Donor-derived dengue infections - A review of screening protocol and outcomes in an endemic country.

BACKGROUND: Donor-derived dengue infections present significant challenges to organ transplantation, particularly in endemic regions like Singapore. Although primarily transmitted by Aedes mosquitoes, dengue can also be transmitted through organ transplantation, occasionally with fatal outcomes. This study aims to evaluate the outcomes and evolution of dengue screening protocols for potential deceased donors in Singapore from 2006 to 2022. METHODS: Initially, screening was done via dengue immunoglobulin M (IgM), targeting donors with specific clinical criteria (thrombocytopenia, drop in platelet count, prolonged prothrombin time/partial thromboplastin time, and discretion of the transplant team), later transitioning to blood dengue reverse transcription-polymerase chain reaction (RT-PCR) in 2007 with similar criteria, and subsequently universal screening in 2016. In 2021, urine dengue RT-PCR was added following a case of donor-derived dengue infection from an aviremic but viruric donor. RESULTS: Out of 431 potential deceased donors, 395 (91.6%) underwent dengue screening, with six (1.5%) testing positive for dengue. In 2006, three positive screens were identified: two through dengue IgM and one via blood dengue RT-PCR; subsequent years saw one positive screen each in 2007, 2008, and 2019 via blood dengue RT-PCR. Potential deceased donors with a positive blood dengue screen were rejected as solid organ and tissue donors. Those with negative blood dengue RT-PCR but positive urine dengue RT-PCR would be rejected as kidney donors, but the use of other organs and tissues was at the discretion of the transplantation team. CONCLUSION: The optimal screening protocol remains uncertain, but our findings suggest that a universal screening strategy utilizing both blood and urine dengue RT-PCR could be considered in dengue-endemic countries.

Donor-derived infections-Insights from Singapore, Japan, and Thailand.

BACKGROUND: Solid organ transplantation (SOT) has expanded significantly in Asia over past few decades. Donor-derived infections (DDIs) remain a significant concern as they may adversely impact transplant outcomes. We aim to review the existing regulatory frameworks, screening protocols, and management practices for DDIs in Asia. METHODS: We reached out to transplant infectious diseases experts in Asia to provide standardized data on annual SOT numbers, incidence of DDIs, regulatory frameworks, donor and recipient screening protocols, and DDI surveillance measures. We present the data from Singapore, Japan, and Thailand. RESULTS: Donor screening for HIV, hepatitis B, hepatitis C, and syphilis is mandatory in all countries. Additionally, Japan screens for HTLV-1 antibody due to its endemicity. We also reviewed the protocols for screening and prevention of endemic infections in Asia. Singapore is the only country implementing universal screening for all donors for dengue, Zika, and chikungunya via blood and urine RT-PCR. Strongyloidiasis screening is not routinely done, although some transplant centers empirically give ivermectin prophylaxis to organ recipients. Tuberculosis screening with a donor questionnaire and chest radiograph is common for deceased donors, and some centers do Interferon Gamma Release Assay test for living donors. We also found a significant gap in the surveillance and reporting of potential DDIs in Asia and the overall incidence of DDIs in Asia is unknown and likely underreported. CONCLUSION: The experiences of Singapore, Japan, and Thailand offer valuable insights into current practices and the unmet needs regarding a DDI registry and call for coordinated efforts to address this critical issue in the region.

ChatGPT on guidelines: Providing contextual knowledge to GPT allows it to provide advice on appropriate colonoscopy intervals.

BACKGROUND AND AIM: Colonoscopy is commonly used in screening and surveillance for colorectal cancer. Multiple different guidelines provide recommendations on the interval between colonoscopies. This can be challenging for non-specialist healthcare providers to navigate. Large language models like ChatGPT are a potential tool for parsing patient histories and providing advice. However, the standard GPT model is not designed for medical use and can hallucinate. One way to overcome these challenges is to provide contextual information with medical guidelines to help the model respond accurately to queries. Our study compares the standard GPT4 against a contextualized model provided with relevant screening guidelines. We evaluated whether the models could provide correct advice for screening and surveillance intervals for colonoscopy. METHODS: Relevant guidelines pertaining to colorectal cancer screening and surveillance were formulated into a knowledge base for GPT. We tested 62 example case scenarios (three times each) on standard GPT4 and on a contextualized model with the knowledge base. RESULTS: The contextualized GPT4 model outperformed the standard GPT4 in all domains. No high-risk features were missed, and only two cases had hallucination of additional high-risk features. A correct interval to colonoscopy was provided in the majority of cases. Guidelines were appropriately cited in almost all cases. CONCLUSIONS: A contextualized GPT4 model could identify high-risk features and quote appropriate guidelines without significant hallucination. It gave a correct interval to the next colonoscopy in the majority of cases. This provides proof of concept that ChatGPT with appropriate refinement can serve as an accurate physician assistant.

