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Implantable cardioverter defibrillators (ICDs) are implanted in increasing numbers of patients with the aim of treating ventricular arrhythmias in high-risk patients and reducing their risk of dying. Individuals are also living longer with these devices. As a result, a greater number of patients with an ICD will deteriorate either with worsening cardiac failure, another non-cardiac condition or general frailty and will have a limited prognosis. Frequently, they will be cared for by non-cardiac teams who may be less familiar with ICDs. Therefore, to ensure the person receives high-quality end-of-life care, they should have the opportunity to consider and discuss the option to deactivate the shock function of their ICD. If the ICD shock therapy is not discontinued, there is an increased risk that, as a person reaches the last days of life, the ICD may deliver multiple, painful shocks that are distressing. There is also a risk that the device may delay the person's natural death, which the person would not have chosen if they had been given the opportunity to discuss discontinuation. The British Heart Rhythm Society has developed a practical guideline to support all healthcare professionals who are caring for patients who have an ICD. This includes descriptions of different device types, ethical and legal aspects, timing and nature of ICD discussions and practical advice regarding how the devices may be deactivated. It aims to promote awareness and timely discussion between professionals and patients and to encourage best practice., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Aim: Prehospital termination of resuscitation (ToR) rules are used to predict medical futility in adult out-of-hospital cardiac arrest (OHCA), however, the available evidence for pediatric patients is limited. The primary aim of this study is to derive a Pediatric Termination of Resuscitation (PToR) prediction rule for use in pediatric non-traumatic OHCA patients., Methods: We analyzed a retrospective cohort of pediatric OHCA patients within the CARES database over a 10-year period (2013-2022). We split the dataset into training and test datasets and fit logistic regressions with Least Absolute Shrinkage and Selection Operator (LASSO) to select predictor variables and estimate predictive test characteristics for the primary outcome of death and a secondary composite outcome of death or survival to hospital discharge with unfavorable neurologic status., Results: We analyzed a sample of 21,240 children where 2,326 (11.0%) survived to hospital discharge, and 1,894 (8.9%) survived to hospital discharge with favorable neurologic status. We derived a PToR rule for death demonstrating a specificity of 99.1% and a positive predictive value (PPV) of 99.8% and a PToR rule for death or survival with poor neurologic status with a specificity of 99.7% and PPV of 99.9% within the test dataset., Conclusion: We derived a clinical prediction rule with high specificity and positive predictive value in prehospital settings utilizing Advanced Life Support (ALS) providers which may inform termination of resuscitation considerations in pediatric patients. Further prospective and validation studies will be necessary to define the appropriateness and applicability of these PToR criteria for routine use., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: This study aims to understand the breadth of practice around end-of-life withdrawal of non-invasive advanced respiratory support (encompassing both continuous positive airway pressure and non-invasive ventilation) by analysing NHS-published guidelines and guidance for clinicians. This study seeks validity in the guidelines through a confluence of findings and reassurance of practice despite having little to no high-quality research to inform the content of the guidelines. Ultimately, where discordance is found between guidelines, there will be a strong mandate for future research., Methods: Guidelines were gathered through snowball sampling and analysed using document analysis techniques. Analysis was mixed in inductive and deductive and facilitated across several authors using framework analysis. 20 guidelines were analysed but saturation was found after 15. Further guidelines were analysed beyond saturation to provide reassurance of the endpoint of the study., Results: There were common components to the guidelines presented as themes: legal and ethical frameworks, decision-making around withdrawal, the process of withdrawal, post-withdrawal care and when to contact palliative care. There were significant areas of confluence, where multiple guidelines were in agreement on best practice. However, there was significant discordance in some key areas including the use of post-withdrawal oxygen therapy and pressure weaning practice., Conclusion: This study provides reassurance through a confluence of findings for the majority of withdrawal practices. However, key areas of discordance highlight an urgent need for further research to support clinicians, patients and their families during challenging clinical events., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: Withholding or withdrawing life-sustaining treatment in end-of-life patients is a challenging ethical issue faced by physicians. Understanding physicians' experiences and factors influencing their decisions can lead to improvement in end-of-life care., Objectives: To investigate the experiences of Thai physicians when making decisions regarding the withholding or withdrawal of life-sustaining treatments in end-of-life situations. Additionally, the study aims to assess the consensus among physicians regarding the factors that influence these decisions and to explore the influence of families or surrogates on the decision-making process of physicians, utilizing case-based surveys., Methods: A web-based survey was conducted among physicians practicing in Chiang Mai University Hospital (June - October 2022)., Results: Among 251 physicians (response rate 38.3%), most of the respondents (60.6%) reported that they experienced withholding or withdrawal treatment in end-of-life patients. Factors that influence their decision-making include patient's preferences (100%), prognosis (93.4%), patients' quality of life (92.8%), treatment burden (89.5%), and families' request (87.5%). For a chronic disease with comatose condition, the majority of the physicians (47%) chose to continue treatments, including cardiopulmonary resuscitation (CPR). In contrast, only 2 physicians (0.8%) would do everything, in cases when families or surrogates insisted on stopping the treatment. This increased to 78.1% if the families insisted on continuing treatment., Conclusion: Withholding and withdrawal of life-sustaining treatments are common in Thailand. The key factors influencing their decision-making process included patient's preferences and medical conditions and families' requests. Effective communication and early engagement in advanced care planning between physicians, patients, and families empower them to align treatment choices with personal values., (© 2024. The Author(s).)

