Combined baseline HBcrAg and end-of-treatment HBsAg predict HBV relapse after entecavir or tenofovir cessation.

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.

ACE inhibitors, angiotensin receptor blockers and endothelial injury in COVID-19.

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 m2 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.

Early discontinuation of PD-1 blockade upon achieving a complete or partial response in patients with advanced melanoma: the multicentre prospective Safe Stop trial.

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.

Framework to Support the Process of Decision-Making on Life-Sustaining Treatments in the ICU: Results of a Delphi Study.

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.

Pediatric Out-of-Hospital Traumatic Cardiopulmonary Arrest After Traffic Accidents and Termination of Resuscitation.

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.

[Bioethics guide on scarce medical resource allocation in Mexico]. / Guía bioética de asignación de recursos de medicina crítica del Consejo de Salubridad General en México.

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.

El tema bioético sobre la asignación de recursos escasos no es nuevo, todos los países que han sido gravemente afectados por el SARS-CoV-2 han tenido que desarrollar y utilizar guías de triaje. Esto resulta más adecuado pues así la asignación de recursos limitados se hace de manera ética y justa, y no de manera discrecional y abierta a la corrupción. En México, en anticipación a la fase exponencial de la pandemia por SARS-CoV-2, el 30 de abril el Consejo de Salubridad General publicó la Guía bioética para asignación de recursos limitados de medicina crítica en situación de emergencia. Dicha guía tiene como base criterios de justicia social y parte de la tesis: todas las vidas tienen el mismo valor. Este texto tiene como objetivo propor-cionar las razones bioéticas y biojurídicas que conforman esta guía de triaje en nuestro país. En resumen, proporciona una breve exploración de las razones éticas que justifican cierta manera específica de asignar recursos escasos en medicina crítica, así como del sustento procedimental apegado a los estándares en materia de derechos humanos.

Allocating medical resources fairly:the CSG bioethics guide.

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.

El 12 de abril de 2020, se publicó en el sitio web del Consejo de Salubridad General (CSG) del Gobierno de México una guía de bioética para asignar recursos hospitalarios escasos durante la actual pandemia de Covid-19. La guía titulada Guía bioética para asignación de recursos limitados de medicina crítica en situación de emergencia pretendía ser un documento pre-liminar, pero la publicación en el sitio web no lo describió como un primer paso en el proceso. La publicación resultó en una amplia gama de comentarios y críticas. La primera versión publicada en el sitio web del CSG contenía un cri-terio basado en la edad para romper el empate entre dos o más pacientes médicamente elegibles que necesitaran un ventilador: los pacientes más jóvenes tendrían preferencia sobre los de mayor edad. La versión final de la guía eliminó ese criterio y, en cambio, se basó en el principio principal de salud pública, "salvar la mayoría de las vidas", sin tener en cuenta las características personales que no sean la posibilidad de beneficiarse de los escasos recursos médicos.

In dubio pro CPR? The Controversial Status of 'Do Not Resuscitate' Imprints on the Human Body - a Swiss Innovation.

'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.

Differing Thresholds for Overriding Parental Refusals of Life-Sustaining Treatment.

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.

Patient Characteristics and General Practitioners' Advice to Stop Statins in Oldest-Old Patients: a Survey Study Across 30 Countries.

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 (ORadj) 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 (ORadj 13.8, 95%CI 12.6-15.1), with side effects compared to without ORadj 1.62 (95%CI 1.5-1.7) and with frailty (ORadj 4.1, 95%CI 3.8-4.4) compared to without. Shortened life expectancy increased advice to stop (ORadj 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.

Perioperative bridging of vitamin K antagonist treatment in patients with atrial fibrillation: only a very small group of patients benefits.

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.

When to stop renal replacement therapy in anticipation of renal recovery in AKI: The need for consensus guidelines.