Contextual and individual factors associated with knowledge, awareness and attitude on liver diseases: A large-scale Asian study.

There are limited data to provide better understanding of the knowledge/awareness of general population towards liver health in Asia. We sought to identify the knowledge gaps and attitudes towards liver health and liver diseases as well as evaluate associated individual-level and macro-level factors based on contextual analysis. An online survey assessing knowledge, awareness and attitudes towards liver health and disease was conducted among 7500 respondents across 11 countries/territories in Asia. A liver index was created to measure the respondents' knowledge level and the degree of awareness and attitudes. Multilevel logistic regression was performed to identify individual factors and contextual effects that were associated with liver index. The overall liver index (0-100-point scale) was 62.4 with 6 countries/territories' liver indices greater than this. In the multilevel model, the inclusion of geographical information could explain for 9.6% of the variation. Residing in a country/territory with higher HBV prevalence (80% IOR: 1.20-2.79) or higher HCV death rate (80% IOR: 1.35-3.13) increased the individual probability of obtaining a high overall liver index. Individual factors like age, gender, education, household income, disease history and health screening behaviour were also associated with liver index (all p-values<0.001). The overall liver index was positively associated with the two macro-level factors viz. HBV prevalence and HCV death rate. There is a need to formulate policies especially in regions of lower HBV prevalence and HCV death rate to further improve the knowledge, awareness and attitudes of the general public towards liver diseases.

Poor Outcomes of Cirrhosis due to Nonalcoholic Steatohepatitis Compared With Hepatitis B After Decompensation With Ascites.

INTRODUCTION: Decompensation with ascites portends a poor prognosis in cirrhosis. The aim of this study was to compare the outcomes of patients with nonalcoholic steatohepatitis (NASH) with hepatitis B virus (HBV) cirrhosis after decompensation with ascites. METHODS: We conducted a retrospective study to evaluate the outcomes of patients with NASH and HBV cirrhosis who were admitted to hospital for first-onset ascites from January 1, 2004, to June 30, 2015. They were followed up until death, liver transplantation, or loss to follow up. RESULTS: Patients with NASH had lower median (interquartile range) Model for End-Stage Liver Disease score (11 [9-14] vs 14 [11-17], P < 0.001). Over 60 months, patients with NASH cirrhosis had higher cumulative incidence of dilutional hyponatremia (P < 0.001) and refractory ascites (P = 0.028). They also had higher cumulative incidence of cirrhosis-related deaths and liver transplantation compared with HBV cirrhosis (65.7%; [95% confidence interval (CI) 53.6-75.4] vs 42.5% [95% CI 32.4-55.2], P = 0.008). Multivariable competing risk analysis showed that NASH (subdistribution hazard ratio [sHR] 1.88 [95% CI 1.14-3.11], P = 0.014), non-Chinese ethnicity (sHR 1.63 [95% CI 1.06-2.50], P = 0.027), history of hepatocellular carcinoma (sHR 1.76 [95% CI 1.05-2.95], P = 0.033), estimated glomerular filtration rate <60 mL/min/1.73 m2 (sHR 1.70 [95% CI 1.09-2.65], P = 0.020), and Model for End-Stage Liver Disease score ≥15 (sHR 3.26 [95% CI 2.11-5.05], P < 0.001) were independent predictors of poor transplant-free survival. DISCUSSION: Patients with decompensated cirrhosis due to NASH had much poorer prognosis compared with HBV with more complications and greater healthcare resource utilization. Greater awareness is necessary for early diagnosis of NASH before decompensation.

qFIBS: An Automated Technique for Quantitative Evaluation of Fibrosis, Inflammation, Ballooning, and Steatosis in Patients With Nonalcoholic Steatohepatitis.

