Antibiogram data from private hospitals in Hong Kong: 6-year retrospective study.

INTRODUCTION: The surveillance of antibiotic resistance is critical for the establishment of effective control strategies. The antibiotic resistance situations in private hospitals in Hong Kong have not been systematically described. The objective of the study was to analyse antibiogram data from private hospitals and describe the temporal trends of non-susceptibility percentages in this setting. METHODS: This retrospective descriptive study used antibiogram data from all private hospitals in Hong Kong that had been collected annually for 6 years (2014-2019). Data on six targeted bacteria and their corresponding multidrug-resistant organisms were included. RESULTS: The non-susceptibility percentages of isolates remained stable or decreased during the study period: methicillin-resistant Staphylococcus aureus had a stable prevalence of approximately 20%; extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella species had stable prevalences of 20% to 30% and 10% to 20%, respectively; multidrug-resistant Acinetobacter species had prevalences of approximately 2% to 8%, which decreased over time; multidrug-resistant Pseudomonas aeruginosa had prevalences of 0.0% to 0.3%; Streptococcus pneumoniae penicillin and macrolide non-susceptibility percentages were 2% to 9% and 71% to 79%, respectively. These values generally were comparable with findings from public hospitals and Residential Care Homes for the Elderly in Hong Kong. However, the prevalences of carbapenem-resistant Enterobacteriaceae, which are increasing in Hong Kong and other nations, were also increasing in our dataset despite their currently low values (<1% for Escherichia coli and <2% for Klebsiella species). CONCLUSION: The antibiotic resistance landscape among private hospitals in Hong Kong is satisfactory overall; there remains a need for surveillance, antibiotic stewardship, and other infection control measures.

Cardiovascular diseases among diffuse large B-cell lymphoma long-term survivors in Asia: a multistate model study.

BACKGROUND: We modeled the clinical course of a cohort of diffuse large B-cell lymphoma (DLBCL) patients with no prior cardiovascular diseases (CVDs) using a multistate modeling framework. PATIENTS AND METHODS: Data on 2600 patients with DLBCL diagnosed between 2000 and 2018 and had received chemotherapy with or without radiotherapy were obtained from a population-wide electronic health database of Hong Kong. We used the Markov illness-death model to quantify the impact of doxorubicin and various risk factors (therapeutic exposure, demographic, comorbidities, cardiovascular risk factors, and lifestyle factors which included smoking) on the clinical course of DLBCL (transitions into incident CVD, lymphoma death, and other causes of death). RESULTS: A total of 613 (23.6%) and 230 (8.8%) of 2600 subjects died of lymphoma and developed incident CVD, respectively. Median follow-up was 7.0 years (interquartile range 3.8-10.8 years). Older ages [hazard ratio (HR) for >75 versus ≤60 years 1.88; 95% confidence interval (CI) 1.25-2.82 and HR for 61-75 versus ≤60 years 1.60; 95% CI 1.12-2.30], hypertension (HR 4.92; 95% CI 2.61-9.26), diabetes (HR 1.43; 95% CI 1.09-1.87), and baseline use of aspirin (HR 5.30; 95% CI 3.93-7.16) were associated with an increased risk of incident CVD. In a subgroup of anticipated higher-risk patients (aged 61-75 years, smoked, had diabetes, and received doxorubicin), we found that they remained on average 7.9 (95% CI 7.2-8.8) years in the DLBCL state and 0.1 (95% CI 0.0-0.4) years in the CVD state, if they could be followed up for 10 years. The brief time in the CVD state is consistent with the high chance of death in patients who developed CVD. Other causes of death have overtaken DLBCL-related death after about 5 years. CONCLUSIONS: In this Asian population-based cohort, we found that incident CVDs can occur soon after DLBCL treatment and continued to occur throughout survivorship. Clinicians are advised to balance the risks and benefits of treatment choices to minimize the risk of CVD.

Comparing Parent and Teacher Ratings of Emotional and Behavioural Difficulties in 5-year old Children who are Deaf or Hard-of-Hearing.

