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Abstract Background To investigate the sociodemographic, anthropometric, biochemical, lifestyle and cardiometabolic risk factors associated with type 2 diabetes (T2D) among First Nations Australians. Methods A systematic review of prospective cohorts and cross-sectional studies was conducted. Electronic data sources (MEDLINE/PubMed, Embase, CINHAL, and PsycINFO) were searched for peer-reviewed articles until August 2023. We reviewed observational and interventional studies on T2D that reported sociodemographic, anthropometric, lifestyle, and biochemical risk factors for Australian First Nations people. Narrative synthesis was applied without meta-analysis. We highlighted the major risk factors for T2D by reporting the most significant findings from individual studies in the results. The review followed PRISMA guidelines. Results The review included 20 eligible studies: 12 cross-sectional studies and 8 prospective cohort studies. The findings from these studies showed that First Nations people who resided in very remote areas (Modified Monash Category 7; MM7) (OR = 1.61; 95% CI: 1.03, 2.52), living adjacent to food store stocking “Western” food items (OR = 2.92; 95% CI: 1.51, 5.63), rented their home (OR = 2.07; 95% CI: 1.30, 3.30) and part-time employment (OR = 2.47; 95% CI: 1.54, 3.95) were associated with a statistically higher risk of developing T2D. First Nations people who had obesity class 1 (BMI > 30 kg/m2), central obesity (WC > 88 cm in women; >102 cm in men), and higher waist-to-hip ratio (WHR) (≥ 1.0 in men and 0.85 in women) were more likely to have T2D. First Nations people with elevated triglycerides (≥ 1.7 mmol/L) (OR = 4.9; 95% CI: 2.7, 8.8), one standard deviation (SD) increase in C-reactive protein (CRP) value (AHR = 1.23; 95% CI: 1.05, 1.45) and lower levels of vitamin D (

Abstract Much higher risk of cancer has been found in diabetes patients. Insulin receptor (IR) and insulin-like growth factor 1 receptor (IGF1R) have been extensively studied in both breast cancer and diabetes therapies. Interestingly, a recent study proposed that IR/IGF1R ratio is an important factor for breast cancer prognosis. Women with higher IR/IGF1R ratio showed poor breast cancer prognosis as well as hyperinsulinemia. Here, we propose a novel mechanism that oncogenic protein TRIP-Br1 renders breast cancer cells and insulin deficient mice to have higher IR/IGF1R ratio by positively and negatively regulating IR and IGF1R expression at the protein level, respectively. TRIP-Br1 repressed IR degradation by suppressing its ubiquitination. Meanwhile, TRIP-Br1 directly interacts with both IGF1R and NEDD4-1 E3 ubiquitin ligase, in which TRIP-Br1/NEDD4-1 degrades IGF1R via ubiquitin/proteasome system. TRIP-Br1-mediated higher IR/IGF1R ratio enhanced the proliferation and survival of breast cancer cells. In conclusion, current study may provide an important information in the regulatory mechanism of how breast cancer cells have acquired higher IR/IGF1R ratio.

Abstract Background Despite advancements in therapies, brain metastasis in patients with triple negative subtype of breast cancer remains a therapeutic challenge. Activated microglia are often observed in close proximity to, or within, malignant tumor masses, suggesting a critical role that microglia play in brain tumor progression. Annexin-A1 (ANXA1), a glucocorticoid-regulated protein with immune-regulatory properties, has been implicated in the growth and metastasis of many cancers. Its role in breast cancer-microglia signaling crosstalk is not known. Methods The importance of microglia proliferation and activation in breast cancer to brain metastasis was evaluated in MMTV-Wnt1 spontaneous mammary tumor mice and BALBc mice injected with 4T1 murine breast cancer cells into the carotid artery using flow cytometry. 4T1 induced-proliferation and migration of primary microglia and BV2 microglia cells were evaluated using 2D and coculture transwell assays. The requirement of ANXA1 in these functions was examined using a Crispr/Cas9 deletion mutant of ANXA1 in 4T1 breast cancer cells as well as BV2 microglia. Small molecule inhibition of the ANXA1 receptor FPR1 and FPR2 were also examined. The signaling pathways involved in these interactions were assessed using western blotting. The association between lymph node positive recurrence-free patient survival and distant metastasis-free patient survival and ANXA1 and FPR1 and FPR2 expression was examined using TCGA datasets. Results Microglia activation is observed prior to brain metastasis in MMTV-Wnt1 mice with primary and secondary metastasis in the periphery. Metastatic 4T1 mammary cancer cells secrete ANXA1 to promote microglial migration, which in turn, enhances tumor cell migration. Silencing of ANXA1 in 4T1 cells by Crispr/Cas9 deletion, or using inhibitors of FPR1 or FPR2 inhibits microglia migration and leads to reduced activation of STAT3. Finally, elevated ANXA1, FPR1 and FPR2 is significantly associated with poor outcome in lymph node positive patients, particularly, for distant metastasis free patient survival. Conclusions The present study uncovered a network encompassing autocrine/paracrine ANXA1 signaling between metastatic mammary cancer cells and microglia that drives microglial recruitment and activation. Inhibition of ANXA1 and/or its receptor may be therapeutically rewarding in the treatment of breast cancer and secondary metastasis to the brain.

