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1.
Hong Kong Med J ; 29(3): 214-223, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37349138

ABSTRACT

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has led to an increase in global awareness of relevant public health preventive measures. This awareness can be explored using online search trends from major search engines, such as Google Trends. We investigated the relationship between public awareness of preventative measures and progression of the COVID-19 pandemic. METHODS: Search data for five queries ('mask', 'hand washing', 'social distancing', 'hand sanitizer', and 'disinfectant') were extracted from Google Trends in the form of relative search volume (RSV). Global incidence data for COVID-19 were obtained from 1 January to 30 June 2020. These data were analysed and illustrated using a global temporal RSV trend diagram, a geographical RSV distribution chart, scatter plots comparing geographical RSV with average number of daily cases, and heat maps comparing temporal trends of RSV with average number of daily cases. RESULTS: Global temporal trends revealed multiple increases in RSV, associated with specific COVID-19-related news events. The geographical distribution showed top regions of interest for various preventive measures. For the queries 'mask', 'hand washing', 'hand sanitizer', and 'disinfectant', heat maps demonstrated patterns of early RSV peaks in regions with lower average number of daily cases, when the temporal element was incorporated into the analysis. CONCLUSION: Early public awareness of multiple preventive measures was observed in regions with lower average number of daily cases. Our findings indicate optimal public health communication regarding masks, hand washing, hand sanitiser, and disinfectant in the general population during early stages of the COVID-19 pandemic. Early public awareness may facilitate future disease control efforts by public health authorities.


Subject(s)
COVID-19 , Disinfectants , Humans , COVID-19/epidemiology , COVID-19/prevention & control , Pandemics/prevention & control , Infodemiology , Public Health , Communication
2.
Neuroophthalmology ; 45(4): 246-252, 2021.
Article in English | MEDLINE | ID: mdl-34366512

ABSTRACT

The increasing incidence of idiopathic intracranial hypertension (IIH) with the obesity epidemic is leading to increased pressures on service capacity. Evidence shows that group consultations (GCs) deliver effective, person-centred healthcare, but the feasibility for IIH is unknown. We set out to develop and test a safe and effective GC service for IIH. Through an interactive approach, we co-designed a bespoke in-person and virtual GC model, where patients are reviewed in a group setting. Improvements were made following each session following patient input and team reflections. Outcomes measured included patient satisfaction, self-perceived health literacy, and successful implementation of the GCs. During the pilot, eight in-person GCs were delivered: once-monthly (Oct-Dec 2019), then twice-monthly (Jan-Feb 2020). Feedback was received from 49/53 patients. 100% felt more satisfied and heard, 100% felt more involved in decision-making, 98% had a better understanding of their condition, 96% felt more able to cope with their condition and keep themselves healthy, 94% rated this as a positive experience, and 90% reported improved access and more time with their clinician compared with existing 1:1 appointments. Since September 2020, in response to the COVID-19 pandemic, we transitioned to weekly virtual GCs, receiving overwhelmingly positive feedback (median scores: patient satisfaction 9.5/10; being listened to by clinician 10/10; involved by clinician in treatment decisions 10/10; clinician explanation of treatment 10/10; and opportunity to discuss condition or treatment 10/10). GCs are safe and effective for IIH, and preferred in our patient cohort. This allowed ongoing high-quality, person-centred care despite challenges from the COVID-19 pandemic.

3.
Med J Malaysia ; 75(6): 660-665, 2020 11.
Article in English | MEDLINE | ID: mdl-33219174

ABSTRACT

BACKGROUND: Some surgeons advocate the usage of tranexamic acid (TXA) in traumatic brain injury (TBI). The aim of this study is to determine the effectiveness and safety of TXA in improving the outcome of TBI patients and in reducing the rate of clot expansion and mortality in TBI as compared to those without TXA. METHODS: This is a prospective observational cohort study conducted in Sarawak General Hospital, Malaysia. Patients 12 years of age and older with mild to severe TBI who had a brain computed tomography (CT) done within eight hours of injury were enrolled in the study. A total of 334 patients were recruited from the 5th of August 2016 until the 8th of March 2018 in Sarawak General Hospital. In all 167 of them were administered with TXA and another 167 of the patients were not. The primary outcome expected is the number of good outcomes in isolated TBI patients given TXA. Good outcome is defined by Glasgow Outcome Score-Extended (GOSE) of five and above. Secondary outcome was clot expansion of an intracranial bleed seen on the first scan that had expanded by 25% or more on any dimension on the second scan. RESULTS: The TXA did not show significant trend of good outcome in terms of GOSE (p=0.763). However, for moderate and severe acute subdural haemorrhage (SDH) subgroups, there was a significant difference (p=0.042). Clot expansion was present in 14 patients (12.7%) with TXA given and in 54 patients (38.8%) without TXA. The difference was statistically significant (p<0.001). Of the patients who received TXA, there was one case (0.6%) of deep vein thrombosis. Apart from that, TXA showed non-significant trend in reducing mortality (p=0.474). CONCLUSIONS: Tranexamic acid reduces the rate of clot expansion in TBI by 26.1% (38.8-12.7%) without significantly increasing the risk of a thrombotic event. It can also improve the outcome of moderate and severe TBI patients with acute SDH.