Children who are deaf or hard of hearing (DHH) are at higher risk of developing mental health problems. This study reports on the parent and teacher ratings of emotional and behavioural difficulties (EBD) in 5-year old DHH children. It explores the similarities and differences between informants, and the risk and protective factors associated with parent and teacher-ratings of EBD. Parents and teachers of 224 DHH children completed questionnaires on children's EBD and functional auditory behaviour. Children completed standardised assessments of non-verbal cognitive and language abilities. On average, parent- and teacher-rated EBD were 0.42 and 0.20 standard deviations higher than typically developing children. Parents reported more behavioural problems (hyperactivity and conduct), whereas teachers reported poorer prosocial behaviour. Inter-rater correlations were generally low to moderate (0.29 to 0.50). Overall, children with additional disabilities, lower non-verbal cognitive ability, and poor functional auditory behaviour were at higher risk of EBD. Language ability was only a significant predictor of teacher-rated EBD for children with hearing aids but not cochlear implants. Differences in informant-ratings emphasize the need for a multi-informant approach to get a global perspective on the psychopathology of DHH children. The findings indicate that parents may need assistance with managing behavioural problems at home, and teachers should facilitate more opportunities to practice prosocial behaviour at school. Intervention efforts should focus on facilitating good functional listening skills, as this may in turn, improve the mental health of young DHH children.

Alcohol drinking exacerbates neural and behavioral pathology in the 3xTg-AD mouse model of Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that represents the most common cause of dementia in the United States. Although the link between alcohol use and AD has been studied, preclinical research has potential to elucidate neurobiological mechanisms that underlie this interaction. This study was designed to test the hypothesis that nondependent alcohol drinking exacerbates the onset and magnitude of AD-like neural and behavioral pathology. We first evaluated the impact of voluntary 24-h, two-bottle choice home-cage alcohol drinking on the prefrontal cortex and amygdala neuroproteome in C57BL/6J mice and found a striking association between alcohol drinking and AD-like pathology. Bioinformatics identified the AD-associated proteins MAPT (Tau), amyloid beta precursor protein (APP), and presenilin-1 (PSEN-1) as the main modulators of alcohol-sensitive protein networks that included AD-related proteins that regulate energy metabolism (ATP5D, HK1, AK1, PGAM1, CKB), cytoskeletal development (BASP1, CAP1, DPYSL2 [CRMP2], ALDOA, TUBA1A, CFL2, ACTG1), cellular/oxidative stress (HSPA5, HSPA8, ENO1, ENO2), and DNA regulation (PURA, YWHAZ). To address the impact of alcohol drinking on AD, studies were conducted using 3xTg-AD mice that express human MAPT, APP, and PSEN-1 transgenes and develop AD-like brain and behavioral pathology. 3xTg-AD and wild-type mice consumed alcohol or saccharin for 4 months. Behavioral tests were administered during a 1-month alcohol-free period. Alcohol intake induced AD-like behavioral pathologies in 3xTg-AD mice including impaired spatial memory in the Morris Water Maze, diminished sensorimotor gating as measured by prepulse inhibition, and exacerbated conditioned fear. Multiplex immunoassay conducted on brain lysates showed that alcohol drinking upregulated primary markers of AD pathology in 3xTg-AD mice: Aß 42/40 ratio in the lateral entorhinal and prefrontal cortex and total Tau expression in the lateral entorhinal cortex, medial prefrontal cortex, and amygdala at 1-month post alcohol exposure. Immunocytochemistry showed that alcohol use upregulated expression of pTau (Ser199/Ser202) in the hippocampus, which is consistent with late-stage AD. According to the NIA-AA Research Framework, these results suggest that alcohol use is associated with Alzheimer's pathology. Results also showed that alcohol use was associated with a general reduction in Akt/mTOR signaling via several phosphoproteins (IR, IRS1, IGF1R, PTEN, ERK, mTOR, p70S6K, RPS6) in multiple brain regions including hippocampus and entorhinal cortex. Dysregulation of Akt/mTOR phosphoproteins suggests alcohol may target this pathway in AD progression. These results suggest that nondependent alcohol drinking increases the onset and magnitude of AD-like neural and behavioral pathology in 3xTg-AD mice.

Favourable outcome of AIDS-related multi-centric central nervous system Epstein-Barr virus-associated smooth muscle tumour with surgery and adjuvant radiation therapy: a case study and literature review.

