Moral distress and psychological status among healthcare workers in a newly established paediatric intensive care unit.

INTRODUCTION: Healthcare workers in intensive care units often experience moral distress, depression, and stress-related symptoms. These conditions can lower staff retention and influence the quality of patient care. This study aimed to evaluate the prevalence of moral distress and psychological status among healthcare workers in a newly established paediatric intensive care unit (PICU) in Hong Kong. METHODS: A cross-sectional questionnaire survey was conducted in the PICU of the Hong Kong Children's Hospital; healthcare workers (doctors, nurses and allied health professionals) were invited to participate. The Revised Moral Distress Scale (MDS-R) Paediatric Version and Depression Anxiety and Stress Scale-21 items were used to assess moral distress and psychological status, respectively. Demographic characteristics were examined in relation to moral distress, depression, anxiety, and stress scores to identify risk factors for poor psychological outcomes. Correlations of moral distress with depression, anxiety, and stress were examined. RESULTS: Forty-six healthcare workers completed the survey. The overall median MDS-R moral distress score was 71. Nurses had a significantly higher median moral distress score, compared with doctors and allied health professionals (102 vs 47 vs 20). Nurses also had the highest median anxiety and stress scores (11 and 20, respectively). Moral distress scores were correlated with depression (r=0.445; P=0.002) and anxiety scores (r=0.417; P<0.05). Healthcare workers intending to quit their jobs had significantly higher moral distress scores (P<0.05). CONCLUSION: Among PICU healthcare workers, nurses had the highest level of moral distress. Moral distress was associated with greater depression, anxiety, and intention to quit. Healthcare workers need support and a sustainable working environment to cope with moral distress.

Airway management in children with COVID-19.

The novel coronavirus disease (COVID-19) may result in acute respiratory distress syndrome and respiratory failure, necessitating mechanical respiratory support. Healthcare professionals are exposed to a particularly high risk of contracting the virus while providing resuscitation and respiratory support, which may in turn result in grave consequences and even death. Although COVID-19 has been shown to cause milder disease in children, paediatricians and intensivists who provide care for children must be prepared to provide optimal respiratory support without putting themselves or other medical, nursing, and paramedical staff at undue risk. We propose an airway management approach that is especially relevant in the current COVID-19 pandemic and provides instructions for: (1) Elective intubation for respiratory failure; and (2) Emergency intubation during cardiopulmonary resuscitation. To minimise risk, intubation methods must be kept as straightforward as possible and should include the provision of appropriate personal protection and equipment to healthcare workers. We identify two key considerations: that bag-mask ventilation should be avoided if possible and that bacterial and viral filters should be placed in the respiratory circuit. Our novel approach provides a framework for airway management that could benefit paediatric critical care practitioners who provide care for any children with a novel viral illness, with a focus on infection prevention during high-risk airway management procedures.

Sudden arrhythmia death syndrome in young victims: a five-year retrospective review and two-year prospective molecular autopsy study by next-generation sequencing and clinical evaluation of their first-degree relatives.

OBJECTIVE: Sudden arrhythmia death syndrome (SADS) accounts for about 30% of causes of sudden cardiac death (SCD) in young people. In Hong Kong, there are scarce data on SADS and a lack of experience in molecular autopsy. We aimed to investigate the value of molecular autopsy techniques for detecting SADS in an East Asian population. METHODS: This was a two-part study. First, we conducted a retrospective 5-year review of autopsies performed in public mortuaries on young SCD victims. Second, we conducted a prospective 2-year study combining conventional autopsy investigations, molecular autopsy, and cardiac evaluation of the first-degree relatives of SCD victims. A panel of 35 genes implicated in SADS was analysed by next-generation sequencing. RESULTS: There were 289 SCD victims included in the 5-year review. Coronary artery disease was the major cause of death (35%); 40% were structural heart diseases and 25% were unexplained. These unexplained cases could include SADS-related conditions. In the 2-year prospective study, 21 SCD victims were examined: 10% had arrhythmogenic right ventricular cardiomyopathy, 5% had hypertrophic cardiomyopathy, and 85% had negative autopsy. Genetic analysis showed 29% with positive heterozygous genetic variants; six variants were novel. One third of victims had history of syncope, and 14% had family history of SCD. More than half of the 11 first-degree relatives who underwent genetic testing carried related genetic variants, and 10% had SADS-related clinical features. CONCLUSION: This pilot feasibility study shows the value of incorporating cardiac evaluation of surviving relatives and next-generation sequencing molecular autopsy into conventional forensic investigations in diagnosing young SCD victims in East Asian populations. The interpretation of genetic variants in the context of SCD is complicated and we recommend its analysis and reporting by qualified pathologists.