Subject(s)
Antifibrinolytic Agents , Brain Injuries, Traumatic , Thrombosis , Tranexamic Acid , Antifibrinolytic Agents/therapeutic use , Brain Injuries, Traumatic/drug therapy , Humans , Prospective Studies , Tranexamic Acid/therapeutic use
4.
Med J Malaysia ; 75(6): 666-671, 2020 11.
Article in English | MEDLINE | ID: mdl-33219175

ABSTRACT

INTRODUCTION: Chiari malformation (CM) is a disorder of mesodermal origin and is commonly associated with syringomyelia. Foramen magnum decompression is the first-line of standard treatment in symptomatic patients with a confirmed radiographic diagnosis. Magnetic resonance (MR) cine allows accurate evaluation of cerebrospinal fluid (CSF) physiology at the craniovertebral junction but often this is under-utilised in Malaysia. METHODS: In this series, we looked into nine cases of CM with syringomyelia from clinical and radiological perspective before and after surgery. The radiological parameters were herniated tonsillar length, syrinx: cord ratio, syrinx length and diameter. Flow velocity and morphologic changes in Chiari were illustrated. RESULTS: Seven patients showed either reduction in syrinx length, syrinx: cord ratio or both postoperatively. Clinical recovery somewhat varied in motor and sensory symptoms. Four patients gained better functional grade in modified Rankin scale (MRS) while the rest remained similar. The study highlighted the advantage of CSF flow dynamics information over MR anatomical radiographic improvement in addressing the neurologic and functional recovery. We also discussed the practicality of cine sequence in preoperative patient selection, syrinx analysis and postoperative flow evaluation in anticipation of clinical outcome. CONCLUSION: Phase-contrast cine MRI is a useful tool dictated by resource availability. We recommend its routine use in preoperative analysis and subsequent observational follow-up after surgery.


Subject(s)
Arnold-Chiari Malformation , Syringomyelia , Arnold-Chiari Malformation/complications , Arnold-Chiari Malformation/diagnostic imaging , Arnold-Chiari Malformation/surgery , Decompression, Surgical , Foramen Magnum/diagnostic imaging , Foramen Magnum/surgery , Humans , Magnetic Resonance Imaging , Magnetic Resonance Spectroscopy , Syringomyelia/complications , Syringomyelia/diagnostic imaging , Syringomyelia/surgery , Treatment Outcome
5.
Hong Kong Med J ; 26(3): 227-235, 2020 06.
Article in English | MEDLINE | ID: mdl-32554817

ABSTRACT

Osteoporosis is highly prevalent but underdiagnosed and undertreated in Hong Kong. Fragility fractures associated with osteoporosis often result in loss of independence and increased mortality for home-dwelling patients, imposing a high socio-economic burden on society. This issue requires urgent attention given the rapid growth of the elderly population in Hong Kong by approximately 4.3% each year. To address this situation, a group of experts convened to discuss practical ways to reduce the burden of fractures and formulated three recommendations: first, all men (aged ≥70 years) and women (aged ≥65 years) should receive universal dual-energy X-ray absorptiometry assessment for osteoporosis. Second, all men (aged ≥70 years) and women (aged ≥65 years) with a fracture-risk assessment-derived 10-year risk (hip fracture with bone mineral density) ≥3% should receive ≥3 years of anti-osteoporotic treatment. Third, comprehensive structured assessment (including dual-energy X-ray absorptiometry) should be conducted in older patients with a history of falling. By implementing these recommendations, we estimate that we could prevent 5234 hip fractures in 10 years, an annual incidence reduction of approximately 7%, and save HK$425 million in direct medical costs plus substantial indirect savings. Ample clinical and cost-effectiveness data support these recommendations, and studies in Hong Kong and abroad could serve as models on how to implement them. We are confident that by applying these recommendations rigorously and systematically, a significant reduction in hip fractures in Hong Kong is achievable.


