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Background: Chronic kidney disease (CKD) poses a global health challenge with high morbidity and mortality rates. Early detection and prompt intervention are critical in preventing progression to end-stage kidney disease (ESKD) and cardiovascular complications. Effective CKD management requires comprehensive care packages that integrate both pharmacological and non-pharmacological interventions within collaborative, team-based models, aiming to enhance patient outcomes and overall quality of life. The goal of the Strategies for Kidney Outcomes Prevention and Evaluation (SKOPE) study is to establish effective multicomponent intervention (MCI) strategies for evaluating and preventing kidney outcomes in patients with moderate to advanced CKD within primary care settings in Singapore., Methods: This study is a 3-year randomized controlled trial among 896 participants aged between 40 and 80 years with moderate or advanced CKD in five government-subsidized polyclinics in Singapore. The components of the MCI are (1) nurses/service coordinators trained as health coaches for motivational conversation and CKD-specific lifestyle counseling on diet and exercise, using a hybrid follow-up approach of in-person, telephone, and secure video meetings; (2) training physicians in algorithm-based standardized management of CKD; (3) subsidy on SGLT2i medications for CKD; and (4) regular CKD case review meetings. The primary outcome is the estimated glomerular filtration rate (eGFR) total slope from randomization to final follow-up at 36 months., Discussion: If shown to be effective, cost-effective, and acceptable, SKOPE should be considered for scaling country-wide and in similar regional healthcare systems., Trial Registration: ClinicalTrials.gov NCT05295368. Registered on March 25, 2022., (© 2024. The Author(s).)

Background: The Diabetic Retinopathy Extended Screening Study (DRESS) aims to develop and validate a new DR/diabetic macular edema (DME) risk stratification model in patients with Type 2 diabetes (DM) to identify low-risk groups who can be safely assigned to biennial or triennial screening intervals. We describe the study methodology, participants' baseline characteristics, and preliminary DR progression rates at the first annual follow-up., Methods: DRESS is a 3-year ongoing longitudinal study of patients with T2DM and no or mild non-proliferative DR (NPDR, non-referable) who underwent teleophthalmic screening under the Singapore integrated Diabetic Retinopathy Programme (SiDRP) at four SingHealth Polyclinics. Patients with referable DR/DME (> mild NPDR) or ungradable fundus images were excluded. Sociodemographic, lifestyle, medical and clinical information was obtained from medical records and interviewer-administered questionnaires at baseline. These data are extracted from medical records at 12, 24 and 36 months post-enrollment. Baseline descriptive characteristics stratified by DR severity at baseline and rates of progression to referable DR at 12-month follow-up were calculated., Results: Of 5,840 eligible patients, 78.3% (n = 4,570, median [interquartile range [IQR] age 61.0 [55-67] years; 54.7% male; 68.0% Chinese) completed the baseline assessment. At baseline, 97.4% and 2.6% had none and mild NPDR (worse eye), respectively. Most participants had hypertension (79.2%) and dyslipidemia (92.8%); and almost half were obese (43.4%, BMI ≥ 27.5 kg/m 2 ). Participants without DR (vs mild DR) reported shorter DM duration, and had lower haemoglobin A1c, triglycerides and urine albumin/creatinine ratio (all p < 0.05). To date, we have extracted 41.8% (n = 1909) of the 12-month follow-up data. Of these, 99.7% (n = 1,904) did not progress to referable DR. Those who progressed to referable DR status (0.3%) had no DR at baseline., Conclusions: In our prospective study of patients with T2DM and non-referable DR attending polyclinics, we found extremely low annual DR progression rates. These preliminary results suggest that extending screening intervals beyond 12 months may be viable and safe for most participants, although our 3-year follow up data are needed to substantiate this claim and develop the risk stratification model to identify low-risk patients with T2DM who can be assigned biennial or triennial screening intervals., (© 2024. The Author(s).)

