Factors Affecting Patient and Caregiver Preferences for Treatment of Myeloma and Indolent Lymphoma.

PURPOSE: Treatment options for myeloma and indolent lymphoma are increasing exponentially, with distinct efficacy, side effects, and cost. We aim to determine the factors influencing patient and caregiver treatment preferences. METHODS: Patients and caregivers of patients with myeloma and indolent lymphoma were recruited from two cancer centers in Singapore. Preferences were elicited using a discrete choice experiment. Attributes and levels were selected based on a previous qualitative study. The relative preference for levels within each attribute (part worth utility values) and the extent to which an attribute would influence decision making (relative importance) were calculated. Patient and caregiver participation in the treatment plan selection process were assessed using the Control Preference Scale. RESULTS: One hundred ninety-nine patients and 169 caregivers were recruited. Patients placed the highest importance on out-of-pocket costs (relative importance = 35%), followed by efficacy (25%), persistent side effects (19%), administration route (8%), treatment duration (7%), and short-term side effects (5%). Caregivers ranked efficacy (27%) as the most important attribute, over out-of-pocket costs (24%). Most patients preferred a collaborative role in the shared decision-making process, while similar proportions of caregivers favored active and collaborative roles. CONCLUSION: Our study demonstrates that both patients and caregivers consider cost seriously when making treatment decisions. Furthermore, as patient and caregiver preferences may differ, there are implications for treatment selection and counseling, especially in cultures where caregivers have more prominent roles in treatment planning.

Cost-effectiveness of transcatheter aortic valve implantation in patients with severe symptomatic aortic stenosis of intermediate surgical risk in Singapore.

OBJECTIVE: The objective was to assess the cost-effectiveness of transcatheter aortic valve implantation (TAVI) in patients with severe aortic stenosis with intermediate surgical risk in Singapore. METHODS: A de novo Markov model with three health states - stroke with long-term sequelae, no stroke, and death - was developed and simulated using Monte Carlo simulations with 10,000 iterations over a five-year time horizon from the Singapore healthcare system perspective. A 3% annual discount rate for costs and outcomes and monthly cycle lengths were used. By applying the longest available published clinical evidence, simulated patients received either TAVI or surgical aortic valve replacement (SAVR) and were at risk of adverse events (AEs) such as moderate-to-severe paravalvular aortic regurgitation (PAR). RESULTS: When five-year PARTNER 2A data was applied, base-case analyses showed that the incremental cost-effectiveness ratio (ICER) for TAVI compared to SAVR was US$315,760 per quality-adjusted life year (QALY) gained. The high ICER was due to high incremental implantation and procedure costs of TAVI compared to SAVR, and marginal improvement of 0.10 QALYs as simulated mortality of TAVI exceeded SAVR at 3.75 years post-implantation. One-way sensitivity analysis showed that the ICERs were most sensitive to cost of PAR, utility values of SAVR patients, and cost of TAVI and SAVR implants and procedures. When disutilities for AEs were additionally applied, the ICER decreased to US$300,070 per QALY gained. TAVI was dominated by SAVR when the time horizon increased to 20 years. Clinical outcomes projected from one-year PARTNER S3i data further reduced the ICER to US$86,337 per QALY gained for TAVI, assuming early all-cause mortality benefits from TAVI continued to persist. This assumption was undermined when longer term data showed that TAVI's early mortality benefits diminished at five years. LIMITATIONS AND CONCLUSION: TAVI is unlikely to be cost-effective in intermediate surgical-risk patients compared to SAVR in Singapore.

The interplay between PCOS pathology and diet on gut microbiota in a mouse model.