Subject(s)
Accidental Falls/prevention & control , Geriatric Assessment , Hip Fractures/prevention & control , Mass Screening/methods , Osteoporotic Fractures/prevention & control , Absorptiometry, Photon , Aged , Aged, 80 and over , Female , Hip Fractures/epidemiology , Hong Kong/epidemiology , Humans , Male , Osteoporotic Fractures/epidemiology , Prevalence , Risk Assessment
6.
Osteoporos Int ; 31(5): 805-826, 2020 May.
Article in English | MEDLINE | ID: mdl-31788717

ABSTRACT

The Asia -Pacific Bone Academy (APBA) Fracture Liaison Service (FLS) Focus Group educational initiative has stimulated activity across the Asia -Pacific region with the intention of supporting widespread implementation of new FLS. In 2017, the APBA FLS Focus Group developed a suite of tools to support implementation of FLS across the Asia-Pacific region as a component of a multi-faceted educational initiative. This article puts this initiative into context with a narrative review describing the burden of fragility fractures in the region, the current secondary fracture prevention care gap and a summary of emerging best practice. The results of a survey to evaluate the impact of the APBA educational initiative is presented, in addition to commentary on recent activities intended to improve the care of individuals who sustain fragility fractures across the Asia -Pacific. A FLS Toolbox for Asia-Pacific was developed which included the following sections:1. The burden of fragility fractures in the Asia-Pacific region.2. A summary of evidence for FLS in the Asia-Pacific.3. A generic, fully referenced FLS business plan template.4. Potential cost savings accrued by each country, based on a country-specific FLS Benefits Calculator.5. How to start and expand FLS programmes in the Asia-Pacific context.6. A step-by-step guide to setting up FLS in countries in the Asia-Pacific region.7. Other practical tools to support FLS establishment.8. FLS online resources and publications.The FLS Toolbox was provided as a resource to support FLS workshops immediately following the 5th Scientific Meeting of the Asian Federation of Osteoporosis Societies (AFOS) held in Kuala Lumpur in October 2017. The FLS workshops addressed three key themes:• The FLS business case.• Planning the FLS patient pathway.• The role of the FLS coordinator in fragility fracture care management.A follow-up survey of 142 FLS workshop participants was conducted in August-September 2018. The survey included questions regarding how FLS were developed, funded, the scope of service provision and the support provided by the educational initiative. Almost one-third (30.3%) of FLS workshop participants completed the survey. Survey responses were reported for those who had established a FLS at the time the survey was conducted and, separately, for those who had not established a FLS. Findings for those who had established a FLS included:• 78.3% of respondents established a multidisciplinary team to develop the business case for their FLS.• 87.0% of respondents stated that a multidisciplinary team was established to design the patient pathway for their FLS.• 26.1% of respondents stated that their FLS has sustainable funding.• The primary source of funding for FLS was from public hospitals (83.3%) as compared with private hospitals (16.7%).Most hospitals that had not established a FLS at the time the survey was conducted were either in the process of setting-up a FLS (47%) or had plans in place to establish a FLS for which approval is being sought (29%). The primary barrier to establishing a new FLS was lack of sustainable funding. The APBA FLS Focus Group educational initiative has stimulated activity across the Asia-Pacific region with the intention of supporting widespread implementation of new FLS. A second edition of the FLS Toolbox is in development which is intended to complement ongoing efforts throughout the region to expedite widespread implementation of FLS.


Subject(s)
Osteoporosis , Osteoporotic Fractures , Asia/epidemiology , Humans , Osteoporosis/prevention & control , Osteoporotic Fractures/epidemiology , Osteoporotic Fractures/prevention & control , Secondary Prevention
7.
Hong Kong Med J ; 25(3): 178-182, 2019 06.
Article in English | MEDLINE | ID: mdl-31178437

