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Background: The Act on Life-Sustaining Treatment (LST) for patients at the end of life (the Korean LST Decision Act), implemented in the Republic of Korea in February 2018, has led to changes in the end-of-life decision-making (EOLDM) process in children. This study aimed to investigate changes in pediatric EOLDM process and LST practices since the Korean LST Decision Act. Methods: This retrospective cohort study included 107 patients who died at Kyungpook National University Children's Hospital from January 2015 to December 2020. Patients were divided into two groups: pre-law (January 2015–January 2018, n = 55) and post-law (February 2018–December 2020, n = 52). We analyzed medical records for EOLDM process, patient characteristics, intensive care unit (ICU) admission, documentation types, and LST withholding or withdrawal decisions. Results: After the Korean LST Decision Act, the median total hospitalization duration decreased significantly (14 days [IQR, 3–80] vs. 6 days [IQR, 2–18], p = 0.020), as did the median ICU length of stay (3 days [IQR 1–33] vs. 2.5 days [IQR 1–10.3], p = 0.002). The time from admission to end-of-life decision documentation was significantly shorter in group 2 (6 days [IQR 1–31] vs. 4 days [IQR 1–9], p = 0.027). The use of physician orders for life-sustaining treatment (POLST) documents increased (0% to 33.3%), while do-not-resuscitate (DNR) orders decreased (85.3% to 16.7%). Notably, LST withdrawal decisions increased from 0% to 27.8% (p = 0.001) in the post-legislation period. Conclusions: The Korean LST Decisions Act has led to significant changes in the EOLDM process for terminally ill children, including earlier decision-making, increased use of POLST documents, more frequent LST withdrawal decisions, and shorter hospital and ICU stays. These findings suggest a shift towards more structured and timely end-of-life care discussions in pediatric settings. [ABSTRACT FROM AUTHOR]

Background This study aimed to determine the proportion of organ donors suitable for donation after circulatory death and investigate the current process followed by critical care physicians for declaring circulatory death to establish organ donation. Methods This observational study involved potential organ donors who had recently died after discontinuation of life support. We conducted an online survey of intensivists to determine how these deaths were confirmed. Results Among the 177 patients who died after withdrawal of life-sustaining treatment across 19 intensive care units in 11 institutions, 49 (27.7%) were considered potential donors. According to general medical criteria for organ donation, 20 (11.3%) patients were identified as medically suitable donors. Notably, 116 (73.9%) patients exhibited a flat electrocardiogram within 5 min after the loss of pulse. In the survey, 90 physicians (59.2%) agreed to implement the concept of the 5-min no-touch period for the declaration of circulatory death. Conclusions This study found that 11.3% of the patients who died following the withdrawal of life-sustaining treatment in the intensive care units were identified as suitable donors after circulatory death. Most of critical care physicians agree with the concept of a 5-min no-touch period for the declaration of circulatory death. [ABSTRACT FROM AUTHOR]

Abstract Background This study aimed to determine the proportion of organ donors suitable for donation after circulatory death and investigate the current process followed by critical care physicians for declaring circulatory death to establish organ donation. Methods This observational study involved potential organ donors who had recently died after discontinuation of life support. We conducted an online survey of intensivists to determine how these deaths were confirmed. Results Among the 177 patients who died after withdrawal of life-sustaining treatment across 19 intensive care units in 11 institutions, 49 (27.7%) were considered potential donors. According to general medical criteria for organ donation, 20 (11.3%) patients were identified as medically suitable donors. Notably, 116 (73.9%) patients exhibited a flat electrocardiogram within 5 min after the loss of pulse. In the survey, 90 physicians (59.2%) agreed to implement the concept of the 5-min no-touch period for the declaration of circulatory death. Conclusions This study found that 11.3% of the patients who died following the withdrawal of life-sustaining treatment in the intensive care units were identified as suitable donors after circulatory death. Most of critical care physicians agree with the concept of a 5-min no-touch period for the declaration of circulatory death.

Objective: The incidence of sepsis in older adults has been increasing with the general aging of the Japanese population. However, it has been shown that age is a critical factor in determining both the risk for sepsis and subsequent vital outcomes; aggressive treatment is often discouraged in this vulnerable patient group. This study aimed to determine whether aggressive therapeutic interventions were associated with mortality in older Japanese patients experiencing septic shock. Design: Single-center retrospective cohort study. Setting: Medical Intensive Care Unit of a city hospital (Kishiwada Tokushukai Hospital) in Japan between January 2020 and September 2021. Patients: Patients diagnosed with septic shock at the time of admission and older patients over 65 years of age were included and divided into two groups: a withholding group that received only minimal peripheral infusion and antibiotic therapy and a treatment group (non-withholding group) that received intensive care, such as vas- opressor use or mechanical ventilator management. Interventions: None. Measurements and results: One hundred patients were included in this study. There were 13 and 87 patients in the withholding and non-withholding groups, respectively. There was no significant difference in 30-day mortality between the two groups (53.85% vs 39.08%, p=0.127). However, the 72-hour mortality was significantly higher in the withholding group (53.8% vs 25.3%, p=0.034). Conclusions: Among older patients with septic shock, the withholding group showed a survival rate that was not significantly different from that of the non-withholding group. On the other hand, some level of survival may be expected in patients who withhold treatment after 72 hours or more. Further studies are needed to determine the impact of withholding treatment on patients, not only in terms of mortality but also in terms of long-term prognosis and activities of daily living after discharge from the hospital. [ABSTRACT FROM AUTHOR]

Objective: To investigate ED and intensive care unit healthcare professionals' perspectives and knowledge of the law that underpins end‐of‐life decision‐making in Queensland, Australia. Methods: An online survey with questions about perspectives, perceived, and actual, knowledge of the law was distributed by the professional organisations of medical practitioners, nurses and social workers who work in Queensland EDs and intensive care units. Results: The survey responses of 126 healthcare professionals were included in the final analysis. Most respondents agreed that the law was relevant to end‐of‐life decision‐making, but that clinician and family consensus mattered more than following the law. Generally, doctors' legal knowledge was higher than nurses'; however, there were significant gaps in the knowledge of all respondents about the operation of advance health directives in Queensland. Conclusions: The legal framework that supports end‐of‐life decision‐making for adults who lack decision‐making capacity has been in place for more than two decades. Despite frequently being involved in making or enacting these decisions, gaps in the legal knowledge of healthcare professionals who work in EDs and intensive care units in Queensland are evident. Further research to better understand how to improve knowledge and application of the law is warranted. [ABSTRACT FROM AUTHOR]

BACKGROUND: No Escalation of Treatment (NoET) designations are used in ICUs internationally to limit treatment for critically ill patients. However, they are the subject of debate in the literature and have not been qualitatively studied. RESEARCH QUESTION: How do physicians understand and perceive NoET designations, especially regarding their usefulness and associated challenges? What mechanisms do hospitals provide to facilitate the use of NoET designations? STUDY DESIGN AND METHODS: Qualitative study at seven US hospitals, employing semistructured interviews with 30 physicians and review of relevant institutional records (eg, hospital policies, screenshots of ordering menus in the electronic health record). RESULTS: At all hospitals, participants reported the use of NoET designations, which were understood to mean that providers should withhold new or higher-intensity interventions (escalations) but not withdraw ongoing interventions. Three hospitals provided a specific mechanism for designating a patient as NoET (eg, a DNR/Do Not Escalate code status order); at the remaining hospitals, a variety of informal methods (eg, verbal hand-offs) were used. We identified five functions of NoET designations: (1) Defining an intermediate point of treatment limitation, (2) helping physicians navigate prearrest clinical decompensations, (3) helping surrogate decision-makers transition toward comfort care, (4) preventing patient harm from invasive measures, and (5) conserving critical care resources. Across hospitals, participants reported implementation challenges related to the ambiguity in meaning of NoET designations. INTERPRETATION: Despite ongoing debate, NoET designations are used in a varied sample of hospitals and are perceived as having multiple functions, suggesting they may fulfill an important need in the care of critically ill patients, especially at the end of life. The use of NoET designations can be improved through the implementation of a formal mechanism that encourages consistency across providers and clarifies the meaning of escalation for each patient.

