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Abstract Background Concerns about ethical conflicts, moral distress, and burnout in veterinary practice are steadily increasing. Root causes of these problems have not been rigorously identified. Little research has been done to evaluate the existence of moral distress in North American veterinarians or to explore its impact on career sustainability and poor well-being. Hypothesis/Objectives Ethical conflict and resultant moral distress are common occurrences in contemporary veterinary practice and negatively impact daily practice life, but may not be identified or labeled by veterinarians as such. Animals No animals were used in this study. Methods Mixed methods sequential explanatory design; confidential and anonymous on-line sampling of 889 veterinarians in North America. Results A majority of respondents reported feeling conflict over what care is appropriate to provide. Over 70% of respondents felt that the obstacles they faced that prevented them from providing appropriate care caused them or their staff moderate to severe distress. Seventy-nine percent of participants report being asked to provide care that they consider futile. More than 70% of participants reported no training in conflict resolution or self-care. Conclusions and Clinical Importance Veterinarians report widespread ethical conflict and moral distress across many practice types and demographics. Most veterinarians have little to no training on how to decrease the impact of these problems. Ethical conflict and resulting moral distress may be an important source of stress and poor well-being that is not widely recognized or well defined. Well-researched and effective tools used to decrease moral distress in human healthcare could be adapted to ameliorate this problem.

In many academic fields, the number of papers published each year has increased significantly over time. Policy measures aim to increase the quantity of scientists, research funding, and scientific output, which is measured by the number of papers produced. These quantitative metrics determine the career trajectories of scholars and evaluations of academic departments, institutions, and nations. Whether and how these increases in the numbers of scientists and papers translate into advances in knowledge is unclear, however. Here, we first lay out a theoretical argument for why too many papers published each year in a field can lead to stagnation rather than advance. The deluge of new papers may deprive reviewers and readers the cognitive slack required to fully recognize and understand novel ideas. Competition among many new ideas may prevent the gradual accumulation of focused attention on a promising new idea. Then, we show data supporting the predictions of this theory. When the number of papers published per year in a scientific field grows large, citations flow disproportionately to already well-cited papers; the list of most-cited papers ossifies; new papers are unlikely to ever become highly cited, and when they do, it is not through a gradual, cumulative process of attention gathering; and newly published papers become unlikely to disrupt existing work. These findings suggest that the progress of large scientific fields may be slowed, trapped in existing canon. Policy measures shifting how scientific work is produced, disseminated, consumed, and rewarded may be called for to push fields into new, more fertile areas of study.

Background Varoglutamstat (PQ912) is an oral small molecule inhibitor of glutaminyl cyclases which reduces the pyroglutamate formation of Aβ and CCL2. Preclinical and Ph1 trials support this Ph2 evaluation in early AD. Our objectives included selecting the highest safe and well‐tolerated dose of varoglutamstat with futility analysis at 24 weeks (Ph2A) followed by seamless evaluation of longer‐term safety and efficacy at 72 weeks at this dose (Ph2B). Method Participants with biomarker confirmed early AD were randomized to varoglutamstat or placebo. A sequential design tested 3 descending doses (600mg, 300mg, 150mg BID) using a continuous Pocock safety boundary. A Stage Gate futility analysis of the first 180 subjects at 24 weeks was designed to guide the decision from Ph2A‐B (Figure 1). The Ph2B primary endpoint was CDR‐sum‐of‐boxes (CDR‐SB), with secondary endpoints CFC2, ABC score, spectral EEG, FAQ, ADAS‐Cog‐13, and NPI. Result Table 1 presents baseline characteristics of the 109 randomized and dosed participants. The first dose cohort of varoglutamstat 600mg or placebo did not cross the safety boundary in Ph2A, supporting this dose selection for all participants thereafter. An abbreviated futility analysis was conducted after the trial was terminated prematurely for administrative reasons, with the provisional result of ‘halt enrollment’(yellow) (Figure 1). There were 74% of participants who completed week 24 and 31% week 72 (Figure 2). There were no significant differences between varoglutamstat and placebo in LS mean squares from baseline to week 72 in CDR‐SB (‐0.05 [95% CI ‐1.03, 0.92]), CFC2 (0.97 [95% CI ‐3.34, 5.28]), ABC score (0.10 [95% CI ‐0.10, 0.30]), FAQ (‐0.60 [95% CI ‐4.22, 3.01]), ADAS‐Cog‐13 (2.03 [95% CI ‐2.29, 6.36]); or NPI (‐3.09 [95% CI ‐7.81, 1.62]). At least one TEAE during treatment was reported in 84.9% varoglutamstat and 76.8% placebo with treatment discontinuations due to AE 11.3% varoglutamstat and 3.4% placebo. Severe TEAEs occurred with similar frequencies across arms. Frequency of SAEs/AESIs was 18.9/1.9% varoglutamstat versus 8.9%/5.4% placebo. Conclusion Varoglutamstat was safe and well‐tolerated in this VIVA‐MIND early AD RCT. Efficacy assessment did not demonstrate any significant treatment benefits however, the available sample was limited. Biomarker results and PK/PD are pending.