Background: For patients with chronic hepatitis B (CHB), the optimal stopping criteria for entecavir or tenofovir disoproxil fumarate treatment remain unclear., Methods: This study recruited CHB patients with levels of hepatitis B surface antigen (HBsAg) <100 IU/mL at the end of treatment (EOT) from Kaohsiung (n = 190) and Linkou (n = 188) Chang Gung Memorial Hospitals for use as development and validation groups, respectively., Results: In the development group, 108 patients with HBsAg ≤40 IU/mL were used for analysis of predictors of HBV relapse and HBsAg loss. Multivariate analysis showed that age, nucleos(t)ide analogue (NA)-experienced status, baseline hepatitis B core-related antigen (HBcrAg) and HBsAg at EOT were associated independently with virological and clinical relapse. An HBsAg level of 20 IU/mL at EOT was the best cut-off value for minimizing HBV relapse. Patients with EOT HBsAg ≤20 IU/mL had lower virological and clinical relapse rates and higher HBsAg loss rates than those with EOT HBsAg 21-40 IU/mL and HBsAg 41-100 IU/mL in the development and validation groups. The virological and clinical relapse rates were very low (5-year rates: 6.5% and 0%, respectively) and HBsAg loss rate was very high (5-year rate: 81.7%) in patients with a combination of baseline HBcrAg ≤4 log U/mL and EOT HBsAg ≤20 IU/mL in the development group., Conclusions: A combination of baseline HBcrAg ≤4 log U/mL and EOT HBsAg level ≤20 IU/mL might reduce the risk of HBV relapse and increase HBsAg loss rate, and might be helpful for off-NA follow-up strategy., (© The Author(s) 2022. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Antiplatelet agents are typically withheld perioperatively because of bleeding concerns. Dual antiplatelet therapy, such as aspirin and clopidogrel, has significant morbidity and mortality benefits in patients with ischemic heart disease or peripheral vascular disease. This study aims to evaluate the impact of perioperative dual antiplatelet therapy in the lower extremity free tissue transfer population., Methods: Lower extremity free tissue transfers performed by the senior author (K.K.E.) from 2011 to 2019 were retrospectively reviewed. Demographics, comorbidities, perioperative dual antiplatelet therapy, and free tissue transfer characteristics were recorded. Outcomes of interest included flap success, hematoma formation, blood transfusion requirements, and cardiac event occurrence., Results: One hundred ninety-five free tissue transfers were included. Median age at the time of free tissue transfer was 56.5 years. Median Charlson Comorbidity Index was 3. Thirty-four patients were on clopidogrel, which was either withheld (n = 20) or continued (n = 14) on the day of free tissue transfer. Incidence of blood transfusion was significantly higher in both the withheld and continued versus nonclopidogrel groups. Flap success was statistically equivalent between groups (withheld, 90.0 percent; continued, 92.9 percent; nonclopidogrel, 95.0 percent; p = 0.346). Cardiac events occurred most often in the continued group (21.4 percent) compared to the withheld (5.0 percent) and nonclopidogrel (0.6 percent) groups. On multivariate analysis, holding clopidogrel remained significant for increased odds of postoperative transfusion. The clopidogrel group was no longer significant for intraoperative transfusion., Conclusions: Despite increases in volume of blood products transfused, free tissue transfer can be performed safely with perioperative dual antiplatelet therapy. Withholding dual antiplatelet therapy on the day of free tissue transfer was not associated with decreased intraoperative transfusion; thus, dual antiplatelet therapy can safely be continued throughout the operative course to minimize cardiovascular risk., Clinical Question/level of Evidence: Therapeutic, III., Competing Interests: Disclosure: The authors have no financial disclosures, commercial associations, or any other conditions posing a conflict of interest to report., (Copyright © 2021 by the American Society of Plastic Surgeons.)

Background: Decannulation from venovenous extracorporeal membrane oxygenation (ECMO) at the earliest and safest possible time may improve outcomes and reduce cost. Yet, no prospective studies have compared weaning strategies for liberation from ECMO., Research Question: Is a protocolized daily assessment of readiness to liberate from venovenous ECMO safe and feasible?, Study Design and Methods: We conducted a prospective, single-arm safety and feasibility study of a protocol for daily assessment of readiness to liberate from venovenous ECMO among consecutive adult patients receiving venovenous ECMO across four ICUs at a single center between June 20, 2020, and November 24, 2020. The ECMO-free protocol included three phases: (1) the safety screening, (2) non-ECMO Fio 2 titration, and (3) the ECMO-free trial. Enrollment, interventions, and data collection were performed prospectively by trained study staff., Results: Twenty-six patients received the ECMO-free protocol on 385 patient-days. The safety screening was passed during a total of 59 ECMO-free daily assessments (15.3%) among 20 patients. Every passed safety screening proceeded to an ECMO-free trial. Twenty-eight passed ECMO-free trials (47.5%) occurred among 16 patients (61.5%). No missed safety screenings, protocol deviations, or adverse events occurred. Of the 16 patients who passed an ECMO-free trial, 14 patients (87.5%) were decannulated. Among decannulated patients, 12 patients (85.7%) were decannulated on the same day as a passed ECMO-free trial, 6 patients (42.9%) were decannulated on the first day that they passed an ECMO-free trial, and 6 patients (42.9%) passed an ECMO-free trial at least twice consecutively before decannulation. The median time from first passed ECMO-free trial to decannulation was 2 days (interquartile range, 0-3 days)., Interpretation: The ECMO-free protocol is feasible and may identify patients for decannulation earlier than gradual approaches to weaning., (Copyright © 2021 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background Premature discontinuation of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention is related to higher short-term risks of adverse outcomes. Whether these risks persist in the long-term is uncertain. Methods and Results We assessed all patients having percutaneous coronary intervention with coronary second- or first-generation drug-eluting stents in the Veterans Affairs healthcare system between 2006 and 2012 who were free of major ischemic or bleeding events in the first 12 months. The characteristics of patients who stopped DAPT prematurely (1-9 months duration), compared with >9 to 12 months, or extended duration (>12 months) were assessed by odds ratios (ORs) from multivariable logistic models. The risk of adverse clinical outcomes over a mean 5.1 years in patients who stopped DAPT prematurely was assessed by hazard ratios (HRs) and 95% CIs from Cox regression models. A total of 14 239 had second-generation drug-eluting stents, and 8583 had first-generation drug-eluting stents. Premature discontinuation of DAPT was more likely in Black patients (OR, 1.54; 95% CI, 1.40-1.68), patients with greater frailty (OR, 1.04; 95% CI, 1.03-1.05), and patients with higher low-density lipoprotein cholesterol, and less likely in patients on statins (OR, 0.87; 95% CI, 0.80-0.95). Patients who stopped DAPT prematurely had higher long-term risks of death (second-generation drug-eluting stents: HR, 1.35; 95% CI, 1.19-1.56), myocardial infarction (second-generation drug-eluting stents: HR, 1.46; 95% CI, 1.22-1.74), and repeated coronary revascularization (second-generation drug-eluting stents: HR, 1.24; 95% CI, 1.08-1.41). Conclusions Patients who stop DAPT prematurely have features that reflect greater frailty, poorer medication use, and other social factors. They continue to have higher risks of major adverse outcomes over the long-term and may require more intensive surveillance many years after percutaneous coronary intervention.