\nIntroduction: Most neonatal deaths in industrialized countries follow a process of redirection of care. The objectives of this study were to describe how neonates die in a middle-income country, whether there was redirection of care, and the reason for this decision. Methods: This was a prospective, multicenter, cross-sectional study. Neonates who died in the delivery room or in the neonatal intensive care unit in 97 hospitals over a 6-month period were included. After each neonatal death, one investigator interviewed a member of the healthcare team who had been involved in the end-of-life care process. Perinatal data, conditions that led to death, whether there was redirection of care, and details of the end-of-life process were recorded. Results: Data from 697 neonatal deaths were analyzed, which represent 80% of the total deaths occurring in Argentina in that period. The main causes of death were complications of prematurity (47%) and congenital anomalies (27%). Overall, 32% of neonates died after a process of redirection of care, and this was less frequent in the neonatal intensive care unit (28%) than in the delivery room (70%, p < 0.001). The reasons for withholding/withdrawing care were inevitable death (75%) and severe compromise of expected quality of life (25%). Redirection of care consisted in withholding therapies in 66% and withdrawal in 34%. A diagnosis of a major congenital anomaly increased the odds of redirection of care (OR 5.45; 95% CI: 3.59–8.27). Conclusion: Most neonates who die in Argentina do so while receiving full support. Redirection of care mainly follows a condition of inevitable death. The death of a newborn seems a contradiction, an error of nature. However, neonatal death is a reality and a problem that concerns different disciplines such as public health and bioethics. While the causes are obviously important to develop strategies to decrease them, the way neonates die is essential, including the shared decisions about specific therapies and the care provided at the end of life. To avoid therapies without beneficial effects, neonatal deaths in more industrialized countries follow a process of redirection of care, that is, addressing comfort and avoiding pain instead of looking for a cure that is not possible. The objectives of this study were to describe how neonates die in a middle-income country, whether there was redirection of care, and the reason for this decision. Over a 6-month period, health professionals who were involved in the terminal care of neonates were interviewed within 7 days of the death, and data of the end-of-life process were recorded. We gathered information on 697 neonatal deaths, which represent 80% of the total deaths occurring in Argentina in that period. Overall, 32% of neonates died after a process of redirection of care, most of them because of an inevitable death and a lower percentage because of severe compromise of expected quality of life. In conclusion, in contrast to more industrialized countries, most neonates who die in Argentina do so while receiving full support and when care is redirected, this decision mainly follows a condition of inevitable death. [ABSTRACT FROM AUTHOR]

Aim: This work explores the experiences and meaning attributed by parents who underwent the decision‐making process of withholding and/or withdrawing life‐sustaining treatment for their newborn. Methods: Audio‐recorded face‐to‐face interviews were led and analysed using interpretative phenomenological analysis. Eight families (seven mothers and five fathers) whose baby underwent withholding and/or withdrawing of life‐sustaining treatment in three neonatal intensive care units from two regions in France were included. Results: The findings reveal two paradoxes within the meaning‐making process of parents: role ambivalence and choice ambiguity. We contend that these paradoxes, along with the need to mitigate uncertainty, form protective psychological mechanisms that enable parents to cope with the decision, maintain their parental identity and prevent decisional regret. Conclusion: Role ambivalence and choice ambiguity should be considered when shared decision‐making in the neonatal intensive care unit. Recognising and addressing these paradoxical beliefs is essential for informing parent support practices and professional recommendations, as well as add to ethical discussions pertaining to parental autonomy and physicians' rapport to uncertainty. [ABSTRACT FROM AUTHOR]

Objective. There is limited evidence about how legal frameworks that underpin end-of-life decisions are applied in practice. This study aimed to identify how end-of-life decisions are made and documented in emergency departments and intensive care units. The secondary aim was to explore the extent to which the legal processes featured in these decisions. Methods. A retrospective chart audit of 85 adult patients who died in the emergency departments and intensive care units of a Queensland health service was undertaken. Quantitative data were analysed and reported using descriptive statistics. Qualitative textual data were analysed using inductive content analysis. Results. Nearly all admissions were unplanned (97.6%), and most patients (74.1%) were admitted from home. Only one patient had an advance health directive, although all had an eligible substitute decision-maker. The qualitative analysis revealed two main concepts -- 'healthcare professionals choreograph the end of life' and 'patients and families are carried on an unplanned journey'. Conclusions. There was limited documentation related to the application of the legal framework in these decisions. Healthcare professionals relied on their clinical judgment about what was in the best interest of the patient. It was common for there to be a substantial effort to achieve consensus in decision-making which coincidentally complied with the law. [ABSTRACT FROM AUTHOR]

Abstract Purpose To develop an ethical and cultural infrastructure for Life-Sustaining Treatment (LST) plan, it is crucial to carefully analyze its impact and ensure that healthcare utilization is maintained at an appropriate level, avoiding excessive medical interventions. This study aims to investigate the effects of LST decisions on both healthcare expenditure and utilization. Methods This cohort study utilized claims data from the National Health Insurance Service, encompassing all medical claims in South Korea. We included individuals who had planned to withdraw or withhold their LST between January and December 2018, identified by claim code IA71, IA72, IA73. We followed a total of 28,295 participants with documented LST plan who were deceased by June 2020. Participants were categorized into LST withdrawal / withholding and LST continuation groups. The dependent variables were healthcare expenditure and utilization. We construct a generalized linear model to analyze the association between these variables. Results Out of the 28,295 participants, 24,436 (86.4%) chose to withdraw or withhold LST, while the rest opted for its continuation. Compared to the LST continuation group, those who chose to withdraw or withhold LST had 0.91 times lower odds for total cost. Additionally, they experienced 0.91 times fewer hospitalization days and 0.92 times fewer outpatient visits than those in the LST continuation group. Conclusion Healthcare expenditure and utilization deceased among those choosing to withdraw or withhold LST compared to those continuing it. These findings underscore the significance of patients actively participating in decision regarding their treatment to ensure appropriate levels of medical intervention for LST. Furthermore, they emphasize the critical role of proper education and the establishment of a cultural framework for LST plans.

BackgroundThe World Health Organization (WHO) recommends annual mass azithromycin distribution until districts drop below 5% prevalence of trachomatous inflammation-follicular (TF). Districts with very low TF prevalence may have little or no transmission of the ocular strains of Chlamydia trachomatis that cause trachoma, and additional rounds of mass azithromycin distribution may not be useful. Here, we describe the protocol for a randomized controlled trial designed to evaluate whether mass azithromycin distribution can be stopped prior to the current WHO guidelines.MethodsThe Azithromycin Reduction to Reach Elimination of Trachoma (ARRET) study is a 1:1 community randomized non-inferiority trial designed to evaluate whether mass azithromycin distribution can be stopped in districts with baseline prevalence of TF under 20%. Communities in Maradi, Niger are randomized after baseline assessment either to continued annual mass azithromycin distribution or stopping annual azithromycin distribution over a 3-year period. We will compare the prevalence of ocular C. trachomatis (primary outcome), TF and other clinical signs of trachoma, and serologic markers of trachoma after 3 years. We hypothesize that stopping annual azithromycin distribution will be non-inferior to continued annual azithromycin distributions for all markers of trachoma prevalence and transmission.DiscussionThe results of this trial are anticipated to provide potentially guideline-changing evidence for when mass azithromycin distributions can be stopped in low TF prevalence areas. TRIAL REGISTRATION NUMBER: This study is registered at clinicaltrials.gov ( NCT04185402 ). Registered December 4, 2019; prospectively registered pre-results.