The clinical characteristics of pediatric patients infected by SARS-CoV-2 Omicron variant and whole viral genome sequencing analysis.

Pediatric population was generally less affected clinically by SARS-CoV-2 infection. Few pediatric cases of COVID-19 have been reported compared to those reported in infected adults. However, a rapid increase in the hospitalization rate of SARS-CoV-2 infected pediatric patients was observed during Omicron variant dominated COVID-19 outbreak. In this study, we analyzed the B.1.1.529 (Omicron) genome sequences collected from pediatric patients by whole viral genome amplicon sequencing using Illumina next generation sequencing platform, followed by phylogenetic analysis. The demographic, epidemiologic and clinical data of these pediatric patients are also reported in this study. Fever, cough, running nose, sore throat and vomiting were the more commonly reported symptoms in children infected by Omicron variant. A novel frameshift mutation was found in the ORF1b region (NSP12) of the genome of Omicron variant. Seven mutations were identified in the target regions of the WHO listed SARS-CoV-2 primers and probes. On protein level, eighty-three amino acid substitutions and fifteen amino acid deletions were identified. Our results indicate that asymptomatic infection and transmission among children infected by Omicron subvariants BA.2.2 and BA.2.10.1 are not common. Omicron may have different pathogenesis in pediatric population.

Acetylation and chromosomal functions.

Since the initial discovery of histone acetyltransferases, numerous reports have established that histone acetyltransferases and histone deacetylases regulate transcription by acetylating and deacetylating histones, respectively. Recent studies have focused on the effects of histone acetylation on gene expression regulation during development and the roles of histone hypoacetylation in the maintenance of centromeric structure, X-inactivation and genomic imprinting. Recent findings have also shown that the functions of non-histone proteins can also be regulated by acetylation. Together, these data highlight the importance of acetylation of histones and non-histone proteins in a variety of chromosomal functions.

Inhibition of myogenic bHLH and MEF2 transcription factors by the bHLH protein Twist.

The myogenic basic helix-loop-helix (bHLH) and MEF2 transcription factors are expressed in the myotome of developing somites and cooperatively activate skeletal muscle gene expression. The bHLH protein Twist is expressed throughout the epithelial somite and is subsequently excluded from the myotome. Ectopically expressed mouse Twist (Mtwist) was shown to inhibit myogenesis by blocking DNA binding by MyoD, by titrating E proteins, and by inhibiting trans-activation by MEF2. For inhibition of MEF2, Mtwist required heterodimerization with E proteins and an intact basic domain and carboxyl-terminus. Thus, Mtwist inhibits both families of myogenic regulators and may regulate myotome formation temporally or spatially.

In vitro chondrogenic differentiation of human mesenchymal stem cells in collagen microspheres: influence of cell seeding density and collagen concentration.

Given the inadequacies of existing repair strategies for cartilage injuries, tissue engineering approach using biomaterials and stem cells offers new hope for better treatments. Recently, we have fabricated injectable collagen-human mesenchymal stem cell (hMSC) microspheres using microencapsulation. Apart from providing a protective matrix for cell delivery, the collagen microspheres may also act as a bio-mimetic matrix facilitating the functional remodeling of hMSCs. In this study, whether the encapsulated hMSCs can be pre-differentiated into chondrogenic phenotype prior to implantation has been investigated. The effects of cell seeding density and collagen concentration on the chondrogenic differentiation potential of hMSCs have been studied. An in vivo implantation study has also been conducted. Fabrication of cartilage-like tissue micro-masses was demonstrated by positive immunohistochemical staining for cartilage-specific extracellular matrix components including type II collagen and aggrecan. The meshwork of collagen fibers was remodeled into a highly ordered microstructure, characterized by thick and parallel bundles, upon differentiation. Higher cell seeding density and higher collagen concentration favored the chondrogenic differentiation of hMSCs, yielding increased matrix production and mechanical strength of the micro-masses. These micro-masses were also demonstrated to integrate well with the host tissue in NOD/SCID mice.

pRb is required for MEF2-dependent gene expression as well as cell-cycle arrest during skeletal muscle differentiation.