Epstein-Barr virus-associated smooth muscle tumour (EBV-SMT) is a unique condition which affects immunocompromised patients. We describe the favourable outcome of a patient with acquired immune deficiency syndrome (AIDS)-related multi-centric EBV-SMT involving the posterior fossa and spine treated with surgery and adjuvant volumetric modulated arc therapy comprising 50 Gy in 25 fractions to four sites initially to the brain and lumbar spine followed by sixth to ninth thoracic vertebrae (T6-T9) and sacrum a year later. Reported literature suggests that AIDS-related EBV-SMTs are more sensitive to radiotherapy. However, compliance to the highly active anti-retroviral therapy is paramount in preventing future recurrence. This case also emphasises the importance of multidisciplinary management in ensuring the best possible outcome.

Establishing a conceptual model for photochemical ozone pollution in subtropical Hong Kong.

Photochemical ozone (O3) formation is related to its precursors and meteorological conditions. A conceptual model of O3 air pollution is developed based on the analysis of data obtained at Tung Chung (TC) in Hong Kong. By comparing meteorological parameters between O3 and non-O3 episode days, it was found that high temperatures, strong solar radiation, low wind speeds and relative humidity, northeasterly and/or northwesterly prevailing winds were favorable for the O3 formation, while tropical cyclones were most conducive to the occurrence of O3 episodes. Backward trajectories simulation and graphical illustration of O3 pollution suggested that super-regional (i.e. central and eastern China) and regional (i.e. Pearl River Delta, southern China) transport was another factor that contributed to high O3 levels in Hong Kong. The photochemical O3 formation, generally VOC-limited in Hong Kong, was controlled by a small number of volatile organic compounds (VOCs). Furthermore, the positive matrix factorization (PMF) simulation suggested that solvent usage and vehicular emissions are the major contributors to ambient VOCs in Hong Kong. Finally, this paper presents recommendations for further O3 research and implementation of O3 control strategies.

Lanosterol induces mitochondrial uncoupling and protects dopaminergic neurons from cell death in a model for Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disorder marked by the selective degeneration of dopaminergic neurons in the nigrostriatal pathway. Several lines of evidence indicate that mitochondrial dysfunction contributes to its etiology. Other studies have suggested that alterations in sterol homeostasis correlate with increased risk for PD. Whether these observations are functionally related is, however, unknown. In this study, we used a toxin-induced mouse model of PD and measured levels of nine sterol intermediates. We found that lanosterol is significantly (∼50%) and specifically reduced in the nigrostriatal regions of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated mice, indicative of altered lanosterol metabolism during PD pathogenesis. Remarkably, exogenous addition of lanosterol rescued dopaminergic neurons from 1-methyl-4-phenylpyridinium (MPP+)-induced cell death in culture. Furthermore, we observed a marked redistribution of lanosterol synthase from the endoplasmic reticulum to mitochondria in dopaminergic neurons exposed to MPP+, suggesting that lanosterol might exert its survival effect by regulating mitochondrial function. Consistent with this model, we find that lanosterol induces mild depolarization of mitochondria and promotes autophagy. Collectively, our results highlight a novel sterol-based neuroprotective mechanism with direct relevance to PD.

The prevalence of obesity among clinical students in a Malaysian medical school.

INTRODUCTION: This study aimed to determine the prevalence of obesity among medical students and its relationship with their dietary intake and physical activities. METHODS: This observational study was carried out on 240 medical students during the clinical phase of their medical course in a private medical school. Their body weight and height were measured, and a standardised questionnaire was used to collect information on their physical activities and dietary intake. RESULTS: The median body weight of the participants was 59.0 kg (interquartile range: 51.3-66.8), the mean body height was 166.1 cm (standard deviation [SD] 8.5 cm), and the mean body mass index (BMI) was 21.8 kg/m2 (SD 3.4 kg/m2). Based on the World Health Organization BMI cut-offs for the Asian population, 30.1 percent (n is equal to 72) of the students were overweight or obese, with a BMI that was equal to or greater than 23.0 kg/m2. Logistic regression analysis showed that, after controlling for various potential confounders, the only significant risk factors associated with overweight/obesity among these students were: male gender (adjusted odds ratio [OR] 2.1; 95 percent confidence intervals [CI] of 1.1 and 4.1; p is equal to 0.03), Malay ethnic group (adjusted OR 2.4; 95 percent CI 1.0 and 5.7; p is equal to 0.04), Indian ethnic group (adjusted OR 3.6; 95 percent CI 1.5 and 8.9; p is equal to 0.005), and the number of soft drinks consumed per week (adjusted OR 1.3; 95 percent CI 1.0 and 1.5; p is equal to 0.02). Skipping breakfast, the frequency of physical exercise per week, the number of hours of sleep per day, and eating noodles or roti canai (a type of Malaysian pancake) for breakfast were not significant risk factors. CONCLUSION: Obesity remains a common problem among medical students in their clinical years.