BackgroundSurgery is the main modality of cure for solid cancers and was prioritised to continue during COVID-19 outbreaks. This study aimed to identify immediate areas for system strengthening by comparing the delivery of elective cancer surgery during the COVID-19 pandemic in periods of lockdown versus light restriction.MethodsThis international, prospective, cohort study enrolled 20 006 adult (≥18 years) patients from 466 hospitals in 61 countries with 15 cancer types, who had a decision for curative surgery during the COVID-19 pandemic and were followed up until the point of surgery or cessation of follow-up (Aug 31, 2020). Average national Oxford COVID-19 Stringency Index scores were calculated to define the government response to COVID-19 for each patient for the period they awaited surgery, and classified into light restrictions (index 60). The primary outcome was the non-operation rate (defined as the proportion of patients who did not undergo planned surgery). Cox proportional-hazards regression models were used to explore the associations between lockdowns and non-operation. Intervals from diagnosis to surgery were compared across COVID-19 government response index groups. This study was registered at ClinicalTrials.gov, NCT04384926.FindingsOf eligible patients awaiting surgery, 2003 (10·0%) of 20 006 did not receive surgery after a median follow-up of 23 weeks (IQR 16-30), all of whom had a COVID-19-related reason given for non-operation. Light restrictions were associated with a 0·6% non-operation rate (26 of 4521), moderate lockdowns with a 5·5% rate (201 of 3646; adjusted hazard ratio [HR] 0·81, 95% CI 0·77-0·84; p

Abstract Background Although the Life-Sustaining Treatment (LST) Decision Act was enforced in 2018 in Korea, data on whether it is well established in actual clinical settings are limited. Hospital-acquired pneumonia (HAP) is a common nosocomial infection with high mortality. However, there are limited data on the end-of-life (EOL) decision of patients with HAP. Therefore, we aimed to examine clinical characteristics and outcomes according to the EOL decision for patients with HAP. Methods This multicenter study enrolled patients with HAP at 16 referral hospitals retrospectively from January to December 2019. EOL decisions included do-not-resuscitate (DNR), withholding of LST, and withdrawal of LST. Descriptive and Kaplan–Meier curve analyses for survival were performed. Results Of 1,131 patients with HAP, 283 deceased patients with EOL decisions (105 cases of DNR, 108 cases of withholding of LST, and 70 cases of withdrawal of LST) were analyzed. The median age was 74 (IQR 63–81) years. The prevalence of solid malignant tumors was high (32.4% vs. 46.3% vs. 54.3%, P = 0.011), and the ICU admission rate was lower (42.9% vs. 35.2% vs. 24.3%, P = 0.042) in the withdrawal group. The prevalence of multidrug-resistant pathogens, impaired consciousness, and cough was significantly lower in the withdrawal group. Kaplan–Meier curve analysis revealed that 30-day and 60-day survival rates were higher in the withdrawal group than in the DNR and withholding groups (log-rank P = 0.021 and 0.018). The survival of the withdrawal group was markedly decreased after 40 days; thus, the withdrawal decision was made around this time. Among patients aged below 80 years, the rates of EOL decisions were not different (P = 0.430); however, mong patients aged over 80 years, the rate of withdrawal was significantly lower than that of DNR and withholding (P = 0.001). Conclusions After the LST Decision Act was enforced in Korea, a DNR order was still common in EOL decisions. Baseline characteristics and outcomes were similar between the DNR and withholding groups; however, differences were observed in the withdrawal group. Withdrawal decisions seemed to be made at the late stage of dying. Therefore, advance care planning for patients with HAP is needed.

Purpose: To develop an ethical and cultural infrastructure for Life-Sustaining Treatment (LST) plan, it is crucial to carefully analyze its impact and ensure that healthcare utilization is maintained at an appropriate level, avoiding excessive medical interventions. This study aims to investigate the effects of LST decisions on both healthcare expenditure and utilization. Methods: This cohort study utilized claims data from the National Health Insurance Service, encompassing all medical claims in South Korea. We included individuals who had planned to withdraw or withhold their LST between January and December 2018, identified by claim code IA71, IA72, IA73. We followed a total of 28,295 participants with documented LST plan who were deceased by June 2020. Participants were categorized into LST withdrawal / withholding and LST continuation groups. The dependent variables were healthcare expenditure and utilization. We construct a generalized linear model to analyze the association between these variables. Results: Out of the 28,295 participants, 24,436 (86.4%) chose to withdraw or withhold LST, while the rest opted for its continuation. Compared to the LST continuation group, those who chose to withdraw or withhold LST had 0.91 times lower odds for total cost. Additionally, they experienced 0.91 times fewer hospitalization days and 0.92 times fewer outpatient visits than those in the LST continuation group. Conclusion: Healthcare expenditure and utilization deceased among those choosing to withdraw or withhold LST compared to those continuing it. These findings underscore the significance of patients actively participating in decision regarding their treatment to ensure appropriate levels of medical intervention for LST. Furthermore, they emphasize the critical role of proper education and the establishment of a cultural framework for LST plans. [ABSTRACT FROM AUTHOR]

ObjectiveMethamphetamine use is associated with systolic dysfunction, pulmonary arterial hypertension and may also be associated with diastolic dysfunction. The impact of methamphetamine cessation on methamphetamine-associated heart failure (MethHF) remains poorly characterised. We aimed to longitudinally characterise methamphetamine-associated heart failure patients with reduced (METHrEF) and preserved (METHpEF) left ventricular ejection fraction (EF), and evaluate the relationship between methamphetamine cessation and clinical outcomes.MethodsWe performed a retrospective cohort study, and reviewed medical records of patients with METHrEF, METHpEF and heart failure controls without methamphetamine use. Echocardiographic variables were recorded for up to 12 months, with clinical follow-up extending to 24 months.ResultsAmong METHrEF patients (n=28, mean age 51±9 years, 82.1% male), cessation was associated with improvement in EF (+10.6±13.1%, p=0.009) and fewer heart failure admissions per year compared with continued use (median 0.0, IQR 0.0-1.0 vs median 2.0, IQR 1.0-3.0, p=0.039). METHpEF patients (n=28, mean age 50±8 years, 60.7% male) had higher baseline right ventricular systolic pressure (median 53.44, IQR 43.70-84.00 vs median 36.64, IQR 29.44-45.95, p=0.011), and lower lateral E/E' ratio (8.1±3.6 vs 11.2±4., p

BACKGROUND: Neonatal seizures are associated with death and neurological morbidity; however, little is known about how neonates with seizures die. METHODS: This was a prospective, observational cohort study of neonates with seizures treated at seven sites of the Neonatal Seizure Registry. We characterized the mode of death, evaluated the association between infant characteristics and mode of death, and evaluated predictors of death or transfer to hospice. RESULTS: We enrolled 611 consecutive neonates with seizures, and 90 neonates (15%) died before hospital discharge at a median age of 11 days (range: 1 to 163 days); 32 (36%) died in the first postnatal week. An additional 19 neonates (3%) were transferred to hospice. The most common mode of in-hospital death was death after extubation amidst concerns for poor neurological prognosis, in the absence of life-threatening physiologic instability (n = 43, 48%). Only one infant died while actively receiving cardiopulmonary resuscitation. In an adjusted analysis, premature birth (odds ratio: 3.06, 95% confidence interval 1.59 to 5.90) and high seizure burden (odds ratio: 4.33, 95% confidence interval 1.88 to 9.95) were associated with increased odds of death or transfer to hospice. CONCLUSION: In a cohort of neonates with seizures, death occurred predominantly after decisions to withdraw or withhold life-sustaining intervention(s). Future work should characterize how these decisions occur and develop optimized approaches to support families and clinicians caring for newborns with seizures.

Objective: Literature shows high in-hospital mortality rates following end-of-life decisions in patients with traumatic spinal cord injury. This study investigated 2-year mortality and end-of-life decisions in patients with traumatic spinal cord injury. Design: Explorative retrospective study in a Dutch level 1 trauma centre. Patients: All consecutive patients between 2015 and 2020 with new traumatic spinal cord injury were selected from the trauma registry. Patients were excluded if myelopathy, cauda equina, or conus medullaris injury was absent or if they were referred to another level 1 trauma centre. Methods: Mortality and end-of-life decisions (i.e. withdrawal and withholding of treatment, and euthanasia) within 2 years were analysed. Demographics, injury and clinical characteristics, and hospital treatment outcomes were compared with survivors. Motivations and critical morbidities concerning end-of-life decisions were assessed. Results: The sample included 219 patients. Two-year mortality was 26% (n = 56), in-hospital mortality was 16%. The deceased were older, had more comorbidities and more severe injuries. end-of-life decisions concerned 42 patients (75%), mostly motivated by loss of independence or poor outcomes. Three patients received euthanasia (5%). The largest group with end-of-life decisions also sustained moderate-severe traumatic brain injuries (n = 11; 26%). Conclusion: Most patients with traumatic spinal cord injury died following an end-of-life decision, with the largest group sustaining concomitant traumatic brain injuries. The incidence of euthanasia was low.