BACKGROUND: The onset of differentiation-specific gene expression in skeletal muscle is coupled to permanent withdrawal from the cell cycle. The retinoblastoma tumor-suppressor protein (pRb) is a critical regulator of this process, required for both cell-cycle arrest in G0 phase and high-level expression of late muscle-differentiation markers. Although the cell-cycle defects that are seen in pRb-deficient myocytes can be explained by the well-described function of pRb as a negative regulator of the transition from G1 to S phase, it remains unclear how pRb positively affects late muscle-gene expression. RESULTS: Here, we show that the myogenic defect in Rb-/- cells corresponds to a deficiency in the activity of the transcription factor MEF2. Without pRb, MyoD induces the accumulation of nuclear-localized MEF2 that is competent to bind DNA yet transcriptionally inert. When pRb is present, MyoD stimulates the function of the MEF2C transcriptional activation domain and the activity of endogenous MEF2-type factors. Co-transfection of MyoD together with an activated form of MEF2C containing the Herpesvirus VP16 transcriptional activation domain partially bypasses the requirement for pRb and induces late muscle-gene expression in replicating cells. This ectopic myogenesis is nevertheless significantly augmented by co-expression of an E2F1-pRb chimeric protein that blocks the cell cycle. CONCLUSION: These findings indicate that pRb promotes the expression of late-stage muscle-differentiation markers by both inhibiting cell-cycle progression and cooperating with MyoD to promote the transcriptional activation activity of MEF2.

Cost of tobacco-related diseases, including passive smoking, in Hong Kong.

BACKGROUND: Costs of tobacco-related disease can be useful evidence to support tobacco control. In Hong Kong we now have locally derived data on the risks of smoking, including passive smoking. AIM: To estimate the health-related costs of tobacco from both active and passive smoking. METHODS: Using local data, we estimated active and passive smoking-attributable mortality, hospital admissions, outpatient, emergency and general practitioner visits for adults and children, use of nursing homes and domestic help, time lost from work due to illness and premature mortality in the productive years. Morbidity risk data were used where possible but otherwise estimates based on mortality risks were used. Utilisation was valued at unit costs or from survey data. Work time lost was valued at the median wage and an additional costing included a value of USD 1.3 million for a life lost. RESULTS: In the Hong Kong population of 6.5 million in 1998, the annual value of direct medical costs, long term care and productivity loss was USD 532 million for active smoking and USD 156 million for passive smoking; passive smoking accounted for 23% of the total costs. Adding the value of attributable lives lost brought the annual cost to USD 9.4 billion. CONCLUSION: The health costs of tobacco use are high and represent a net loss to society. Passive smoking increases these costs by at least a quarter. This quantification of the costs of tobacco provides strong motivation for legislative action on smoke-free areas in the Asia Pacific Region and elsewhere.

Promoting smoking cessation among the elderly: what are the predictors of intention to quit and successful quitting?

PURPOSE: To assess the predictors of smoking cessation and intention to quit among the Chinese elderly smokers. DESIGN: A cross-sectional survey of elderly smokers. SETTING: Shamsuipo district, Hong Kong. SUBJECT: A total of 1,318 elderly were interviewed (response rate = 83%). MEASURES: A structured questionnaire was used for data collection. The questionnaire sought information on the subject's sociodemographic background and smoking habits. The predictors for successful quitting and intention to quit were assessed by chi-square tests and multiple logistic regression. RESULTS: Of the respondents, 20.2% were current smokers, 25.4% were ex-smokers, and 54.4% were never smokers. Of the smoker (current and ex-smokers) respondents, 55.7% (335/601) had successfully quit at the time of enumeration. The predictors of quitting were living with others, receiving assistance for mobility, being nondrinkers, smoking for shorter duration, and smoking more cigarettes per day. Having health problems in the past, smoking for shorter duration, and smoking fewer cigarettes per day were predictors of intention to quit smoking. CONCLUSION: The study identified several predictors of successful quitting that could help improve the provision of current smoking cessation services. Population-based smoking cessation programs, especially those targeted to elderly, should take these predictors into consideration in the design of interventions.