The gut microbiome has been implicated in polycystic ovary syndrome (PCOS) pathophysiology. PCOS is a disorder with reproductive, endocrine and metabolic irregularities, and several studies report that PCOS is associated with a decrease in microbial diversity and composition. Diet is an important regulator of the gut microbiome, as alterations in macronutrient composition impact the balance of gut microbial communities. This study investigated the interplay between macronutrient balance and PCOS on the gut microbiome of control and dihydrotestosterone (DHT)-induced PCOS-like mice exposed to diets that varied in protein (P), carbohydrate (C) and fat (F) content. The amount of dietary P, C and F consumed significantly altered alpha (α) and beta (ß) diversity of the gut microbiota of control and PCOS-like mice. However, α-diversity between control and PCOS-like mice on the same diet did not differ significantly. In contrast, ß-diversity was significantly altered by PCOS pathology. Further analysis identified an operational taxonomic unit (OTU) within Bacteroides (OTU3) with 99.2% similarity to Bacteroides acidifaciens, which is inversely associated with obesity, to be significantly decreased in PCOS-like mice. Additionally, this study investigated the role of the gut microbiome in the development of PCOS traits, whereby PCOS-like mice were transplanted with healthy fecal microbiota from control mice. Although the PCOS gut microbiome shifted toward that of control mice, PCOS traits were not ameliorated. Overall, these findings demonstrate that while diet exerts a stronger influence over gut microbiota diversity than PCOS pathology, overall gut microbiota composition is affected by PCOS pathology.

A system dynamics approach to pollution remediation and mitigation based on increasing the share of renewable resources.

This study explores the role of renewable energy (RE) penetration in Malaysia's energy security (ES) and its implications for the country's target of 20% capacity in the energy mix by 2025. Renewable energy (RE) is a critical driver of long-term energy security. In 2018, the share of renewable energy in Malaysia's energy mix was 9%, falling far short of the national target of 20% penetration by 2025. This study employs a system dynamics approach to investigate the relationship between RE penetration and correlated indicators from energy security (ES) dimensions: energy availability, environmental sustainability, and socio-economics. The causal relationships between the three-dimensional indicators of ES have been established using causal and stock and flow logic. Simulated results show that energy consumption has increased sharply, while energy efficiency and economic growth have only increased by a small margin with an increase in RE from 2015 to 2020. The energy intensity is expected to rise slightly by the end of the fifth year. As a result, the overall impact is positive for Malaysia's environmental sustainability while reducing its reliance on energy imports and meeting national economic growth demands.

Cost-effectiveness of daratumumab in combination with lenalidomide and dexamethasone for relapsed and/or refractory multiple myeloma.

OBJECTIVE: This study evaluates the cost-effectiveness of daratumumab (D) in combination with lenalidomide and dexamethasone (Rd) for treatment of relapsed and/or refractory multiple myeloma in patients who have received at least one prior therapy in Singapore. METHODS: A 3-state partitioned survival model was developed to evaluate the cost-effectiveness of lenalidomide and dexamethasone with or without daratumumab from a healthcare system perspective over 10 years. Clinical inputs were obtained from the POLLUX trial. Health state utilities were derived from the literature and direct medical costs obtained from public healthcare institutions. Sensitivity and scenario analyses were conducted to explore uncertainties. RESULTS: DRd was associated with a high base-case incremental cost-effectiveness ratio (ICER) of US$576,247 per quality-adjusted life year (QALY) gained, compared with Rd. According to one-way sensitivity analysis, ICER was most heavily influenced by time horizon, discount rate for outcomes, progression-free utility and cost of daratumumab. Regardless of the variation, DRd remained not cost-effective. Even when the cost of both daratumumab and lenalidomide dropped by 20% and 80%, the ICERs remained high at US$470,400 and US$152,860 per QALY gained. CONCLUSIONS: At current prices, the addition of daratumumab to lenalidomide and dexamethasone does not represent cost-effective use of healthcare resources in Singapore.

Fluorescence "turn-off/turn-on" biosensing of metal ions by gold nanoclusters, folic acid and reduced graphene oxide.