Background: Although the Life-Sustaining Treatment (LST) Decision Act was enforced in 2018 in Korea, data on whether it is well established in actual clinical settings are limited. Hospital-acquired pneumonia (HAP) is a common nosocomial infection with high mortality. However, there are limited data on the end-of-life (EOL) decision of patients with HAP. Therefore, we aimed to examine clinical characteristics and outcomes according to the EOL decision for patients with HAP. Methods: This multicenter study enrolled patients with HAP at 16 referral hospitals retrospectively from January to December 2019. EOL decisions included do-not-resuscitate (DNR), withholding of LST, and withdrawal of LST. Descriptive and Kaplan–Meier curve analyses for survival were performed. Results: Of 1,131 patients with HAP, 283 deceased patients with EOL decisions (105 cases of DNR, 108 cases of withholding of LST, and 70 cases of withdrawal of LST) were analyzed. The median age was 74 (IQR 63–81) years. The prevalence of solid malignant tumors was high (32.4% vs. 46.3% vs. 54.3%, P = 0.011), and the ICU admission rate was lower (42.9% vs. 35.2% vs. 24.3%, P = 0.042) in the withdrawal group. The prevalence of multidrug-resistant pathogens, impaired consciousness, and cough was significantly lower in the withdrawal group. Kaplan–Meier curve analysis revealed that 30-day and 60-day survival rates were higher in the withdrawal group than in the DNR and withholding groups (log-rank P = 0.021 and 0.018). The survival of the withdrawal group was markedly decreased after 40 days; thus, the withdrawal decision was made around this time. Among patients aged below 80 years, the rates of EOL decisions were not different (P = 0.430); however, mong patients aged over 80 years, the rate of withdrawal was significantly lower than that of DNR and withholding (P = 0.001). Conclusions: After the LST Decision Act was enforced in Korea, a DNR order was still common in EOL decisions. Baseline characteristics and outcomes were similar between the DNR and withholding groups; however, differences were observed in the withdrawal group. Withdrawal decisions seemed to be made at the late stage of dying. Therefore, advance care planning for patients with HAP is needed. [ABSTRACT FROM AUTHOR]

Decisions in end-of-life care are influenced by several factors, many of which are not identified by the decision maker. These influencing factors modify important decisions in this scenario, such as in decisions to adapt to therapeutic support. This presented scoping review aims to map the factors that influence end-of-life care decisions for adult and older adult patients, by a scoping review. The review was carried out in 19 databases, with the keyword 'clinical decision-making' AND 'terminal care' OR 'end-of-life care' and its analogues, including publications from 2017 to 2022. The study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews. The search resulted in 3474 publications, where the presence of influencing factors in end-of-life decision-making for adults and the elderly was applied as a selection criterion. Fifty-four (54) of them were selected, which means 1.5% of all the results. Among the selected publications, 89 influencing factors were found, distributed in 54 (60.6%) factors related to the health team, 18 (20.2%) to patients, 10 (11.2%) related to family or surrogates and 7 (7.8%) factors related to the decision environment. In conclusion, we note that the decision-making in end-of-life care is complex, mainly because there is an interaction of different characters (health team, patient, family, or surrogates) with a plurality of influencing factors, associated with an environment of uncertainty and that result in a critical outcome, with a great repercussion for the end of life, making it imperative the recognition of these factors for more competent and safe decision- making. [ABSTRACT FROM AUTHOR]

INTRODUCTION: To describe patient-reported outcomes and toxicities at time of treatment discontinuation secondary to progression or toxicities in advanced/recurrent cervical cancer patients receiving chemotherapy with bevacizumab. METHODS: Summarize toxicity, grade, and health-related quality of life within 1 month of treatment discontinuation for women receiving chemotherapy with bevacizumab in GOG240. RESULTS: Of the 227 patients who received chemotherapy with bevacizumab, 148 discontinued study protocol treatment (90 for disease progression and 58 for toxicity). The median survival time from treatment discontinuation to death was 7.9 months (95% CI 5.0 to 9.0) for those who progressed versus 12.1 months (95% CI 8.9 to 23.2) for those who discontinued therapy due to toxicities. The most common grade 3 or higher toxicities included hematologic, gastrointestinal, and pain. Some 57% (84/148) of patients completed quality of life assessment within 1 month of treatment discontinuation. Those patients who discontinued treatment due to progression had a mean decline in the FACT-Cx TOI of 3.2 points versus 2.2 in patients who discontinued therapy due to toxicity. This was a 9.9 point greater decline in the FACT-Cx TOI scores than those who discontinued treatment due to progression (95% CI 2.8 to 17.0, p=0.007). The decline in quality of life was due to worsening physical and functional well-being. Those who discontinued treatment due to toxicities had worse neurotoxicity and pain. DISCUSSION: Patients who discontinued chemotherapy with bevacizumab for toxicity experienced longer post-protocol survival but significantly greater declination in quality of life than those with progression. Future trial design should include supportive care interventions that optimize physiologic function and performance status for salvage therapies.

IntroductionTo describe patient-reported outcomes and toxicities at time of treatment discontinuation secondary to progression or toxicities in advanced/recurrent cervical cancer patients receiving chemotherapy with bevacizumab.MethodsSummarize toxicity, grade, and health-related quality of life within 1 month of treatment discontinuation for women receiving chemotherapy with bevacizumab in GOG240.ResultsOf the 227 patients who received chemotherapy with bevacizumab, 148 discontinued study protocol treatment (90 for disease progression and 58 for toxicity). The median survival time from treatment discontinuation to death was 7.9 months (95% CI 5.0 to 9.0) for those who progressed versus 12.1 months (95% CI 8.9 to 23.2) for those who discontinued therapy due to toxicities. The most common grade 3 or higher toxicities included hematologic, gastrointestinal, and pain. Some 57% (84/148) of patients completed quality of life assessment within 1 month of treatment discontinuation. Those patients who discontinued treatment due to progression had a mean decline in the FACT-Cx TOI of 3.2 points versus 2.2 in patients who discontinued therapy due to toxicity. This was a 9.9 point greater decline in the FACT-Cx TOI scores than those who discontinued treatment due to progression (95% CI 2.8 to 17.0, p=0.007). The decline in quality of life was due to worsening physical and functional well-being. Those who discontinued treatment due to toxicities had worse neurotoxicity and pain.DiscussionPatients who discontinued chemotherapy with bevacizumab for toxicity experienced longer post-protocol survival but significantly greater declination in quality of life than those with progression. Future trial design should include supportive care interventions that optimize physiologic function and performance status for salvage therapies.

BackgroundIdentification of nonviral markers of human immunodeficiency virus (HIV) infection that increase before viral rebound during analytical treatment interruption (ATI) may affect HIV persistence research. We previously showed that HIV ribonucleic acid (RNA) is enriched in CD30+CD4+ T cells in many individuals. Here, we studied CD30+CD4+ T-cell dynamics before ATI, during ATI (before detectable plasma RNA), and after HIV rebound.MethodsPeripheral blood mononuclear cells from 23 participants collected longitudinally from 5 Adult AIDS Clinical Trials Group studies incorporating ATI were included in this study. Flow cytometric characterization of expression of CD30 and markers of T-cell activation and exhaustion were performed along with HIV-1 RNA and deoxyribonucleic acid quantification and measurement of soluble plasma CD30 and CD30 ligand.ResultsThe percentage of CD4+ T cells expressing CD30 significantly increased from pre-ATI to postinterruption time points before detectible viremia (1.65 mean relative increase, P = .005). Seventy-seven percent of participants experienced an increase in CD30+ cells before viral rebound. In contrast, there were no significant differences between pre-ATI and postinterruption pre-rebound time points in percentages of lymphocytes expressing CD69, CD38/HLA-DR, or PD-1 until after HIV recrudescence.ConclusionsCD30 may be a surrogate marker of early replication or viral transcriptional activity before detection by routine peripheral blood sampling.

