End-of-life practices in Hong Kong intensive care units: results from the Ethicus-2 study.

INTRODUCTION: The need for end-of-life care is common in intensive care units (ICUs). Although guidelines exist, little is known about actual end-of-life care practices in Hong Kong ICUs. The study aim was to provide a detailed description of these practices. METHODS: This prospective, multicentre observational sub-analysis of the Ethicus-2 study explored end-of-life practices in eight participating Hong Kong ICUs. Consecutive adult ICU patients admitted during a 6-month period with life-sustaining treatment (LST) limitation or death were included. Follow-up continued until death or 2 months from the initial decision to limit LST. RESULTS: Of 4922 screened patients, 548 (11.1%) had LST limitation (withholding or withdrawal) or died (failed cardiopulmonary resuscitation/brain death). Life-sustaining treatment limitation occurred in 455 (83.0%) patients: 353 (77.6%) had decisions to withhold LST and 102 (22.4%) had decisions to withdraw LST. Of those who died without LST limitation, 80 (86.0%) had failed cardiopulmonary resuscitation and 13 (14.0%) were declared brain dead. Discussions of LST limitation were initiated by ICU physicians in most (86.2%) cases. Shared decision-making between ICU physicians and families was the predominant model; only 6.0% of patients retained decision-making capacity. Primary medical reasons for LST limitation were unresponsiveness to maximal therapy (49.2%) and multiorgan failure (17.1%). The most important consideration for decision-making was the patient's best interest (81.5%). CONCLUSION: Life-sustaining treatment limitations are common in Hong Kong ICUs; shared decision-making between physicians and families in the patient's best interest is the predominant model. Loss of decision-making capacity is common at the end of life. Patients should be encouraged to communicate end-of-life treatment preferences to family members/surrogates, or through advance directives.

Admission triage tool for adult intensive care unit admission in Hong Kong during the COVID-19 outbreak.

Intensive care is expensive, and the numbers of intensive care unit (ICU) beds and trained specialist medical staff able to provide services in Hong Kong are limited. The most recent increase in coronavirus disease 2019 (COVID-19) infections over July to August 2020 resulted in more than 100 new cases per day for a prolonged period. The increased numbers of critically ill patients requiring ICU admission posed a capacity challenge to ICUs across the territory, and it may be reasonably anticipated that should a substantially larger outbreak occur, ICU services will be overwhelmed. Therefore, a transparent and fair prioritisation process for decisions regarding patient ICU admission is urgently required. This triage tool is built on the foundation of the existing guidelines and framework for admission, discharge, and triage that inform routine clinical practice in Hospital Authority ICUs, with the aim of achieving the greatest benefit for the greatest number of patients from the available ICU resources. This COVID-19 Crisis Triage Tool is expected to provide structured guidance to frontline doctors on how to make triage decisions should ICU resources become overwhelmed by patients requiring ICU care, particularly during the current COVID-19 pandemic. The triage tool takes the form of a detailed decision aid algorithm based on a combination of established prognostic scores, and it should increase objectivity and transparency in triage decision making and enhance decision-making consistency between doctors within and across ICUs in Hong Kong. However, it remains an aid rather than a complete substitute for the carefully considered judgement of an experienced intensive care clinician.

Posttraumatic Stress after Treatment in an Intensive Care Unit.

OBJECTIVE: To study posttraumatic stress in patients after treatment in an intensive care unit (ICU). METHODS: This prospective cohort study included 136 adult patients with critical medical and surgical problems who were discharged from the ICU of the Caritas Medical Centre, Hong Kong. Their occurrence of posttraumatic stress disorder (PTSD), anxiety, and depression after ICU treatment were measured using the Impact of Event Scale-Revised and Hospital Anxiety and Depression Scale. Patient ICU experience was measured using the ICU Memory Tool. Multivariable analyses were conducted to examine the predictors of PTSD symptoms, anxiety, and depression. RESULTS: Symptoms of PTSD, anxiety, and depression were reported in 10% to 17% of patients. Symptom severity was associated with less factual memory, more vivid memory of feelings about and more delusional memory of the ICU experience, low emotional support, and high perceived life threat. CONCLUSIONS: Symptoms of posttraumatic stress, anxiety, and depression may occur after ICU treatment. Early identification and appropriate intervention for PTSD are important for rehabilitation.

