Cost-Effectiveness of Dupilumab and Oral Janus Kinase Inhibitors for the Treatment of Moderate-to-Severe Atopic Dermatitis in Singapore.

BACKGROUND: Atopic dermatitis (AD) affects both adults and children, impacting their quality of life and productivity; however, traditional systemic treatments such as cyclosporine have limitations. Emerging novel systemic interventions, including monoclonal antibodies and Janus kinase (JAK) inhibitors, have been shown to improve patient outcomes. OBJECTIVE: This study evaluates the cost-effectiveness of novel systemic interventions for moderate-to-severe AD in adults compared with the best supportive care (BSC) in Singapore. METHODS: The economic evaluation used a hybrid model consisting of a decision tree and Markov model. Treatment responses at 16 weeks were based on a network meta-analysis that was developed specifically for this study. Long-term response, discontinuation rates, episodes of flares and treatment-emergent adverse events were obtained from key dupilumab, abrocitinib, baricitinib and upadacitinib trials. The study had a 5-year time horizon and considered the healthcare payer's perspective. Sensitivity and scenario analyses were performed as well. RESULTS: Baricitinib 4 mg and 2 mg have the lowest incremental cost-effectiveness ratios, at Singapore dollars (S$) 60,730/quality-adjusted life-year (QALY) and S$66,842/QALY, respectively. Upadacitinib 30 mg offers the highest incremental QALY gain, while baricitinib 2 mg offers the least. The cost of the intervention drugs accounted for the highest proportion of the overall expenses (68-93%) for those in the maintenance state. Other influential factors within the model included (1) the incremental utility derived from intervention response; (2) the probability of achieving Eczema Area and Severity Index 75 (EASI-75) with BSC; and (3) the relative risk of achieving EASI-75 with the interventions. In a scenario where the cost of all drugs is matched to the lowest-priced drug, the top three cost-effectiveness interventions are dupilumab, upadacitinib 30 mg and abrocitinib 200 mg, respectively. CONCLUSION: The interventions are found to be cost-effective at their existing prices when compared with BSC. Ideally, a composite score of treatment success and quality-of-life scores ought to be included, but such data were unavailable. Future research should consider conditional discontinuation data and long-term outcomes when such data become accessible.

Advancing Colorectal Cancer Detection With Blood-Based Tests: Qualitative Study and Discrete Choice Experiment to Elicit Population Preferences.

BACKGROUND: Colorectal cancer (CRC) is the second most deadly form of cancer, inducing an estimated 1.9 million incidence cases and 0.9 million deaths worldwide in 2020. Despite the availability of screening tests, their uptake remains suboptimal. However, blood-based tests that look for signs of cancer-specific markers in the body are increasingly available as an alternative for more invasive tests for cancer. Compared with existing tests, the benefits of blood-based tests for CRC include not needing pretest preparation, stool handling, and dietary or medication restrictions. OBJECTIVE: This study aims to explore the population's preferences for CRC screening tests, with a focus on blood-based tests, and investigate the factors influencing test uptake. METHODS: We used a mixed methods approach, combining semistructured interviews and a discrete choice experiment (DCE) survey. Interviews were analyzed using thematic analysis to identify salient attributes for CRC screening tests. These attributes informed the design of the DCE survey. The DCE data were analyzed using mixed logit and mixed-mixed multinomial logit models. RESULTS: Qualitative findings from 30 participants revealed that participants preferred blood-based tests due to their perceived low risk, minimal pain, and ease of sample collection. However, concerns about the test's lower accuracy were also expressed. The DCE survey was completed by 1189 participants. In the mixed logit model, participants demonstrated a stronger preference for blood-based tests over a 2-day stool-based test. The mixed-mixed multinomial logit model identified 2 classes, strong supporters and weak supporters, for CRC screening. Weak supporters, but not strong supporters, had a higher preference for blood-based tests. Women, ethnic Chinese, and people aged 40 to 60 years were more likely to be weak supporters. Both models highlighted the high influence of cost and test sensitivity on participants' preferences. Transitioning from a 2-day stool-based test to a blood-based test, assuming a national screening program at a base price of Singapore $5 (US $3.75), was estimated to have the potential to increase the relative uptake by 5.9% (95% CI 3.6%-8.2%). CONCLUSIONS: These findings contribute to our understanding of CRC screening preferences and provide insights into the factors driving test uptake. This study highlights the perceived advantages of blood-based tests and identifies areas of concern regarding their accuracy. Further research is needed to determine the actual increase in uptake rate when blood-based tests are made available.