Metal ions homeostasis plays an important role in biological processes. The ability to detect the concentration of metal ions in biological fluids is often challenged by the obvious interference or competitive binding nature of other alkaline metals ions. Common analytical techniques employed for metal ions detection are electrochemical, fluorescence and colorimetric methods. However, most reported metal ions sensors are complicated, time-consuming and involve costly procedures with limited effectiveness. Herein, a nanobiosensor for detecting sodium and potassium ions using folic acid-functionalised reduced graphene oxide-modified RNase A gold nanoclusters (FA-rGO-RNase A/AuNCs) based on fluorescence "turn-off/turn-on" is presented. Firstly, a facile and optimised protocol for the fabrication of RNase A/AuNCs is developed. The activity of RNase A protein after the formation of RNase A/AuNCs is studied. RNase A/AuNCs is then loaded onto FA-rGO, in which FA-rGO is used as a potential carrier and fluorescence quencher for RNase A/AuNCs. Finally, a fluorescence "turn-on" sensing strategy is developed using the as-synthesised FA-rGO-RNase A/AuNCs to detect sodium and potassium ions. The developed nanobiosensor revealed an excellent sensing performance and meets the sensitivity required to detect both sodium and potassium ions. To the best of our knowledge, this is the first work done on determining the RNase A protein activity in RNase A/AuNCs and exploring the potential application of RNase A/AuNCs as a metal ion sensor. This work serves as a proof-of-concept for combining the potential of drug delivery, active targeting and therapy on cancer cells, as well as biosensing of metal ions into a single platform.

Cost-effectiveness Analysis of Breast Cancer Screening Using Mammography in Singapore: A Modeling Study.

BACKGROUND: Limited research is available on the cost-effectiveness of breast cancer screening programs in Asian countries. We evaluated the cost-effectiveness of Singapore's national mammography screening program, implemented in 2002, recommending annual screening between ages 40 and 49 and biennial screening between ages 50 and 69, and alternative screening scenarios taking into account important country-specific factors. METHODS: We used national data from Singapore in the MIcrosimulation SCreening ANalysis-Fatal diameter (MISCAN-Fadia) model to simulate 302 screening scenarios for 10 million women born between 1910 and 1969. Screening scenarios varied by starting and ending age, screening interval, and attendance. Outcome measures included life-years gained (LYG), breast cancer deaths averted, false positives, overdiagnosis, quality-adjusted life years (QALY), costs (in 2002 Singapore dollars; S$), and incremental cost-effectiveness ratios (ICER). Costs and effects were calculated and discounted with 3% using a health care provider's perspective. RESULTS: Singapore's current screening program at observed attendance levels required 54,158 mammograms per 100,000 women, yielded 1,054 LYG, and averted 57 breast cancer deaths. At attendance rates ≥50%, the current program was near the efficiency frontier. Most scenarios on the efficiency frontier started screening at age 40. The ICERs of the scenarios on the efficiency frontiers ranged between S$10,186 and S$56,306/QALY, which is considered cost-effective at a willingness-to-pay threshold of S$70,000/QALY gained. CONCLUSIONS: Singapore's current screening program lies near the efficiency frontier, and starting screening at age 40 or 45 is cost-effective. Furthermore, enhancing screening attendance rates would increase benefits while maintaining cost-effectiveness. IMPACT: Screening all women at age 40 or 45 is cost-efficient in Singapore, and a policy change may be considered.

Integrating gold nanoclusters, folic acid and reduced graphene oxide for nanosensing of glutathione based on "turn-off" fluorescence.

Glutathione (GSH) is a useful biomarker in the development, diagnosis and treatment of cancer. However, most of the reported GSH biosensors are expensive, time-consuming and often require complex sample treatment, which limit its biological applications. Herein, a nanobiosensor for the detection of GSH using folic acid-functionalized reduced graphene oxide-modified BSA gold nanoclusters (FA-rGO-BSA/AuNCs) based on the fluorescence quenching interactions is presented. Firstly, a facile and optimized protocol for the fabrication of BSA/AuNCs is developed. Functionalization of rGO with folic acid is performed using EDC/NHS cross-linking reagents, and their interaction after loading with BSA/AuNCs is demonstrated. The formation of FA-rGO, BSA/AuNCs and FA-rGO-BSA/AuNCs are confirmed by the state-of-art characterization techniques. Finally, a fluorescence turn-off sensing strategy is developed using the as-synthesized FA-rGO-BSA/AuNCs for the detection of GSH. The nanobiosensor revealed an excellent sensing performance for the detection of GSH with high sensitivity and desirable selectivity over other potential interfering species. The fluorescence quenching is linearly proportional to the concentration of GSH between 0 and 1.75 µM, with a limit of detection of 0.1 µM under the physiological pH conditions (pH 7.4). Such a sensitive nanobiosensor paves the way to fabricate a "turn-on" or "turn-off" fluorescent sensor for important biomarkers in cancer cells, presenting potential nanotheranostic applications in biological detection and clinical diagnosis.