Introduction: as the opportunity to receive lifesustaining treatments expands in sub-Saharan Africa (SSA), so do potential ethical dilemmas. Little is known regarding the attitudes, beliefs, and practices of physicians in SSA regarding end-of-life care ethics. Methods: we used validated survey items addressing physician end-of-life care views and added SSA-context specific items. We identified a convenience sample using the authors' existing African professional contacts and snowball recruitment. Participants were invited via email to an anonymous online survey. Results: we contacted 78 physicians who practice critical care in Africa, and 68% (n=53) completed the survey. Of those, 66% were male, 55% were aged 36-45, 75% were Christian. They were from Kenya (30%), Zambia (28%), Rwanda (25%), Botswana (11%), and other countries (6%). Most (75%) agreed that competent patients can refuse even life-saving care. Only 32% agreed that their hospital had clear policies regarding withdrawing and withholding care, 11% agreed that their country had legal precedent for end-of-life care, and 43% believed that doctors could face legal or financial consequences for allowing patients to die by forgoing treatment. Pain control at the end of life, even if it may hasten death, was supported by 83%. However, 75% felt that clinicians undertreat pain due to fear of hastening death. Conclusion: participants strongly supported patient autonomy and end-of-life pain control but expressed concern that inadequate policy and legal frameworks exist to guide care and that pain is undertreated. Humane and actionable end-oflife care frameworks are needed to guide decisions in SSA. [ABSTRACT FROM AUTHOR]

Aim: The decrease in childhood mortality, the growing clinical complexity and the greater technification of intensive care units have changed the circumstances of death of paediatric patients. The aim of this study is to describe the context of death and end‐of‐life decision‐making. Methods: Single‐centre, retrospective, observational study of deaths in inpatients or home hospitalised children under 18 years old between 2011 and 2021. Demographic data, pathological history and circumstances of death were obtained from the medical record. The whole study period was divided into two halves for the analysis of the temporal trends. Results: A total of 358 patients died, 63.2% under the age of 1 year old; 86.9% had underlying life‐limiting illnesses and 73.2% died in the intensive care unit, with no differences between the two time periods. Death at home was significantly higher in the second study period (3.8% vs. 9%). A total of 20.1% died during advanced cardiopulmonary resuscitation. Life‐sustaining treatment was withheld or withdrawn in 53.6%, with no differences between the time courses. Life‐sustaining treatment was withheld mainly in patients with neurological, metabolic and oncological conditions, and less frequently in patients with cardiovascular or respiratory diseases or who were previously healthy. Most patients coded as palliative care (PC) or followed up by PC teams had an advance care plan (ACP) recorded, while in the others it was infrequent. PC coding, following by PC teams and ACP recording increased in the last years of the study. Conclusions: Death of children in our setting usually occurs in relation to complex underlying pathology and after the decision of withdrawing or withholding life‐sustaining treatment. In this context, PC and ACP acquire greater importance. In our study, PC involvement resulted in better documentation of ACP and PC coding. [ABSTRACT FROM AUTHOR]

ObjectivesOptimistic expectations about prognosis by surrogate decision-makers in ICUs are common, but there are few data about the causes and clinical consequences. Our objective was to determine the causes of optimistic expectations about prognosis among surrogates and whether it is associated with more use of life support at the end of life.DesignProspective, multicenter cohort study from 2009 to 2012.SettingTwelve ICUs from multiple regions of the United States.SubjectsThe surrogates and physicians of 275 incapacitated ICU patients at high risk of death.InterventionsNone.Measurements and main resultsSurrogates and physicians completed a validated instrument assessing their prognostic expectations for hospital survival. We determined the proportion of surrogates with optimistic expectations, defined as a prognostic estimate that was at least 20% more optimistic than the physician's, then determined how frequently this arose from surrogates miscomprehending the physicians' prognosis versus holding more hopeful beliefs compared with the physician. We used multivariable regression to examine whether optimistic expectations were associated with length of stay, stratified by survival status, and time to withdrawal of life support among nonsurvivors. Overall, 45% of surrogates (95% CI, 38-51%) held optimistic expectations about prognosis, which arose from a combination of misunderstanding the physician's prognostic expectations and from holding more hopeful beliefs compared with the physician. Optimistic expectations by surrogates were associated with significantly longer duration of ICU treatment among nonsurvivors before death (β coefficient = 0.44; 95% CI, 0.05-0.83; p = 0.027), corresponding to a 56% longer ICU stay. This difference was associated with a significantly longer time to withdrawal of life support among dying patients whose surrogates had optimistic prognostic expectations compared with those who did not (β coefficient = 0.61; 95% CI, 0.16-1.07; p = 0.009).ConclusionsThe prevalent optimism about prognosis among surrogates in ICUs arises both from surrogates' miscomprehension of physicians' prognostications and from surrogates holding more hopeful beliefs. This optimism is associated with longer duration of life support at the end of life.

BackgroundIntermittent preventive treatment (IPT) of malaria with dihydroartemisinin-piperaquine is a promising strategy for malaria prevention in young African children. However, the optimal dosing strategy is unclear and conflicting evidence exists regarding the risk of malaria after cessation of chemoprevention. We aimed to compare two dosing strategies of IPT with dihydroartemisinin-piperaquine in young Ugandan children, and to evaluate the risk of malaria after cessation of IPT.MethodsIn this double-blind, randomised controlled phase 2 trial, women and their unborn children were recruited at Tororo District Hospital (Tororo, Uganda). Eligible participants were HIV-negative women aged 16 years or older with a viable pregnancy (gestational age 12-20 weeks). Women and their unborn children were randomly assigned (1:1:1:1) to one of four treatment groups, all receiving dihydroartemisinin-piperaquine, on the basis of the IPT intervention received by the woman during pregnancy: women every 8 weeks, children every 4 weeks; women every 4 weeks, children every 4 weeks; women every 8 weeks, children every 12 weeks; and women every 4 weeks, children every 12 weeks. Block randomisation was done by an independent investigator using a computer-generated randomisation list (permuted block sizes of six and 12). We analysed children on the basis of their random assignment to receive dihydroartemisinin-piperaquine (20 mg/160 mg tablets) once daily for 3 consecutive days every 4 weeks or 12 weeks. Children received study drugs from age 8 weeks to 24 months and were followed-up to age 36 months. Participants and investigators were masked to treatment allocation. The primary outcome was the incidence of symptomatic malaria during the intervention and following cessation of the intervention, adjusted for potential confounders. The primary outcome and safety were assessed in the modified intention-to-treat population, which included all children who reached 8 weeks of age and received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, number NCT02163447.FindingsBetween Oct 21, 2014, and May 18, 2015, 191 children were born, of whom 183 reached 8 weeks of age and received at least one dose of study drug and thus were included in the primary analysis (96 children in the 4-week group and 87 in the 12-week group). During the intervention, the incidence of symptomatic malaria was significantly lower among children treated every 4 weeks than children treated every 12 weeks; three episodes occurred among children treated every 4 weeks (incidence 0·018 episodes per person-year) compared with 61 episodes among children treated every 12 weeks (incidence 0·39 episodes per person-year; adjusted incidence rate ratio [aIRR] 0·041, 95% CI 0·012-0·150, p

Nonbullous congenital ichthyosis erythroderma (CIE) is an autosomal recessive disorder of ineffective keratinization. We present a unique case of a 16-year-old female with CIE who developed Cushing disease (CD) at age 13 with concomitant worsening of her skin disease. After transsphenoidal resection of her pituitary adenoma, she had both resolution of her Cushing symptoms and significantly milder skin manifestations of her CIE. To the best of our knowledge, this is the first reported case of a patient with both CD and CIE, one that is important in demonstrating the role of glucocorticoids in this disorder.