Clinical staff as mentors in pre-registration undergraduate nursing education: students' perceptions of the mentors' roles and responsibilities.

This paper reports part of a multiple-phase action research initiated by a university nursing department in Hong Kong. Local hospitals were invited to collaborate in a joint mentoring programme which recruited clinical staff to mentor pre-registration nursing students during clinical placement. Interviews based on the five roles -assisting, befriending, guiding, advising and counselling, as outlined by the English National Board, were conducted to explore students' views of the mentor's roles. Findings showed that students in general agreed that the five roles depicted were necessary roles of the mentors. They saw the roles of assisting and guiding as most crucial, while the befriending role was useful to facilitate their settling into the ward. The advising and counselling roles were seen as less important. It was concluded that students tended to be more instrumental in viewing their mentor's behaviours; activities that have a direct effect on their learning are considered as more important, while other factors which have a less immediate or less direct effect on their learning, are seen as of lower priority.

Students' perceptions of the effectiveness of mentors in an undergraduate nursing programme in Hong Kong.

AIM OF THE PAPER: This paper reports the results of a multiple-phase study on a mentoring scheme for nursing students in one of the universities in Hong Kong. Using a qualitative approach, students' perceptions of the various roles of mentors were collected, and this information was used as the basis to design a tool for subsequent evaluation of the mentoring scheme. BACKGROUND: The nursing department in one of the universities in Hong Kong initiated and developed the idea of an 'Honorary Clinical Instructors' scheme (HCI scheme) for the supervision of the pre-registration nurses. The scheme was examined in a local context, where the Chinese culture dominated, so that a standardized protocol that takes into account the potential cultural dimensions could be established. DESIGN: The mentoring roles outlined by the English National Board (ENB) for Nursing, Midwifery, Health Visiting were used as a framework to identify undergraduate nursing students' perception of the effectiveness of mentors. Information gathered from interviews with Year 2 students (n=12) and Year 3 students (n=10) was used as the basis to design a questionnaire for subsequent programme evaluation. An evaluation questionnaire based on the interviewing results was developed for further evaluation of the mentoring scheme. FINDINGS: After the mentoring scheme was evaluated in semester one, a series of strategies were designed to improve the preparation of mentors and the implementation of the scheme. The strategies were identified as effective by the significant differences in the perceptions students had towards the mentoring scheme in semester one and semester two (t189=-4.80, P < 0.001), with semester two (n=81) having a mean score difference of 8.69 higher than in semester one (n=110). CONCLUSIONS: It was concluded that the questionnaire developed in the project could be adopted as a useful instrument to evaluate the effectiveness of mentoring programmes for nursing courses, and that the results of this study may also stimulate more research interest in this area to improve the quality of clinical teaching in the pre-registration nursing education programmes in the future.

The acetylcholinesterase defect in paroxysmal nocturnal hemoglobinuria: evidence that the enzyme is absent from the cell membrane.

Paroxysmal nocturnal hemoglobinuria (PNH) is a myelodysplastic disease characterized by erythrocytes that show abnormally increased sensitivity to complement-mediated lysis. Complement-sensitive PNH erythrocyte membranes have previously been shown to lack acetylcholinesterase (AchE) activity, but the molecular basis of this deficiency has been unclear. We have used monoclonal antibodies to four different epitopes on the AchE molecule to show that abnormal PNH erythrocytes failed to bind these antibodies. Moreover, abnormal PNH erythrocytes contained no protein immunoprecipitable by these antibodies, while normal complement-insensitive erythrocytes from PNH patients showed normal amounts of immunoprecipitable AchE which had normal electrophoretic mobility. These data suggest that abnormal PNH erythrocytes lack AchE enzyme activity due to the absence of the AchE molecule from the cell membrane.

Separation of the acetylcholinesterase-deficient red cells in paroxysmal nocturnal hemoglobinuria.