Background: COVID-19 is caused by the coronavirus SARS-CoV-2, which uses angiotensin-converting enzyme 2 (ACE-2) as a receptor for cellular entry. It is theorized that ACE inhibitors (ACE-Is) or angiotensin receptor blockers (ARBs) may increase vulnerability to SARS-CoV-2 by upregulating ACE-2 expression, but ACE-I/ARB discontinuation is associated with clinical deterioration., Objective: To determine whether ACE-I and ARB use is associated with acute kidney injury (AKI), macrovascular thrombosis and in-hospital mortality., Methods: A retrospective, single-centre study of 558 hospital inpatients with confirmed COVID-19 admitted from 1 March to 30 April 2020, followed up until 24 May 2020. AKI and macrovascular thrombosis were primary end-points, and in-hospital mortality was a secondary end-point., Results: AKI occurred in 126 (23.1%) patients, 34 (6.1%) developed macrovascular thrombi, and 200 (35.9%) died. Overlap propensity score-weighted analysis showed no significant effect of ACE-I/ARB use on the risk of occurrence of the specified end-points. On exploratory analysis, severe chronic kidney disease (CKD) increases odds of macrovascular thrombi (OR: 8.237, 95% CI: 1.689-40.181, P = 0.009). The risk of AKI increased with advancing age (OR: 1.028, 95% CI: 1.011-1.044, P = 0.001) and diabetes (OR: 1.675, 95% CI: 1.065-2.633, P = 0.025). Immunosuppression was associated with lower risk of AKI (OR: 0.160, 95% CI: 0.029-0.886, P = 0.036). Advancing age, dependence on care, male gender and eGFR < 60 mL min -1 /1.73 m 2 increased odds of in-hospital mortality., Conclusion: We did not identify an association between ACE-I/ARB use and AKI, macrovascular thrombi or mortality. This supports the recommendations of the European and American Societies of Cardiology that ACE-Is and ARBs should not be discontinued during the COVID-19 pandemic., (© 2020 The Association for the Publication of the Journal of Internal Medicine.)

Background: The introduction of programmed cell death protein 1 (PD-1) blockers (i.e. nivolumab and pembrolizumab) has significantly improved the prognosis of patients with advanced melanoma. However, the long treatment duration (i.e. two years or longer) has a high impact on patients and healthcare systems in terms of (severe) toxicity, health-related quality of life (HRQoL), resource use, and healthcare costs. While durable tumour responses have been observed and PD-1 blockade is discontinued on an individual basis, no consensus has been reached on the optimal treatment duration. The objective of the Safe Stop trial is to evaluate whether early discontinuation of first-line PD-1 blockade is safe in patients with advanced and metastatic melanoma who achieve a radiological response., Methods: The Safe Stop trial is a nationwide, multicentre, prospective, single-arm, interventional study in the Netherlands. A total of 200 patients with advanced and metastatic cutaneous melanoma and a confirmed complete response (CR) or partial response (PR) according to response evaluation criteria in solid tumours (RECIST) v1.1 will be included to early discontinue first-line monotherapy with nivolumab or pembrolizumab. The primary objective is the rate of ongoing responses at 24 months after discontinuation of PD-1 blockade. Secondary objectives include best overall and duration of response, need and outcome of rechallenge with PD-1 blockade, and changes in (serious) adverse events and HRQoL. The impact of treatment discontinuation on healthcare resource use, productivity losses, and hours of informal care will also be assessed. Results will be compared to those from patients with CR or PR who completed 24 months of treatment with PD-1 blockade and had an ongoing response at treatment discontinuation. It is hypothesised that it is safe to early stop first-line nivolumab or pembrolizumab at confirmed tumour response while improving HRQoL and reducing costs., Discussion: From a patient, healthcare, and economic perspective, shorter treatment duration is preferred and overtreatment should be prevented. If early discontinuation of first-line PD-1 blockade appears to be safe, early discontinuation of PD-1 blockade may be implemented as the standard of care in a selected group of patients., Trial Registration: The Safe Stop trial has been registered in the Netherlands Trial Register (NTR), Trial NL7293 (old NTR ID: 7502), https://www.trialregister.nl/trial/7293 . Date of registration September 30, 2018.

Decisions on weaning from veno-venous extra-corporeal membrane oxygenation (VV-ECMO) requires the ability to maintain adequate gas exchange and work of breathing with reductions in ECMO pump flow and fresh gas flow. Testing of the readiness to wean the patient from ECMO however may vary dependent upon local protocols and clinical judgment. This study sought to validate the use of the LUS-score during VV-ECMO against the changes in chest x-ray infiltrates, dynamic lung compliance (CLdyn) and VV-ECMO settings (as standard measures of native lung function and the level of ECMO support) during the ECMO cycle. This prospective cohort study of 10 patients on VV-ECMO compared the LUS score (range 0-36) within 48-h, day 5 and day 10 of commencement of ECMO (or on the day of ECMO decannulation) to dynamic lung compliance, Murray Lung Injury Score and ECMO settings. Seven Male and three Female patients were included (average age 37 years (SD 14.8) and weight 71 Kg (SD 16.9). Median (IQR) duration of ECMO, ICU and hospital length of stay was 7.5 days (5.2-19.0), 12.5 days (8.5-22.7), 19.0 days (12.1- 36.1), respectively. There was a strong negative association between LUS-score and dynamic lung compliance (r s (33) = -0.66, p < .001) providing some validation on the use of the LUS score as a potential surrogate measure of lung aeration and lung mechanics during VV-ECMO weaning.

Many healthcare providers agree that reduction or stopping of medication, so-called deprescribing, would be good in vulnerable people with polypharmacy. However, deprescribing is not yet widely conducted. Physicians and pharmacists experience barriers, such as lack of evidence and guidance to support this process. There is also a tendency to maintain the status quo when there are no acute problems. Patients do want fewer pills but the proposal to stop certain medication can lead to resistance or confusion. The needs and concerns from a patient's perspective are a good starting point for desprescribing. It is important to set new goals and to prioritize together which medication can be stopped. It is not only relevant to react to existing problems but also to act proactively when the potential benefits no longer outweigh the medication burden or risks. Recently, more guidance and tools to support deprescribing became available in the Netherlands.

Purpose: Withdrawal of dopamine agonist (DA) therapy in patients with prolactinoma who are controlled by a small dose of medication is recommended by several guidelines. So far, the likelihood of reaching withdrawal conditions based on baseline characteristics remains uncertain., Methods: We retrospectively examined early clinical, radiological, or biochemical features that may predict the likelihood of reaching withdrawal conditions in prolactinoma patients. Data were obtained in a single academic medical center in the United States from patients seen between 2000 and 2018. Using multiple logistic regression, we compared patients who reached withdrawal conditions with those who did not., Results: Of 213 patients, 78 (36.6%) reached withdrawal conditions after at least 2 years of DA treatment. Initial maximal tumor diameter was significantly smaller in those who reached withdrawal conditions than in those who did not. Percent prolactin change at the first check from initiation of DA therapy and parasellar invasiveness were predictors of reaching withdrawal conditions. With constant independent variables, there was a 7% increase in odds for reaching withdrawal conditions for every 1% decrease in percent prolactin change at first check after DA therapy start (P = 0.0000). Parasellar invasion decreased the odds of reaching withdrawal conditions by 84% (P = 0.0000)., Conclusions: DA remains a potential life-long treatment modality for most prolactinoma patients. Patients with parasellar invasiveness and low prolactin percent change from baseline to first prolactin check are more likely to require long-term treatment., (© Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