There is wide variation in clinical practice regarding timing of discontinuation of renal replacement therapy (RRT) in patients with acute kidney injury (AKI). Prolonged, unnecessary RRT treatment can contribute to length of stay, overall hospital costs, and risk of complications associated with RRT. In addition, prolonged RRT can paradoxically lengthen the time for which the patient remains dialysis-dependent. Well-designed, randomized clinical trials have utilized varied discontinuation criteria specifically related to urine output and creatinine clearance, which impedes the comparison of outcomes from such studies. Other observational studies have attempted to assess the sensitivity and specificity of various criteria for discontinuation of RRT. Whether diuretics influence renal recovery has not been fully elucidated as well. In this article, we propose a starting framework for RRT discontinuation criteria to guide clinicians and clinical researchers. We emphasize the importance of frequent clinical assessment while considering discontinuation of RRT for AKI patients with a creatinine clearance >15 mL/min on a timed urine collection and/or a urine output >400 mL/24 h without diuretics, or >2000 mL/24 h with diuretics. We also discuss newer biomarkers, methods of GFR estimation, and imaging techniques that may play a greater role in the future. Clinical trials objectively comparing the success of RRT discontinuation criteria will be required to provide high-quality evidence for our proposed guidelines.

Validation of the Change or Stop Testosterone-Lowering Medication (COSTLow) Scale Using the Delphi Method Among Clinical Experts.

Guidelines for pharmacological treatment of patients with paraphilic disorders have been developed by a working group of the World Federation of Societies of Biological Psychiatry (Thibaut et al., 2010 ). With an increasing duration of experience and number of treated patients as well as aging patients, change of or withdrawal from testosterone-lowering medications (TLM) has become an important issue. The current study aimed to assess the quality of a structured professional judgment procedure that helps switching or discontinuing TLM in patients with paraphilic disorders. We used the Delphi method to estimate the quality of 10 factors originally proposed by the authors. A total of 30 experts participated in the first stage; 18 experts participated in the second stage. The experts' assessment resulted in an instrument of 15 factors that can be used to structure the process of changing or discontinuing TLM. These factors can be grouped into five broader categories: age and duration of treatment; therapeutic alliance; psychopathology and risk factors; motivation; and compliance and level of control. The developed COSTLow-R Scale provides an instrument that can be used to structure the process of changing or discontinuing TLM in patients with severe paraphilic disorders.

Effect of Continued Administration of Low-dose Aspirin for Intraoperative Bleeding Control in Gastric Endoscopic Submucosal Dissection.

BACKGROUND: The use of antithrombotic agents for the prevention of cerebro-cardioembolic events has increased, and recent guidelines have recommended the continued administration of low-dose aspirin (LDA) during endoscopic procedures with a high risk of bleeding. However, the influence of LDA on intraoperative bleeding control status during Endoscopic submucosal dissection (ESD) remains unclear. METHODS: We examined 293 consecutive patients who underwent ESD for gastric cancers between January 2014 and February 2018. Patients administered with LDA (n = 52) were compared with those without antithrombotic therapy (n = 241; control) by propensity-score matching (PSM) concerning outcomes of ESD. RESULTS: PSM analysis yielded 50 matched pairs. Comparison showed similar values for frequency of intraoperative major bleeding: 1 (0-4) times (median [range]) in the LDA group and 0 (0-5) in the control group respectively (p = 0.710). Others (frequency of preventive coagulation, procedure time, decrease of hemoglobin levels, en bloc resection, complete resection) were the same with a few adverse events including perforation (0%), and thromboembolism (0%). Postoperative bleeding rate was 1.9% in LDA group. Multivariate analysis indicated that location U and circumference on the posterior wall were associated with for multiple major intraoperative bleeding. CONCLUSION: The study suggests that gastric ESD can be safely accomplished without cessation of LDA.

Kinetic estimated glomerular filtration rate as a predictor of successful continuous renal replacement therapy discontinuation.