BACKGROUND AND AIMS: Nonalcoholic steatohepatitis (NASH) is a common cause of chronic liver disease. Clinical trials use the NASH Clinical Research Network (CRN) system for semiquantitative histological assessment of disease severity. Interobserver variability may hamper histological assessment, and diagnostic consensus is not always achieved. We evaluate a second harmonic generation/two-photon excitation fluorescence (SHG/TPEF) imaging-based tool to provide an automated quantitative assessment of histological features pertinent to NASH. APPROACH AND RESULTS: Images were acquired by SHG/TPEF from 219 nonalcoholic fatty liver disease (NAFLD)/NASH liver biopsy samples from seven centers in Asia and Europe. These were used to develop and validate qFIBS, a computational algorithm that quantifies key histological features of NASH. qFIBS was developed based on in silico analysis of selected signature parameters for four cardinal histopathological features, that is, fibrosis (qFibrosis), inflammation (qInflammation), hepatocyte ballooning (qBallooning), and steatosis (qSteatosis), treating each as a continuous rather than categorical variable. Automated qFIBS analysis outputs showed strong correlation with each respective component of the NASH CRN scoring (P < 0.001; qFibrosis [r = 0.776], qInflammation [r = 0.557], qBallooning [r = 0.533], and qSteatosis [r = 0.802]) and high area under the receiver operating characteristic curve values (qFibrosis [0.870-0.951; 95% confidence interval {CI}, 0.787-1.000; P < 0.001], qInflammation [0.820-0.838; 95% CI, 0.726-0.933; P < 0.001), qBallooning [0.813-0.844; 95% CI, 0.708-0.957; P < 0.001], and qSteatosis [0.939-0.986; 95% CI, 0.867-1.000; P < 0.001]) and was able to distinguish differing grades/stages of histological disease. Performance of qFIBS was best when assessing degree of steatosis and fibrosis, but performed less well when distinguishing severe inflammation and higher ballooning grades. CONCLUSIONS: qFIBS is an automated tool that accurately quantifies the critical components of NASH histological assessment. It offers a tool that could potentially aid reproducibility and standardization of liver biopsy assessments required for NASH therapeutic clinical trials.

Public awareness and knowledge of liver health and diseases in Singapore.

BACKGROUND AND AIM: Despite efforts in controlling and managing liver diseases, significant health issues remain. This study aims to evaluate the degree of public awareness and knowledge regarding liver health and diseases in Singapore. METHODS: A cross-sectional, self-reported, web-based questionnaire was administered to 500 adult individuals. Questionnaire items pertained to knowledge and awareness of overall liver health, liver diseases and their associated risk factors. RESULTS: Sixty-four percent of respondents were ≥35 years old and 54.0% were male. While majority agreed that regular screening was important for liver health (91.2%), only 65.4% attended health screening within recent 2 years. Hepatitis B had more awareness than hepatitis C among the respondents. About 70% agreed the consequences of viral hepatitis included liver cirrhosis, failure, and/or cancer. Yet, only 15% knew hepatitis C is not preventable by vaccination and more than half mistaken hepatitis B and C are transmissible via contaminated or raw seafood. Despite 75% being aware of non-alcoholic fatty liver disease, many were not aware of the related risk factors and complications. Awareness of specific screening and diagnostic tests for liver health was poor as one-fifth correctly identified the diagnostic tests for viral hepatitis. Preferences for doctor's consultation, TV, or newspapers (online) as information channels contrasted those currently used in the public health education efforts. CONCLUSIONS: The levels of understanding of liver diseases, risk factors, and potential complications are suboptimal among the Singapore public. More public education efforts aligned with respondents' information-seeking preferences could facilitate addressing misperceptions and increase knowledge about liver diseases.

Validation of the Expanded Baveno-VI Criteria for Screening Gastroscopy in Asian Patients with Compensated Advanced Chronic Liver Disease.