On April 12, 2020, a bioethics guide for allocating scarce hospital resources during the current Covid-19 pandemic was posted on the website of the Consejo de Salubridad General(CSG) of the Government of Mexico. The guide, entitled Guía bioética para asignación de recursos limitados de medicina crítica en situación de emergencia, was intended as a preliminary document, but the website posting did not describe it as a first step in the process. The publicity resulted in a wide array of comments and criticisms. That first version posted on the CSG website contained an age-based criterion for breaking a tie between two or more medically eligible patients who needed of a ventilator: younger patients would have prefer-ence over older ones. The final version of the guide eliminated that criterion and instead, relied on the leading public health principle, "save the most lives", without regard to personal characteristics other than the possibility of benefitting from the scarce medical resources., Competing Interests: Declaration of conflict of interests. The authors declare that they have no conflict of interests.

The bioethical inquiry about allocating fairly scarce health resources is not new, all countries around the world that were seriously afflicted by SARS-CoV-2 have issued triage guidelines in order to address the dilemmas raised by the pandemic. There is no question about the need to create bioethical guidelines, since its creation provides a degree of certainty that fair and ethical decisions are taken. This also prevents that decisions are made in solitary and maybe motivated by corrupted actions. In Mexico, the creation of this guideline was a proactive and preventive measure to what was unavoidable, the exponential contagion phase of the pandemical scenario caused by Covid-19. On April 30, 2020 the General Sanitary Council published the Bioethical Guide to Allocate Scarce Resources on Critical Care Medicine in Emergency Situation. This guide has at its core that principle of utmost importance in social justice which main thesis is: "All lives have the same value". The aim of this contribution is to provide the ethical and legal principles established in the aforementioned bioethi-cal guideline. In sum, a brief exploration of the ethical reasons that support a specific way to allocate scarce health resources is provided, as well as the foundations of the procedural part from a human rights-based approach., Competing Interests: Declaration of conflict of interests. The authors declare that they have no conflict of interests.

Background/aims: Implantable cardiac defibrillators reduce the risk of sudden cardiac death in selected patients. The value of an implantable cardiac defibrillator declines as the patient's disease progresses. Guidelines suggest that the appropriateness of maintaining implantable cardiac defibrillator therapy be regularly reviewed as part of monitoring of the patient's disease trajectory. It is recommended that implantable cardiac defibrillators are deactivated as patients approach the end of life. Patients with a better understanding of their current state of health and the role that the implantable cardiac defibrillator plays within it are more likely to make informed decisions about the timing of deactivation., Methods: A quality improvement project was undertaken on appropriate deactivation of implantable cardiac defibrillators within a large tertiary cardiac centre. This was driven by audit data showing inadequate patient communication and documentation around deactivation. Drivers for change included the introduction of electronic data records, clinical review of comorbid patients approaching elective battery change and an ongoing forum for patient and carer education. Measured outcomes included the number of deactivations performed, evidence of patient discussion and consent, and timing of deactivation of the implantable cardiac defibrillator., Results: There were increased numbers of timely device deactivations undertaken following the interventions with improved documented evidence of patient discussion and consent. The educational forum was received favourably., Conclusions: Focused multidisciplinary interventions can impact favourably on appropriate implantable cardiac defibrillator deactivation and improve patient engagement.

Deprescribing is a holistic process to identify medications that can be ceased, substituted or reduced. This process can improve the health of older patients and also enhance their compliance to the prescribed medications which are actually beneficial. Recommendations and guidelines have been elaborated for extensively prescribed drugs. In clinical cardiology the process of deprescribing is a challenge for doctors because of withdrawal-related adverse effects, but it may be applied in certain clinical conditions such as the discontinuation of statin prescription in patients with advanced senile dementia and those with limited life expectancy. Deprescribing is also focussed on the scarcely known effects of prolonged therapy after the acute phase of a disease is over, especially when continuation may signify potential life-long treatment. There needs to be collaboration between the consultant cardiologist who first prescribes medications and family doctors who are responsible for the long-term care of the patient and reviewing prescribed medications may be necessary.

Systemic therapy for metastatic melanoma has been revolutionized over the past decade with the development of highly effective immune checkpoint inhibition, specifically anti-Programmed Death 1 receptor (PD-1) therapy. However, even though one-third of patients will have durable response to single-agent or combination therapy, the optimal duration of therapy is unknown. Identifying the optimal duration of therapy is important, as exposure to anti-PD-1 therapy increases the risk of developing immune-mediated toxicities that can have significant morbidity and are, at times, fatal. It has long been understood that patients with complete responses to high-dose interleukin-2 and ipilimumab typically maintain their responses after a brief treatment course; thus, it is important to better understand the data to help understand the optimal management of melanoma patients treated with anti-PD-1 therapy. The clinical data with anti-PD-1-based therapy and published data on the duration of therapy suggest that patients may not require a full 2 years of anti-PD-1 therapy and that the risk of toxicity may be mitigated by further understanding the mechanisms and kinetics of response to therapy. Although novel markers to help guide therapeutic decision making are under investigation, there is an ongoing need to improve our tools to monitor response to therapy and disease activity.

'Do not resuscitate' (DNR) imprints on the human body have recently appeared in medical practice. These non-standard DNR orders (e.g., tattoos, stamps, patches) convey the patient's refusal of resuscitation efforts should he be incapable of doing so. The article focuses on such innovative tools to express one's end-of-life wishes. Switzerland provides a unique example, as 'No Cardio-Pulmonary Resuscitation' stamps and patches have been commercialised. The article discusses the challenging legal questions as to the validity of non-standard DNR orders imprinted on the human body. It analyses the obligation of healthcare providers to honour such orders, either as an advance directive or an expression of an individual's presumed wishes, and withhold treatment. Finally, the article addresses the balancing of interests between the presumed wishes of an unconscious patient and his best interests of being resuscitated and potentially staying alive, a dilemma facing healthcare providers in a medical emergency.