What is said about #donateliver or #liverdonor? Reflexive thematic analysis of Twitter (X) posts from 2012 to 2022.

BACKGROUND: There is sustained interest in understanding the perspectives of liver transplant recipients and living donors, with several qualitative studies shedding light on this emotionally charged subject. However, these studies have relied primarily on traditional semi-structured interviews, which, while valuable, come with inherent limitations. Consequently, there remains a gap in our comprehension of the broader public discourse surrounding living liver donation. This study aims to bridge this gap by delving into public conversations related to living liver donation through a qualitative analysis of Twitter (now X) posts, offering a fresh perspective on this critical issue. METHODS: To compile a comprehensive dataset, we extracted original tweets containing the hashtags "#donateliver" OR "#liverdonor", all posted in English from January 1, 2012, to December 31, 2022. We then selected tweets from individual users whose Twitter (X) accounts featured authentic human names, ensuring the credibility of our data. Employing Braun and Clarke's reflexive thematic analysis approach, the study investigators read and analysed the included tweets, identifying two main themes and six subthemes. The Health Policy Triangle framework was applied to understand the roles of different stakeholders involved in the discourse and suggest areas for policy improvement. RESULTS: A total of 361 unique tweets from individual users were analysed. The major theme that emerged was the persistent shortage of liver donors, underscoring the desperation faced by individuals in need of life-saving liver transplants and the urgency of addressing the organ shortage problem. The second theme delved into the experiences of liver donors post-surgery, shedding light on a variety of aspects related to the transplantation process, including the visibility of surgical scars, and the significance of returning to physical activity and exercise post-surgery. CONCLUSION: The multifaceted experiences of individuals involved in the transplantation process, both recipients and donors, should be further studied in our efforts to improve the critical shortage of liver donors.

Comparative policy analysis of national rare disease funding policies in Australia, Singapore, South Korea, the United Kingdom and the United States: a scoping review.

BACKGROUND: Rare diseases pose immense challenges for healthcare systems due to their low prevalence, associated disabilities, and attendant treatment costs. Advancements in gene therapy, such as treatments for Spinal Muscular Atrophy (SMA), have introduced novel therapeutic options, but the high costs, exemplified by Zolgensma® at US$2.1 million, present significant financial barriers. This scoping review aimed to compare the funding approaches for rare disease treatments across high-performing health systems in Australia, Singapore, South Korea, the United Kingdom (UK), and the United States (US), aiming to identify best practices and areas for future research. METHODS: In accordance with the PRISMA-ScR guidelines and the methodological framework by Arksey and O'Malley and ensuing recommendations, a comprehensive search of electronic databases (Medline, EMBASE, and Cochrane) and grey literature from health department websites and leading national organizations dedicated to rare diseases in these countries was conducted. Countries selected for comparison were high-income countries with advanced economies and high-performing health systems: Australia, Singapore, South Korea, the UK, and the US. The inclusion criteria focused on studies detailing drug approval processes, reimbursement decisions and funding mechanisms, and published from 2010 to 2024. RESULTS: Based on a thorough review of 18 published papers and grey literature, various strategies are employed by countries to balance budgetary constraints and access to rare disease treatments. Australia utilizes the Life Saving Drugs Program and risk-sharing agreements. Singapore depends on the Rare Disease Fund, which matches public donations. South Korea's National Health Insurance Service covers specific orphan drugs through risk-sharing agreements. The UK relies on the National Institute for Health and Care Excellence (NICE) to evaluate treatments for cost-effectiveness, supported by the Innovative Medicines Fund. In the US, a combination of federal and state programs, private insurance and non-profit support is used. CONCLUSION: Outcome-based risk-sharing agreements present a practical solution for managing the financial strain of costly treatments. These agreements tie payment to actual treatment efficacy, thereby distributing financial risk and promoting ongoing data collection. Countries should consider adopting and expanding these agreements to balance immediate expenses with long-term benefits, ultimately ensuring equitable access to crucial treatments for patients afflicted by rare diseases.