Patient preferences and predicted relative uptake for targeted therapies in metastatic colorectal cancer: a discrete choice experiment.

OBJECTIVE: Ras wild-type metastatic colorectal cancers (mCRC) may be treated with anti-vascular endothelial growth factor (VEGF) or anti-epidermal growth factor receptor (EGFR) agents. We aim to estimate patients' preferences for mCRC treatment and relative importance of cost, efficacy improvement, avoidance of side effects and therapy convenience, and relative uptake between profiles that resemble Bevacizumab (anti-VEGF) and Cetuximab (anti-EGFR), two commonly prescribed mCRC targeted therapies. METHODS: Discrete choice experiment (DCE) was administered to English- or Chinese-speaking Stage 2 or 3 colon cancer patients at the National Cancer Centre Singapore. DCE attributes comprise progression-free survival (PFS), severity of acne-like skin rashes, severity of bleeding, out-of-pocket cost per month and frequency of drug administration. Mixed logit model was used to calculate preference weights for all attribute levels. Subgroup analyses were conducted by interacting attribute levels with selected respondent characteristics. Relative uptake rates for various medication scenarios were studied. RESULTS: 169 respondents aged 61.5 ± 10.5 years completed the survey. They placed the greatest weight on cost, followed by bleeding and skin rashes, then PFS and finally frequency of drug administration. This was similarly observed in the subgroup analyses. A scenario with shorter PFS but less severe side effects has a slightly higher relative uptake at 55%. One quarter of respondents reported that they would not take the treatment they preferred in the choice task. CONCLUSION: Patients were willing to trade off some degree of efficacy to avoid certain severity of side effects. It is therefore crucial for patients and physicians to discuss patients' preferences and circumstances to understand which attributes are more important, as well as patients' views on the trade-offs between treatment benefits and risks.

Measuring preferences for CYP2C19 genotyping in patients with acute coronary syndrome - a discrete choice experiment.

Aim: To evaluate the relative importance of CYP2C19 genotype-guided treatment attributes to patients. Patients & methods: A discrete choice experiment questionnaire was administered to 63 patients with acute coronary syndrome. Attributes examined in the discrete choice experiment questionnaire were: cost of genetic testing (S$50, S$100, S$200); cost of antiplatelet medication (S$100, S$500, S$1000); heart attack or stroke risk (5 in 100, 15 in 100, 25 in 100); bleeding risk (5 in 100, 15 in 100, 25 in 100); doctor's recommendation (yes, neutral). Mixed logit model was used for analysis. Results & conclusion: All attributes were important in patients' decision-making. Most displayed strong preference for doctor's recommendation and reduced heart attack or stroke risk. Genotyping was chosen by 63.5% of the patients.

Perspective on CYP2C19 genotyping test among patients with acute coronary syndrome - a qualitative study.

Aim: Identify factors patients consider regarding CYP2C19 genotyping test to guide choice of antiplatelet therapy. Patients & methods: Patient's perception and attitude toward use of CYP2C19 genotyping test was gathered according to an interview guide. Thematic analysis was conducted. Results: A total of 14 patients were interviewed. The main factors found to influence uptake of CYP2C19 genotyping test are, convenience of genotyping test (n = 4), physician's recommendation (n = 11), prior explanation of genetic testing by medical personnel (n = 5) and inclination toward clopidogrel, with three sub-factors; less frequent dosing (n = 3), lower cost (n = 7) and lower risk of bleeding (n = 9). Conclusion: This study provided the information needed to develop a discrete choice experiment to empirically quantify patients' preference and willingness to pay for genetic testing and to simulate uptake.