ABSTRACT

INTRODUCTION: Clostridioides difficile infection (CDI) is a leading cause of healthcare-associated infection globally, causing significant morbidity and mortality. Faecal microbiota transplantation (FMT) has emerged as a promising option for recurrent and refractory CDI. This study aimed to assess the safety, efficacy, and feasibility of FMT for CDI in Hong Kong. METHODS: We conducted a single-centre, retrospective study for all consecutive cases of recurrent or refractory CDI who underwent FMT from 2013 to 2018. Clinical demographics, outcome, and safety parameters were collected. RESULTS: A total of 24 patients with recurrent or refractory CDI (median age 70 years, interquartile range=45.0-78.3 years; 67% male) were included. Over 80% had been recently hospitalised or were long-term care facility residents. Faecal microbiota transplantation was delivered by feeding tube in 11 (45.8%), oesophagogastroduodenoscopy in eight (33.3%), and colonoscopy in six (25%) of the patients. Resolution of diarrhoea without relapse within 8 weeks was achieved in 21 out of 24 patients (87.5%) after FMT. No deaths occurred within 30 days. The FMT was well tolerated and no serious adverse events attributable to FMT were reported. CONCLUSION: Our results confirm that FMT is a safe, efficacious, and feasible intervention for patients with refractory or recurrent CDI in Hong Kong. Given the increasing disease burden and the lack of effective alternatives in Hong Kong for difficult-to-treat cases of CDI, we recommend that a territory-wide FMT service be established to address increasing demand for this treatment.


Subject(s)
Clostridium Infections/therapy , Diarrhea/therapy , Fecal Microbiota Transplantation , Aged , Colonoscopy , Endoscopy, Digestive System , Feces/microbiology , Female , Hong Kong , Humans , Male , Middle Aged , Recurrence , Retrospective Studies , Treatment Outcome
10.
Hong Kong Med J ; 24(6): 579-583, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30449735

ABSTRACT

INTRODUCTION: Patients who sustain an osteoporotic fracture are at increased risk of sustaining further osteoporotic fracture. The risk can be reduced by prescription of anti-osteoporosis medication. The aim of the present study was to determine the current practice in Hong Kong regarding secondary drug prevention of fragility fractures after osteoporotic hip fracture. METHODS: Dispensation of anti-osteoporosis medication records from patients with new fragility hip fractures aged ≥65 years were retrieved using the Hospital Authority Clinical Data Analysis and Reporting System from 2009 to 2012. The intervention rate each year was determined from the percentage of patients receiving anti-osteoporosis medication within 1 year after hip fracture. RESULTS: A total of 15 866 patients with osteoporotic hip fracture who met the criteria were included. The intervention rate differed each year from 2009 to 2012, ranging between 9% and 15%. Orthopaedic surgeons initiated 63% of anti-osteoporosis medication, whereas physicians initiated 37%. The anti-osteoporosis drugs being prescribed included alendronic acid (76%), ibandronic acid (12%), strontium ranelate (5%), and zoledronic acid (4%). CONCLUSION: Most patients with hip fracture remained untreated for 1 year after the osteoporotic hip fracture. The Hospital Authority should allocate more resources to implement a best practice framework for treatment of patients with hip fracture at high risk of secondary fracture.


Subject(s)
Bone Density Conservation Agents/administration & dosage , Hip Fractures/prevention & control , Osteoporosis/complications , Osteoporotic Fractures/prevention & control , Aged , Hip Fractures/etiology , Hong Kong , Humans , Osteoporosis/drug therapy , Practice Patterns, Physicians'/statistics & numerical data , Retrospective Studies , Secondary Prevention/methods , Time Factors
11.
Ann Oncol ; 29(11): 2254-2260, 2018 11 01.
Article in English | MEDLINE | ID: mdl-30204835

ABSTRACT

Background: Cancer-related genes are under intense evolutionary pressure. We conjectured that gene size is an important determinant of amplification propensity for oncogenes and thus cancer susceptibility and therefore could be subject to natural selection. Patients and methods: Gene information, including size and genomic locations, of all protein-coding genes were downloaded from Ensembl (release 87). Quantification of gene amplification was based on Genomic Identification of Significant Targets in Cancer scores obtained from available The Cancer Genome Atlas studies. Results: Oncogenes are larger in size as compared with non-cancer genes (mean size: 92.1 kb versus 61.4 kb; P < 0.0001) in the human genome, which is contributed by both increased total exon size (mean size: 4.6 kb versus 3.4 kb; P < 0.0001) and higher intronic content (mean %: 84.8 versus 78.0; P < 0.01). Such non-random size distribution and intronic composition are conserved in mouse and Drosophila (all P < 0.0001). Stratification by gene age indicated that young oncogenes have been subject to a stronger evolutionary pressure for gene expansion than their non-cancer counterparts. Pan-cancer analysis demonstrated that larger oncogenes were amplified to a lesser extent. Tumor-suppressor genes also moved toward small oncogenes in the course of evolution. Conclusions: Oncogenes expand in size whereas tumor-suppressor genes move closer to small oncogenes in the course of evolution to withstand oncogenic somatic amplification. Our findings have shed new light on the previously unappreciated influence of gene size on oncogene amplification and elucidated how cancers have shaped our genome to its present configuration.