Concerns over limited medical equipment and resources, particularly in intensive care units (ICUs), have raised the issue of medical futility. Medical futility draws a contrast between physician's authority and patients' autonomy and it is one of the major issues of end-of-life ethical decision-making. The aim of this study was to review medical futility and its challenges. In this systematized review study, a comprehensive search of the existing literature was performed using an internet search with broad keywords to access related articles in both Persian and English databases. Finally, 89 articles were selected and surveyed. Medical futility is a complex, ambiguous, subjective, situation-specific, value-laden, and goal-dependent concept which is almost always surrounded by some degrees of uncertainty; hence, there is no objective and valid criterion for its determination. This concept is affected by many different factors such as physicians' and patients' value systems, medical goals, and sociocultural and religious context, and individuals' emotions and personal characteristics. It is difficult to achieve a clear consensus over the concept of medical futility; hence, it should be defined and determined at an individual level and based on the unique condition of each patient.

Background Acute-on-chronic liver failure (ACLF) is a severe complication of cirrhosis and is defined by organ failure and high rates of short-term mortality. Patients with ACLF are managed with multiorgan support in the intensive care unit (ICU). Currently, it is unclear when this supportive care becomes futile, particularly in patients who are not candidates for liver transplant. The aim of this study was to determine whether the currently available prognostic scores can identify patients with ACLF in whom prolonged ICU care is likely to be futile despite maximal treatment efforts. Methods Data of 202 consecutive patients with ACLF admitted to the ICU at the Royal Free Hospital London between 2005 and 2012 were retrospectively analyzed. Prognostic scores for chronic liver diseases, such as Child-Pugh, Model for End-Stage Liver Disease (MELD), European Foundation for the study of chronic liver failure (CLIF-C) organ failure (OF), and CLIF-C ACLF, were calculated 48 hours after ICU admission and correlated with patient outcome after 28 days. Results The CLIF-C ACLF score, compared with all other scores, most accurately predicted 28-day mortality, with an area under the receiver operator characteristic of 0.8 (CLIF-C OF, 0.75; MELD, 0.68; Child-Pugh, 0.66). A CLIF-C ACLF score cutoff ≥ 70 identified patients with a 100% mortality within 28 days. These patients had elevated inflammatory parameters representing a systemic inflammatory response, most often renal failure, compared with patients below this cutoff. Conclusions Patients with ACLF and high CLIF-C ACLF score (≥ 70) after 48 hours of intensive care may reach a threshold of futility for further ongoing intensive support. The best treatment options in this scenario remain to be determined but may include palliative care.

BackgroundEnd-of-life (EOL) care involves providing quality medical attention to the dying patient. It is fraught with some ethical challenges, often underexplored in African settings. This communication presents a qualitative analysis of ethical issues encountered by caregivers and their patients receiving EOL care in a teaching hospital in Nigeria.MethodsEthical issues in EOL care encountered by 40 people (dying patients, their families, nurses and doctors) at the University of Nigeria Teaching Hospital, Enugu, Enugu State, Nigeria, were explored over 2 months. The participants' sociodemographic data were analysed using descriptive statistics, while qualitative data were analysed using a thematic framework. The transcripts were coded using NVivo V.12 software.ResultsAll participant groups encountered commonly reported ethical challenges in EOL care, including issues of medical futility, treatment refusal, truthful disclosures, families requesting that a competent patient not be informed about their condition, confidentiality, limiting or withdrawing a treatment, limited or insufficient pain management, conflicting interests in care, an unfair financial burden without the patient consent and an unfair burden on the healthcare system. Additionally, the uncommon issues included the patient’s unwillingness to discuss their terminal status, families withdrawing due care and support prematurely and delayed referrals.ConclusionEthical issues are commonly encountered in caring for the patient at EOL in the Nigerian environment, notwithstanding the paucity of literature on them. This underscores the importance of adopting known preventive measures to eliminate or minimise these issues.