Nanomaterials for Nanotheranostics: Tuning Their Properties According to Disease Needs.

Nanotheranostics is one of the biggest scientific breakthroughs in nanomedicine. Most of the currently available diagnosis and therapies are invasive, time-consuming, and associated with severe toxic side effects. Nanotheranostics, on the other hand, has the potential to bridge this gap by harnessing the capabilities of nanotechnology and nanomaterials for combined therapeutics and diagnostics with markedly enhanced efficacy. However, nanomaterial applications in nanotheranostics are still in its infancy. This is due to the fact that each disease has a particular microenvironment with well-defined characteristics, which promotes deeper selection criteria of nanomaterials to meet the disease needs. In this review, we have outlined how nanomaterials are designed and tailored for nanotheranostics of cancer and other diseases such as neurodegenerative, autoimmune (particularly on rheumatoid arthritis), and cardiovascular diseases. The penetrability and retention of a nanomaterial in the biological system, the therapeutic strategy used, and the imaging mode selected are some of the aspects discussed for each disease. The specific properties of the nanomaterials in terms of feasibility, physicochemical challenges, progress in clinical trials, its toxicity, and their future application on translational medicine are addressed. Our review meticulously and critically examines the applications of nanotheranostics with various nanomaterials, including graphene, across several diseases, offering a broader perspective of this emerging field.

Performance of Single-Nucleotide Polymorphisms in Breast Cancer Risk Prediction Models: A Systematic Review and Meta-analysis.

BACKGROUND: SNP risk information can potentially improve the accuracy of breast cancer risk prediction. We aim to review and assess the performance of SNP-enhanced risk prediction models. METHODS: Studies that reported area under the ROC curve (AUC) and/or net reclassification improvement (NRI) for both traditional and SNP-enhanced risk models were identified. Meta-analyses were conducted to compare across all models and within similar baseline risk models. RESULTS: Twenty-six of 406 studies were included. Pooled estimate of AUC improvement is 0.044 [95% confidence interval (CI), 0.038-0.049] for all 38 models, while estimates by baseline models ranged from 0.033 (95% CI, 0.025-0.041) for BCRAT to 0.053 (95% CI, 0.018-0.087) for partial BCRAT. There was no observable trend between AUC improvement and number of SNPs. One study found that the NRI was significantly larger when only intermediate-risk women were included. Two other studies showed that majority of the risk reclassification occurred in intermediate-risk women. CONCLUSIONS: Addition of SNP risk information may be more beneficial for women with intermediate risk. IMPACT: Screening could be a two-step process where a questionnaire is first used to identify intermediate-risk individuals, followed by SNP testing for these women only.

Women's preferences, willingness-to-pay, and predicted uptake for single-nucleotide polymorphism gene testing to guide personalized breast cancer screening strategies: a discrete choice experiment.

BACKGROUND: Single-nucleotide polymorphism (SNP) gene test is a potential tool for improving the accuracy of breast cancer risk prediction. We seek to measure women's preferences and marginal willingness-to-pay (mWTP) for this new technology. MATERIALS AND METHODS: We administered a discrete choice experiment (DCE) to English-speaking Singaporean women aged 40-69 years without any history of breast cancer, enrolled via door-to-door recruitment with quota sampling by age and ethnicity. DCE attributes comprise: 1) sample type (buccal swab and dried blood spot), 2) person conducting pretest discussion (specialist doctor, non-specialist doctor, and nurse educator), 3) test location (private family clinic, public primary-care clinic, and hospital), and 4) out-of-pocket cost (S$50, S$175, and S$300). Mixed logit model was used to estimate the effect of attribute levels on women's preferences and mWTP. Interactions between significant attributes and respondent characteristics were investigated. Predicted uptake rates for various gene testing scenarios were studied. RESULTS: A total of 300 women aged 52.6±7.6 years completed the survey (100 Chinese, Malay, and Indian women, respectively). Sample type (P=0.046), person conducting pretest discussion, and out-of-pocket cost (P<0.001) are significantly associated with going for SNP gene testing. Women with higher income and education levels are more willing to pay higher prices for the test. Preferences in terms of mWTP across ethnic groups appear similar, but Chinese women have greater preference heterogeneity for the attributes. Predicted uptake for a feasible scenario consisting of buccal swab, pretest discussion with nurse educator at the hospital costing S$50 is 60.5%. Only 3.3% of women always opted out of the SNP gene test in real life. Reasons include high cost, poor awareness, and indifference toward test results. CONCLUSION: SNP gene testing may be tailored according to individual preferences to encourage uptake. Future research should focus on outcomes and cost-effectiveness of personalized breast cancer screening using SNP gene testing.