Subject(s)
Evolution, Molecular , Gene Expression Regulation, Neoplastic , Genome, Human/genetics , Neoplasms/genetics , Oncogenes/genetics , Animals , Computational Biology , Datasets as Topic , Drosophila , Gene Amplification , Genes, Tumor Suppressor , Genomics/methods , Humans , Mice
12.
Hong Kong Med J ; 23(4): 374-80, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28655864

ABSTRACT

INTRODUCTION: Studies have shown that early surgery reduces hospital and 1-year mortality in elderly patients with hip fracture, but no major study has examined such relationship in Hong Kong. This study aimed to explore the relationship of early surgery and mortality in a Chinese elderly population with hip fracture. METHODS: This observational study included patients attending public hospitals in Hong Kong. All patients who underwent surgery for geriatric hip fracture in public hospitals from January 2000 to December 2011 were studied. Data were retrieved and collected from the Clinical Data Analysis and Reporting System of the Hospital Authority. Patients were divided into three groups according to timing of surgery: early (0-2 days after admission), delayed (3-4 days after admission), and late (≥5 days after admission) groups. Based on the date of death, we analysed 30-day and 1-year mortality, regardless of cause of death. Comparison of mortality rates was also made between the period before and after implementation of Key Performance Indicator formulated by the Hospital Authority. RESULTS: The overall 1-year mortality rate was 16.8%. The relative risks of 1-year mortality were 1.21 and 1.52 when the delayed and late groups were compared with the early group, respectively. The hazard ratios of long-term mortality were 1.16 (95% confidence interval, 1.13-1.20) and 1.37 (1.33-1.41), respectively for the same comparison. CONCLUSION: Prevalence of geriatric hip fracture will continue to rise and further increase the burden on our health care system. After implementation of Key Performance Indicator, most elderly patients with hip fracture underwent surgery within 2 days provided they were medically fit. Early surgery can reduce both short-term and long-term mortality. Setting up a fragility fracture registry would be beneficial for further studies.


Subject(s)
Hip Fractures/mortality , Orthopedic Procedures/mortality , Time-to-Treatment/statistics & numerical data , Age Factors , Aged , Aged, 80 and over , Female , Hip Fractures/surgery , Hong Kong/epidemiology , Hospitalization/statistics & numerical data , Humans , Male , Orthopedic Procedures/methods , Proportional Hazards Models , Risk Factors , Time Factors
13.
Hong Kong Med J ; 23(3): 264-71, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28473651

ABSTRACT

INTRODUCTION: In setting up a disease registry for fragility fractures in Hong Kong, we conducted a retrospective systematic study on the management of fragility hip fractures. Patient outcomes were compared with the standards from our orthopaedic working group and those from the British Orthopaedic Association that runs a mature fracture registry in the United Kingdom. METHODS: Clinical data on fragility hip fracture patients admitted to six acute major hospitals in Hong Kong in 2012 were captured. These included demographics, pre- and post-operative assessments, discharge details, complications, and 1-year follow-up information. Analysis was performed according to the local standards with reference to those from the British Orthopaedic Association. RESULTS: Overall, 91.0% of patients received orthopaedic care within 4 hours of admission and 60.5% received surgery within 48 hours. Preoperative geri-orthopaedic co-management was received by 3.5% of patients and was one of the reasons for the delayed surgery in 22% of patients. Only 22.9% were discharged with medication that would promote bone health. Institutionalisation on discharge significantly increased by 16.2% (P<0.001). Only 35.1% of patients attended out-patient follow-up 1 year following fracture, and mobility had deteriorated in 69.9% compared with the premorbid state. Death occurred in 17.3% of patients within a year of surgery compared with 1.6% mortality rate in a Hong Kong age-matched population. CONCLUSIONS: The efficiency and quality of acute care for fragility hip fracture patients was documented. Regular geri-orthopaedic co-management can enhance acute care. Much effort is needed to improve functional recovery, prescription of bone health medications, attendance for follow-up, and to decrease institutionalisation. A Fracture Liaison Service is vital to improve long-term care and prevent secondary fractures.