Objectives: To develop a consensus framework that can guide the process of decision-making on continuing or limiting life-sustaining treatments in ICU patients, using evidence-based items, supported by caregivers, patients, and surrogate decision makers from multiple countries., Design: A three-round web-based international Delphi consensus study with a priori consensus definition was conducted with experts from 13 countries. Participants reviewed items of the decision-making process on a seven-point Likert scale or with open-ended questions. Questions concerned terminology, content, and timing of decision-making steps. The summarized results (including mean scores) and expert suggestions were presented in the subsequent round for review., Setting: Web-based surveys of international participants representing ICU physicians, nurses, former ICU patients, and surrogate decision makers., Patients: Not applicable., Interventions: Not applicable., Measurements and Main Results: In three rounds, respectively, 28, 28, and 27 (of 33 invited) physicians together with 12, 10, and seven (of 19 invited) nurses participated. Patients and surrogates were involved in round one and 12 of 27 responded. Caregivers were mostly working in university affiliated hospitals in Northern Europe. During the Delphi process, most items were modified in order to reach consensus. Seven items lacked consensus after three rounds. The final consensus framework comprises the content and timing of four elements; three elements focused on caregiver-surrogate communication (admission meeting, follow-up meeting, goals-of-care meeting); and one element (weekly time-out meeting) focused on assessing preferences, prognosis, and proportionality of ICU treatment among professionals., Conclusions: Physicians, nurses, patients, and surrogates generated a consensus-based framework to guide the process of decision-making on continuing or limiting life-sustaining treatments in the ICU. Early, frequent, and scheduled family meetings combined with a repeated multidisciplinary time-out meeting may support decisions in relation to patient preferences, prognosis, and proportionality.

When should doctors seek protective custody to override a parent's refusal of potentially lifesaving treatment for their child? The answer to this question seemingly has different answers for different subspecialties of pediatrics. This paper specifically looks at different thresholds for physicians overriding parental refusals of life-sustaining treatment between neonatology, cardiology, and oncology. The threshold for mandating treatment of premature babies seems to be a survival rate of 25-50%. This is not the case when the treatment in question is open heart surgery for a child with congenital heart disease. Most cardiologists would not pursue legal action when parents refuse treatment, unless the anticipated survival rate after surgery is above 90%. In pediatric oncology, there are case reports of physicians requesting and obtaining protective custody for cancer treatment when the reported mortality rates are 40-50%. Such differences might be attributed to differences in care, a reasonable prioritization of quality of life over survival, or the role uncertainty plays on prognoses, especially for the extremely young. Nonetheless, other, non-medical factors may have a significant effect on inconsistencies in care across these pediatric subspecialties and require further examinations.

Objective: To describe the current status of withholding or withdrawal of life-sustaining interventions (LSI) for neonates in Japan and to identify physician- and institutional-related factors that may affect advance care planning (ACP) practices with parents., Study Design: A self-reported questionnaire was administered to assess frequency of withholding and withdrawing intensive care at the respondent's facility, the physician's degree of affirming various beliefs about end-of-life care that was compared to 7 European countries, their self-reported ACP practices and perceived barriers to ACP. Three neonatologists at all 298 facilities accredited by the Japan Society for Neonatal Health and Development were surveyed, with 572 neonatologists at 217 facilities responding., Results: At 76% of facilities, withdrawing intensive care treatments was "never" done, while withholding intensive care had been done "sometimes" or more frequently at 82% of facilities. Japanese neonatologists differed from European neonatologists regarding their degree of affirmation of 3 out of 7 queried beliefs about end-of-life care. In hospitals that were more likely to "sometimes" (or more often) withdraw treatments, respondents were less likely to affirm beliefs about doing "everything possible" or providing the "maximum of intensive care". Self-reported ACP practices did not vary between neonatologists based on their hospital's overall pattern of withholding or withdrawing treatments., Conclusion: Among NICU facilities in Japan, 21% had been sometimes withdrawing LSI and 82% had been "sometimes" withholding LSI. Institutional treatment practices may have a strong association with physicians' beliefs that then affect end-of-life discussions, but not with self-reported ACP practices., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article to disclose., (Copyright © 2019. Published by Elsevier B.V.)

Lithium is the first line therapy of bipolar mood disorder. Lithium-induced nephrogenic diabetes insipidus (Li-NDI) and lithium nephropathy (Li-NP, i.e., renal insufficiency) are prevalent side effects of lithium therapy, with significant morbidity. The objective of this systematic review is to provide an overview of preventive and management strategies for Li-NDI and Li-NP. For this, the PRISMA guideline for systematic reviews was used. Papers on the prevention and/or treatment of Li-NDI or Li-NP, and (influenceable) risk factors for development of Li-NDI or Li-NP were included. We found that the amount of evidence on prevention and treatment of Li-NDI and Li-NP is scarce. To prevent Li-NDI and Li-NP we advise to use a once-daily dosing schedule, target the lowest serum lithium level that is effective and prevent lithium intoxication. We emphasize the importance of monitoring for Li-NDI and Li-NP, as early diagnosis and treatment can prevent further progression and permanent damage. Collaboration between psychiatrist, nephrologist and patients themselves is essential. In patients with Li-NDI and/or Li-NP cessation of lithium therapy and/or switch to another mood stabilizer should be considered. In patients with Li-NDI, off label therapy with amiloride can be useful., (Copyright © 2019 Elsevier B.V. and ECNP. All rights reserved.)