BACKGROUND: The expanded Baveno-VI criteria may further reduce the need for screening gastroscopy compared to Baveno-VI criteria. AIM: We sought to validate the performance of these criteria in a cohort of compensated advanced chronic liver disease (cACLD) patients with predominantly hepatitis B infection. METHODS: Consecutive cACLD patients from 2006 to 2012 with paired liver stiffness measurements and screening gastroscopy within 1 year were included. The expanded Baveno-VI criteria were applied to evaluate the sensitivity (SS), specificity (SP), positive predictive value (PPV) and negative predictive value (NPV) for the presence of high-risk varices (HRV). RESULTS: Among 165 cACLD patients included, 17 (10.3%) had HRV. The commonest etiology of cACLD was chronic hepatitis B (36.4%) followed by NAFLD (20.0%). Application of expanded Baveno-VI criteria avoided more screening gastroscopy (43.6%) as compared to the original Baveno-VI criteria (18.8%) without missing more HRV (1 with both criteria). The overall SS, SP, PPV and NPV of the expanded Baveno-VI criteria in predicting HRV were 94.1%, 48.0%, 17.2% and 98.6%, respectively. CONCLUSION: Application of the expanded Baveno-VI criteria can safely avoid screening gastroscopy in 43.6% of cACLD patients with an excellent ability to exclude HRV.

High-stakes examinations during the COVID-19 pandemic: to proceed or not to proceed, that is the question.

The COVID-19 pandemic has disrupted education-related activities, including the conduct of examinations. We review the literature regarding high-stakes examinations during the pandemic, discuss the decision-making process of whether to proceed with a high-stakes examination and share published experiences in conducting high-stakes examinations during the pandemic. We illustrate our own recent experiences of decision-making and conduct of our high-stakes gastroenterology licencing examinations during the height of the COVID-19 pandemic. It is possible to conduct high-stakes examinations virtually during pandemic situations with fidelity and adherence to the established format and standards.

Comparison of Hepatocellular Carcinoma in Patients with Cryptogenic Versus Hepatitis B Etiology: A Study of 1079 Cases Over 3 Decades.

BACKGROUND: Traditionally in Asia, hepatitis B (HBV) accounts for the majority of hepatocellular carcinoma (HCC), but increasingly, non-viral or nonalcoholic steatohepatitis (NASH) etiology may play a more prominent role with current socioeconomic changes. There remains a paucity in data comparing NASH-HCC to HBV-related HCC. In this study, we explored the differences in clinical characteristics between HBV- and cryptogenic-related HCC. METHODS: Patients with HCC seen in the Department of Gastroenterology and Hepatology, Singapore General Hospital were enrolled in an ongoing database since 1980. Patients with HCC attributed to HBV or cryptogenic etiology were identified. Comparison of clinical characteristics was performed between the two groups. RESULTS: There were 916 HBV-HCC patients and 163 cryptogenic HCC patients, accounting for 70.9% and 12.6% of the total HCC cases (1292 patients), respectively. Out of the total cohort enrolled from 1980 to 2005, the ratio of cryptogenic to HBV patients was 1:6.7, while from 2006 to the current year, the ratio of cryptogenic to HBV patients has increased significantly to 1:3.9. Relative to patients with HBV, cryptogenic HCC patients were older (67.6 vs. 59.4 years old; p < 0.001), had lower proportion of male patients (69.9% vs. 83.8%; p < 0.001), and had higher incidence of smoking (32.2% vs. 25.8%; p = 0.008). HBV group had higher alanine transaminase (60.9 ± 85.7 U/L vs. 48.0 ± 52.1 U/L; p = 0.003), hemoglobin (12.7 ± 2.28 g/dL vs. 12.0 ± 2.46 g/dL, p < 0.001), albumin (32.9 ± 6.8 g/L vs. 31.3 ± 7.7 g/L; p = 0.007), and prothrombin time (13.2 ± 2.95 s vs. 12.7 ± 2.01 s, p = 0.023), as compared to the cryptogenic group. Cryptogenic HCC patients presented more frequently with unifocal HCC (55.2% vs. 46.5%; p = 0.002). There was no difference in the proportions of patients receiving surgical resection in both groups (23.5% in HBV group vs. 17.9% in cryptogenic group; p = 0.202). Cox regression analysis revealed no survival difference between cryptogenic-related HCC and HBV-related HCC (p = 0.367). CONCLUSION: Temporal trends suggest that HCC attributed to HBV is on the decline, while cryptogenic- or NASH-related HCC is an emerging clinical entity. A paradigm shift in approach to screening, surveillance, and management of HCC may be required in view of the changing landscape of HCC epidemiology into an increasing non-viral etiology.