Abstract Background Healthcare professionals’ empathetic behaviors have been known to lead to higher satisfaction levels and produce better health outcomes for patients. However, empathy could decrease over time especially during training and clinical practice. This study explored factors that contributed to the development of empathy in the healthcare setting. Findings could be used to improve the effectiveness and sustainability of empathy training. Method A qualitative approach, informed by aspects of grounded theory, was utilized to identify factors that enabled the development of empathy from the perspectives of doctors, nurses, allied healthcare workers and students. Twelve sessions of focus group discussions were conducted with 60 participants from two hospitals, a medical school, and a nursing school. Data was analyzed independently by three investigators who later corroborated to refine the codes, subthemes, and themes. Factors which influence the development of empathy were identified and categorized. This formed the basis of the creation of a tentative theory of empathy development for the healthcare setting. Results The authors identified various personal (e.g. inherent characteristics, physiological and mental states, professional identity) and external (e.g. work environment, life experience, situational stressors) factors that affected the development of empathy. These could be further categorized into three groups based on the stability of their impact on the individuals’ empathy state, contributed by high, medium, or low stability factors. Findings suggest empathy is more trait-like and stable in nature but is also susceptible to fluctuation depending on the circumstances faced by healthcare professionals. Interventions targeting medium and low stability factors could potentially promote the development of empathy in the clinical setting. Conclusions Understanding factors that impact the development of empathy allows us to develop measures that could be implemented during training or at the workplace leading to improve the quality of care and higher clinical work satisfaction.

Abstract Background The World Health Organization (WHO) estimated that 29% of global tuberculosis (TB) and almost 47% of childhood TB cases were not reported to national TB programs in 2019. In Cambodia, most childhood TB cases were reported from health facilities supported by the Global Fund to Fight AIDS, Tuberculosis, and Malaria in 2019. This study aimed to compare the healthcare providers' knowledge, attitude, and practices (KAP) on childhood TB case detection in operational districts (ODs) with high and low childhood TB case detection in Cambodia. Methods We conducted a cross-sectional study between November and December 2020 among healthcare providers in 10 purposively selected ODs with high childhood TB case detection and 10 ODs with low childhood TB case detection. A total of 110 healthcare providers from referral hospitals (RHs) and 220 from health centers (HCs) were interviewed. We collected information on socio-demographic characteristics, training, and KAP on childhood TB. Pearson's Chi-square or Fisher's exact and Student's t-tests were performed to explore the differences in KAP of healthcare providers from ODs with low vs. high childhood TB detection. Results Of the 330 respondents, 193 were from ODs with high childhood TB case detection, and 66.67% were from HCs. A significantly higher proportion (46.11%) of respondents from ODs with high childhood TB case detection received training on childhood TB within the past two years than those from low childhood TB case detection ODs (34.31%) (p = 0.03). Key knowledge on childhood TB was not significantly different among respondents from ODs with high and low childhood TB case detection. A significantly higher proportion of respondents from ODs with high childhood TB case detection had a good attitude (98.96 vs. 97.08%, p = 0.002) and performed good practices (58.55 vs. 45.26%, p = 0.02) on contact investigation in the community than those from low childhood TB case detection ODs. Conclusions Healthcare providers from ODs with high childhood TB detection had better attitudes and practices towards childhood TB. The attitudes and practices need to be improved among healthcare providers in ODs with low case detection. Further investment in training and experience sharing on childhood TB case detection among healthcare providers is needed to improve childhood TB case detection.

Abstract Background The ongoing spread of artemisinin resistant Plasmodium falciparum malaria is a major threat to global health. In response, countries in the Greater Mekong Sub-region, including Cambodia, have declared ambitious goals to eliminate malaria. Major challenges include the lack of information on the at-risk population-individuals who live or work in or near the forest where the malaria vectors are found, including plantation workers. This study aimed to address this knowledge gap through a cross-sectional survey conducted in rubber plantations in Cambodia in 2014. Methods The survey was conducted in two rounds in four provinces and included a malaria prevalence survey, analysis for the K13 genetic mutation, and a comprehensive behavioural questionnaire. Forty plantations were included in each round, and 4201 interviews were conducted. An additional 701 blood samples were collected from family members of plantation workers. Results Overall malaria prevalence was relatively low with adjusted PCR prevalence rate of 0.6% for P. falciparum and 0.3% for Plasmodium vivax, and was very heterogenous between plantations. There was little difference in risk between permanent residents and temporary workers, and between the two rounds. The main risk factors for P. falciparum infection were smaller plantations, age under 30 years, lack of self-reported use of a treated net and recent travel, especially to the Northeastern provinces. Proximity of plantations to the forest was also a risk factor for malaria in round one, while male gender was also a risk factor for malaria by either species. Conclusions With Cambodia’s P. falciparum elimination target on the horizon, identifying every single malaria case will become increasingly important. Plantations workers are relatively accessible compared to some other at-risk groups and will likely remain a high priority. Ongoing surveillance and adaptive strategies will be critical if malaria elimination is to be achieved in this setting.

Abstract Background Bladder cancer (BC) is one of the most common malignancies of the urinary tract. The role of transient receptor potential melastatin 7 (TRPM7) in BC remains unclear. The aim of this study was to investigate the function and signal transduction pathway of TRPM7 in BC. Methods T24 and UMUC3 cells were used to evaluate the molecular mechanism of TRPM7 by immunoblot analysis. Small interfering RNA was used to knockdown TRPM7, and the effect of silencing TRPM7 was studied by wound healing, migration, and invasion assays in T24 and UMUC3 cells. Xenograft model study was obtained to analyze the effect of TRPM7 inhibition in vivo. Results Silencing of TRPM7 decreased the migration and invasion ability of T24 and UMUC3 cells. The phosphorylation of Src, Akt, and JNK (c-Jun N-terminal kinase) was also suppressed by TRPM7 silencing. Src, Akt, and JNK inhibitors effectively inhibited the migration and invasion of T24 and UMUC3 cells. In addition, the TRPM7 inhibitor, carvacrol, limited the tumor size in a xenograft model. Conclusion Our data reveal that TRPM7 regulates the migration and invasion of T24 and UMUC3 cells via the Src, Akt, and JNK signaling pathway. Therefore, TRPM7 suppression could be a potential treatment for BC patients.