Study Objective: We describe the characteristics and outcomes of pediatric traumatic out-of-hospital cardiac arrest after traffic accidents and validate the termination of resuscitation clinical criteria for adult traumatic out-of-hospital cardiac arrest in pediatrics., Methods: We analyzed the records of pediatric (≤18 years) traumatic out-of-hospital cardiac arrest cases after traffic accidents in a prospectively collected nationwide database (2012 to 2016). Endpoints were 1-month favorable neurologic outcomes and 1-month survival. Validation of termination of resuscitation criteria, cardiac arrest at the scene, and unsuccessful resuscitation after cardiopulmonary resuscitation (CPR) greater than 15 minutes was performed based on specificity and positive predictive value., Results: Of the 582 patients who were eligible for analyses, 8 (1.4%) and 20 (3.4%) had 1-month favorable neurologic outcome and survival, respectively. All patients with favorable neurologic outcomes had out-of-hospital return of spontaneous circulation, and the duration of CPR was significantly shorter than for those with unfavorable neurologic outcomes (4 versus 23 minutes; absolute difference -21.9 minutes; 95% confidence interval -36.3 to -7.4 minutes). The duration of out-of-hospital CPR beyond which the possibility of favorable neurologic outcomes and survival diminished to less than 1% was 15 minutes. For predicting unfavorable neurologic outcomes, the termination of resuscitation criteria provided a specificity of 1.00 (95% confidence interval 0.52 to 1.00) and a positive predictive value of 1.00 (95% confidence interval 0.99 to 1.00)., Conclusion: The outcomes of pediatric patients with traumatic out-of-hospital cardiac arrest after traffic accidents were as poor as those of adults in previous studies. Out-of-hospital return of spontaneous circulation was a significant indicator of favorable outcomes, and the duration of out-of-hospital CPR beyond which the possibility of favorable neurologic outcomes and survival diminished to less than 1% was 15 minutes. Termination of resuscitation criteria provided an excellent positive predictive value for 1-month unfavorable neurologic outcomes after out-of-hospital cardiac arrest., (Copyright © 2019 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Elderly, patients with chronic kidney disease (CKD) and patients with heart failure who continue using renin-angiotensin-aldosterone-system (RAAS) inhibitors, diuretics, or non-steroidal-anti-inflammatory drugs (NSAIDs) during times of fluid loss have a high risk of developing complications like acute kidney injury (AKI). The aim of this study was to assess how often advice to discontinue high-risk medication was offered to high-risk patients consulting the general practitioner (GP) with increased fluid loss. Furthermore, we assessed the number and nature of the complications that occurred after GP consultation., Methods: We performed a cross-sectional study with patients from seven Dutch general practices participating in the Family Medicine Network between 1 and 6-2013 and 1-7-2018. We included patients who used RAAS-inhibitors, diuretics, or NSAIDs, and had at least one of the following risk factors: age ≥ 70 years, CKD, or heart failure. From this population, we selected patients with a 'dehydration-risk' episode (vomiting, diarrhoea, fever, chills, or gastrointestinal infection). We manually checked their electronic patient files and assessed the percentage of episodes in which advice to discontinue the high-risk medication was offered and whether a complication occurred in 3 months after the 'dehydration-risk' episode., Results: We included 3607 high-risk patients from a total of 44.675 patients (8.1%). We found that patients were advised to discontinue the high-risk medication in 38 (4.6%) of 816 'dehydration-risk' episodes. In 59 of 816 episodes (7.1%) complications (mainly AKI) occurred., Conclusions: Dutch GPs do not frequently advise high-risk patients to discontinue high-risk medication during 'dehydration-risk' episodes. Complications occur frequently. Timely discontinuation of high-risk medication needs attention.

Simply treating opioid addiction isn't enough. Instead, reposition your patient's singular circumstances and needs at the center of efforts to end use of these agents.

As it is recommended that most assessments for treatment-free remission (TFR) in patients with chronic myeloid leukemia be conducted as prospective trials, we conducted a systematic review and meta-analysis to investigate which study-level factors affected the TFR rate. The MEDLINE, Embase, and Cochrane databases were systematically searched from inception to July 2018. A random effect model was used to estimate the overall mean TFR rate, subgroup differences, and regression coefficients with continuous variables. Overall, 12 tyrosine kinase inhibitor (TKI) stopping studies comprising 1699 chronic myeloid leukemia patients were included in this analysis. The overall mean TFR rate at 24 months after entering TFR phase was 55% [95% confidence interval (CI) 0.51-0.58]. Trials with molecular criteria of MR4.5 or better for stopping TKI reported higher TFR rates than those of MR4.0 (57.2% vs. 50.5%). Trials with eligible criteria for at least 24 months of deep molecular response (DMR) duration demonstrated higher TFR rates than those for 18 or 12 months (60.2% vs. 49.9%). Our results suggest that TKI stopping trials with sufficient duration of DMR and molecular criteria of MR4.5 or better may account for approximately 60% of the TFR rate at 24 months after stopping TKI.

Purpose: Bariatric surgery is the method of choice for the management or treatment of obesity. Bariatric surgery brings about several physiological changes in the body and is associated with set of complications. The aim of this study is to provide guidelines on post bariatric surgery management based on consensus by the Spanish society for Obesity Surgery (Sociedad Española de Cirugía de la Obesidad) (SECO) and the Spanish Society for the Study of Obesity (Sociedad Española para el Estudio de la Obesidad) (SEEDO)., Method: The boards proposed seven experts from each society. The experts provided the evidence and a grade of recommendation on the selected topics based on systematic reviews/meta-analysis. A list of clinical practical recommendations levels of evidence and grades of these recommendations was derived from the consensus statements from the members of these societies., Results: Seventeen topics related to post-operative management were reviewed after bariatric surgery. The experts came with 47 recommendations and statements. The mean number of persons voting at each statement was 54 (range 36-76)., Conclusion: In this consensus, we have designed a set of guidelines to be followed while managing patients after bariatric surgery. Expertise and knowledge of the clinicians are required to convey suitable considerations to the post-bariatric patients. There should also be extensive follow-up plans for the bariatric surgery patients.

Aim: The study investigated psychiatrists' views towards the issue of medication discontinuation for patients in remission from first-episode psychosis in four countries (Hong Kong, Korea, Singapore and Japan) that are part of the Asian Network for Early Psychosis, focusing on whether the views of these countries differ with one another., Methods: A questionnaire was distributed to psychiatrists for completion. The questionnaire contained three sections: direct questions probing at views on medication discontinuation, case vignettes to assess applied decision-making and a checklist of criteria psychiatrists may view as necessary for the patient to satisfy before discontinuation. Total of 484 psychiatrists (97 from Hong Kong, 88 from Korea, 64 from Singapore and 233 from Japan) completed the questionnaire., Results: We found that (a) Asian psychiatrists believed that 1% to 19% of remitted patients can discontinue medication, an estimation that was lower than Western psychiatrists; (b) in agreement with clinical guidelines, Asian psychiatrists believed that patients should remain on medication for at least 1 to 2 years following the absence of psychotic symptoms; (c) "Absence of any relapsing episode following first episode" was considered the most important criterion when making a decision; and (d) there were significant differences in clinicians' perceptions across the four countries: for instance, Korean psychiatrists were more conservative with the duration of antipsychotics maintenance, while Singaporean psychiatrists were more open-minded towards clinical trials., Conclusions: Culture and social norms appear to determine the relative importance of factors that psychiatrists might consider during the decision-making process, thereby producing variations in the views held in different countries., (© 2018 John Wiley & Sons Australia, Ltd.)

Objective: Treatment limitation, as well as do-not-resuscitate (DNR) directives, are difficult but important to improve patients' quality of life and minimize dysthanasia. We aimed to study the approach to withholding, withdrawal, and DNR decisions, patients' characteristics, and process documentation in a general Intensive Care Unit (ICU) in Portugal., Methods: A retrospective analysis of data regarding the limitation of treatment decisions collected from previously-designed forms and complemented by medical record consultation., Results: A total of 1602 patients were admitted to the ICU between 2011 and 2016. DNR decisions were documented in 127 cases (7.9%). Patients with treatment limitations were older and had higher Simplified Acute Physiology Score II. The most frequent diagnosis preceding these decisions was sepsis (52.0%, n = 66); the most common main reason for limiting treatment was a poor prognosis of acute illness. Of the patients to whom a DNR was implemented, 117 (92.1%) died in the ICU (40.1% of the total number of ICU deaths), and hospital mortality was 100%. Participants in these decisions, as well as types of treatment withdrawn and their respective timings, were not registered in medical records., Conclusion: Treatment limitation and DNR decisions were relatively common, in line with other Southern European studies, but behind Northern European and North American centers. Patients with these limitations were older and more severely ill than patients without such decisions. Documentation of these processes should be clear and detailed, either in specific forms or computerized clinical records; there is room for improvement in this area.