Background: Specialist palliative care is often provided late in the patient's disease trajectory in response to uncontrolled symptoms. Shifting from this reactionary illness-stress paradigm to a proactive health-wellness approach, the ENABLE (Educate, Nurture, Advise, Before Life Ends) telehealth model aims to enhance the coping, stress and symptom management, self-care, and advance care planning skills of patients with advanced cancers and their caregivers. The ENABLE model has been culturally adapted to Singapore (ENABLE-SG) and pilot-tested. A hybrid type 1 effectiveness-implementation design will be used to evaluate the effectiveness of ENABLE-SG while collecting real-world implementation data., Methods: This single-centre, assessor-blind, wait-list (immediately vs. 6 months) randomized controlled trial will recruit 300 adult patients within 60 days of an advanced cancer diagnosis and their family caregivers from the National Cancer Centre of Singapore. ENABLE-SG comprises structured psychoeducational sessions with a telehealth coach, covering essential topics of early palliative care. Participants will be assessed at baseline and every 3 months until patient's death, 12 months (caregivers), or end of study (patients). The primary outcome is patient quality of life 6 months after baseline. Secondary patient-reported outcomes include mood, coping, palliative care concerns, and health status. Secondary caregiver-reported outcomes include caregiver quality of life, mood, coping, and care satisfaction. Mixed-effects regression modelling for repeated measurements will be used. To assess the effectiveness of ENABLE-SG versus usual care, patient and caregiver outcomes at 6 months will be compared. To compare earlier versus delayed ENABLE-SG, patient and caregiver outcomes at 12 months will be compared. Within the hybrid type 1 effectiveness-implementation design, implementation outcomes will be evaluated in both the early and delayed groups. Acceptability, adoption, appropriateness, and feasibility will be assessed using a feedback survey and semi-structured interviews with a purposive sample of patients, caregivers, and healthcare providers. Transcribed interviews will be analysed thematically. Other implementation outcomes of penetration, fidelity, and cost will be assessed using records of study-related processes and summarized using descriptive statistics. A cost-effectiveness analysis will also be conducted., Discussion: This study will assess both effectiveness and implementation of ENABLE-SG. Insights into implementation processes can facilitate model expansion and upscaling., Trial Registration: Registered prospectively on ClinicalTrials.gov, NCT06044441. Registered on 21/09/2023., (© 2024. The Author(s).)

Background: For patients on dialysis with poor quality of life and prognosis, dialysis withdrawal and subsequent transition to palliative care is recommended. This study aims to understand multi-stakeholder perspectives regarding dialysis withdrawal and identify their information needs and support for decision-making regarding withdrawing from dialysis and end-of-life care., Methods: Participants were recruited through purposive sampling from eight dialysis centers and two public hospitals in Singapore. Semi-structured in-depth interviews were conducted with 10 patients on dialysis, 8 family caregivers, and 16 renal healthcare providers. They were held in-person at dialysis clinics with patients and caregivers, and virtually via video-conferencing with healthcare providers. Interviews were audio-recorded, transcribed, and thematically analyzed. The Ottawa Decision Support Framework's decisional-needs manual was used as a guide for data collection and analysis, with two independent team members coding the data., Results: Four themes reflecting perceptions and support for decision-making were identified: a) poor knowledge and fatalistic perceptions; b) inadequate resources and support for decision-making; c) complexity of decision-making, unclear timing, and unpreparedness; and d) internal emotions of decisional conflict and regret. Participants displayed limited awareness of dialysis withdrawal and palliative care, often perceiving dialysis withdrawal as medical abandonment. Patient preferences regarding decision-making ranged from autonomous control to physician or family-delegated choices. Cultural factors contributed to hesitancy and reluctance to discuss end-of-life matters, resulting in a lack of conversations between patients and providers, as well as between patients and their caregivers., Conclusions: Decision-making for dialysis withdrawal is complicated, exacerbated by a lack of awareness and conversations on end-of-life care among patients, caregivers, and providers. These findings emphasize the need for a culturally-sensitive tool that informs and prepares patients and their caregivers to navigate decisions about dialysis withdrawal and the transition to palliative care. Such a tool could bridge information gaps and stimulate meaningful conversations, fostering informed and culturally aligned decisions during this critical juncture of care., (© 2023. The Author(s).)

Background: The epidemic of non-communicable diseases (NCDs) is a growing concern worldwide and Singapore is no exception to this global trend. As part of measures to address this concern, the Singapore government will implement a mandatory color-coded front-of-package (FOP) nutrition label for beverages, called Nutri-Grade (NG), which will complement the existing FOP label, Healthier Choice Symbol (HCS) logos, currently displayed on select food and beverage items. NG grades beverages on a four-point scale, A (healthiest) to D (least healthy), in terms of sugar and saturated fat levels. This study aimed to evaluate the effectiveness of the NG label on nutritional quality of pre-packaged beverages using a fully functional online grocery store., Methods: We conducted a 2-arm crossover trial involving actual purchases with 138 participants randomly exposed to: 1) Control with HCS logos displayed on qualifying items; 2) Similar to Control except that all beverages displayed the NG label. The effects of the NG label were estimated using a linear mixed-effects model that addresses correlations between repeated measures and accommodates missing data., Results: We found that the NG label encouraged consumers to choose beverages with higher ratings. This led to a reduction in sugar from beverages purchased by 1.51 g [95% CI: - 2.68, - 0.34] per serving but was not effective at reducing saturated fat purchased (- 0.009 g [95% CI: - 0.22, 0.20]) per serving or improvements in overall diet quality, measured by the weighted (by the number of servings) average Nutri-Score value ranging from 1 to 5 (- 0.024 [95% CI: - 0.13, 0.08])., Conclusions: Results suggest that the Nutri-Grade label is likely to reduce sugar purchased from beverages. However, to improve overall diet quality in Singapore, additional measures will be needed., Trial Registration: This trial was registered on ClinicalTrials.gov under the identifier: NCT05018026 on 24th August 2021., (© 2023. The Author(s).)