Chronic Infection With Camelid Hepatitis E Virus in a Liver Transplant Recipient Who Regularly Consumes Camel Meat and Milk.

There have been increasing reports of food-borne zoonotic transmission of hepatitis E virus (HEV) genotype 3, which causes chronic infections in immunosuppressed patients. We performed phylogenetic analyses of the HEV sequence (partial and full-length) from 1 patient from the Middle East who underwent liver transplantation, and compared it with other orthohepevirus A sequences. We found the patient to be infected by camelid HEV. This patient regularly consumed camel meat and milk, therefore camelid HEV, which is genotype 7, might infect human beings. Our finding links consumption of camel-derived food products to post-transplantation hepatitis E, which, if detected at early stages, can be cured with antiviral therapy and reduced administration of immunosuppressive agents.

Re-evaluating transarterial chemoembolization for the treatment of hepatocellular carcinoma: Consensus recommendations and review by an International Expert Panel.

Patients with unresectable hepatocellular carcinoma (HCC) usually receive transarterial chemoembolization (TACE) or systemic therapies with intermediate and advanced-stage disease. However, intermediate-stage HCC patients often have unsatisfactory clinical outcomes with repeated TACE and there is considerable uncertainty surrounding the criteria for repeating or stopping TACE treatment. In July 2012, an Expert Panel Opinion on Interventions in Hepatocellular Carcinoma (EPOIHCC) was re-convened in Shanghai in an attempt to provide a consensus on the practice of TACE, particularly in regard to evaluating TACE 'failure'. To that end, current clinical practice throughout Asia was reviewed in detail including safety and efficacy data on TACE alone as well as in combination with targeted systemic therapies for intermediate HCC. This review summarizes the evidence discussed at the meeting and provides expert recommendations regarding the use of TACE for unresectable intermediate-stage HCC. A key consensus of the Expert Panel was that the current definitions of TACE failure are not useful in differentiating between situations where TACE is no longer effective in controlling disease locally vs. systemically. By redefining these concepts, it may be possible to provide a clearer indication of when TACE should be repeated and more importantly, when TACE should be discontinued.

Use of Machine Learning to Predict Onset of NAFLD in an All-Comers Cohort-Development and Validation in 2 Large Asian Cohorts.

Background and Aims: Nonalcoholic fatty liver disease (NAFLD) is one of the most common liver diseases. There are no universally accepted models that accurately predict time to onset of NAFLD. Machine learning (ML) models may allow prediction of such time-to-event (ie, survival) outcomes. This study aims to develop and independently validate ML-derived models to allow personalized prediction of time to onset of NAFLD in individuals who have no NAFLD at baseline. Methods: The development dataset comprised 25,599 individuals from a South Korean NAFLD registry. A random 70:30 split divided it into training and internal validation sets. ML survival models (random survival forest, extra survival trees) were fitted, with time to NAFLD diagnosis in months as the target variable and routine anthropometric and laboratory parameters as predictors. The independent validation dataset comprised 16,173 individuals from a Chinese open dataset. Models were evaluated using the concordance index (c-index) and Brier score on both the internal and independent validation sets. Results: The datasets (development vs independent validation) had 1,331,107 vs 543,874 person months of follow-up, NAFLD incidence of 25.7% (6584 individuals) vs 14.4% (2322 individuals), and median time to NAFLD onset of 60 (interquartile range 38-75) vs 24 (interquartile range 13-37) months, respectively. The ML models achieved a good c-index of >0.7 in the validation cohort-random survival forest 0.751 (95% confidence interval 0.742-0.759), extra survival trees 0.752 (95% confidence interval 0.744-0.762). Conclusion: ML models can predict time-to-onset of NAFLD based on routine patient data. They can be used by clinicians to deliver personalized predictions to patients, which may facilitate patient counseling and clinical decision making on interval imaging timing.

Hepatocellular Carcinoma in Asia: Physician and Patient Perspectives on Surveillance, Diagnosis, and Treatment.