Abstract Background Febrile urinary tract infection (UTI) is one of the most common complications after ureteroscopic lithotripsy (URS). We evaluated the effect of secondary signs on preoperative computed tomography (CT) for febrile UTI after URS. Methods In total, 182 patients who underwent URS for ureteral stones from January 2013 to December 2015 were retrospectively included in this study. These patients were divided into two groups according to the presence of postoperative febrile UTI after URS. We compared the clinical factors, stone factors, and secondary signs between the groups. Predictive factors for febrile UTI after URS were analyzed using a multivariate logistic regression model. Results Febrile UTI occurred in 26 of the 182 patients. In univariate analysis, presence of comorbid chronic kidney disease (CKD) and stone size were significantly different between UTI and non-UTI groups. Among secondary signs, presence of hydroureter, perinephric fat stranding, periureteral fat stranding, and tissue rim sign were significantly different between the groups. In multivariate logistic regression analysis, comorbid CKD, stone size, perinephric fat stranding, and tissue rim sign were independent predictive factors for febrile UTI after URS. Conclusion This study demonstrated that secondary signs including perinephric fat stranding and tissue rim sign on preoperative CT, CKD, and stone size are independent predictive factors for febrile UTI after URS.

Abstract Background Cambodia is among the 30 countries in the world with the highest burden of tuberculosis (TB), and it is estimated that 40% of people with TB remain undiagnosed. In this study, we aimed to investigate the determinants of delayed diagnosis and treatment of TB in Cambodia. Methods This mixed-method explanatory sequential study was conducted between February and September 2019 in 12 operational districts in Cambodia. It comprised of a retrospective cohort study of 721 people with TB, followed by a series of in-depth interviews. We assessed factors associated with time to TB diagnosis and treatment initiation using Cox proportional hazards model. Subsequently, we conducted in-depth interviews with 31 people with TB purposively selected based on the time taken to reach TB diagnosis, sex, and residence. Transcripts were coded, and thematic analyses were performed. Results The median time from the onset of symptoms to TB diagnosis was 49 days (Interquartile range [IQR]: 21–112). We found that longer time to diagnosis was significantly associated with living in rural area (Adjusted hazards ratio [aHR] = 1.25; 95% confidence interval [CI]: 1.06–1.48); TB symptoms—cough (aHR: 1.52; 95% CI: 1.18–1.94), hemoptysis (aHR 1.32; 95% CI: 1.07–1.63), and night sweats (aHR: 1.24; 95% CI: 1.05–1.46); seeking private health care/self-medication (aHR: 1.23; 95% CI: 1.04–1.45); and higher self-stigma (aHR: 1.02; 95% CI: 1.01–1.03). Participants who received education level above the primary level were inversely associated with longer time to diagnosis (aHR: 0.78; 95% CI: 0.62–0.97). The median time from TB diagnosis to the initiation of treatment was two days (IQR: 1–3). The use of smear microscopy for TB diagnosis (aHR: 1.50; 95% CI: 1.16–1.95) was associated with longer time to treatment initiation. Seeking private health care and self-medication before TB diagnosis, lack of perceived risk, threat, susceptibility, and stigma derived qualitatively further explained the quantitative findings. Conclusions TB diagnostic delay was substantial. Increasing public awareness about TB and consciousness regarding stigma, engaging the private healthcare providers, and tailoring approaches targeting the rural areas could further improve early detection of TB and narrowing the gap of missing cases in Cambodia.

Abstract Background Healthy corneal epithelium acts as a barrier against damage to the deeper structures in the eye. Failure in the mechanisms of corneal epithelization can lead to persistent epithelial defects of the cornea (PEDs) and can compromise its function. Epidermal growth factor (EGF) promotes the proliferation, migration, and differentiation of epithelial cells, endothelial cells, and fibroblasts during wound healing and may be beneficial in treating patients with PEDs. We, therefore, investigated the effect of EGF ointment on patients with PEDs. Methods Fifteen patients with PEDs refractory to conventional treatment were treated twice a day with EGF ointment. Patient demographics and comorbidities were noted. The epithelial healing time was determined along with the primary outcome measures in the areas of the epithelial defects, visual acuity, visual analog scale (VAS) scores, and esthesiometer scores 1 month and 2 months after treatment. Results Five eyes of herpetic keratitis (33.3%), 3 eyes of dry eye disease (20.0%), 3 eyes of bacterial keratitis (20.0%), 2 eyes of limbal stem cell deficiency (13.3%), 1 eye of diabetic neurotrophic keratitis (6.7%), and 1 eye of filamentary keratitis (6.7%) were associated with PEDs, respectively. Two months following treatment with EGF ointment, there was a reduction in the area of the epithelial defects (5.7 ± 3.9 to 0.1 ± 0.3 mm2) as well as a significant improvement in best-corrected visual acuity (0.9 ± 0.8 to 0.6 ± 0.5 LogMAR) and VAS scores (4.5 ± 1.2 to 2.5 ± 0.7) in 12 eyes (80%). Among these cases, the mean epithelial healing time was 5.5 ± 1.8 weeks. Amniotic membrane transplantation was performed on the remaining 3 (20.0%) patients that did not respond to EGF treatment. Conclusions EGF ointment could reduce symptoms and promotes corneal epithelialization of refractory PEDs. It may, therefore, be well-tolerated and a potentially beneficial addition in the management of refractory PEDs.