Patient preferences for types of community-based cardiac rehabilitation programme.

INTRODUCTION: Cardiac rehabilitation (CR) improves mortality, morbidity and quality of life of cardiovascular patients. However, its uptake is poor especially in the hospitals due to long travel distances and office hours constraints. Community-based CR is a possible solution. OBJECTIVES: To understand the type of community-based CR preferred and identify patient characteristics associated with certain programme combinations. METHODS: A cross-sectional survey was administered to a randomised list of patients at risk for or with cardiovascular diseases at two community-based CR centres. Participants were presented with nine hypothetical choice sets and asked to choose only one of the two alternative programme combinations in each choice set. Attributes include support group presence, cash incentives, upfront deposit and out-of-pocket cost. The counts for each combination were tallied and corrected for repeats. Chi-square test and logistic regression were performed to understand the characteristics associated with the preferred CR combination. RESULTS: After correcting for repeats, patients most (85.2%) prefer CR programmes with new group activities, support group, cash rewards, deposit and out-of-pocket cost, and few exercise equipment with physiotherapist presence without the need for monitoring equipment. Patients with more than three bedrooms in their house are less likely (OR 0.367; CI 0.17 to 0.80; P=0.011) to choose the choice with no physiotherapist and few equipment available. CONCLUSION: This is the first study to explore patients' preferences for different types of community CR. Higher income patients prefer physiotherapist presence and are willing to settle for less equipment. Our study serves as a guide for designing future community-based CR programmes.

A qualitative study on Singaporean women's views towards breast cancer screening and Single Nucleotide Polymorphisms (SNPs) gene testing to guide personalised screening strategies.

BACKGROUND: Breast cancer is the top cancer by incidence and mortality in Singaporean women. Mammography is by far its best screening tool, but current recommended age and interval may not yield the most benefit. Recent studies have demonstrated the potential of single nucleotide polymorphisms (SNPs) to improve discriminatory accuracy of breast cancer risk assessment models. This study was conducted to understand Singaporean women's views towards breast cancer screening and SNPs gene testing to guide personalised screening strategies. METHODS: Focus group discussions were conducted among English-speaking women (n = 27) between 40 to 65 years old, both current and lapsed mammogram users. Women were divided into four groups based on age and mammogram usage. Discussions about breast cancer and screening experience, as well as perception and attitude towards SNPs gene testing were conducted by an experienced moderator. Women were also asked for factors that will influence their uptake of the test. Transcripts were analysed using thematic analysis to captured similarities and differences in views expressed. RESULTS: Barriers to repeat mammogram attendance include laziness to make appointment and painful and uncomfortable screening process. However, the underlying reason may be low perceived susceptibility to breast cancer. Facilitators to repeat mammogram attendance include ease of making appointment and timely reminders. Women were generally receptive towards SNPs gene testing, but required information on accuracy, cost, invasiveness, and side effects before they decide whether to go for it. Other factors include waiting time for results and frequency interval. On average, women gave a rating of 7.5 (range 5 to 10) when asked how likely they will go for the test. CONCLUSION: Addressing concerns such as pain and discomfort during mammogram, providing timely reminders and debunking breast cancer myths can help to improve screening uptake. Women demonstrated a spectrum of responses towards a novel test like SNPs gene testing, but need more information to make an informed decision. Future public health education on predictive genetic testing should adequately address both benefits and risks. Findings from this study is used to inform a discrete choice experiment to empirically quantify women preferences and willingness-to-pay for SNPs gene testing.