Data on massive transfusion (MT) in geriatric trauma patients is lacking. This study aims to determine geriatric transfusion futility thresholds (TT) and TT variations based on frailty. Patients from 2013 to 2018 TQIP database receiving MT were stratified by age and frailty. TTs and outcomes were compared between geriatric and younger adults and among geriatric adults based on frailty status. The TT was lower for geriatric than younger adults (34 vs 39 units; p ​= ​0.03). There was no difference in TT between the non-frail, frail, and severely frail geriatric adults (37, 30 and 25 units, respectively, p ​> ​0.05). Geriatric adults had higher mortality than younger adults (63.1% vs 45.8%, p < 0.01). Non-frail geriatric adults had the highest mortality (69.4% vs 56.5% vs 56.2%, p < 0.01). Geriatric patients have a lower TT than younger adults, irrespective of frailty. This may help improve outcomes and optimize MT utilization. •More blood will not always improve survival.•This point in number of units is a transfusion threshold (TT).•The TT for geriatric patients is lower than the TT for nongeriatric patients.•Among geriatric patients, the TT is not impacted by frailty.•Outcomes for geriatric patients receiving MTP are worse than of younger adults.

While the concept of futility has been used widely in somatic medicine, to date, there has been limited consideration of its relevance to psychiatry. We summarize the findings of an international, multidisciplinary workshop involving clinicians, ethicists, philosophers, patient advocates, and persons with lived experience, which was focused on describing futility in psychiatry and developing ethical guidelines for making futility judgments. We outline three leading concepts of futility as they have been used in somatic medicine: physiological futility, quantitative futility, and qualitative futility. We examine the application of these concepts to the care of persons with mental illness, finding that the notion of qualitative futility is most likely to be fruitful. We consider how the concept of qualitative futility in psychiatry could relate to other ethically salient concepts such as terminal mental illness and recovery. We consider (1) who should have authority to make futility judgments in psychiatry (i.e. patients, providers, others), (2) what the process for introducing and evaluating futility judgments should be, and (3) how futility assessments should respond to patients’ goals and values. We identify potential risks of futility assessments, including psychological harms and premature treatment discontinuation, as well as potential benefits, such as reductions in harmful treatments and helpful reevaluation of the goals of care. Workshop participants regarded the concept of psychiatric futility as potentially useful. They identified how the concept could be applied to psychiatric care, as well as ethical limits on doing so.

There is controversy about how to manage requests by patients or surrogates for treatments that clinicians believe should not be administered. This multisociety statement provides recommendations to prevent and manage intractable disagreements about the use of such treatments in intensive care units. The recommendations were developed using an iterative consensus process, including expert committee development and peer review by designated committees of each of the participating professional societies (American Thoracic Society, American Association for Critical Care Nurses, American College of Chest Physicians, European Society for Intensive Care Medicine, and Society of Critical Care). The committee recommends: (1) Institutions should implement strategies to prevent intractable treatment conflicts, including proactive communication and early involvement of expert consultants. (2) The term \"potentially inappropriate\" should be used, rather than futile, to describe treatments that have at least some chance of accomplishing the effect sought by the patient, but clinicians believe that competing ethical considerations justify not providing them. Clinicians should explain and advocate for the treatment plan they believe is appropriate. Conflicts regarding potentially inappropriate treatments that remain intractable despite intensive communication and negotiation should be managed by a fair process of conflict resolution; this process should include hospital review, attempts to find a willing provider at another institution, and opportunity for external review of decisions. When time pressures make it infeasible to complete all steps of the conflict-resolution process and clinicians have a high degree of certainty that the requested treatment is outside accepted practice, they should seek procedural oversight to the extent allowed by the clinical situation and need not provide the requested treatment. (3) Use of the term \"futile\" should be restricted to the rare situations in which surrogates request interventions that simply cannot accomplish their intended physiologic goal. Clinicians should not provide futile interventions. (4) The medical profession should lead public engagement efforts and advocate for policies and legislation about when life-prolonging technologies should not be used. The multisociety statement on responding to requests for potentially inappropriate treatments in intensive care units provides guidance for clinicians to prevent and manage disputes in patients with advanced critical illness.