Subject(s)
Hip Fractures/surgery , Orthopedic Procedures/methods , Quality of Health Care , Registries , Aged , Aged, 80 and over , Female , Follow-Up Studies , Hip Fractures/mortality , Hip Fractures/pathology , Hong Kong , Hospitalization/statistics & numerical data , Humans , Male , Middle Aged , Recovery of Function , Retrospective Studies
14.
Physiol Behav ; 174: 170-177, 2017 05 15.
Article in English | MEDLINE | ID: mdl-28257937

ABSTRACT

This study examined the effect of carbohydrate (CHO) and protein (PRO) co-ingestion on energy substrate metabolism, sense of effort, and affective responses during prolonged strenuous endurance exercise. In a four-stage randomized cross-over design, 10 male endurance runners (age: 27.3±1.4yrs; height: 172.9±1.1cm, weight: 63.5±1.6kg; body fat: 9.0±1.4%; V̇O2max: 62.9±1.8ml/kg/min) ran on a treadmill at 70% of their individual V̇O2max for 90min. There were two CHO and PRO treatments (CA: CHO+alpha-lactalbumin and CW: CHO+whey PRO isolate), one CHO treatment (CC: CHO+CHO), and a placebo control (CON). On each occasion, subjects consumed 5ml/kg according to their body weight (kg) immediately before and 2ml/kg every 15min during exercise. Blood samples were collected at 0min, 30min, 60min and 90min of exercise to measure glucose, lactate, insulin, and cortisol levels. The extent of physical sensation (abdominal discomfort, leg muscle pain), the sense of effort (rating of perceive exertion, RPE), and affective responses (pleasure-displeasure, arousal) were evaluated by numeric scales before, during, and immediately after exercise. Blood glucose and insulin concentrations in the CA, CW, and CC treatments were higher than in the CON at 90min (P<0.05). Muscle pain (evaluated by a single item, 0 to 10 pain intensity scale from "no pain at all" to "extremely unbearable") was lower following CA ingestion than CON and CW ingestion, at 75min (vs. CON and CW, 1.95±0.61 vs. 3.70±1.00 and 3.60±1.02, P<0.05) and 90min (vs. CON & CW: 2.40±0.76 vs. 4.20±0.99 and 4.05±1.1, P<0.05). RPE (evaluated by a 15-point, 6 to 20 rating scale ranging from "very, very light" to "very, very hard") following treatment with CA was lower than with CON and CW at 90min (vs. CON and CW: 11.30±1.14 vs. 14.20±1.30 and 13.30±1.24, P<0.05). Compared with CON and CW, CA enhanced the feeling of pleasure (evaluated by feeling scale from -5, "very bad" to +5, "very good") at 90min (vs. CON and CW, 2.20±0.67 vs. -0.30±0.94 and 0.20±0.91, P<0.05). Co-ingestion of CHO and alpha-lactalbumin protein attenuates muscle pain, and therefore alleviates the sense of effort and enhances affective responses during 90min of strenuous running at 70% V̇O2max.


Subject(s)
Affect/drug effects , Carbohydrates/pharmacology , Energy Metabolism/drug effects , Oxygen Consumption/drug effects , Physical Endurance/physiology , Proteins/pharmacology , Abdominal Pain/etiology , Adolescent , Adult , Blood Glucose/drug effects , Healthy Volunteers , Humans , Hydrocortisone/blood , Insulin/blood , Lactic Acid/blood , Male , Myalgia/etiology , Physical Endurance/drug effects , Time Factors , Young Adult
15.
Oncogene ; 36(31): 4415-4426, 2017 08.
Article in English | MEDLINE | ID: mdl-28346420