Blood of patients with paroxysmal nocturnal hemoglobinuria (PNH) most often contains two or more populations of erythrocytes--one population with normal sensitivity to lysis by complement (PNH I cells) and a second population of moderately abnormal cells (PNH II cells) or markedly abnormal cells (PNH III cells). PNH II and III cells exhibit moderately and markedly increased sensitivity to lysis by complement, respectively, as well as other membrane defects. We have devised a method for isolating pure, intact PNH II and III cells from mixed populations by use of monoclonal antibodies and cell affinity chromatography. Study of purified cell populations has led to the identification of a further subtype, PNH IIIb, of PNH erythrocytes. PNH IIIb erythrocytes are less sensitive to complement lysis than PNH IIIa cells but are lysed by fluid-phase activation of complement, unlike PNH II erythrocytes.

Macromolecular binding of [3H]6-nitrobenzo[a]pyrene in male rats.

Generally labelled [3H]6-nitrobenzo[a]pyrene (6NBP) when administered to male rats by i.p. injection was widely distributed throughout the body. After a single injection of 4.2 mg/kg the highest concentration was found in the liver (5% at 2 h) followed by the spleen greater than kidney greater than lung. Maximal covalent binding to macromolecules occurred between 8 and 24 h depending upon the organ; the order of binding/mg macromolecule was RNA greater than DNA greater than protein for all organs studied. In the liver maximal binding was found 8 h after 6NBP administration at which time there were 45 +/- 7 pmol 6NBP/mg bound to DNA and 114 +/- 40 pmol/mg to RNA following a dose of 4.2 mg/kg. These levels fall to 14 +/- 4 and 12 +/- 6 pmol/mg, respectively, after 168 h, the longest time point so far studied. At a lower dose of 1.4 mg/kg the values for DNA at 8 h were 14 +/- 2 pmol/mg and at 168 h 3 +/- 2 pmol/mg while for RNA the corresponding values were 29 +/- 8 and 15 +/- 3 pmol/mg. After gastric intubation at a dose of 4.2 mg/kg there was no difference in liver macromolecular binding at 24 h between conventional and germ-free animals. Enzymic digestion of liver DNA from [3H]6NBP injected animals and reversed-phase h.p.l.c. of the digests showed two peaks of radioactivity. The percentage of total radioactivity in each peak varied from preparation to preparation suggesting that one peak may be a degradation product of the other although experimental variability cannot be ruled out. The implications of these findings in relation to the potential carcinogenicity of 6NBP are discussed.

Bacterial mutagenicity and chemical analysis of polycyclic aromatic hydrocarbons and some nitro derivatives in environmental samples collected in West Germany.

Snow and air particulate samples collected in Upper Frankonia, Federal Republic of Germany, have been analyzed for nitro-polycyclic aromatic hydrocarbons (PAH) and PAH content. A novel clean-up technique has been developed enabling interfering organochlorine environmental contaminants to be removed prior to analysis of the hydrocarbons by GC-MS. Mass fragmentation patterns are presented for 1-nitropyrene, 6-nitrobenzo(a)pyrene, 6-nitrochrysene, and 3-nitrofluoranthene. The level of these compounds found in air samples was in the range of 0.2-2.0 ng.m-3 with the exception of 6-nitrobenzo(a)pyrene, which was not detected. This compares with PAH values of between 1 and 6 ng.m-3. The freshly fallen snow sample collected at the side of a motorway had no detectable PAHs or nitro-PAHs. Parallel studies on the bacterial mutagenicity of the collected air samples using Salmonella typhimurium TA98 and TA100 in the presence and absence of aroclor-induced rat liver "S9" revealed both "direct" and "indirect" activity. Larger numbers of mutants were induced in the presence of S9 than in its absence. The snow sample was devoid of mutagenic activity. These studies show the utility of the biological approach to screen environmental samples prior to expensive and time-consuming chemical analysis.

Evidence for N-(deoxyguanosin-8-yl)-1-aminopyrene as a major DNA adduct in female rats treated with 1-nitropyrene.