A Systematic Review of the Reliability and Validity of the Patient Activation Measure Tool.

Patient activation, broadly defined as the ability of individuals to manage their health and navigate the healthcare system effectively, is crucial for achieving positive health outcomes. The Patient Activation Measure (PAM), a popularly used tool, was developed to assess this vital component of health care. This review is the first to systematically examine the validity of the PAM, as well as study its reliability, factor structure, and validity across various populations. Following the PRISMA and COSMIN guidelines, a search was conducted in MEDLINE, EMBASE, and Cochrane Library, from inception to 1 October 2023, using combinations of keywords related to patient activation and the PAM. The inclusion criteria were original quantitative or mixed methods studies focusing on PAM-13 or its translated versions and containing data on psychometric properties. Out of 3007 abstracts retrieved, 39 studies were included in the final review. The PAM has been extensively studied across diverse populations and geographical regions, including the United States, Europe, Asia, and Australia. Most studies looked at populations with chronic conditions. Only two studies applied the PAM to community-dwelling individuals and found support for its use. Studies predominantly showed a high internal consistency (Cronbach's alpha > 0.80) for the PAM. Most studies supported a unidimensional construct of patient activation, although cultural differences influenced the factor structure in some cases. Construct validity was established through correlations with health behaviors and outcomes. Despite its strengths, there is a need for further research, particularly in exploring content validity and differential item functioning. Expanding the PAM's application to more diverse demographic groups and community-dwelling individuals could enhance our understanding of patient activation and its impact on health outcomes.

Hype or hope? Ketamine for the treatment of depression: results from the application of deep learning to Twitter posts from 2010 to 2023.

Objective: To investigate societal perceptions of ketamine's use in depression therapy by analysing Twitter posts from January 1, 2010 to April 1, 2023. Methods: Using Twitter as the social media platform of choice, and employing search terms based on (depression OR depressed OR depressive) AND (ketamine OR esketamine OR Spravato), we collected English-language tweets from January 1, 2010, to April 1, 2023. Using unsupervised machine learning and natural language processing (NLP) techniques, including Bidirectional Encoder Representations from Transformers (BERT) and BERTopic, the study identified prevalent topics surrounding public chatter around the use of ketamine in depression treatment. Manual thematic analyses further refined these topics into themes. Results: Out of an initial dataset of 99,405 tweets, after removing duplicate tweets, re-tweets and tweets posted by organizations over Twitter, 18,899 unique tweets from presumably individual users were analysed. Analysis of temporal trends revealed a shift in public attitudes, particularly after the United States Food and Drug Administration (FDA)'s 2019 approval of ketamine for depression. Three major themes emerged: a changing regulatory landscape, cautious optimism, and personal experiences with the drug. There was an initial spike in discussions post-FDA approval in 2019. Thereafter, cautious optimism (Theme 2) decreased among the general public, with more personal accounts (Theme 3) highlighting the potential benefits for some treatment-resistant patients. Limitations of the study include Twitter's inherent biases towards younger, English-speaking demographics. Conclusion: In summary, the public's multifaceted perception leans towards a hopeful stance on ketamine's therapeutic potential for depression.

Intraoperative adverse events among surgeons in Singapore: a multicentre cross-sectional study on impact and support.