BACKGROUND: The deleterious effects of discontinuation of digoxin on outcomes in ambulatory patients with chronic heart failure (HF) with reduced ejection fraction (HFrEF) receiving angiotensin-converting enzyme inhibitors are well-documented. OBJECTIVES: The authors sought to determine the relationship between digoxin discontinuation and outcomes in hospitalized patients with HFrEF receiving more contemporary guideline-directed medical therapies including beta-blockers and mineralocorticoid receptor antagonists. METHODS: Of the 11,900 hospitalized patients with HFrEF (EF ≤45%) in the Medicare-linked OPTIMIZE-HF (Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure) registry, 3,499 received pre-admission digoxin, which was discontinued in 721 patients. Using propensity scores for digoxin discontinuation, estimated for each of the 3,499 patients, a matched cohort of 698 pairs of patients, balanced on 50 baseline characteristics (mean age 76 years; mean EF 28%; 41% women; 13% African American; 65% on beta-blockers) was assembled. RESULTS: Four-year post-discharge, digoxin discontinuation was associated with significantly higher risks of HF readmission (hazard ratio [HR]: 1.21; 95% confidence interval [CI]: 1.05 to 1.39; p = 0.007), all-cause readmission (HR: 1.16; 95% CI: 1.04 to 1.31; p = 0.010), and the combined endpoint of HF readmission or all-cause mortality (HR: 1.20; 95% CI: 1.07 to 1.34; p = 0.002), but not all-cause mortality (HR: 1.09; 95% CI: 0.97 to 1.24; p = 0.163). Discontinuation of digoxin was associated with a significantly higher risk of all 4 outcomes at 6 months and 1 year post-discharge. At 30 days, digoxin discontinuation was associated with higher risks of all-cause mortality (HR: 1.80; 95% CI: 1.26 to 2.57; p = 0.001) and the combined endpoint (HR: 1.36; 95% CI: 1.09 to 1.71; p = 0.007), but not of HF readmission (HR: 1.19; 95% CI: 0.90 to 1.59; p = 0.226) or all-cause readmission (HR: 1.03; 95% CI: 0.84 to 1.26; p = 0.778). CONCLUSIONS: Among hospitalized older patients with HFrEF on more contemporary guideline-directed medical therapies, discontinuation of pre-admission digoxin therapy was associated with poor outcomes.

In this discussion, 2 established researchers and clinical trialists debate their opposing views on the utility, benefits, and risks of the use of analytical interruption of antiretroviral therapy as a clinical trial end point and outcome measure in human studies seeking to induce remission of or eradicate human immunodeficiency virus infection.

OBJECTIVES: Among kidney disease patients ≥80 years progressing to end-stage renal disease, there is growing interest in conservative nondialytic management approaches. However, among those who have initiated hemodialysis, little is known about the impact of withdrawal from dialysis on mortality, nor the patient characteristics associated with withdrawal from dialysis. STUDY DESIGN: Historical cohort study. SETTING AND PARTICIPANTS: We examined 133,162 incident hemodialysis patients receiving care within a large national dialysis organization from 2007 to 2011. MEASURES: We identified patients who withdrew from dialysis, either as a listed cause of death or censor reason. Incidence rates and subdistribution hazard ratios for withdrawal from dialysis as well as 4 other censoring reasons were examined across age groups. In addition, demographic and clinical characteristics associated with withdrawal from dialysis therapy among patients ≥80 years old was assessed using logistic regression analysis. RESULTS: Among 17,296 patients aged ≥80 years, 10% of patients withdrew from dialysis. Duration from the last hemodialysis treatment to death was 10 [interquartile range 6-16] days in patients with available data. Withdrawal from dialysis was the second and third most common cause of death among patients aged ≥80 years and

The Immune Tolerance Network ITN030ST A-WISH assessed immunosuppression withdrawal in liver transplant recipients with hepatitis C or nonimmune nonviral liver disease. Of 275 recipients enrolled before transplantation, 95 were randomly assigned 4:1 to withdrawal (n = 77) or maintenance (n = 18) 1- to 2-years posttransplant. Randomization eligibility criteria included stable immunosuppression monotherapy; adequate liver and kidney function; ≤Stage 2 Ishak fibrosis; and absence of rejection on biopsy. Immunosuppression withdrawal followed an 8-step reduction algorithm with ≥8 weeks per level. Fifty-two of 77 subjects (67.5%) reduced to ≤50% of baseline dose, and 10 of 77 (13.0%) discontinued all immunosuppression for ≥1 year. Acute rejection and/or abnormal liver tests were treated with increased immunosuppression; 5 of 32 rejection episodes required a methylprednisolone bolus. The composite end point (death or graft loss; grade 4 secondary malignancy or opportunistic infection; Ishak stage ≥3; or >25% decrease in glomerular filtration rate within 24 months of randomization) occurred in 12 of 66 (18%) and 4 of 13 (31%) subjects in the withdrawal and maintenance groups. Early immunosuppression minimization is feasible in selected liver recipients, while complete withdrawal is successful in only a small proportion. The composite end point comparison was inconclusive for noninferiority of the withdrawal to the maintenance group.

Although liver biopsy is the gold standard for assessing allograft health, its attendant risk has deterred its use in routine monitoring of stable liver transplant recipients during long-term follow-up. We utilized prospectively collected data on adverse events from 2 clinical trials of immunosuppression withdrawal to quantify the risk of liver biopsy in pediatric liver transplant recipients. The trials included 451 liver biopsies in 179 children. No biopsies led to bleeding requiring transfusion or intervention, suggesting a clinically significant bleeding risk of

Analytical antiretroviral treatment interruption (ATI) is an important feature of HIV research, seeking to achieve sustained viral suppression in the absence of antiretroviral therapy (ART) when the goal is to measure effects of novel therapeutic interventions on time to viral load rebound or altered viral setpoint. Trials with ATIs also intend to determine host, virological, and immunological markers that are predictive of sustained viral control off ART. Although ATI is increasingly incorporated into proof-of-concept trials, no consensus has been reached on strategies to maximise its utility and minimise its risks. In addition, differences in ATI trial designs hinder the ability to compare efficacy and safety of interventions across trials. Therefore, we held a meeting of stakeholders from many interest groups, including scientists, clinicians, ethicists, social scientists, regulators, people living with HIV, and advocacy groups, to discuss the main challenges concerning ATI studies and to formulate recommendations with an emphasis on strategies for risk mitigation and monitoring, ART resumption criteria, and ethical considerations. In this Review, we present the major points of discussion and consensus views achieved with the goal of informing the conduct of ATIs to maximise the knowledge gained and minimise the risk to participants in clinical HIV research.

ObjectivesThis study aimed to determine the timing and level of HIV rebound in blood and seminal plasma and to characterize the HIV rebounding populations after antiretroviral treatment interruption (ATI) in HIV-1-infected participants enrolled in a therapeutic vaccine trial.DesignA 12-week (W) ATI period was proposed at W36 to patients enrolled in the VRI02/ANRS149-LIGHT trial. Paired blood and semen samples were collected before (W32 or W36) and during ATI (W38, W40, W42, W44, and W48).MethodsHIV-RNA and HIV-DNA were quantified sequentially from blood and semen samples. Ultradeep sequencing (UDS; Roche/454) of partial env HIV-DNA/RNA (C2V3) was performed in both compartments.ResultsHIV-RNA rebounded in blood plasma and seminal plasma of all ten participants after ATI [median peak of 5.12 log10 cp/ml (range: 4.61-6.35) and 4.26 log10 cp/ml (3.20-4.67), respectively]. HIV-RNA rebound was detected in blood plasma as soon as W38 in 8/10 patients, and in seminal plasma between W38 and W40 in 8/10 patients. Phylogenetic approaches showed intermingled HIV-RNA populations from plasma and semen during ATI, suggesting a lack of viral compartmentalization between blood and semen.ConclusionOur data demonstrate rapid and high HIV rebound in semen after ATI, raising concerns about high risk of HIV sexual transmission during HIV cure trials.