Patients' preference for radiotherapy fractionation schedule in the palliation of symptomatic unresectable lung cancer.

The palliative radiotherapeutic management of unresectable non-small-cell lung cancer is controversial, with various fractionation (Fx) schedules available. We aimed to determine patient's choice of Fx schedule after involvement in a decision-making process using a decision board. A decision board outlining the various advantages and disadvantages apparent in the Medical Research Council study of Fx schedules (17 Gy in two fractions vs 39 Gy in 13 fractions) was discussed with patients who met Medical Research Council eligibility criteria. Patients were then asked to indicate their preferred Fx schedules, reasons and their level of satisfaction with being involved in the decision-making process. Radiation oncologists (RO) could prescribe radiotherapy schedules irrespective of patients' preferences. Of 92 patients enrolled, 55% chose the longer schedule. English-speaking patients were significantly more likely to choose the longer schedule (P = 0.02, 95% confidence interval: 1.2-7.6). Longer Fx was chosen because of longer survival (90%) and better local control (12%). Shorter Fx was chosen for shorter overall treatment duration (80%), cost (61%) and better symptom control (20%). In all, 56% of patients choosing the shorter schedule had their treatment altered by the treating RO, whereas only 4% of patients choosing longer Fx had their treatment altered (P < 0.001). Despite this, all (100%) patients were satisfied with being involved in the decision-making process. The decision board was useful in aiding decision-making, with both Fx schedules being acceptable to patients. Interestingly, despite the longer average survival associated with longer Fx, nearly half of the patients believed that this was not as important as a shorter duration of treatment and lower cost. Despite patients' preferences, there were significant alterations of preferred schedules because of RO's own biases.

Outcomes of adjuvant chemoradiotherapy after a radical gastrectomy and a D2 node dissection for gastric adenocarcinoma.

PURPOSE: Intergroup 0116 (INT-0116) established adjuvant chemoradiation as the standard of care for resected high-risk adenocarcinoma of the stomach in the United States. However, adjuvant chemoradiation remains controversial in many parts of Asia and Europe, where patients tend to undergo a more thorough D2 dissection. In INT-0116, 90% of patients had a limited or inadequate node dissection (D0 or D1). Also, 17% of patients in the chemoradiation arm had to discontinue treatment because of toxicities. The objectives of this retrospective study are to report the clinical outcomes of a cohort of patients who were mostly treated with a D2 node dissection and received adjuvant chemoradiation as per INT-0116, and the toxicities of chemoradiation in the context of more aggressive surgery. METHODS: After the results of INT-0116 became apparent, we adopted an institutional policy whereby patients who would otherwise fit the inclusion criteria of INT-0116 received adjuvant chemoradiation. Between March 1999 and November 2004, 70 consecutive patients with pathologic stage T3, T4, or node-positive disease were treated according to the chemoradiation arm of INT-0116. Patients received intravenous 5-fluorouracil 425 mg/m and leucovorin 20 mg/m in cycles 1, 3, and 4. Concurrent chemoradiation was given in cycle 2 and consisted of bolus 5-fluorouracil and leucovorin and radiotherapy (45 Gy over 25 fractions in 5 weeks). All patients were operated on by dedicated Japan-trained Surgical Oncologists. RESULTS: Sixty-seven patients (96%) had a D2 nodal dissection. Sixty-five patients (93%) had negative pathologic margins (R0 resection) and 5 (7%) had microscopically involved margins (R1 resection). The median follow-up was 27 months (range, 10.1-60.3). The 3-year overall survival, disease-free survival, and local control were 60.6%, 54.1%, and 84.3%, respectively. Of the 30 patients who relapsed, 5 (17%) had isolated locoregional recurrences only. The National Cancer Institute--Common Terminology Criteria version 3.0 acute grade 3 or 4 gastrointestinal and hematological toxicity rates were 15.7% and 4.3%, respectively. Toxicities led to chemotherapy dose-reductions in 18 patients and dose-delay in 19 patients. Including chemotherapy dose-reductions and delays, 66 patients (94%) completed the entire chemoradiation regimen. There were no toxicity-related deaths. CONCLUSION: In our cohort of 70 patients who had a more thorough D2 node dissection, adjuvant chemoradiation was well tolerated with acceptable toxicities and reasonable tumor control.