[3H]1-Nitropyrene was administered at a dose of 25 mg/kg by i.p. injection to female Wistar rats. Animals were killed 24 h later and DNA was isolated from kidney, liver and mammary gland, enzymically hydrolysed and analysed by reverse-phase h.p.l.c. A major adduct peak was detected in DNA from each of the three organs. Enzymic hydrolysates of DNA, which had been reacted in vitro with 1-nitropyrene in the presence of xanthine oxidase, were similarly analysed by h.p.l.c. One major adduct peak was obtained which had the same retention time as the in vivo product. Confirmatory evidence that the in vivo adduct and the in vitro adduct were structurally similar was obtained from the determination of the pH-dependent solvent partitioning profiles. Further, treatment of the in vivo adduct from liver, kidney or mammary gland DNA hydrolysates and the in vitro adduct with sodium hydroxide resulted in the formation of a more polar product which eluted earlier on h.p.l.c. This behaviour is consistent with scission of the imidazole ring of a deoxyguanosine adduct. The major DNA adduct formed in vitro following xanthine oxidase reduction of 1-nitropyrene has previously been identified by others as N-(deoxyguanosin-8-yl)-1-aminopyrene. The present data suggest that the in vivo 1-nitropyrene-DNA adduct has the same structure.

Comparative lung tumorigenicity of parent and mononitro-polynuclear aromatic hydrocarbons in the BLU:Ha newborn mouse assay.

A BLU:Ha newborn mouse lung adenoma bioassay was employed to compare the tumorigenicity of selected mononitroarenes and unsubstituted parent compounds 6 months after initial treatment. The presence of a nitro group had a variable effect upon compound potency in which tumorigenicity was increased, abolished, or unchanged. On the basis of results with equimolar doses, the potency of benzo[a]pyrene was greater than 6-nitrobenzo[a]pyrene (inactive), 6-nitrochrysene was much greater than chrysene (inactive), 3-nitrofluoranthene (active) was equal to fluoranthene (active), and 1-nitropyrene (inactive) was equivalent to pyrene (inactive). The potency series among the mononitroarenes was 6-nitrochyrsene much greater than 3-nitrofluoranthene greater than 6-nitrobenzo[a]pyrene (inactive) = 1-nitropyrene (inactive). Lung tumor incidence and multiplicity were similar for both males and females. No consistent pattern was observed for the occasional appearance of lymphoma or hepatic nodular hyperplasia in the various treatment groups.

Nitration of carcinogenic and non-carcinogenic polycyclic aromatic hydrocarbons results in products able to induce transformation of Syrian hamster cells.

Five nitrated polycyclic aromatic hydrocarbons, synthesized from benzo[a]pyrene, fluoranthene, pyrene, and chrysene induced dose-dependent transformation of Syrian hamster embryo cells. Benzo[a]pyrene, a known carcinogen, induced transformation while the other parental compounds, which are non-carcinogens, were not effective. The transforming potential of the nitro derivatives varied from compound to compound; on a molar basis, 1,8-dinitropyrene was the most effective nitrated hydrocarbon followed in order by 3-nitrofluoranthene, 1-nitropyrene, 6-nitrochrysene, and 6-nitrobenzo[a]pyrene. The ability to obtain dose-dependent transformation frequencies indicates that hamster cell transformation represents a responsive model for elucidating the mechanism of action of nitrated carcinogens. Because of their ubiquitous distribution and their ability to induce morphological transformation in mammalian cells, nitrated polycyclic aromatic hydrocarbons must be considered as potential carcinogens.

6-Nitrochrysene is a potent tumorigen in newborn mice.

A newborn mouse (BLU:Ha) lung adenoma bioassay demonstrated that 6-nitrochrysene was a highly potent tumorigen. It induced 100% incidence of lung tumors and a 150-fold increase in their number (20.84 tumors/mouse) at the lowest dose level tested (total dose: 38.5 micrograms/mouse). 70% of the 6-nitrochrysene treated mice had malignant lung tumors (adenocarcinomas). Lymphomas and nodular hyperplasia of the liver were also observed in treated, but not control, animals. The tumorigenicity of 6-nitrochrysene relative to other polynuclear aromatic hydrocarbons and their mononitro-derivatives has been discussed.