BackgroundAutoantibodies against glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1) cause chylomicronemia by blocking the ability of GPIHBP1 to bind lipoprotein lipase (LPL) and transport the enzyme to its site of action in the capillary lumen.ObjectiveA patient with multiple sclerosis developed chylomicronemia during interferon (IFN) β1a therapy. The chylomicronemia resolved when the IFN β1a therapy was discontinued. Here, we sought to determine whether the drug-induced chylomicronemia was caused by GPIHBP1 autoantibodies.MethodsWe tested plasma samples collected during and after IFN β1a therapy for GPIHBP1 autoantibodies (by western blotting and with enzyme-linked immunosorbent assays). We also tested whether the patient's plasma blocked the binding of LPL to GPIHBP1 on GPIHBP1-expressing cells.ResultsDuring IFN β1a therapy, the plasma contained GPIHBP1 autoantibodies, and those autoantibodies blocked GPIHBP1's ability to bind LPL. Thus, the chylomicronemia was because of the GPIHBP1 autoantibody syndrome. Consistent with that diagnosis, the plasma levels of GPIHBP1 and LPL were very low. After IFN β1a therapy was stopped, the plasma triglyceride levels returned to normal, and GPIHBP1 autoantibodies were undetectable.ConclusionThe appearance of GPIHBP1 autoantibodies during IFN β1a therapy caused chylomicronemia. The GPIHBP1 autoantibodies disappeared when the IFN β1a therapy was stopped, and the plasma triglyceride levels fell within the normal range.

Ethical dilemmas in nursing are most pronounced in palliative and end-of-life care, where we meet the most demanding and complex needs of nursing care. The research discusses the importance of ethics, religion and spirituality in palliative care, from the perspective of three monotheistic religions and the emphasis on end-of-life ethical dilemmas and how religious beliefs can affect end-of-life medical care and nursing. The importance of ethics, religion and spirituality is presented in the research within three basic ethical principles, such as withholding and withdrawal of treatment, unjustified treatment and treatment with palliative sedation, and tried to justify its assessment in light of Jewish, Catholic and Islamic perspectives.

No Escalation of Treatment (NoET) designations are used in ICUs internationally to limit treatment for critically ill patients. However, they are the subject of debate in the literature and have not been qualitatively studied. How do physicians understand and perceive NoET designations, especially regarding their usefulness and associated challenges? What mechanisms do hospitals provide to facilitate the use of NoET designations? Qualitative study at seven US hospitals, employing semistructured interviews with 30 physicians and review of relevant institutional records (eg, hospital policies, screenshots of ordering menus in the electronic health record). At all hospitals, participants reported the use of NoET designations, which were understood to mean that providers should withhold new or higher-intensity interventions ("escalations") but not withdraw ongoing interventions. Three hospitals provided a specific mechanism for designating a patient as NoET (eg, a DNR/Do Not Escalate code status order); at the remaining hospitals, a variety of informal methods (eg, verbal hand-offs) were used. We identified five functions of NoET designations: (1) Defining an intermediate point of treatment limitation, (2) helping physicians navigate prearrest clinical decompensations, (3) helping surrogate decision-makers transition toward comfort care, (4) preventing patient harm from invasive measures, and (5) conserving critical care resources. Across hospitals, participants reported implementation challenges related to the ambiguity in meaning of NoET designations. Despite ongoing debate, NoET designations are used in a varied sample of hospitals and are perceived as having multiple functions, suggesting they may fulfill an important need in the care of critically ill patients, especially at the end of life. The use of NoET designations can be improved through the implementation of a formal mechanism that encourages consistency across providers and clarifies the meaning of "escalation" for each patient. [Display omitted] [ABSTRACT FROM AUTHOR]

Purpose: To grasp public opinion accurately, we conducted an opinion poll on beliefs and attitudes toward physician-assisted suicide (PAS). Methods: A randomized telephone survey ensuring a representative sample was conducted, 1,007 participants aged 18 years or older (response rate, 9.5%). Results: The main results are as follows: i) 61.1% of participants thought that the current social support system for terminally ill patients and their families is insufficient; ii) 60% of participants did not recognize the term "hospice and palliative care"; iii) 81.7% of participants would not like to receive life-sustaining treatment if there is no possibility of recovery; iv) 58.4% of participants would like to receive hospice and palliative care if they are diagnosed with a terminal illness; v) the priorities for dignified dying were preparing a support system to reduce the burden of care (28.6%), economic support including reduction of medical expenses (26.7%), expansion of hospice and palliative care services (25.4%), and legalization of PAS (13.6%); and vi) 58.3% of participants agreed that the expansion of hospice and palliative care should precede the legalization of PAS. Conclusion: Koreans currently want other efforts, including expansion of hospice and palliative care services, instead of the legalization of PAS. [ABSTRACT FROM AUTHOR]

Background The Life-Sustaining Treatment (LST) Decisions Act allows withholding and withdrawal of LST, including cardiopulmonary resuscitation (CPR). In the present study, the incidence of CPR before and after implementation of the Act was compared. Methods This was a retrospective review involving hospitalized patients who underwent CPR at a single center between February 2016 and January 2020 (pre-implementation period, February 2016 to January 2018; post-implementation period, February 2018 to January 2020). The primary outcome was monthly incidence of CPR per 1,000 admissions. The secondary outcomes were duration of CPR, return of spontaneous circulation (ROSC) rate, 24-hour survival rate, and survival-to-discharge rate. The study outcomes were compared before and after implementation of the Act. Results A total of 867 patients who underwent CPR was included in the analysis. The incidence of CPR per 1,000 admissions showed no significant difference before and after implementation of the Act (3.02±0.68 vs. 2.81±0.75, P=0.255). The ROSC rate (67.20±0.11 vs. 70.99±0.12, P=0.008) and survival to discharge rate (20.24±0.09 vs. 22.40±0.12, P=0.029) were higher after implementation of the Act than before implementation. Conclusions The incidence of CPR did not significantly change for 2 years after implementation of the Act. Further studies are needed to assess the changes in trends in the decisions of CPR and other LSTs in real-world practice.

ObjectiveThe impact of short-term analytical treatment interruptions (ATI) on the levels of cellular HIV and of residual activation after subsequent antiretroviral therapy (ART)-mediated plasma HIV viral load re-suppression remains under active investigation.DesignPeripheral blood mononuclear cells (PBMC) from 23 ART-suppressed, chronically HIV-1-infected patients were evaluated at the initiation of an ATI, during ATI, and following plasma re-suppression of HIV with ART.MethodsT-cell activation was measured by flow cytometry. Total cellular HIV DNA, and episomal 2-long terminal repeat (2-LTR) circles were measured by droplet digital PCR (ddPCR). Cellular HIV multiply spliced RNA (tat/rev), unspliced (gag), and poly(A) tailed transcripts [poly(A)] were measured by reverse transcriptase-ddPCR. Analyses were performed using R version 2.5.1 or JMP Pro 11.ResultsATI (median ATI duration, 4 weeks) resulted in a rise of plasma HIV RNA (median = 72900 copies/ml), decrease in CD4+ T cells/μl (median = 511.5 cells/μl; P = 0.0001), increase in T-cell activation, and increase in cellular HIV DNA and RNA. Mean fluorescence intensity of CD38 on CD4+HLA-DR+ T cells at baseline was positively associated with total HIV DNA levels during ATI (pol: P = 0.03, Rho = 0.44). Upon ART resumption, plasma HIV re-suppression occurred after a median of 13 weeks and resulted in restoration of pre-ATI CD4+ T cells/μl, T-cell activation, and levels of cellular HIV DNA and RNA.ConclusionMonitored viremia and immune activation during an ATI in ART-suppressed chronic HIV-infected patients does not change the amount of persistent cellular HIV RNA or total HIV DNA after ART-mediated re-suppression.