Risk factors for mortality in patients with gastric adenocarcinoma presenting with acute haemorrhage.

We collected clinical, laboratory and endoscopic data prospectively in patients presenting with acute non-variceal upper gastrointestinal bleeding admitted to the care of one surgical team. During a 30-month period 52 patients were subsequently proven to have gastric adenocarcinoma; 30 patients underwent elective operation, and emergency surgery for bleeding was performed on 14 occasions. There were 13 hospital deaths (25%), 13.5% at 30 days. Emergency surgery was associated with a higher mortality rate (42.9%) than elective procedures (13.3%) (P less than 0.03). Factors associated with a poor prognosis were active haemorrhage at initial endoscopy, an admission blood urea nitrogen greater than 16 mmol/l, preoperative transfusion greater than 4 units, total transfusion greater than or equal to 9 units and a lowest recorded haemoglobulin during hospitalization of less than 7.5 g/dl. The unacceptably high mortality rate associated with surgery for continued haemorrhage or rebleeding episodes suggest that earlier elective operative intervention be advocated in patients presenting with acute bleeding and in whom gastric cancer is visualized. This is recommended particularly if the initial bleeding episode is severe, or active haemorrhage is visualized during initial endoscopy.

Community-acquired pneumonia--implementation of a prediction rule to guide selection of patients for outpatient treatment.

The aim of this study was to determine the outcomes of outpatient treatment of community-acquired pneumonia (CAP) when a prediction rule was followed by emergency physicians to guide the selection of patients. This was a prospective observational study conducted at the emergency department of a university-affiliated hospital in Hong Kong, China. A clinical prediction rule was implemented to guide the selection of patients with CAP for outpatient treatment. All subsequent hospitalizations gial presentation were recorded, and the reasons were assessed. The utilization of the observation unit was incorporated into the treatment algorithm. Of 72 patients with CAP followed up as outpatients, 60 (83.3%) were treated successfully, nine (12.5%) required subsequent hospitalization within 30 days, and three (4.2%) were lost to follow-up. None of the patients died, and none required admission to the intensive care unit. Factors associated with subsequent hospitalization include: tuberculosis, underlying malignancy, persistent fever, comorbidity (rheumatoid arthritis and severe osteoporosis), intravenous drug addiction and alcoholism. The observation ward was utilized in 10 (16.7%) patients successfully treated as outpatients. It is concluded that the prediction rule can be safely implemented as a guide for emergency physicians. The short-stay observation unit may be usefully employed for treating low-risk CAP.

Acute bacterial gastroenteritis: a study of adult patients with positive stool cultures treated in the emergency department.