Abstract Background Rates of childhood undernutrition are persistently high in Cambodia. Existing ready-to-use supplementary and therapeutic foods (RUSFs and RUTFs) have had limited acceptance and effectiveness. Therefore, our project developed and trialled a locally-produced, multiple micronutrient fortified lipid-based nutrient supplement (LNS) with therapeutic and supplementary versions. This ready-to-use food (RUF) is innovative in that, unlike many RUFs, it contains fish instead of milk. Development began in 2013 and the RUF was finalised in 2015. From 2015 until the present, both the RUTF and the RUSF versions were trialled for acceptability and effectiveness. Methods This paper draws on project implementation records and semi-structured interviews to describe the partnership between the Cambodian Ministries of Health and Agriculture, Forestry and Fisheries, UNICEF, the French National Research Institute for Sustainable Development (IRD), universities, and Vissot factory. It discusses the project implementation and lessons learned from the development and trialling process, and insights into positioning nutrition on the health agenda in low and middle-income countries. Results The lessons learned relate to the importance of project planning, management, and documentation in order to seize opportunities in the research, policy, advocacy, and programming environment while ensuring adequate day-to-day project administration and resourcing. Conclusions We conclude that projects such as ours, that collaborate to develop and test novel, locally-produced RUTFs and RUSFs, offer an exciting opportunity to respond to both local programmatic and broader research needs.

Abstract Background A complete enumeration study was conducted to evaluate trends in national practice patterns and direct medical costs for prostate cancer (PCa) in Korea over a 10-year retrospective period using data from the Korean National Health Insurance Service. Methods Reimbursement records for 874,924 patients diagnosed between 2002 and 2014 with primary PCa according to the International Classification of Disease (ICD) 10th revision code C61 were accessed. To assess direct medical costs for patients newly diagnosed after 2005, data from 68,596 patients managed between January 2005 and 31 December 2014 were evaluated. Results From 2005 to 2014, the total number of PCa patients showed a 2.6-fold increase. Surgery and androgen deprivation therapy were the most common first-line treatment, alone or within the context of combined therapy. Surgery as a monotherapy was performed in 23.5% of patients in 2005, and in 39.4% of patients in 2014. From 2008, the rate of robot-assisted RP rose sharply, showing a similar rate to open RP in 2014. Average total treatment costs in the 12 months post-diagnosis were around 10 million Korean won. Average annual treatment costs thereafter were around 5 million Korean won. Out-of-pocket expenditure was highest in the first year post-diagnosis, and ranged from 12 to 17% thereafter. Conclusions Between 2005 and 2014, a substantial change was observed in the national practice pattern for PCa in Korea. The present data provide a reliable overview of treatment patterns and medical costs for PCa in Korea.

Abstract Background Cambodia, a lower middle-income country of about 16 million individuals in southeast Asia, endures a high burden of both tuberculosis and other lower respiratory infections. Differentiating tuberculosis from other causes of respiratory infection has important clinical implications yet may be challenging to accomplish in the absence of diagnostic microbiology facilities. Furthermore, co-infection of tuberculosis with other bacterial lower respiratory infections may occur. The objective of this study was to determine the prevalence and etiologies of tuberculosis and other bacterial co-infection and to analyze the clinical and radiographic characteristics of patients presenting with respiratory infection to a provincial referral hospital in Cambodia. Methods We performed a retrospective, cross-sectional analysis of laboratory and clinical data, on patients presenting with respiratory symptoms to a chest clinic of a 260-bed provincial referral hospital in Cambodia. We analyzed mycobacterial and bacterial sputum test results, and demographics, medical history and chest radiography. Results Among 137 patients whose treating clinicians ordered sputum testing for tuberculosis and other bacteria, the median age was 52 years, 54% were male, 3% had HIV infection, and 26% were current smokers. Nearly all had chronic respiratory symptoms (> 96%) and abnormal chest radiographs (87%). Sputum testing was positive for tuberculosis in 40 patients (30%) and for bacteria in 60 patients (44%); 13 had tuberculosis and bacterial co-infection (9% overall; 33% of tuberculosis patients). Clinical characteristics were generally similar across pulmonary infection types, although co-infection was identified in 43% of patients with one or more cavitary lesions on chest radiography. Among those with bacterial growth on sputum culture, Gram negative bacilli (Klebsiella and Pseudomonas spp.) were the most commonly isolated. Conclusions Among patients with symptoms of respiratory infections whose treating clinicians ordered sputum testing for tuberculosis and other bacteria, 9% of all patients and 33% of tuberculosis patients had tuberculosis and bacterial co-infection. Greater availability of microbiologic diagnostics for pulmonary tuberculosis and bacterial infection is critical to ensure appropriate diagnosis and management.

Abstract Background In Singapore, the burden of hypertension disproportionately falls on the elderly population of low socio-economic status. Despite availability of effective treatment, studies have shown high prevalence of sub-optimal blood pressure control in this group. Poor hypertension management can be attributed to a number of personal factors including awareness, management skills and overall adherence to treatment. However, these factors are also closely linked to a broader range of community and policy factors. This paper explores the perceived social and physical environments of low socio-economic status and elderly patients with hypertension; and how the interplay of factors within these environments influences their ability to mobilise resources for hypertension management. Methods In-depth interviews were conducted in English, Chinese, Chinese dialects and Malay with 20 hypertensive patients of various ethnic backgrounds. Purposive sampling was adopted for recruitment of participants from a previous community health screening campaign. Interviews were translated into English and transcribed verbatim. We deductively analysed leveraging on the Social Model of Health to identify key themes, while inductive analysis was used simultaneously to allow sub-themes to emerge. Results and discussion Our finding shows that financing is an overarching topic embedded in most themes. Despite the availability of multiple safety nets, some patients were left out and lacked capital to navigate systems effectively, which resulted in delayed treatment or debt. The built environment played a significant role in enabling patients to access care easily and lead a more active lifestyle. A closer look is needed to enhance the capacity of patients with mobility challenges to enjoy equitable access. Furthermore, the establishment of community based elderly centres has enabled patients to engage in meaningful and healthy social activities. In contrast, participants’ descriptions showed that their communication with healthcare professionals remained brief, and that personalised and meaningful interactions that are context and culturally specific are essential to advocate for patients’ overall treatment adherence and lifestyle modification. Conclusion Elderly patients with hypertension from lower socio-economic background have various unmet needs in managing their hypertension and other comorbidities. These needs are closely related to broader societal factors such as socio-demographic characteristics, support systems, urban planning and public policies, and health systems factors. Policy decisions to address these needs require an integrated multi-sectoral approach grounded in the principles of health equity.