Analytic treatment interruption (ATI) studies are required to evaluate strategies aimed at achieving ART-free HIV remission, but the impact of ATI on the viral reservoir remains unclear. We validated a DNA size selection-based assay for measuring levels of integrated HIV DNA and applied it to assess the effects of short-term ATI on the HIV reservoir. Samples from participants from four AIDS Clinical Trials Group ATI studies were assayed for integrated HIV DNA levels. Cryopreserved peripheral blood mononuclear cells (PBMCs) were obtained for 12 participants with available samples pre-ATI and approximately 6 months after ART resumption. Four participants also had samples available during the ATI. The median duration of ATI was 12 weeks. Validation of the HIV integrated DNA size-exclusion (HIDE) assay was performed using samples spiked with unintegrated HIV DNA, HIV-infected cell lines, and participant PBMCs. The HIDE assay eliminated 99% of unintegrated HIV DNA species and strongly correlated with the established Alu-gag assay. For the majority of individuals, integrated DNA levels increased during ATI and subsequently declined upon ART resumption. There was no significant difference in the levels of integrated HIV DNA between the pre- and post-ATI time points, with a median ratio of post- to pre-ATI HIV DNA levels of 0.95. Using a new integrated HIV DNA assay, we found minimal change in the levels of integrated HIV DNA in participants who underwent an ATI, followed by 6 months of ART. This suggests that short-term ATI can be conducted without a significant impact on the levels of integrated proviral DNA in the peripheral blood.IMPORTANCE Interventions aimed at achieving sustained antiretroviral therapy (ART)-free HIV remission require treatment interruption trials to assess their efficacy. However, these trials are accompanied by safety concerns related to the expansion of the viral reservoir. We validated an assay that uses an automated DNA size-selection platform for quantifying levels of integrated HIV DNA and is less sample- and labor-intensive than current assays. Using stored samples from AIDS Clinical Trials Group studies, we found that short-term ART discontinuation had minimal impact on integrated HIV DNA levels after ART resumption, providing reassurance about the reservoir effects of short-term treatment interruption trials.

A diagnostic criterion for drug addiction, persistent drug-craving continues to be the most treatment-resistant aspect of addiction that maintains the chronic, relapsing, nature of this disease. Despite the high prevalence of psychomotor stimulant addiction, there currently exists no FDA-approved medication for craving reduction. In good part, this reflects our lack of understanding of the neurobiological underpinnings of drug-craving. In humans, cue-elicited drug-craving is associated with the hyperexcitability of prefrontal cortical regions. Rodent models of cocaine addiction indicate that a history of excessive cocaine-taking impacts excitatory glutamate signaling within the prefrontal cortex to drive drug-seeking behavior during protracted withdrawal. This review summarizes evidence that the capacity of cocaine-associated cues to augment craving in highly drug-experienced rats relates to a withdrawal-dependent incubation of glutamate release within prelimbic cortex. We discuss how stimulation of mGlu1/5 receptors increases the activational state of both canonical and noncanonical intracellular signaling pathways and present a theoretical molecular model in which the activation of several kinase effectors, including protein kinase C, extracellular signal-regulated kinase and phosphoinositide 3-kinase (PI3K) might lead to receptor desensitization to account for persistent cocaine-craving during protracted withdrawal. Finally, this review discusses the potential for existing, FDA-approved, pharmacotherapeutic agents that target kinase function as a novel approach to craving intervention in cocaine addiction.

Neurofibromatosis type 1 (NF1)-related lung disease is a rare but increasingly recognised, high morbidity associated feature of the condition. We present a 48-year-old male patient with NF1, who was initially admitted for a subarachnoid haemorrhage requiring aneurysmal coil embolisation. During his recovery, he developed a left-sided pneumothorax requiring chest tube placement followed by concerns for re-expansion pulmonary oedema requiring intubation. Subsequently, the patient also developed a right-sided pneumothorax requiring additional chest tube placement but did not develop right-sided pulmonary oedema. During his hospitalisation, the patient also exemplified other important NF1-related pathophysiology including pheochromocytoma, cerebrovascular abnormalities and cardiovascular manifestations. Due to his multiple comorbidities and poor prognosis, we held a goals of care discussion with the patient's mother, and with her agreement, the patient underwent compassionate withdrawal of artificial life support.

Aim: The 2018 life-sustaining treatment (LST) decision law is expected to improve end-of-life quality in Korea. This study evaluated the national effect of the LST decision law on the cardiopulmonary resuscitation (CPR) rate among pediatric patients who died during hospital admission.Methods: This retrospective cohort study was based on the Korean National Health Insurance database. Pediatric admissions within 12 months before or after implementation of the LST decision law were compared, allowing a 1-month transition period (February 2018). The changes in mortality, CPR, and documentation of LST decision were evaluated.Results: The CPR rate of patients who died in hospital decreased after establishment of the LST decision law (49.6 vs 43.4 %, P = 0.04), without change of in-hospital mortality between pre/post-LST decision law activation (0.83 vs 0.81 per 1000 admissions, P = 0.67). In addition, in-hospital CPR (0.73 vs 0.67 per 1000 admissions, P = 0.15) and survival to discharge after in-hospital CPR (43.6 vs 47.2 %, P = 0.27) were slightly improved, although there was no statistical significance. Patients with LST decision documentation were less frequently mechanically ventilated (69.8 % vs 80.4 %, P < 0.01) and used fewer inotropes (76.5 % vs 90.1 %, P < 0.01) and more frequent opioids (67.1 % vs 57.4 %, P = 0.04).Conclusions: The legally guided process of LST decision can decrease the CPR rate of children who die in hospitals. This result highlights the possibility of improving end-of-life quality by reducing non-beneficial in-hospital CPR. [ABSTRACT FROM AUTHOR]

Cardiac implantable electronic devices have transformed medicine as they improve quality of life and prevent premature death. In palliative care settings, deactivation of these devices must be discussed, particularly at end-of-life. In terminally ill patients it is consensual to recommend implantable cardioverter defibrillator deactivation once shocks are frequent and painful. Concerning pacemakers, the decision to deactivate is controversial and it usually is not an option at patients' end-of-life, since in pacing-dependent patients, such low heart rates might induce symptoms of bradycardia, with no impact on survival. Regarding cardiac resynchronization therapy, deactivation is not recommended as it can worsen symptoms. Left ventricular assistance device deactivation at end-of-life is a well-accepted practice, since it has the benefit of ending the physical burden associated with the device. Advance care planning should be encouraged and patients should be informed that deactivation is possible., (Published by Elsevier España, S.L.U.)

Background: Atypical hemolytic uremic syndrome (aHUS) is a rare, life-threatening thrombotic microangiopathy (TMA) related to congenital mutations impeding control of the alternative pathway of complement. Following approval of the complement C5 inhibitor eculizumab by the European Medicines Agency and the US Food and Drug Administration, initial guidelines suggested lifelong therapy. Yet, growing evidence indicates that discontinuation of eculizumab, or its long-acting form ravulizumab, is possible for many patients. This mixed-methods study sought to explore international experts' perspectives and experiences related to treatment duration in adult patients with aHUS, while also estimating the financial and potential health consequences of early discontinuation., Methods: Between January and December 2023, we conducted 10 qualitative interviews with experts in the treatment of aHUS, based upon which we constructed a quantitative decision tree, designed to estimate time on treatment and treatment- and disease-related adverse events., Results: Thematic analysis of the interview data identified four main themes: (1) Concerns and prior experience; (2) High-risk vs. low-risk groups; (3) Patient preference and adherence; and (4) Funding for monitoring and re-treatment. Although most interviewees were in favour of considering treatment discontinuation for many patients (citing the high cost, burden, and potential side effects of lifelong treatment as key reasons), a prior negative experience of discontinuation seemed to make others more reluctant to stop. Deciding which patients required lifelong treatment and which not involved consideration of a wide range of factors, including patient- and system-related factors. Cost-consequence analysis demonstrated the financial savings associated with early treatment discontinuation at the expense of increased risk of recurrent TMA events. Close monitoring for these events had the potential to minimise any long-term injury, primarily renal, with an estimated one event per 100 patient years. For patients at high risk of TMA and with poor adherence to monitoring, rates of renal injury rose to three events per 100 patient years., Conclusions: aHUS treatment protocols are changing globally in response to new clinical evidence. Against this backdrop, our mixed-methods study provides compelling evidence on the complexity of factors influencing treatment discontinuation decisions in aHUS, as well as the financial and health consequences of early discontinuation., Competing Interests: Declarations Ethics approval and consent to participate The study was approved by the Biomedical Research Alliance of New York LLC Organizational Review Board and the Weill Cornell Institutional Review Board (Study Protocol: 21-07023785). Written informed consent was obtained from all experts participating in the interviews. Consent for publication The consent process involved informing all participants that interviews would form the basis of a publication and that no identifying information would be used. Competing interests AB and JL have received consultancy payments from Alexion Pharmaceuticals in addition to the funding reported here., (© 2024. The Author(s).)