STOPPING NUCLEOS(T)IDE ANALOGUES IN CHRONIC HEPATITIS B USING HBSAG THRESHOLDS: A META-ANALYSIS AND META-REGRESSION.

BACKGROUND AND AIMS: Recommendations for stopping nucleoside analogue(NA) therapy in HBeAg-negative Chronic Hepatitis B(CHB) are unclear. End-of-treatment quantitative HBsAg(EOTqHBsAg) thresholds<100IU/ml or <1000IU/ml have been proposed as stopping criterion. We assessed this by meta-analysis and meta-regression. DESIGN: We searched PubMed, EMBASE and conference abstracts for studies of HBeAg-negative CHB NA discontinuation. Extracted studies were analysed for risk-of-bias, pooled risk of HBsAg loss, virological(VR) and biochemical relapse(BR). Significant heterogeneity(I2) was addressed by subgroup analysis and random-effects meta-regression with known important covariables, including EOTqHBsAg thresholds, ethnicity, duration of therapy and followup. RESULTS: We found 24 papers(3732 subjects), 16 had low and 8 had moderate risk of bias. The pooled risks of HBsAg loss, VR and BR for stopping therapy at EOTqHBsAg<100IU/ml were 41.8%, 33.4% and 17.3%, versus 4.6%, 72.1% and 34.6% respectively for EOTqHBsAg≥100IU/ml. The pooled risks of HBsAg loss, VR and BR for stopping therapy at EOTqHBsAg<1000IU/ml were 22.0%, 52.7% and 15.9%, versus 3.4%, 63.8% and 26.4% respectively for EOTqHBsAg≥1000IU/ml. Multivariable analysis for HBsAg loss showed ethnicity, followup duration and EOTqHBsAg<100≥IU/ml explained 85% of the variance in heterogeneity; Asians with EOTqHBsAg<100IU/ml had 28.2%, while non-Asians with EOTqHBsAg<1000IU/ml had 38.4% HBsAg loss. Multivariable analysis showed EOTqHBsAg<100≥IU/ml and other covariables only explained 43% and 63% of the variance in heterogeneity for VR and BR respectively, suggesting that other factors are also important for relapse. CONCLUSIONS: While EOTqHBsAg thresholds, ethnicity and followup duration strongly predict HBsAg loss, this is not true for VR and BR, hence stopping NA therapy should be considered cautiously.

A Machine Learning Approach for Early Diagnosis of Cognitive Impairment Using Population-Based Data.

BACKGROUND: The major mechanisms of dementia and cognitive impairment are vascular and neurodegenerative processes. Early diagnosis of cognitive impairment can facilitate timely interventions to mitigate progression. OBJECTIVE: This study aims to develop a reliable machine learning (ML) model using socio-demographics, vascular risk factors, and structural neuroimaging markers for early diagnosis of cognitive impairment in a multi-ethnic Asian population. METHODS: The study consisted of 911 participants from the Epidemiology of Dementia in Singapore study (aged 60- 88 years, 49.6% male). Three ML classifiers, logistic regression, support vector machine, and gradient boosting machine, were developed. Prediction results of independent classifiers were combined in a final ensemble model. Model performances were evaluated on test data using F1 score and area under the receiver operating curve (AUC) methods. Post modelling, SHapely Additive exPlanation (SHAP) was applied on the prediction results to identify the predictors that contribute most to the cognitive impairment prediction. FINDINGS: The final ensemble model achieved a F1 score and AUC of 0.87 and 0.80 respectively. Accuracy (0.83), sensitivity (0.86), specificity (0.74) and predictive values (positive 0.88 negative 0.72) of the ensemble model were higher compared to the independent classifiers. Age, ethnicity, highest education attainment and neuroimaging markers were identified as important predictors of cognitive impairment. CONCLUSION: This study demonstrates the feasibility of using ML tools to integrate multiple domains of data for reliable diagnosis of early cognitive impairment. The ML model uses easy-to-obtain variables and is scalable for screening individuals with a high risk of developing dementia in a population-based setting.

The clinical journey and healthcare resources required for dialysis access of end-stage kidney disease patients during their first year of hemodialysis.