Ethnicity is a factor to be considered before dose planning in ovarian cancer patients to be treated with topotecan.

The objective of this study was to determine the efficacy and toxicity of topotecan in Chinese patients with ovarian cancer. A retrospective analysis on recurrent ovarian cancer patients receiving topotecan 1.25 mg/m(2) daily for 5 consecutive days on a 21-day cycle from 1997 to 2002 was conducted. The patients included were all treated with at least two cycles of topotecan. The patient characteristics were compared in relation to their toxicity profile and their response to treatment. Response was evaluated by physical findings, imaging techniques, and serum CA125 level. A total of 60 patients were included in the study. All patients were evaluable for response and toxicities. A total of 361 cycles were given (median, 5 per patient; range 2-15). The major toxicity was neutropenia, which was grade 4 in 45.0% of the patients and 10.2% of the cycles. Age was the only covariate predicting the occurrence of grade 4 neutropenia (logistic regression P= 0.046, CI 1.01-1.12). Neutropenic fever occurred in 8.3% of the patients. Eighteen (30%) patients were required to delay their chemotherapy and 11 (18.3%) required dose reduction. Nonhematologic toxicities were mild. The overall response rate was 21.6%, with eight (13.3%) complete responses and five (8.3%) partial responses. The median duration of response and median time to progression were 11 and 5 months, respectively. The median survival was 14 months. Topotecan 1.25 mg/m(2) in a five-times-daily schedule was well tolerated in a cohort of Chinese patients. Myelotoxicity was the most important side effect in our study, but the incidence is much lower than that reported in other studies. Age was an independent factor predicting the occurrence of grade 4 neutropenia.

Effect of individual psychological intervention in Chinese women with gynecologic malignancy: a randomized controlled trial.

PURPOSE: To evaluate the effectiveness of psychological intervention in the care of cancer patients and to determine whether routine use of individual psychological therapies is indicated. PATIENTS AND METHODS: Patients with newly diagnosed gynecologic malignancies from August 1999 to November 2000 were recruited and randomly assigned to either a control group receiving routine medical care or to an intervention group receiving individual psychotherapy. A set of fixed-choice, self-report questionnaires assessing the patients' psychological status, quality of life, and their perceptions related to the medical consultations was completed at recruitment and then every 3 months for 18 months. Data analysis was performed according to the intention-to-treat principle by fitting the data into a linear mixed-effects model. Multivariable analyses were performed to examine the effects of confounding factors. RESULTS: One hundred fifty-five patients participated in the trial. There were no statistically significant differences between the two groups at baseline. There was a trend toward better quality of life and functional status and also improvement of the symptoms over time for both groups. No differences were found between the groups in the scores measured by any of the instruments at baseline and at any time points after the cancer diagnosis. Psychological intervention had no significant effects on the psychosocial parameters. CONCLUSION: Routine use of psychological therapies as given in our format has no significant effect on the patients' quality of life and psychological status.

Lethal cytomegalovirus ischemic colitis presenting with fever of unknown origin.

We report a fatal case of cytomegalovirus (CMV) ischemic colitis in a renal transplant recipient. The disease was manifested with fever of unknown origin for 27 days followed by progressive right lower abdominal pain. The clinical condition deteriorated rapidly with development of disseminated intravascular coagulopathy and internal bleeding despite right hemicolectomy and antiviral therapy. The patient died 11 days after the onset of abdominal pain. We conclude that the possibility of CMV ischemic colitis should be suspected if a patient presents with fever and abdominal pain in the early months after transplantation, and that early viral detection by CMV polymerase chain reaction can be lifesaving.