected sample size was 2-22% lower in the null scenario, while in the alternative scenario power fluctuated between 15.7% lower and 0.2% higher and expected sample size was 0-15% lower. CONCLUSIONS: In this proof-of-concept simulation study, we evaluated the potential for upstrapping as a resampling-based method for futility monitoring in clinical trials. The trade-offs in expected sample size, power, and type I error rate control indicate that the upstrap can be calibrated to implement futility monitoring with varying degrees of aggressiveness and that performance similarities can be identified relative to considered alpha-spending and conditional power futility monitoring methods.

Ethical Considerations in Pediatric Surgery.

Pediatric surgeons need to learn to give as much importance to the ethical approach as they have been giving to the systemic methodology in their clinical approach all along. The law of the land and the governmental rules also need to be kept in mind before deciding the final solution. They need to always put medical problems in the background of ethical context, reach a few solutions keeping in mind the available resources, and apply the best solution in the interest of their pediatric patients.