BACKGROUND: It is known that many surgeons encounter intraoperative adverse events which can result in Second Victim Syndrome (SVS), with significant detriment to their emotional and physical health. There is, however, a paucity of Asian studies in this space. The present study thus aimed to explore the degree to which the experience of an adverse event is common among surgeons in Singapore, as well as its impact, and factors affecting their responses and perceived support systems. METHODS: A self-administered survey was sent to surgeons at four large tertiary hospitals. The 42-item questionnaire used a systematic closed and open approach, to assess: Personal experience with intraoperative adverse events, emotional, psychological and physical impact of these events and perceived support systems. RESULTS: The response rate was 57.5% (n = 196). Most respondents were male (54.8%), between 35 and 44 years old, and holding the senior consultant position. In the past 12 months alone, 68.9% recalled an adverse event. The emotional impact was significant, including sadness (63.1%), guilt (53.1%) and anxiety (45.4%). Speaking to colleagues was the most helpful support source (66.7%) and almost all surgeons did not receive counselling (93.3%), with the majority deeming it unnecessary (72.2%). Notably, 68.1% of the surgeons had positive takeaways, gaining new insight and improving vigilance towards errors. Both gender and surgeon experience did not affect the likelihood of errors and emotional impact, but more experienced surgeons were less likely to have positive takeaways (p = 0.035). Individuals may become advocates for patient safety, while simultaneously championing the cause of psychological support for others. CONCLUSIONS: Intraoperative adverse events are prevalent and its emotional impact is significant, regardless of the surgeon's experience or gender. While colleagues and peer discussions are a pillar of support, healthcare institutions should do more to address the impact and ensuing consequences.

On Orthorexia Nervosa: A Systematic Review of Reviews.

INTRODUCTION: Orthorexia nervosa (ON), characterized by a pathological preoccupation with "extreme dietary purity," is increasingly observed as a mental health condition among young adults and the general population. However, its diagnosis is not formally recognized and has remained contentious. OBJECTIVE: In this systematic review, we attempt to overview previous reviews on ON, focusing on the methodological and conceptual issues with ON. This would serve both as a summary and a way to highlight gaps in earlier research. METHODS: This systematic review took reference from the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines, and using combinations of the search terms ("orthorexia" OR "orthorexia nervosa" OR "ON") AND ("review" OR "systematic review" OR "meta-analysis"), a literature search was performed on EMBASE, Medline and PsycINFO databases from inception up to October 31, 2023. Articles were included if (1) they were written or translated into English and (2) contained information pertaining to the diagnostic stability or validity of ON, or instruments used to measure ON symptoms and behaviors. Only review articles with a systematic literature search approach were included. RESULTS: A total of 22 reviews were qualitatively reviewed. Several studies have reported variable prevalence of ON and highlighted the lack of thoroughly evaluated measures of ON with clear psychometric properties, with no reliable estimates. ORTO-15 and its variations such as ORTO-11, ORTO-12 are popularly used, although their use is discouraged. Existing instruments lack specificity for pathology and several disagreements on the conceptualization and hence diagnostic criteria of ON exist. DISCUSSION: Previous reviews have consistently highlighted the highly variable (and contradictory) prevalence rates with different instruments to measure ON, lack of stable factor structure and psychometrics across ON measures, paucity of data on ON in clinical samples, and a need for a modern re-conceptualization of ON. The diagnosis of ON is challenging as it likely spans a spectrum from "normal" to "abnormal," and "functional" to "dysfunctional." "Non-pathological" orthorexia is not related to psychopathological constructs in the same way that ON is.

Cost-of-illness studies of inherited retinal diseases: a systematic review.

BACKGROUND: While health care and societal costs are routinely modelled for most diseases, there is a paucity of comprehensive data and cost-of-illness (COI) studies for inherited retinal diseases (IRDs). This lack of data can lead to underfunding or misallocation of resources. A comprehensive understanding of the COI of IRDs would assist governmental and healthcare leaders in determining optimal resource allocation, prioritizing funding for research, treatment, and support services for these patients. METHODS: Following PRISMA guidelines, a literature search was conducted using Medline, EMBASE and Cochrane databases, from database inception up to 30 Jun 2023, to identify COI studies related to IRD. Original studies in English, primarily including patients with IRDs, and whose main study objective was the estimation of the costs of IRDs and had sufficiently detailed methodology to assess study quality were eligible for inclusion. To enable comparison across countries and studies, all annual costs were standardized to US dollars, adjusted for inflation to reflect their current value and recalculated on a "per patient" basis wherever possible. The review protocol was registered in PROSPERO (registration number CRD42023452986). RESULTS: A total of nine studies were included in the final stage of systematic review and they consistently demonstrated a significant disease burden associated with IRDs. In Singapore, the mean total cost per patient was roughly US$6926/year. In Japan, the mean total cost per patient was US$20,833/year. In the UK, the mean total cost per patient with IRD ranged from US$21,658 to US$36,549/year. In contrast, in the US, the mean total per-patient costs for IRDs ranged from about US$33,017 to US$186,051 per year. In Canada, these mean total per-patient costs varied between US$16,470 and US$275,045/year. Non-health costs constituted the overwhelming majority of costs as compared to healthcare costs; 87-98% of the total costs were due to non-health costs, which could be attributed to diminished quality of life, poverty, and increased informal caregiving needs for affected individuals. CONCLUSION: IRDs impose a disproportionate societal burden outside health systems. It is vital for continued funding into IRD research, and governments should incorporate societal costs in the evaluation of cost-effectiveness for forthcoming IRD interventions, including genomic testing and targeted therapies.