ABSTRACT

Cyclooxygenase (COX)-2 is upregulated in hepatocellular carcinoma (HCC). However, the direct causative effect of COX-2 in spontaneous HCC formation remains unknown. We thus investigate the role and molecular pathogenesis of COX-2 in HCC by using liver-specific COX-2 transgenic (TG) mice. We found spontaneous HCC formation with elevated inflammatory infiltrates and neovessels in male TG mice (3/21, 14.3%), but not in any of male WT mice (0/19). Reduced representation bisulfite sequencing (RRBS) and gene expression microarrays were performed in the HCC tumor and non-HCC liver tissues to investigate the molecular mechanisms of COX-2-driven HCC. By RRBS, DNA promoter hypermethylation was identified in HCC from TG mice. Induction of promoter hypermethylation was associated with reduced tet methylcytosine dioxygenase 1 (TET1) expression by COX-2. TET1 could catalyze the conversion of 5-methylcytosine into 5-hydroxymethylcytosine (5hmC) and prevents DNA hypermethylation. In keeping with this, loss of 5hmC was demonstrated in COX-2-induced HCC. Consistently, COX-2 overexpression in human HCC cell lines could reduce both TET1 expression and 5hmc levels. Integrative analyses of DNA methylation and gene expression profiles further identified significantly downregulated genes including LTBP1, ADCY5 and PRKCZ by promoter methylation in COX-2-induced HCC. Reduced expression of LTBP1, ADCY5 and PRKCZ by promoter hypermethylation was further validated in human HCCs. Bio-functional investigation revealed that LTBP1 inhibited cell proliferation in HCC cell lines, suggesting its potential role as a tumor suppressor in HCC. Gene expression microarrays revealed that signaling cascades (AKT (protein kinase B), STK33 (Serine/Threonine kinase 33) and MTOR (mechanistic target of rapamycin) pathways) were enriched in COX-2-induced HCC. In conclusion, this study demonstrated for the first time that enhanced COX-2 expression in hepatocytes is sufficient to induce HCC through inducing promoter hypermethylation by reducing TET1, silencing tumor-suppressive genes and activating key oncogenic pathways. Inhibition of COX-2 represents a mechanism-based target for HCC prevention.


Subject(s)
Carcinoma, Hepatocellular/etiology , Cyclooxygenase 2/physiology , Liver Neoplasms/etiology , Liver/enzymology , Animals , Cell Line, Tumor , DNA Methylation , DNA-Binding Proteins/physiology , Humans , Latent TGF-beta Binding Proteins/physiology , Male , Mice , Promoter Regions, Genetic , Proto-Oncogene Proteins/physiology
16.
Best Pract Res Clin Gastroenterol ; 31(6): 607-618, 2017 Dec.
Article in English | MEDLINE | ID: mdl-29566903

ABSTRACT

Advances in research techniques have made it possible to map the microbial communities in the gastrointestinal (GI) tract, where the majority of bacteria in the human body reside. Disturbances in these communities are referred to as dysbiosis and have been associated with GI cancers. Although dysbiosis is observed in several GI malignancies, the specific role of these changes has not been understood to the extent of Helicobacter pylori (HP) in gastric cancer (GC). This review will address the bacterial communities along the GI tract, from the oral cavity to the anal canal, particularly focusing on bacterial dysbiosis and carcinogenesis. Just as non-HP bacteria in the stomach may interact with HP in gastric carcinogenesis, the same may hold true for other GI tract malignancies, where an interplay between microbes in carcinogenesis seems conceivable, especially in colorectal cancer (CRC). In the last part of this review we will discuss the potential mechanisms of bacterial dysbiosis in GI carcinogenesis.


Subject(s)
Carcinogenesis/genetics , Cell Transformation, Neoplastic/genetics , Gastrointestinal Microbiome/genetics , Gastrointestinal Neoplasms/genetics , Gastrointestinal Neoplasms/microbiology , Gastrointestinal Neoplasms/pathology , Humans
17.
Hong Kong Med J ; 23(1): 63-6, 2017 Feb.
Article in English | MEDLINE | ID: mdl-27966433

ABSTRACT

INTRODUCTION: International clinical guidelines recommend early surgical treatment for geriatric patients with hip fracture. There are, however, few data concerning the operative outcome of centenarians. This study aimed to report the epidemiology of hip fracture and postoperative mortality rate, and to discuss whether operation is justified in centenarians in Hong Kong. METHODS: This observational study was carried out in all public hospitals of Hong Kong. All patients aged 100 years or above who underwent hip fracture surgery in any public hospital between 1 January 2010 and 31 December 2013 were included. Their postoperative mean and median survival time was recorded. RESULTS: Of 114 centenarians, 96 (84%) were female. The age of patients ranged from 100 to 109 years, with the largest number (44%) aged 100 years. The follow-up interval ranged from 5 to 1619 days (median, 412 days; interquartile range, 683 days). The 1-month, 6-month, and 1-year mortalities were 8%, 25%, and 37%, respectively. By Kaplan-Meier analysis, the postoperative mean survival was 2 years 2 months (95% confidence interval, 680-936 days) and the median survival time was 2 years (interquartile range, 1234 days). CONCLUSION: The 1-year mortality among Hong Kong centenarians with hip fracture was 37%, which is lower than the 41.1% in the general centenarian population in Japan. The median survival time after hip fracture surgery was 2 years, suggesting that surgery even at an extreme age is worthwhile to maintain quality of life. Extreme age should not be a barrier to operative treatment.