Background: Many patients with a solid metastatic cancer are treated aggressively during their last month of life. Using data from a large prospective cohort study of patients with an advanced cancer, we aimed to assess the number and predictors of aggressive interventions during last month of life among patients with solid metastatic cancer and its association with bereaved caregivers' outcomes., Methods: We used data of 345 deceased patients from a prospective cohort study of 600 patients. We surveyed patients every 3 months until death for their physical, psychological and functional health, end-of-life care preference and palliative care use. We surveyed their bereaved caregivers 8 weeks after patients' death regarding their preparedness about patient's death, regret about patient's end-of-life care and mood over the last week. Patient data was merged with medical records to assess aggressive interventions received including hospital death and use of anti-cancer treatment, more than 14 days in hospital, more than one hospital admission, more than one emergency room visit and at least one intensive care unit admission, all within the last month of life., Results: 69% of patients received at least one aggressive intervention during last month of life. Patients hospitalized during the last 2-12 months of life, male patients, Buddhist or Taoist, and with breast or respiratory cancer received more aggressive interventions in last month of life. Patients with worse functional health prior to their last month of life received fewer aggressive interventions in last month of life. Bereaved caregivers of patients receiving more aggressive interventions reported feeling less prepared for patients' death., Conclusion: Findings suggest that intervening early in the sub-group of patients with history of hospitalization prior to their last month may reduce number of aggressive interventions during last month of life and ultimately positively influence caregivers' preparedness for death during the bereavement phase., Trial Registration: NCT02850640 ., (© 2022. The Author(s).)

Background: A systematic understanding of socio-economic inequalities in end-of-life (EOL) suffering among advanced cancer patients is required to inform efforts to reduce these inequalities as part of Universal Health Coverage goals., Aims: To assess inequalities in multiple domains of EOL suffering among advanced cancer patients - physical, functional, psychological, social, and spiritual -, using two socio-economic status (SES) indicators, education and perceived economic status of the household., Methods: We used cross-sectional data from surveys of stage IV cancer patients (n = 1378) from seven hospitals across five countries (China, Sri Lanka, India, Vietnam and Myanmar). We conducted separate multivariable linear regression models for each EOL suffering domain. We also tested interactions between the two SES indicators and between each SES indicator and patient age., Results: Patients living in low economic status households /with fewer years of education reported greater suffering in several domains. We also found significant interaction effects between economic status of the household and years of education for all EOL suffering outcomes. Age significantly moderated the association between economic status of the household and social suffering and between years of education and psychological, social, and spiritual suffering (p < 0.05 for all)., Conclusion: Results highlight that SES inequalities in EOL suffering vary depending on the suffering domain, the SES indicator assessed, and by patient age. Greater palliative care resources for patients with low SES may help reduce these inequalities.

Following publication of the original article [1], the corresponding author reported an error on the name of the fourth author.