Abstract Background New biological prognostic predictors have been studied; however, some factors have limited clinical application due to tissue-specific expression and high cost. There is the need for a promising predictive factor that is simple to detect and that is closely linked to oncological outcomes in patients with urothelial bladder cancer (BC) who have undergone radical cystectomy (RC). Therefore, we investigated the clinical prognostic value of the preoperative De Ritis ratio (aspartate aminotransferase/alanine aminotransferase) on oncological outcomes in patients with urothelial BC after RC. Methods We retrospectively evaluated clinicopathological data of 118 patients with non-metastatic urothelial BC after RC between 2008 and 2013 at a single center. The association between the De Ritis ratio and clinicopathological findings was assessed. The potential prognostic value of the De Ritis ratio was analyzed using the Kaplan-Meier method, and multivariate Cox analyses were performed to identify the independent predictors of metastasis-free survival, cancer-specific survival, and overall survival. Results According to the receiver operating curve of the De Ritis ratio for metastasis, we stratified the patients into 2 groups using a threshold of 1.3. A high De Ritis ratio was more likely to be associated with old age and the female sex. Kaplan-Meier estimates revealed that patients with a high De Ritis ratio had inferior metastasis-free survival, cancer-specific survival, and overall survival outcomes (P = 0.012, 0.024, and 0.022, respectively). Multivariate analysis revealed that a high De Ritis ratio was an independent prognostic factor for metastasis (hazard ratio [HR], 2.389; 95% confidence interval [CI], 1.161–4.914; P = 0.018), cancer-related death (HR, 2.755; 95% CI, 1.214–6.249; P = 0.015), and overall death (HR, 2.761; 95% CI, 1.257–6.067; P = 0.011). Conclusions An elevated De Ritis ratio was significantly associated with worse prognosis in patients who underwent RC for urothelial BC. This ratio might further improve the predictive accuracy for prognosis in BC.

Abstract Background Sedentary behaviour and falls are important interrelated health issues in older people. One in three people aged 65 years and above fall at least once a year and sedentary behaviour has been identified as one of the risk factors for falls. Studies have shown that the duration of sedentary time increases with age. These dual problems need to be addressed effectively as the ageing population grows. Accelerometers enable accurate measurement of sedentary time. This study aims to establish the feasibility and effect of an individualized goal-setting health coaching intervention using feedback initially from an accelerometer and then pedometer over a period of 12 weeks (intervention) compared with providing a one-off advice through a brochure (control), on sedentary time in older people with a recent fall or at risk of one. Methods A single-blinded randomized controlled feasibility trial involving 80 community-dwelling people aged 65 years and above will be conducted with 40 randomized to the intervention and another 40 to control. Primary outcomes will be the feasibility of the intervention and change in total sedentary time at 12 and 24 weeks. Secondary outcomes include a change in fear of falling based on the falls efficacy scale, gait speed, self-reported sedentary time, the proportion of fallers and number of falls. Four focus groups (two from each arm) will be conducted at the end of the study to evaluate the feasibility and effectiveness of this intervention. Feasibility findings will be primarily descriptive. Mean group differences will be examined using independent samples t test for normally distributed data and nonparametric tests (Kruskal-Wallis and Mann-Whitney U) for non-normally distributed data. Differences in frequency of variables will be compared using chi-square test. Analysis of variance (ANOVA) will be used to test the post-intervention difference between the two groups at 12 and 24 weeks. Discussion The trial will address a key gap in evidence about sedentary behaviour and falls amongst older people and will evaluate the feasibility of an intervention that could be implemented within the primary health care settings. Trial registration Australian New Zealand Clinical Trials Registry 12617001186347, Registered 11 August 2017.

Abstract Background To investigate the concentrations of oxidative stress markers, 8-hydroxy-2′-deoxyquanosine (8-OHdG) and malondialdehyde (MDA), in tears and their correlation with the clinical activity score (CAS) in patients with Graves’ orbitopathy (GO) according to disease activity. Methods We recruited 27 participants with inactive stage GO, 35 participants with active stage GO, and 25 healthy controls without GO. The tear concentrations of 8-OHdG and MDA were determined by enzyme-linked immunosorbent assay. The correlation between CAS and the concentrations of tear 8-OHdG and MDA were analyzed according to the disease activity in the GO patients. Results The levels of 8-OHdG and MDA were 56.30 ± 16.81 ng/mL and 5.39 ± 1.31 pmol/mg, respectively, in the control subjects, and 123.46 ± 22.67 ng/mL and 13.59 ± 3.93 pmol/mg, respectively, in patients with inactive stage GO, and 215.14 ± 35.61 ng/mL and 22.52 ± 4.63 pmol/mg, in patients with active stage GO. The mean concentrations of 8-OHdG and MDA were higher in patients with inactive and active stage GO compared with the control group (all P