Subject(s)
Hip Fractures/mortality , Hip Fractures/surgery , Age Distribution , Aged, 80 and over , Female , Follow-Up Studies , Hong Kong/epidemiology , Hospitals, Public , Humans , Kaplan-Meier Estimate , Male , Postoperative Period , Quality of Life , Risk Factors , Sex Distribution , Time Factors
19.
Ned Tijdschr Geneeskd ; 160: D546, 2016.
Article in Dutch | MEDLINE | ID: mdl-27758724

ABSTRACT

Sexual abuse is very common. In the Netherlands 42% of women and 13% of men aged over 25 years have experienced unacceptable sexual behaviour. Most victims do not seek professional help nor do they report the abuse to the police, and most of the victims who do seek medical help do not mention the abuse. Doctors often do not recognize the signs of sexual abuse. Most victims of rape have symptoms that may develop into posttraumatic stress disorder (PTSD) if they persist for more than 4 weeks, such as sleep problems or panic attacks. Victims of sexual abuse also more often develop a psychiatric disorder or medically unexplained symptoms (MUS). Doctors should ask about sexual abuse in cases of MUS or unexplained mental problems. The complications of abuse can be treated with eye movement desensitization and reprocessing (EMDR) or cognitive processing therapy (CPT).


Subject(s)
Child Abuse, Sexual/diagnosis , Rape/diagnosis , Adult , Child , Child Abuse, Sexual/psychology , Child Abuse, Sexual/statistics & numerical data , Child Abuse, Sexual/therapy , Female , Humans , Netherlands , Rape/psychology , Rape/rehabilitation , Rape/statistics & numerical data , Stress Disorders, Post-Traumatic/diagnosis , Stress Disorders, Post-Traumatic/etiology , Stress Disorders, Post-Traumatic/therapy
20.
Aliment Pharmacol Ther ; 43(7): 755-64, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26858128

ABSTRACT

BACKGROUND: The performance of faecal occult blood tests (FOBTs) to screen proximally located colorectal cancer (CRC) has produced inconsistent results. AIM: To assess in a meta-analysis, the diagnostic accuracy of FOBTs for relative detection of CRC according to anatomical location of CRC. METHODS: Diagnostic studies including both symptomatic and asymptomatic cohorts assessing performance of FOBTs for CRC were searched from MEDINE and EMBASE. Primary outcome was accuracy of FOBTs according to the anatomical location of CRC. Bivariate random-effects model was used. Subgroup analyses were performed to evaluate test performance of guaiac-based FOBT (gFOBT) and immunochemical-based FOBT (iFOBT). RESULTS: Thirteen studies, with 17 cohorts, reporting performance of FOBT were included; a total of 26 342 patients (mean age 58.9 years; 58.1% male) underwent both colonoscopy and FOBT. Pooled sensitivity, specificity, positive likelihood ratio and negative likelihood ratio of FOBTs for CRC detection in the proximal colon were 71.2% (95% CI 61.3-79.4%), 93.6% (95% CI 90.7-95.7%), 11.1 (95% CI 7.8-15.8) and 0.3 (95% CI 0.2-0.4) respectively. Corresponding findings for CRC detection in distal colon were 80.1% (95% CI 70.9-87.0%), 93.6% (95% CI 90.7-95.7%), 12.6 (95% CI 8.8-18.1) and 0.2 (95% CI 0.1-0.3). The area-under-curve for FOBT detection for proximal and distal CRC were 90% vs. 94% (P = 0.0143). Both gFOBT and iFOBT showed significantly lower sensitivity but comparable specificity for the detection of proximally located CRC compared with distal CRC. CONCLUSION: Faecal occult blood tests, both guaiac- and immunochemical-based, show better diagnostic performance for the relative detection of colorectal cancer in the distal colon than in the proximal bowel.


Subject(s)
Colon/pathology , Colonoscopy/standards , Colorectal Neoplasms/diagnosis , Early Detection of Cancer/standards , Occult Blood , Aged , Cohort Studies , Colonoscopy/methods , Colorectal Neoplasms/blood , Early Detection of Cancer/methods , Female , Guaiac/analysis , Humans , Male , Middle Aged
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