Purpose: The purpose of this systematic review is to assess if Do Not Resuscitate (DNR) orders should be routinely rescinded during anesthesia, determine if consensus on retaining DNR orders exists in the literature, and explore the current state of clinical practice., Design: This systematic review followed preferred reporting items for systematic reviews and meta-analyses guidelines., Methods: In June 2018, the Cumulative Index to Nursing and Allied Health Literature and PubMed databases were systematically searched using defined inclusion/exclusion criteria., Findings: Ninety-one articles from the databases were pooled with 16 works identified as formative to the research questions. Forty-nine articles were analyzed and included in this study., Conclusions: It is unethical to automatically rescind DNR orders during anesthesia. Patients have the right to retain their DNR orders unaltered or modify them for the perianesthesia period. Sufficient evidence exists to create meaningful policy at every level. A consensus exists among professional organizations that the standard of care is a required reconsideration of DNR orders before anesthesia., (Copyright © 2019 American Society of PeriAnesthesia Nurses. Published by Elsevier Inc. All rights reserved.)

Background: Immunosuppression has undoubtedly raised the overall positive outcomes in the post-operative management of solid organ transplantation. However, long-term exposure to immunosuppression is associated with critical systemic morbidities. De novo malignancies following orthotopic liver transplants (OLTs) are a serious threat in pediatric and adult transplant individuals. Data from different experiences were reported and compared to assess the connection between immunosuppression and de novo malignancies in liver transplant patients., Aim: To study the role of immunosuppression on the incidence of de novo malignancies in liver transplant recipients., Methods: A systematic literature examination about de novo malignancies and immunosuppression weaning in adult and pediatric OLT recipients was described in the present review. Worldwide data were collected from highly qualified institutions performing OLTs. Patient follow-up, immunosuppression discontinuation and incidence of de novo malignancies were reported. Likewise, the review assesses the differences in adult and pediatric recipients by describing the adopted immunosuppression regimens and the different type of diagnosed solid and blood malignancy., Results: Emerging evidence suggests that the liver is an immunologically privileged organ able to support immunosuppression discontinuation in carefully selected recipients. Malignancies are often detected in liver transplant patients undergoing daily immunosuppression regimens. Post-transplant lymphoproliferative diseases and skin tumors are the most detected de novo malignancies in the pediatric and adult OLT population, respectively. To date, immunosuppression withdrawal has been achieved in up to 40% and 60% of well-selected adult and pediatric recipients, respectively. In both populations, a clear benefit of immunosuppression weaning protocols on de novo malignancies is difficult to ascertain because data have not been specified in most of the clinical experiences., Conclusion: The selected populations of tolerant pediatric and adult liver transplant recipients greatly benefit from immunosuppression weaning. There is still no strong clinical evidence on the usefulness of immunosuppression withdrawal in OLT recipients on malignancies. An interesting focus is represented by the complete reconstitution of the immunological pathways that could help in decreasing the incidence of de novo malignancies and may also help in treating liver transplant patients suffering from cancer., Competing Interests: Conflict-of-interest statement: The authors declare they have no conflicts of interest to disclose.

Introduction: Research supports the use of specific strategies to discontinue mechanical ventilation (MV) in critically ill patients. Little is known about how clinicians actually wean and discontinue MV in practice or the association between different discontinuation strategies and outcomes. The primary objective of this study is to describe international practices in the use of (1) daily screening for readiness to discontinue MV, (2) modes of MV used before initial discontinuation attempts, (3) weaning and spontaneous breathing trial (SBT) protocols, (4) SBT techniques and (5) sedation and mobilisation practices to facilitate weaning and discontinuation. The secondary objectives are to identify patient characteristics and time-dependent factors associated with use of selected strategies, investigate associations between SBT outcome (failure vs success) and outcomes, explore differences between patients who undergo an SBT early versus later in their intensive care unit (ICU) stay, and investigate the associations between different SBT techniques and humidification strategies on outcomes., Methods and Analysis: We will conduct an international, prospective, observational study of MV discontinuation practices among critically ill adults who receive invasive MV for at least 24 hours at approximately 150 ICUs in six geographic regions (Canada, USA, UK, Europe, India and Australia/New Zealand). Research personnel at participating ICUs will collect demographic data, data to characterise the initial strategy or event that facilitated discontinuation of MV (direct extubation, direct tracheostomy, initial successful SBT, initial failed SBT or death before any attempt could be made), clinical outcomes and site information. We aim to collect data on at least 10 non-death discontinuation events in each ICU (at least 1500 non-death discontinuation events)., Ethics and Dissemination: This study received Research Ethics Approval from St. Michael's Hospital (11-024) Research ethics approval will be sought from all participating sites. The results will be disseminated through publications in peer-reviewed journals., Trial Registration Number: NCT03955874., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Clinical outcomes in acute coronary syndrome patients treated with P2Y 12 inhibitors who require urgent coronary artery bypass grafting (CABG) have not been well studied., Methods: We examined clinical outcomes in acute coronary syndrome patients in relation to the timing of CABG following P2Y 12 inhibitor discontinuation (<72 h, 72 h to five days, >5 days). The primary ischemic outcome was a composite of death, reinfarction, need for revascularization, or stroke. The primary safety outcome was bleeding of at least moderate severity as defined by a Universal Definition of Perioperative Bleeding class ≥2., Results: Among 508 patients (95 ticagrelor, 413 clopidogrel), the timing of CABG following P2Y 12 inhibitor discontinuation was <72 h in 32.1%, 72 h to five days in 23.2% and >5 days in 44.7%. Compared with CABG within 72 h, CABG 72 h to five days (adjusted odds ratio (OR) 0.35; 95% confidence interval (CI) 0.14-0.85; p =0.02) but not >5 days (adjusted OR 0.62; 95% CI 0.33-1.16; p =0.14) after P2Y 12 inhibitor discontinuation was associated with lower odds of the primary ischemic outcome. Compared with CABG within 72 h, CABG 72 h to five days (adjusted OR 0.38; 95% CI 0.22-0.66; p =0.001) and >5 days (adjusted OR 0.33; 95% CI 0.20-0.53; p <0.001) after P2Y 12 inhibitor discontinuation were associated with lower rates of Universal Definition of Perioperative Bleeding class ≥2 bleeding., Conclusions: CABG within 72 h after P2Y 12 inhibitor discontinuation is associated with excess ischemia and bleeding. The rates of ischemic and bleeding events were comparable in patients undergoing CABG 72 h to five days compared with >5 days after P2Y 12 inhibitor discontinuation.