PURPOSE: In several Asian countries, hepatocellular carcinoma (HCC) is a leading cause of cancer deaths. HCC risk factors in Asia differ from those elsewhere and are changing with the treatment landscape as systemic treatment options increase. This study was conducted to gain insight from physicians and patients into HCC screening, diagnosis, and treatment strategies in Indonesia, Korea, Malaysia, Singapore, Taiwan, Thailand, and Vietnam. METHODS: Two cross-sectional, anonymized, online surveys were completed between July and December 2022 by physicians diagnosing and treating HCC (55 questions on risk factors, surveillance, diagnosis, and treatment) and patients ≥ 18 years old diagnosed with HCC (36 questions on disease knowledge, quality of life, and experiences of diagnosis and treatment). RESULTS: Responses were received from 276 physicians in all 7 countries and 130 patients in Thailand, Taiwan, and Vietnam. From the physician's perspective, surveillance programs are widespread but identify insufficient HCC cases; only 18% are early-stage HCC at diagnosis. From the patient's perspective, knowledge of risk factors increases after diagnosis, but few seek support from patient associations; patients would benefit from better communication from their doctors. Treatment affordability and side effects are key issues for patients. CONCLUSIONS: Awareness of the risk factors for HCC should be raised in primary care and the general population, and surveillance should identify early-stage HCC. Because patients rely on their doctors for support, doctors should better understand their patients' needs, and patients could be supported by trained nurses or case managers. Programs are needed to increase patients' access to proven HCC treatments.

Consensus recommendations and review by an International Expert Panel on Interventions in Hepatocellular Carcinoma (EPOIHCC).

Hepatocellular carcinoma (HCC) presents with a high burden of disease in East Asian countries. Intermediate-stage HCC as defined by the Barcelona Clinic Liver Cancer (BCLC) staging system poses a clinical challenge as it includes a heterogeneous population of patients that can vary widely in terms of tumour burden, liver function and disease aetiology. Intermediate HCC patients often have unsatisfactory clinical outcomes with repeated transarterial chemoembolization (TACE, due to non-response of the target tumour or the development of further metastasis indicating progressive disease. In September 2011, an Expert Panel Opinion on Interventions in Hepatocellular Carcinoma (EPOIHCC) was convened in HK in an attempt to provide a consensus on the practice of TACE. To that end, current clinical practice throughout Asia was reviewed in detail including safety and efficacy data on TACE alone as well as in combination with targeted systemic therapies. This review summarises the evidence discussed at the meeting and provides expert recommendation regarding the available therapeutic options for unresectable intermediate stage HCC. A key consensus of the Expert Panel was that in order to improve patient outcomes and long-term survival, the possibility of using TACE in combination with targeted agents given systemically should be explored. While the currently available clinical data is promising, the expected completion of several pivotal phase II and III RCTs will provide further evidence in support of the rationale for combination therapy regimens.

Organ donation: what else can be done besides legislature?

With the ongoing organ shortage for transplantation, Singapore has adopted an organ opt-out scheme: Human Organ Transplant Act (HOTA) that presumes consent unless specified otherwise. Likewise, receptivity of doctors and medical students (MS), as future doctors, can positively influence organ donation (OD) rates. We explored the knowledge and attitudes of MS toward OD. MS from all five yr of medical school were recruited using self-administered questionnaires. There were 294 completed questionnaires with 49.3% males and 45.6% pre-clinical students. The MS were generally knowledgeable about organ transplantation, but deficient in the knowledge of some aspects of HOTA. The majority of the MS were receptive toward OD. Traditional values rather than religion were possible barriers toward OD. 50.7% of the MS were concerned that donated organs may be inappropriately used, while 32% had concerns that doctors would prematurely terminate treatment if the patient is a potential organ donor. Fewer clinical students shared such concerns, compared with the pre-clinical students. The MS have a good understanding of basic tenets of OD and are receptive toward OD. Potential barriers for OD advocation are local traditional values and reservations regarding the appropriate use of harvested organs and provision of appropriate care to donor patients. These concerns are areas to address.

Real-world impact of a subsidy decision of sofosbuvir-velpatasvir for treatment of chronic hepatitis C on clinical practice and patient outcomes.