Background: Patients with advanced cancer often experience poor health-related quality-of-life (HRQoL) due to cancer and treatment-related side-effects. With India's palliative care landscape in its infancy, there is a concern that advanced cancer patients, especially individuals who are from disadvantaged populations experience poor HRQoL outcomes. We aim to assess HRQoL of advanced cancer patients in terms of general well-being (physical, functional, emotional, and social/family well-being), pain experiences, psychological state, and spiritual well-being, and determine the relationship between belonging to a disadvantaged group and HRQoL outcomes. We hypothesize that patients from disadvantaged or minority backgrounds, identified in this paper as financially distressed, female, lower years of education, lower social/family support, minority religions, and Non-General Castes, would be associated with worse HRQoL outcomes compared to those who are not from a disadvantaged group., Methods: We administered a cross-sectional survey to 210 advanced cancer patients in a regional cancer center in India. The questionnaire included standardized instruments for general well-being (FACT-G), pain experiences (BPI), psychological state (HADS), spiritual well-being (FACT-SP); socio-economic and demographic characteristics., Results: Participants reported significantly lower general well-being (mean ± SD) (FACT-G = 62.4 ± 10.0) and spiritual well-being (FACT-SP = 32.7 ± 5.5) compared to a reference population of cancer patients in the U.S. Patients reported mild to moderate pain severity (3.2 ± 1.8) and interference (4.0 ± 1.6), normal anxiety (5.6 ± 3.1) and borderline depressive symptoms (9.7 ± 3.3). Higher financial difficulty scores predicted most of the HRQoL domains (p ≤ 0.01), and being from a minority religion predicted lower physical well-being (p ≤ 0.05) and higher pain severity (p ≤ 0.05). Married women reported lower social/family well-being (p ≤ 0.05). Pain severity and interference were significant predictors of most HRQoL domains., Conclusions: Advanced cancer patients, especially those with lower financial well-being and belonging to minority religions, reported low physical, functional, emotional, social/family, and spiritual well-being, and borderline depressive symptoms. Future studies should be directed at developing effective interventions supporting vulnerable groups such as those with financial distress, and those belonging to minority religions.

Background: Hypertension is a major risk factor for cardiovascular disease (CVD), yet treatment and control rates for hypertension are very low in low- and middle-income countries (LMICs). Lack of effective referral networks between different levels of the health system is one factor that threatens the ability to achieve adequate blood pressure control and prevent CVD-related morbidity. Health information technology and peer support are two strategies that have improved care coordination and clinical outcomes for other disease entities in other settings; however, their effectiveness and cost-effectiveness in strengthening referral networks to improve blood pressure control and reduce CVD risk in low-resource settings are unknown., Methods/design: We will use the PRECEDE-PROCEED framework to conduct transdisciplinary implementation research, focused on strengthening referral networks for hypertension in western Kenya. We will conduct a baseline needs and contextual assessment using a mixed-methods approach, in order to inform a participatory, community-based design process to fully develop a contextually and culturally appropriate intervention model that combines health information technology and peer support. Subsequently, we will conduct a two-arm cluster randomized trial comparing 1) usual care for referrals vs 2) referral networks strengthened with our intervention. The primary outcome will be one-year change in systolic blood pressure. The key secondary clinical outcome will be CVD risk reduction, and the key secondary implementation outcomes will include referral process metrics such as referral appropriateness and completion rates. We will conduct a mediation analysis to evaluate the influence of changes in referral network characteristics on intervention outcomes, a moderation analysis to evaluate the influence of baseline referral network characteristics on the effectiveness of the intervention, as well as a process evaluation using the Saunders framework. Finally, we will analyze the incremental cost-effectiveness of the intervention relative to usual care, in terms of costs per unit decrease in systolic blood pressure, per percentage change in CVD risk score, and per disability-adjusted life year saved., Discussion: This study will provide evidence for the implementation of innovative strategies for strengthening referral networks to improve hypertension control in LMICs. If effective, it has the potential to be a scalable model for health systems strengthening in other low-resource settings worldwide., Trial Registration: Clinicaltrials.gov, NCT03543787 . Registered on 29 June 2018.

Background: Sevelamer is an alternative to calcium carbonate for the treatment of hyperphosphatemia among non-dialysis dependent patients with chronic kidney disease (CKD). Although some studies show that it may reduce mortality and delay the onset of dialysis when compared to calcium carbonate, it is also significantly more expensive. Prior studies looking at the incremental cost-effectiveness of sevelamer versus calcium carbonate in pre-dialysis patients are based on data from a single clinical trial. The goal of our study is to use a wider range of clinical data to achieve a more contemporary and robust cost-effectiveness analysis., Methods: We used a Markov model to estimate the lifetime costs and quality-adjusted life years (QALYs) gained for treatment with sevelamer versus calcium carbonate. The model simulated transitions among three health states (CKD not requiring dialysis, end-stage renal disease, and death). Data on transition probabilities and utilities were obtained from the published literature. Costs were calculated from a third party payer perspective and included medication, hospitalization, and dialysis. Sensitivity analyses were also run to encompass a wide range of assumptions about the dose, costs, and effectiveness of sevelamer., Results: Over a lifetime, the average cost per patient treated with sevelamer is S$180,724. The estimated cost for patients treated with calcium carbonate is S$152,988. A patient treated with sevelamer gains, on average, 6.34 QALYs relative to no treatment, whereas a patient taking calcium carbonate gains 5.81 QALYs. Therefore, sevelamer produces an incremental cost-effectiveness ratio (ICER) of S$51,756 per QALY gained relative to calcium carbonate., Conclusion: Based on established benchmarks for cost-effectiveness, sevelamer is cost effective relative to calcium carbonate for the treatment of hyperphosphatemia among patients with chronic kidney disease initially not on dialysis.