Abstract Background Malaria remains a critical public health problem in Southeast Asia despite intensive containment efforts. The continued spread of multi-drug-resistant Plasmodium falciparum has led to calls for malaria elimination on the Thai-Cambodian border. However, the optimal approach to elimination in difficult-to-reach border populations, such as the Military, remains unclear. Methods/design A two-arm, cluster-randomized controlled, open-label pilot study is being conducted in military personnel and their families at focal endemic areas on the Thai-Cambodian border. The primary objective is to compare the effectiveness of monthly malaria prophylaxis (MMP) with dihydroartemisinin-piperaquine and weekly primaquine for 12 weeks compared with focused screening and treating (FSAT) following current Cambodian national treatment guidelines. Eight separate military encampments, making up approximately 1000 military personnel and their families, undergo randomization to the MMP or FSAT intervention for 3 months, with an additional 3 months’ follow-up. In addition, each treatment cluster of military personnel and civilians is also randomly assigned to receive either permethrin- or sham (water)-treated clothing in single-blind fashion. The primary endpoint is risk reduction for malaria infection in geographically distinct military encampments based on their treatment strategy. Monthly malaria screening in both arms is done via microscopy, PCR, and rapid diagnostic testing to compare both the accuracy and cost-effectiveness of diagnostic modalities to detect asymptomatic infection. Universal glucose-6-phosphate dehydrogenase (G6PD) deficiency screening is done at entry, comparing the results from a commercially available rapid diagnostic test, the fluorescence spot test, and quantitative testing for accuracy and cost-effectiveness. The comparative safety of the interventions chosen is also being evaluated. Discussion Despite the apparent urgency, the key operational elements of proposed malaria elimination strategies in Southeast Asian mobile and migrant populations, including the Military, have yet to be rigorously tested in a well-controlled clinical study. Here, we present a protocol for the primary evaluation of two treatment paradigms – monthly malaria prophylaxis and focused screening and treatment – to achieve malaria elimination in a Cambodian military population. We will also assess the feasibility and incremental benefit of outdoor-biting vector intervention – permethrin-treated clothing. In the process, we aim to define the cost-effectiveness of the inputs required for success including a responsive information system, skilled human resource and laboratory infrastructure requirements, and quality management. Despite being a relatively low transmission area, the complexities of multi-drug-resistant malaria and the movement of vulnerable populations require an approach that is not only technically sound, but simple enough to be achievable. Trial registration ClinicalTrials.gov, ID: NCT02653898. Registered on 13 January 2016.

Abstract Background Adolescents living with HIV experience worse HIV care outcomes compared to adults, especially during transition from pediatric to adult care. However, data regarding adolescents are limited. This paper describes and compares characteristics of male and female adolescents living with HIV preparing for transition from pediatric to adult care in Cambodia. Methods This cross-sectional study was conducted in August 2016 among 328 adolescents aged 15–17, randomly selected from 11 antiretroviral therapy (ART) clinics. Data were collected using a structured questionnaire, and descriptive analyses were conducted to compare characteristics of male and female adolescents. Results Of total, 55.2% were male, and 40.8% were living with parents. Majority (82.6%) got HIV infection from their mothers. Overall, adolescents had received ART for an average of 8.4 years, and HIV care for 9.5 years. Additionally, 82.4% were on first line ART regimen. Mean CD4 count from the most recent test was 672 cells/mm3, and viral load was 7686 copies/mL. Overall, 95.6% were adherent to ART on Visual Analogue Scale. About half (50.7%) had never disclosed their HIV status to anyone, while the remaining had disclosed it to their siblings (24.2%), friends (13.0%), schoolteachers (2.4%), or other (5.8%). A fifth reported having had boy or girlfriends, but few (2.1%) had ever had sexual intercourse. Females were more likely to have been engaged in sexual intercourse, and none reported having used a condom in their last intercourse. Few participants reported having ever used tobacco (1.8%), or any kind of illicit drugs (0.9%), but almost a fifth (20.7%) had a history of alcohol use. The majority (82.1%) were aware that they were receiving ART. HIV-related knowledge was suboptimal among the sample. Conclusions This study provides a snapshot of immunological, virological, adherence, and disclosure outcomes that should be tracked during and following healthcare transition to evaluate the effectiveness of the transition program. Findings showed high ART adherence, low likelihood of disclosure outside of family circles, sub-optimal condom use, and poor knowledge of HIV. To provide individualized support for healthcare transition, pediatric and adult clinics need to ensure that these characteristics are taken into account.

Abstract Background In Malaysia, refugees and asylum-seekers are a vulnerable group that often face circumstances in which their health and wellbeing can be compromised. This qualitative study sought to examine the key health concerns and barriers to healthcare access among refugees and asylum-seekers in Malaysia through the lens of healthcare professionals, program staff and experts on refugee and migrant health. Methods We conducted 20 semi-structured in-depth interviews with experts, healthcare professionals, program managers or executives from UN agencies, public healthcare facilities, civil society organizations, and academic institutions in Malaysia. Interviews were transcribed and analyzed both deductively and inductively using thematic analysis. Results Participant narratives highlight that the health needs of refugees and asylum-seekers in Malaysia are complex. As reported, access to healthcare is underpinned by numerous social, cultural and economic determinants compounded by a legal environment that lacks inclusivity of refugees and asylum-seekers. Apart from the health risks associated with the migration process, limited access to comprehensive healthcare post-arrival remain a problem for refugees and asylum-seekers in Malaysia. Key barriers to healthcare access are linked to poor health literacy and the lack of awareness on one’s right to healthcare; language and cultural differences; protection issues resulting from a lack of legal status; and an inability to afford healthcare due to inadequate livelihoods. Overall, poor access to healthcare is perceived to have detrimental consequences on the health status of refugees, asylum-seekers and its host population, and may incur greater costs to the health system in the long run. Conclusion Comprehensive efforts in practice and research that tackle the social, cultural and economic determinants of health, and more inclusive health policies are crucial in strengthening healthcare access among refugees and asylum-seekers in Malaysia. Practical recommendations include improving the health literacy of refugees and asylum-seekers for better navigation of the health system; bridging language and cultural gaps through translation support and inter-cultural orientation; implementing policies grounded in the right to healthcare for all regardless of legal status and in the interest of public health; and establishing a larger evidence base to drive policy development and implementation for refugee health within the Malaysian context.