BACKGROUND: Creation and maintenance of dialysis vascular access (VA) is a major component of healthcare resource utilization and cost for patients newly started on hemodialysis (HD). Different VA format arises due to patient acceptance of anticipatory care versus late preparation, and clinical characteristics. This study reviews the clinical journey and resource utilization required for different VA formats in the first year of HD. METHOD: Data of patients newly commenced on HD between July 2015 and June 2016 were reviewed. Patients were grouped by their VA format: (A) pre-emptive surgically created VA (SCVA), (B) tunneled central venous catheter (CVC) followed by SCVA creation, (C) long-term tunneled CVC only. Clinical events, number of investigations and procedures, hospital admissions, and incurred costs of the three groups were compared. RESULTS: In the multivariable analysis, the cost incurred by the group A patients had no significant difference to that incurred in the group B patients (p = 0.08), while the cost of group C is significantly lower (p < 0.001). Both the 62.7% of group A with successful SCVA who avoided tunneled CVC usage, and those with a functionally matured SCVA in group B (66.1%), used fewer healthcare resources and incurred less cost for their access compared to those did not (p = 0.01, p = 0.02, respectively) during the first year of HD. CONCLUSION: With comparable cost, a pre-emptive approach enables avoidance of tunneled CVC. Tunneled CVC only access format incurred lower cost and is suitable for carefully selected patients. Successful maturation of SCVA greatly affects patients' clinical journey and healthcare cost.

Establishing the national top 10 priority research questions to improve diabetes-related foot health and disease: a Delphi study of Australian stakeholders.

INTRODUCTION: Diabetes-related foot disease is a large cause of the global disease burden yet receives very little research funding to address this large burden. To help address this gap, it is recommended to first identify the consensus priority research questions of relevant stakeholders, yet this has not been performed for diabetes-related foot disease. The aim of this study was to determine the national top 10 priority research questions for diabetes-related foot health and disease from relevant Australian stakeholders. RESEARCH DESIGN AND METHODS: A modified three-round Delphi online survey design was used to seek opinions from relevant Australian stakeholders including those with diabetes or diabetes-related foot disease or their carers (consumers), health professionals, researchers and industry. Participants were recruited via multiple public invitations and invited to propose three research questions of most importance to them (Round 1), prioritize their 10 most important questions from all proposed questions (Round 2), and then rank questions in order of importance (Round 3). RESULTS: After Round 1, a total of 226 unique questions were proposed by 210 participants (including 121 health professionals and 72 consumers). Of those participants, 95 completed Round 2 and 69 completed Round 3. The top 10 priority research questions covered a range of topics, including health economics, peripheral neuropathy, education, infection, technology, exercise, and nutrition. Consumers prioritized peripheral neuropathy and prevention-related questions. Health professionals prioritized management-related questions including Australia's First Peoples foot health, health economics and infection questions. CONCLUSIONS: These priority research questions should guide future national research agendas, funding and projects to improve diabetes-related foot disease burdens in Australia and globally. Future research should focus on consumer priority research questions to improve the burden of diabetes-related foot disease on patients and nations. Further research should also investigate reasons for different priorities between consumers and health professionals.

The impact of shipping CO2 emissions from marine traffic in Western Singapore Straits during COVID-19.

The maritime industry plays a key role in reducing greenhouse gas (GHG) emissions, as an effort to combat the global issue of climate change. The International Maritime Organization (IMO) is targeting a 50% reduction in GHG emissions by 2050 compared to 2008. To measure Singapore's progress towards this target, we have conducted a comprehensive analysis of carbon dioxide (CO2) emissions from the Western Singapore Straits based on the voyage data from Automatic Identification System (AIS) and static information from Singapore Maritime Data Hub (SG-MDH). Two methodologies, the MEET and TRENDS frameworks were applied to estimate the emission volume per vessel per hour. The data analysis results were next aggregated and visualised to answer key questions such as: How did the carbon emission level change from 2019 to 2020, in general, and for specific vessel types? What are the top vessel types and flags that had the highest carbon emissions? Did the traffic volume and emission level decrease during the Circuit Breaker period in 2020? The results of this study can be used to review Singapore's emission control measures and will be of value to the Maritime and Port Authority (MPA) of Singapore responsible for managing CO2 emissions at the Singapore Port.