Background: There is high variability in end-of-life (EOL) treatments. Some of this could be due to differences in physician treatment recommendations, their knowledge/attitude regarding palliative care, and their perceived roles in treating patients with advanced serious illness (ASI). Thus, the objective of this paper was to identify potential variation in physician recommendations, their knowledge/attitude regarding palliative care and perceived roles in treating ASI patients., Methods: A cross-sectional survey consisting of vignettes describing patient characteristics that varied by age, expected survival, cognitive status and treatment costs and asked physicians whether they would recommend life-extending treatments for each scenario, was administered to 285 physicians who treat ASI patients in Singapore. Physicians were also assessed on their knowledge/attitude in palliative care. They were administered a best-worst scaling exercise requiring them to select their most and least important role as a physician caring for an ASI patient., Results: There was a wide variation in physician recommendations for life-extending treatments for patients with similar profiles, which can partly be attributed to physician characteristics (years of experience and place of training). Only about one-fourth of the physicians answered all knowledge/attitude questions correctly. Statements assessing knowledge/attitude regarding pain management had the fewest correct responses. The most important perceived role regarding provision of EOL care concerned symptom management., Conclusions: Results suggest that variation in physician treatment recommendations may be partly related to their own characteristics, raising concerns regarding the EOL care being provided to patients. Efforts should be made to better understand this variation and to provide the physicians with additional training in key aspects of palliative care management.

Background: Glaucoma is the leading cause of irreversible blindness in the world. Estimated to affect 60 million people worldwide, this figure is expected to rise to 80 million by 2020. Untreated, glaucoma leads to visual decay and eventually to blindness, and can significantly reduce quality of life. First-line treatment in patients with primary open-angle glaucoma and exfoliative glaucoma is topical medical therapy with ocular hypotensives as eye drops. However, eye drops have several disadvantages including cost, possible local and systemic side effects, and adherence and perseverance issues. Randomised controlled trials have demonstrated that selective laser trabeculoplasty is equally as effective in lowering intraocular pressure as eye drops. However, the impact of these two treatment modalities from the patient and economic perspectives has not been adequately determined. Thus, it remains unclear whether topical medical therapy or selective laser trabeculoplasty should be recommended as first-line treatment for glaucoma., Methods/design: This protocol describes an international, multi-centre, randomised controlled trial to determine the optimum first-line therapy for people with primary open-angle glaucoma and exfoliative glaucoma. This study will compare the effect of selective laser trabeculoplasty and topical medication with respect to patients' generic and glaucoma-specific quality of life. The trial will also provide a detailed cost-effectiveness analysis and compare the clinical effectiveness with respect to the degree of intraocular pressure lowering and rates of treatment failure. Research coordinators in each centre will identify and recruit previously untreated patients with primary open-angle glaucoma and exfoliative glaucoma. Those who meet the eligibility criteria will be invited to enter a randomised controlled trial with either selective laser trabeculoplasty or topical ocular hypotensive therapy, according to a stepped regimen. Outcome assessment will be measured at 6 weeks and at 6, 12, and 24 months post-treatment. Regular clinic follow-ups will continue as clinically indicated between study outcome visits., Discussion: The Glaucoma Initial Treatment Study is the first multi-centred RCT to determine the optimum first-line therapy for people with glaucoma. Our trial will have an unprecedented capacity to meaningfully transform the treatment and management of glaucoma in Australia and overseas., Trial Registration: ACTRN12611000720910; Date registered: 11 July 2011.

Surgical therapy remains the only curative treatment of localized non-small cell lung carcinoma (NSCLC). Yet, the results of surgical therapy leave much to be desired. Recently, neoadjuvant chemotherapy for Stage III NSCLC had become an accepted therapeutic modality. Accordingly, a question is raised regarding the feasibility of neoadjuvant chemotherapy in resectable NSCLC (Stage I and II). In this paper we report three patients, in chronological order, with localized NSCLC who were treated with neoadjuvant chemotherapy. Neoadjuvant chemotherapy was given to the first case with poor pulmonary functions. Decrease in size of the tumor made it possible for him to undergo a more conservative lung resection. In the second case, chemotherapy was given with a presumptive diagnosis of metastatic lung lesion. A good response was noted and, histologically, it was a primary lung cancer. In the third case, chemotherapy was given to a patient with obviously resectable lung carcinoma, and an excellent response was observed. According to the results, neoadjuvant chemotherapy for resectable NSCLC may be feasible and beneficial.