Examining the Association between Coffee Intake and the Risk of Developing Irritable Bowel Syndrome: A Systematic Review and Meta-Analysis.

Irritable bowel syndrome (IBS) is a highly prevalent disorder of brain-gut interaction with a significant impact on quality of life. Coffee is a widely consumed beverage with numerous bioactive compounds that have potential effects on human health and disease states. Current studies on the effect of regular coffee consumption on the risk of developing IBS symptoms have yielded conflicting results. This systematic review and meta-analysis aimed to determine whether coffee intake is associated with developing IBS. A systematic literature search was performed in three electronic databases, namely PubMed, EMBASE, and The Cochrane Library, from inception until 31 March 2023. All original studies reporting associations between coffee intake and IBS were considered for inclusion. Odds ratios (ORs) were calculated for each study, and estimates were pooled, and where appropriate, 95% confidence intervals (95% CI) and p-values were calculated. Eight studies comprising 432,022 patients were included in the final meta-analysis. Using a fixed-effects model, coffee drinkers (any intake) had a reduced likelihood of developing IBS compared to controls, with a pooled OR of 0.84 (95% CI: 0.80 to 0.84). Sensitivity analysis confirmed the stability of the estimates. Future research should prioritise prospective cohort studies that are robust and closely track the development of incident IBS in previously healthy individuals.

Examining Public Messaging on Influenza Vaccine over Social Media: Unsupervised Deep Learning of 235,261 Twitter Posts from 2017 to 2023.

Although influenza vaccines are safe and efficacious, vaccination rates have remained low globally. Today, with the advent of new media, many individuals turn to social media for personal health questions and information. However, misinformation may be rife, and health communications may be suboptimal. This study, therefore, aimed to investigate the public messaging related to influenza vaccines by organizations over Twitter, which may have a far-reaching influence. The theoretical framework of the COM-B (capacity, opportunity, and motivation component of behavior) model was used to interpret the findings to aid the design of messaging strategies. Employing search terms such as "flu jab", "flu vaccine", "influenza vaccine", and '" influenza jab", tweets posted in English and by organizations from 1 January 2017 to 1 March 2023 were extracted and analyzed. Using topic modeling, a total of 235,261 tweets by organizations over Twitter were grouped into four main topics: publicizing campaigns to encourage influenza vaccination, public education on the safety of influenza vaccine during pregnancy, public education on the appropriate age to receive influenza vaccine, and public education on the importance of influenza vaccine during pregnancy. Although there were no glaring pieces of misinformation or misconceptions, the current public messaging covered a rather limited scope. Further information could be provided about influenza and the benefits of vaccination (capability), promoting community, pharmacist-led influenza vaccination, and other avenues (opportunity), and providing greater incentivization and support for vaccination (motivation).

COVID-19 and the shifting organisation of sex work markets in Singapore.

While past studies have sought to capture how the COVID-19 pandemic has impacted on the health and sexual lives of sex workers internationally, less attention has been paid to the reorganisation of sex markets as a result of COVID-19. We conducted a sequential exploratory mixed methods study using in-depth interviews, cyber ethnography and surveyor-administered structured surveys among sex workers. We report two key findings on how the pandemic has impacted sex markets in Singapore. First, the organisation of sex markets shifted as a result of lockdown and associated movement control measures. This shift was characterised by the out-migration of sex workers, the reduction in supply and demand for in-person sex work, and a shift towards online spaces. Second, we found that sex workers experienced greater economic hardship as a result of such changes. Given the potential shifts in sex markets as a result of the pandemic, we adopt a World Health Organisation Health Workplace Framework and Model to identify interventions to improve the occupational safety and health of sex workers in a post-COVID-19 era.