AIM: No standardized criteria for continuous renal replacement therapy (CRRT) discontinuation have been established. Kinetic estimated glomerular filtration rate (eGFR) is a newly developed estimation method based on dynamic changes of serum creatinine expected to reflect the true GFR. This study aimed to evaluate the predictive role of kinetic eGFR for CRRT discontinuation. METHODS: A retrospective single-centre cohort study was conducted. Acute kidney injury (AKI) patients who received CRRT between May 2015 and April 2016 were enrolled. Successful CRRT discontinuation was defined as neither resuming CRRT for the next 48 h nor receiving intermittent haemodialysis 7 days from the CRRT discontinuation. Clinical factors associated with CRRT discontinuation were evaluated by receiver operating characteristic (ROC) curve analysis. RESULTS: Of 52 AKI patients treated with CRRT, 38 could discontinue CRRT while 14 could not. Urine volume, regular and kinetic eGFR of days 0 (day of CRRT discontinuation) and 1 were all good predictive parameters (area under the ROC curve (AUC) > 0.7). Kinetic eGFR of day 1 showed the AUC of 0.87 [95% confidence interval 0.73-0.94]). Combining kinetic eGFR of day 1 and urine volume of day 0 gave a high AUC of 0.93 [95% confidence interval 0.82-0.97]. The combination was significantly greater than urine volume of day 0 (P = 0.008). CONCLUSION: Kinetic eGFR combined with urine volume was a better predictor for CRRT discontinuation. Evaluation of kinetic eGFR utility in other clinical settings will be necessary.

Emergency department mortality: Fair and square.

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.

Preventing acute kidney injury in high-risk patients by temporarily discontinuing medication - an observational study in general practice.

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.

Withdrawal of Life-Sustaining Treatments in Perceived Devastating Brain Injury: The Key Role of Uncertainty.

BACKGROUND: Withdrawal of life-sustaining treatment (WOLST) is the leading proximate cause of death in patients with perceived devastating brain injury (PDBI). There are reasons to believe that a potentially significant proportion of WOLST decisions, in this setting, are premature and guided by a number of assumptions that falsely confer a sense of certainty. METHOD: This manuscript proposes that these assumptions face serious challenges, and that we should replace unwarranted certainty with an appreciation for the great degree of multi-dimensional uncertainty involved. The article proceeds by offering a taxonomy of uncertainty in PDBI and explores the key role that uncertainty as a cognitive state, may play into how WOLST decisions are reached. CONCLUSION: In order to properly share decision-making with families and surrogates of patients with PDBI, we will have to acknowledge, understand, and be able to communicate the great degree of uncertainty involved.

Sodium-glucose cotransporter-2 inhibitors: an overview and perioperative implications.

PURPOSE OF REVIEW: Sodium-glucose cotransporter 2 (SGLT-2) inhibitors are a relatively new class of drugs used in the management of diabetes mellitus. This review will highlight key pharmacologic characteristics of this class of drugs; discuss their potential role in management of patients with cardiac disease; and raise several perioperative concerns for anesthesiologists caring for patients on SGLT-2 inhibitors. RECENT FINDINGS: Recent trials have shown a strong mortality benefit in diabetic patients on SGLT 2 inhibitors especially in patients with a high cardiovascular burden. In addition, there is a reduction in HbA1c levels, blood pressure, weight and readmissions secondary to heart failure in this patient population. However, these drugs have been also associated with an increased incidence of adverse events, such as euglycemic ketoacidosis, urinary tract infections, acute kidney injury and limb amputations. SUMMARY: SGLT 2 inhibitors are being increasingly prescribed secondary to their significant salutatory effect in patients with type II diabetes mellitus. Although there are no perioperative consensus guidelines for management of patients on SGLT2 inhibitors, they should be discontinued at least 24-48 h prior to major surgeries. Their overall management in the perioperative period should be carried out on a case-to-case basis using a multidisciplinary approach.

Adult Perianesthesia Do Not Resuscitate Orders: A Systematic Review.

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.