Abstract Background Basic needs (e.g., food security and stable housing) are important determinants of health and well-being, yet their impact on health-related quality of life (HRQoL) in the context of HIV and aging has not been systematically investigated. Methods Multiple linear regression models examined the relationship between unmet basic needs, and physical and mental HRQoL by age strata (20-34, 35-49 and 50+) in a cross-sectional sample of 496 people living with HIV in Ontario, Canada. Results An overwhelming majority of participants (87%) reported unmet needs related to food, clothing or housing. The prevalence of unmet basic needs in the two older groups appeared to be lower than among younger participants, but the difference did not reach statistical significance. The presence of unmet basic needs predicted substantially lower mean physical health and mental health summary scores in the two oldest groups. Notably, age moderated the influence of unmet basic needs on HRQoL. Conclusions The availability and accessibility of food security, appropriate clothing and stable housing for people living with HIV who are aging need to become a higher priority for program planners and decision makers.

Abstract Objective Pseudomonas aeruginosa is an opportunistic bacterial pathogen well known to cause chronic lung infections in individuals with cystic fibrosis (CF). Some strains adapted to this particular niche show distinct phenotypes, such as biofilm hyperproduction. It is necessary to study CF clinical P. aeruginosa isolates, such as Liverpool Epidemic Strains (LES), to acquire a better understanding of the key genes essential for in vivo maintenance and the major virulence mechanisms involved in CF lung infections. Previously, a library of 9216 mutants of the LESB58 strain were generated by signature-tagged mutagenesis (STM) and screened in the rat model of chronic lung infection, allowing the identification of 163 STM mutants showing defects in in vivo maintenance. Results In the present study, these 163 mutants were successively screened in two additional surrogate host models (the amoeba and the fruit fly). The STM PALES_11731 mutant was the unique non-virulent in the three hosts. A competitive index study in rat lungs confirmed that the mutant was 20-fold less virulent than the wild-type strain. This study demonstrated the pertinence to use a multi-host approach to study the genetic determinants of P. aeruginosa strains infecting CF patients.

Abstract Background Existing ready-to-use supplementary and therapeutic foods (RUSFs and RUTFs) have had limited acceptance and effectiveness in Cambodia. This has hampered the treatment and prevention of child malnutrition. An innovative, locally produced, multiple micronutrient fortified lipid-based nutrient supplement (LNS) has been developed for use as an RUSF. Unlike most RUSFs, which contain milk, this product contains fish as the animal protein. Few RUSFs have been formulated using non-milk animal-source foods and they have not been widely tested. An acceptability trial that was conducted on this novel RUSF in June 2015 demonstrated that children will eat the RUSF and that caregivers will feed it to their children. The current trial aims to evaluate the effectiveness of the RUSF in preventing growth faltering and improving micronutrient status in Cambodian children. Methods and analysis This trial is a six-month, prospective, cluster randomised, non-blinded controlled trial among infants in peri-urban Phnom Penh. The trial aims to establish the superiority of the novel RUSF, compared to three alternatives (Corn-Soy Blend Plus Plus (CSB++) and Sprinkles micronutrient powders as active comparators, and the unimproved diet as a control). The allocation ratio is 1:1. Healthy children (N = 540) aged six to eleven months will be recruited. Data will be collected at baseline, and monthly thereafter for a period of six months. Participants will be provided with a monthly supply of the food to which their village has been allocated. Discussion There is an urgent need to develop locally produced and culturally acceptable RUSFs, and to compare these with existing options in terms of their potential for preventing malnutrition, in Cambodia and elsewhere. This trial will contribute much-needed data on the effectiveness of supplementary foods with an animal-source food other than milk, by comparing a novel RUSF based on fish to one that uses milk (CSB++). Moreover, it will deepen the understanding of the impact of multiple micronutrients provided with or without macronutrients, by comparing the novel RUSF and CSB++, which combine macronutrients with multiple micronutrients, to Sprinkles, which contains no macronutrients. In addition, it will augment the body of evidence from Asia. Trial registration ClinicalTrials.gov, Identifier: LNS-CAMB-INFANTS-EFF; NCT02257762.

Abstract Background Globally more registered nurses need to be recruited to meet the needs of aging populations and increased co-morbidity. Nursing recruitment remains challenging when compared to other healthcare programs. Despite healthcare students having similar motivation in joining the healthcare industry, many did not consider nursing as a career choice. This study aims to identify the deterrents to choosing nursing among healthcare undergraduates by examining the differences in the factors influencing healthcare career choices and nursing as a career choice. Methods A cross sectional study was conducted using a 35-parallel items instrument known as Healthcare Career Choice and Nursing Career Choice scale. Six hundred and four (n = 604) first year medical, pharmacy, dentistry and social science students from a university in Singapore completed the survey. Results Nursing as a career was perceived by healthcare students to be more likely influenced by prior healthcare exposure, the nature of the work, job prospects, and social influences. Lack of autonomous decision making, perceived lower ability to make diagnosis, having to attend to patients’ hygiene needs, engendered stigma, and lack of parental support were identified as deterring factors to choosing nursing as a career. Conclusion An understanding of the deterrents to choosing nursing as career allows policy makers and educational leaders to focus on recruitment strategies. These include providing more exposure to nurses’ roles in early school years, helping young people to overcome the fear of providing personal hygiene care, promoting nurses’ autonomous nursing practice, addressing gender stigma, and overcoming parental objection.