Background and Aim: Sofosbuvir-velpatasvir was recommended for subsidy to treat chronic hepatitis C in Singapore in 2018. We measured the impact of the subsidy decision on clinical practice and patient outcomes. Specifically, we looked at pre- and post-subsidy changes in the utilization and prescribing pattern of chronic hepatitis C treatment and the real-world clinical effectiveness. Method: Utilization trends and prescribing patterns were assessed using aggregated drug utilization data from public hospitals' dispensing systems and clinical data from the national electronic health record database, respectively. An audit was conducted to evaluate sustained virological response rate 12 weeks post treatment (SVR12). Results: Use of sofosbuvir-velpatasvir increased sharply since its subsidy listing and dropped subsequently, whereas the utilization of comparator drugs remained low. Prescribing rate of sofosbuvir-velpatasvir increased from 13.7% in the pre-subsidy period to 90.2% in the post-subsidy period; 39.1% of patients previously on pegylated interferon and ribavirin switched to sofosbuvir-velpatasvir following its subsidy listing. In the audit, 365 out of 375 patients (97.3% [95% confidence interval: 95.1-98.6%]) achieved SVR12. Conclusion: The subsidy decision led to increased accessibility to patients and intended changes in clinical practice. Sofosbuvir-velpatasvir was also clinically effective in the real world. These findings augur well for the continued eradication of chronic hepatitis C infection in Singapore.

Readiness for transfer: a mixed-methods study on ICU transfers of care.

OBJECTIVE: Past studies on intensive care unit (ICU) patient transfers compare the efficacy of using standardised checklists against unstructured communications. Less studied are the experiences of clinicians in enacting bidirectional (send/receive) transfers. This study reports on the differences in protocols and data elements between receiving and sending transfers in the ICU, and the elements constituting readiness for transfer. METHODS: Mixed-methods study of a 574-bed general hospital in Singapore with a 74-bed ICU for surgical and medical patients. Six focus group discussions (FGDs) with 34 clinicians comprising 15 residents and 19 nurses, followed by a structured questionnaire survey of 140 clinicians comprising 21 doctors and 119 nurses. FGD transcripts were analysed according to the standard qualitative research guidelines. Survey data were analysed using Student's t-test with Bonferroni corrections. RESULTS: General ward (GW) clinicians are more likely to receive ICU patients with complete discharge summaries while ICU clinicians receiving GW patients get significantly less data. Emergency department (ED), GW and operating theatre physicians accompany their patients to the ICU while ICU nurses accompany their patients to the GW. Not all units, such as the ED, experience bidirectional transfers. CONCLUSION: The protocols and supporting data elements of an ICU transfer vary by the type of transfer and transferring unit. Readiness for transfer means that sending unit protocols affirmatively consider the needs of the receiving unit's data needs and resource constraints.

Gender survival differences in hepatocellular carcinoma: Is it all due to adherence to surveillance? A study of 1716 patients over three decades.

Background and Aims: Hepatocellular carcinoma (HCC) is one of the commonest causes of cancer-related death worldwide. Whether gender is an independent factor for HCC survival is debatable. We studied the influence of gender on the clinical characteristics of HCC and on survival. Methods: The study cohort comprised patients with HCC seen in our department from 1988 to 2021. Clinical data were prospectively collected. We studied and compared demography, HCC characteristics, and survival between females and males. Survival analysis was censored on October 31, 2015. Results: There were 1716 HCC patients. 343 (20.0%) were females. Females were significantly older at diagnosis (median 69 vs 62 years, P < 0.001). More females were diagnosed via regular HCC surveillance (37.9% vs 29.6%, P = 0.003). Hence, as expected, females had less-advanced HCC at diagnosis with smaller median tumor diameter (30 vs 39.5 mm, P = 0.038), lower frequency of portal vein tumor thrombus (19.4% vs 33.4%, P < 0.001), less distant metastases (7.7% vs 11%, P = 0.043), and earlier Barcelona Clinic Liver Cancer (BCLC) stages (0/A, 39.7% vs 28.4%, P < 0.001). On multivariable analysis, HCC diagnosis via surveillance but not female gender was an independent predictor of improved HCC survival. Conclusions: In this large cohort of multi-ethnic Asian patients, females with HCC were significantly more adherent to surveillance and hence presented with less advanced HCC with correspondingly better overall survival than males. The gender difference in survival is likely due to females having better adherence to HCC surveillance. Surveillance to diagnose early-stage HCC remains crucial in improving outcomes.