Background: Legal concerns have been implicated in the occurrence of variability in decisions of limitations of medical treatment (LOMT) before death. Objective: We aimed to assess differences in perceptions between physicians and prosecutors toward LOMT. Measurements: We sent a survey to intensivists, oncologists, and prosecutors from Brazil, from February 2018 to May 2018. Respondents rated the degree of agreement with withholding or withdrawal of therapies in four different vignettes portraying a patient with terminal lung cancer. We measured the difference in agreement between respondents. Results: There were 748 respondents, with 522 (69.8%) intensivists, 106 (14.2%) oncologists, and 120 (16%) prosecutors. Most respondents agreed with withhold of chemotherapy (95.2%), withhold of mechanical ventilation (MV) (90.2%), and withdrawal of MV (78.4%), but most (75%) disagreed with withdrawal of MV without surrogate's consent. Prosecutors were less likely than intensivists and oncologists to agree with withhold of chemotherapy (95.7% vs. 99.2% vs. 100%, respectively, p  < 0.001) and withhold of MV (82.4% vs. 98.3% vs. 97.9%, respectively, p  < 0.001), whereas intensivists were more likely to agree with withdrawal of MV than oncologists (87.1% vs. 76.1%, p  = 0.002). Moreover, prosecutors were more likely to agree with withholding of active cancer treatment than with withholding of MV [difference (95% confidence interval, CI) = 13.2% (5.2 to 21.6), p  = 0.001], whereas physicians were more likely to agree with withholding than with withdrawal of MV [difference (95% CI) = 10.9% (7.8 to 14), p  < 0.001]. Conclusions: This study found differences and agreements in perceptions toward LOMT between prosecutors, intensivists, and oncologists, which may inform the discourse aimed at improving end-of-life decisions.

Background: Statins are widely used to prevent cardiovascular disease (CVD). With advancing age, the risks of statins might outweigh the potential benefits. It is unclear which factors influence general practitioners' (GPs) advice to stop statins in oldest-old patients., Objective: To investigate the influence of a history of CVD, statin-related side effects, frailty and short life expectancy, on GPs' advice to stop statins in oldest-old patients., Design: We invited GPs to participate in this case-based survey. GPs were presented with 8 case vignettes describing patients > 80 years using a statin, and asked whether they would advise stopping statin treatment., Main Measures: Cases varied in history of CVD, statin-related side effects and frailty, with and without shortened life expectancy (< 1 year) in the context of metastatic, non-curable cancer. Odds ratios adjusted for GP characteristics (OR adj ) were calculated for GPs' advice to stop., Key Results: Two thousand two hundred fifty GPs from 30 countries participated (median response rate 36%). Overall, GPs advised stopping statin treatment in 46% (95%CI 45-47) of the case vignettes; with shortened life expectancy, this proportion increased to 90% (95CI% 89-90). Advice to stop was more frequent in case vignettes without CVD compared to those with CVD (OR adj 13.8, 95%CI 12.6-15.1), with side effects compared to without OR adj 1.62 (95%CI 1.5-1.7) and with frailty (OR adj 4.1, 95%CI 3.8-4.4) compared to without. Shortened life expectancy increased advice to stop (OR adj 50.7, 95%CI 45.5-56.4) and was the strongest predictor for GP advice to stop, ranging across countries from 30% (95%CI 19-42) to 98% (95% CI 96-99)., Conclusions: The absence of CVD, the presence of statin-related side effects, and frailty were all independently associated with GPs' advice to stop statins in patients aged > 80 years. Overall, and within all countries, cancer-related short life expectancy was the strongest independent predictor of GPs' advice to stop statins.

Objective: This study explored the therapeutic approaches used for end-of-life (EOL) patients admitted to the emergency department (ED) and examined whether the decision to perform life-extending treatment (LET) or to allow natural death (AND) depends on patient characteristics, medical staff variables, and ED setting., Methods: A retrospective archive study was conducted from January 2015 to December 2017 in the ED of a tertiary hospital. The study sample were 674 EOL patients who had died in the ED. For each patient, data were collected and measured for dying process (LET vs. AND), patient characteristics, ED-setting variables, and medical-staff characteristics., Results: The proportion of EOL patients undergoing LET increased from 18.1% in 2015 to 25.9% in 2016 and to 30.3% in 2017 (p = .010), and a quarter of them were treated by emergency medical services. Males tended to receive LET more than females (p < .001). An association was found between Jewish physicians and nurses and AND (p = .001). Heavier workload in the ED and greater severity of the triage classification predicted more LET (OR-1.67, CI = 1.05-1.76, p = .003 and OR = 1.42, CI-0.60-0.81, p < .001, respectively). Receiver operating characteristic analysis showed that patient characteristics contributed most crucially to the therapeutic approaches (C statistic 0.624-0.675, CI-0.62-0.71)., Conclusions: The therapeutic approach used for EOL patients in the ED depends on variables in all three treatment layers: patient, medical staff, and ED setting. Applicable national programs should be developed to ensure that no external factors influence the dying-process decision., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Aims: Bridging anticoagulation in atrial fibrillation (AF) patients who need to interrupt vitamin K antagonists for procedures is a clinical dilemma. Currently, guidelines recommend clinicians to take the stroke and bleeding risk into consideration, but no clear thresholds are advised. To aid clinical decision making, we aimed to develop a model in which periprocedural bridging therapy is compared with withholding anticoagulation in AF patients, for several bleeding and stroke risk groups., Methods and Results: A model was developed to simulate both a bridge and a non-bridge cohort, using simulated international normalized ratio (INR) values for patients on warfarin, acenocoumarol, and phenprocoumon. For both clinical strategies, stroke and bleeding risks were included and outcomes were stratified by CHA2DS2-VASc or CHADS2 and HAS-BLED groups. Quality-adjusted life expectancy was the main outcome considered. Our analyses show bridging to only be beneficial for patients with HAS-BLED scores equal or lower to 2 and with CHA2DS2-VASc scores of 6 or higher. For patients using acenocoumarol bridging may be beneficial starting at a CHA2DS2-VASc score of 7. Post-procedural time to therapeutic INR has a significant influence on the results: no significant benefit of bridging was found for patients reaching therapeutic INR values within 5 days., Conclusion: When deciding whether to bridge anticoagulation, clinicians should consider the patient's individual stroke and bleeding risk, while also considering the patient's post-procedural INR management. In practice, only a small subset of patients is expected to benefit from bridging anticoagulation treatment., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)