MEchanical DIlatation of the Cervix-- in a Scarred uterus (MEDICS): the study protocol of a randomised controlled trial comparing a single cervical catheter balloon and prostaglandin PGE2 for cervical ripening and labour induction following caesarean delivery.

INTRODUCTION: Labour induction in women with a previous caesarean delivery currently uses vaginal prostaglandin E2 (PGE2), which carries the risks of uterine hyperstimulation and scar rupture. We aim to compare the efficacy of mechanical labour induction using a transcervically applied Foley catheter balloon (FCB) with PGE2 in affected women attempting trial of labour after caesarean (TOLAC). METHODS AND ANALYSIS: This single-centre non-inferiority prospective, randomised, open, blinded-endpoint study conducted at an academic maternity unit in Singapore will recruit a total of 100 women with one previous uncomplicated caesarean section and no contraindications to vaginal delivery. Eligible consented participants with term singleton pregnancies and unfavourable cervical scores (≤5) requiring labour induction undergo stratified randomisation based on parity and are assigned either FCB (n=50) or PGE2 (n=50). Treatments are applied for up to 12 hours with serial monitoring of the mother and the fetus and serial assessment for improved cervical scores. If the cervix is still unfavourable, participants are allowed a further 12 hours' observation for cervical ripening. Active labour is initiated by amniotomy at cervical scores of ≥6. The primary outcome is the rate of change in the cervical score, and secondary outcomes include active labour within 24 hours of induction, vaginal delivery, time-to-delivery interval and uterine hyperstimulation. All analyses will be intention-to-treat. The data generated in this trial may guide a change in practice towards mechanical labour induction if this proves efficient and safer for women attempting TOLAC compared with PGE2, to improve labour management in this high-risk population. ETHICS AND DISSEMINATION: Ethical approval is granted by the Domain Specific Review Board (Domain D) of the National Healthcare Group, Singapore. All adverse events will be reported within 24 hours of notification for assessment of causality. Data will be published and will be available for future meta-analyses. TRIAL REGISTRATION NUMBER: NCT03471858; Pre-results.

A pilot study of preoperative and postoperative chemotherapy in patients with operable gastric cancer: Australasian Gastrointestinal Trials Group Study 9601.

BACKGROUND: With poor cure rates in gastric cancer using surgery alone, the safety, efficacy and feasibility of preoperative and postoperative chemotherapy was investigated. METHODS: Patients with advanced but operable gastric or cardio-oesophageal adenocarcinoma were staged using endoscopy, computed tomography scan and laparoscopy. If considered potentially resectable, they received chemotherapy (epirubicin, cisplatin and 5-fluorouracil) for 9 weeks before and after surgery. RESULTS: Of 59 participants entered, two were found to have metastatic disease and were excluded from the analysis. Of the participants, 10 were women and 47 men; their median age was 58 years (range 27-83 years) and median performance status 0 (range 0-1). Two of the 57 participants commencing chemotherapy did not undergo surgery (one sudden death, one new liver metastases). Grade 3 and 4 preoperative and postoperative toxicity rates were, respectively, neutropenia 22 and 18%, emesis 12 and 14% and other non-haematological toxicity <10 and <10%. Of the 55 who underwent surgery, 40 had apparently curative resections (clear or positive microscopic margins), 2 died after surgery (anastomotic leak, sepsis) and 16 had postoperative complications. Of these, 27 participants commenced postoperative chemotherapy and 21 completed it. Median progression-free survival and overall survival were 19.6 and 22 months, respectively. CONCLUSION: Epirubicin, cisplatin and protracted venous infusion of 5-fluorouracil chemotherapy was well-tolerated in the preoperative setting and did not appear to increase complication rates of surgery for advanced and operable stomach cancer. These findings demonstrate the feasibility of this strategy in the Australasian clinical setting and are in keeping with the results of a recently reported randomized trial, which demonstrated a significant survival advantage using this chemotherapy regimen.