OBJECTIVES: To investigate the presenting clinical features of acute bacterial gastroenteritis in adult patients treated as outpatients in the emergency department (ED), and the pathogens responsible in this setting and population; and to identify the frequency with which positive stool culture result changes management. METHOD: This was a retrospective study of all patients who attended the accident and emergency department of an university affiliated hospital in Hong Kong over a 12 month period, who satisfied the following inclusion criteria: (a) age >/=16, (b) presented with acute gastroenteritis, (c) treated as outpatients with or without observation, and (d) had positive stool cultures. RESULTS: One hundred and thirty patients were included. Pathogens identified were Vibrio parahaemolyticus (42.3%), Samonella spp (34.6%), Plesiomonas spp (9.2%), Campylobacter spp (6.9%), Aeromonas spp (6.9%), and Shigella spp (6.2%). Mean highest body temperature was 37.5 degrees C (95% confidence intervals (CI) 37.3 to 37.6). Bloody diarrhoea was present in 14 patients (10.8%). Mean duration of diarrhoea, from onset to the completion of stay in ED, was 2.2 days (95% CI 1.7 to 2.7). Likewise, mean duration of abdominal pain was 1.8 days (95% CI 1.5 to 2.1). Mean number of unformed stools per day was 9.3 (95% CI 8.3 to 10.3). Change of management, subsequent to the availability of positive stool culture results, was not required in 115 (88.5%) patients. Ciprofloxacin resistance occurred in eight (6.2%) cases, and seven of nine campylobacter isolates. Campylobacter positive patients had a significantly longer duration of abdominal pain (p=0.0236) and were less likely to be dehydrated (p=0.0103). CONCLUSIONS: Most patients with bacterial gastroenteritis do not present with high fever, bloody diarrhoea, or persistent diarrhoea, but generally have quite severe diarrhoea. Stool cultures do not change management for most patients. Vibrio parahaemolyticus is the commonest bacterial pathogen identified.

A dose-response study of thymosin ß4 for the treatment of acute stroke.

BACKGROUND: Thymosin ß4 (Tß4) is a 5K actin binding peptide. Tß4 improves neurological outcome in a rat model of embolic stroke and research is now focused on optimizing its dose for clinical trials. The purpose of this study was to perform a dose-response study of Tß4 to determine the optimal dose of neurological improvement in a rat model of embolic stroke. METHODS: Male Wistar rats were subjected to embolic middle cerebral artery occlusion (MCAo). Rats were divided into 4 groups of 10 animals/group: control, 2, 12 and 18 mg/kg. Tß4 was administered intraperitoneally 24h after MCAo and then every 3 days for 4 additional doses in a randomized controlled fashion. Neurological tests were performed after MCAo and before treatment and up to 8 weeks after treatment. The rats were sacrificed 56 days after MCAo and lesion volumes measured. Generalized estimating equation was used to compare the treatment effect on long term functional recovery at day 56. A quartic regression model was used for an optimal dose determination. RESULTS: Tß4 significantly improved neurological outcome at dose of 2 and 12 mg/kg at day 14 and extended to day 56 (p-values <0.05). The higher dose of 18 mg/kg did not show significant improvement. The estimated optimal dose of 3.75 mg/kg would provide optimal neurological improvement. CONCLUSIONS: This study shown that Tß4 significantly improved the long term neurological functional recovery at day 56 after MCAo with an optimal dose of 3.75 mg/kg. These results provide preclinical data for human clinical trials.

Older people with diabetes have higher risk of depression, cognitive and functional impairments: implications for diabetes services.

OBJECTIVES: To examine the relationship between diabetes and impairments in functional and cognitive status as well as depression in older people. DESIGN: Cross-sectional study. SETTING: Elderly Health Centres (EHC) in Hong Kong. PARTICIPANTS: 66,813 older people receiving baseline assessment at EHC in 1998 to 2001. MEASUREMENTS: Diabetes status was defined by self-report and blood glucose tests. Functional status was assessed by 5 items of instrumental activities of daily living (IADL) and 7 items of activities of daily living (ADL). Cognitive status was screened by the Abbreviated Mental Test-Hong Kong version (AMT). Depressive symptoms were screened by the Geriatric Depression Scale-Chinese version (GDS). RESULTS: Among the subjects, 10.4% reported having regular treatment for diabetes, 3.4% had diabetes but were not receiving regular treatment, and 86.2% did not have diabetes. After controlling for age, sex and education level, those having regular treatment for diabetes were 1.7 times more likely (OR=1.65, 95% CI: 1.51-1.80) to have functional impairment, 1.3 times more likely (OR=1.28, 95% CI: 1.11-1.48) to have cognitive impairment and 1.3 times more likely (OR=1.35, 95% CI: 1.25-1.46) to have depression, than older people without diabetes. CONCLUSION: Older people with diabetes may be less capable of managing the disease than the younger ones as a result of increased risk of both physical and cognitive impairment. This study provided further evidence for the need of an international consensus statement regarding care of diabetes in older people.