The Impact of the Coronavirus Disease (COVID-19) on the Health and Social Needs of Sex Workers in Singapore.

We evaluated the impact of the coronavirus disease (COVID-19) on the sex work industry and assessed how it has impacted the health and social conditions of sex workers in Singapore. We conducted a sequential exploratory mixed methods study amidst the COVID-19 pandemic from April to October 2020, including in-depth interviews with 24 stakeholders from the sex work industry and surveyor-administered structured surveys with 171 sex workers. COVID-19 had a substantial impact on sex workers' income. The illegality of sex work, stigma, and the lack of work documentation were cited as exclusionary factors for access to alternative jobs or government relief. Sex workers had experienced an increase in food insecurity (57.3%), housing insecurity (32.8%), and sexual compromise (8.2%), as well as a decrease in access to medical services (16.4%). Being transgender female was positively associated with increased food insecurity (aPR = 1.23, 95% CI [1.08, 1.41]), housing insecurity (aPR = 1.28, 95% CI [1.03, 1.60]), and decreased access to medical services (aPR = 1.74, 95% CI [1.23, 2.46]); being a venue-based sex worker was positively associated with increased food insecurity (aPR = 1.46, 95% CI [1.00, 2.13]), and being a non-Singaporean citizen or permanent resident was positively associated with increased housing insecurity (aPR = 2.59, 95% CI [1.73, 3.85]). Our findings suggest that COVID-19 has led to a loss of income for sex workers, greater food and housing insecurity, increased sexual compromise, and reduced access to medical services for sex workers. A lack of access to government relief among sex workers exacerbated such conditions. Efforts to address such population health inequities should be implemented.

Association between sexual orientation acceptance and suicidal ideation, substance use, and internalised homophobia amongst the pink carpet Y cohort study of young gay, bisexual, and queer men in Singapore.

BACKGROUND: Gay, bisexual and queer (GBQ) men are frequently subjected to minority stressors that have negative impacts on their health. Milestones that include the acceptance and disclosure of sexual identity amongst GBQ men are hence key instruments in understanding the prevalence of internalised homophobia and predicting health outcomes. As such, this work takes a novel approach to deduce the correlates of delayed acceptance of sexual orientation in young GBQ men as a measure of internalised homophobia through retrospective self-reporting and age-based analysis. METHODS: Participants were recruited as part of a cohort study exploring the syndemic risks associated with HIV acquisition among young GBQ men in Singapore. We examined their levels of internalised, perceived, experienced homophobia, as well as their health behaviours and suicidal tendencies. Two separate variables were also self-reported by the participants - the age of questioning of sexual orientation and the age of acceptance of sexual orientation. We subsequently recoded a new variable, delayed acceptance of sexual orientation, by taking the difference between these two variables, regressing it as an independent and dependent variable to deduce its psychosocial correlates, as well as its association with other measured instruments of health. RESULTS: As a dependent variable, delayed acceptance of sexual orientation is positively associated with an increase of age and internalised homophobia, while being negatively associated with reporting as being gay, compared to being bisexual or queer. As an independent variable, delayed acceptance of sexual orientation was associated with a delayed age of coming out to siblings and parents, suicide ideation, historical use of substances including smoking tobacco cigarettes and consuming marijuana, as well as reporting higher levels of experienced, internalised and perceived homophobia. CONCLUSION: Greater levels of early intervention and efforts are required to reduce the heightened experience of minority stress resulting from communal and institutional hostilities. Areas of improvement may include community-based counselling and psychological support for GBQ men, while not forsaking greater education of the social and healthcare sectors. Most importantly, disrupting the stigma narrative of a GBQ 'lifestyle' is paramount in establishing an accepting social environment that reduces the health disparity faced by GBQ men.