Abstract Background Preparing adolescents for transition into adult care and supporting their acquisition of self-health care management skills is a critical determinant of their post-transition HIV care outcomes. However, there is a scarcity of research on effective transition strategies. This study explores factors associated with adolescent preparedness for transition into adult care in Cambodia. Methods In August 2016, a cross-sectional study was conducted among 223 adolescents living with HIV aged 15–17, randomly selected from 11 antiretroviral therapy clinics, utilizing a structured questionnaire. The level of preparedness was determined using a pre-existing scale, and adolescents were categorized as having a high- or low level of preparedness for transition. Bivariate and multivariate analyses were conducted. Results Of 223 adolescents, 55.2% were male, and their mean age was 15.8 years. Overall, 53.3% had a high level of preparedness for transition. As part of the transition protocol, 2.7% had completed a transfer form, 24.7% had a transition case manager, 29.6% had been counselled about the transition, and 19.7% had visited an adult ART clinic. In multivariate analysis, a higher level of preparedness for transition was independently associated with older age (AOR 2.44, 95% CI 1.34–4.46; p = 0.004), family having received social support for their health (AOR 5.32, 95% CI 1.97–14.36; p = 0.001), knowing the kind of treatment they received (ART) (AOR 12.67, 95% CI 2.91–15.19; p = 0.001), trust in friends or family for HIV treatment (AOR 7.82, 95% CI 1.13–8.89; p = 0.008), receiving counseling on transition (AOR 3.17, 95% CI 1.15–8.76; p = 0.03), having a ‘Case Manager’ identified to support them during the preparation process for transition (AOR 3.89, 95% CI 1.08–13.96; p = 0.04), and satisfaction with preparation process for transition in general (AOR 0.35, 95% CI 0.03–0.87; p = 0.01). Conclusions A range of individual, social and health system and services factors may determine successful transition preparedness among adolescents in Cambodia. Strengthening implementation of age-appropriate and individualized case management transition at all sites, while creating supportive family, peer, and healthcare environments for adolescent transition is required.

Abstract Background Ginger is a popular spice and food preservative. The rhizomes of the common ginger have been used as traditional medicine to treat various ailments. 6-Shogaol, a pungent compound isolated from the rhizomes of jahe gajah (Zingiber officinale var officinale) has shown numerous pharmacological activities, including neuroprotective and anti-neuroinflammatory activities. The aim of this study was to investigate the potential of 6-shogaol to mimic the neuritogenic activity of nerve growth factor (NGF) in rat pheochromocytoma (PC-12) cells. Methods The cytotoxic effect of 6-shogaol was determined by 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The neuritogenic activity was assessed by neurite outgrowth stimulation assay while the concentration of extracellular NGF in cell culture supernatant was assessed by enzyme-linked immunosorbent assay (ELISA). Involvement of cellular signaling pathways, mitogen-activated protein kinase kinase/extracellular signal-regulated kinase1/2 (MEK/ERK1/2) and phosphoinositide-3-kinase/protein kinase B (PI3K/AKT) in 6-shogaol-stimulated neuritogenesis were examined by using specific pharmacological inhibitors. Results 6-Shogaol (500 ng/ml) induced neuritogenesis that was comparable to NGF (50 ng/ml) and was not cytotoxic towards PC-12 cells. 6-Shogaol induced low level of NGF biosynthesis in PC-12 cells, showing that 6-shogaol stimulated neuritogenesis possibly by inducing NGF biosynthesis, and also acting as a substitute for NGF (NGF mimic) in PC-12 cells. The inhibitors of Trk receptor (K252a), MEK/ERK1/2 (U0126 and PD98059) and PI3K/AKT (LY294002) attenuated the neuritogenic activity of both NGF and 6-shogaol, respectively. Conclusions The present findings demonstrated that 6-shogaol induced neuritogenic activity in PC-12 cells via the activation MEK/ERK1/2 and PI3K/AKT signaling pathways. This study suggests that 6-shogaol could act as an NGF mimic, which may be beneficial for preventive and therapeutic uses in neurodegenerative diseases.

Abstract Background Harm reduction interventions in Cambodia face numerous obstacles because of conflicting understanding and interests and inconsistencies in the implementation by law enforcement officials. This study aims to examine how understanding and application of Drug Control Law (DCL) and Village/Commune Safety Policy (VCSP) affects harm reduction interventions in Cambodia from the standpoints of law enforcement officials, people who inject drugs and people who use drugs (PWID/PWUD), as well as other key stakeholders. Methods This qualitative study was conducted in the capital city of Phnom Penh in 2015. We held five focus group discussions (FGDs) with groups of PWID/PWUD, police officers, Sangkat/commune officers, and local non-governmental organization (NGO) field staff. We also conducted ten key informant interviews (KIIs) with representatives from government agencies, donor agencies, and NGOs. FGDs and KIIs with Cambodian participants were transcribed in Khmer and translated into English. KIIs with foreign participants were transcribed in English. Transcripts were read and re-read to identify emerging themes, which were reviewed and refined to develop common and divergent patterns. Results There was a huge gap between what the DCL and VCSP say and how law enforcement officers and PWID/PWUD understood them. The gap was also evident in how law enforcement officers implemented the DCL and VCSP. Harm reduction services, including health- and non-health-related interventions, were limited and challenged by unsupportive attitudes, misinterpretation of the DCL and VCSP, and the lack of full engagement with NGOs in the development of these instruments. The needs of PWID/PWUD in accessing health care services were not met due to misconduct of authorities while practicing the DCL and VCSP. Further, the misconduct and enforcement of the law and policy lead to increased social discrimination and physical abuses against PWID/PWUD. Conclusions There is a lack of common understanding of the drug-related law and policy and their implications to harm reduction services among both law enforcement officers and PWID/PWUD. Thus, there is a need to mainstream and simplify the law and policy for better comprehension among these actors. To improve the quality and coverage of harm reduction interventions, the gap of understanding and enforcement of laws and policies should be narrowed, and coordination between the government and NGOs and other key stakeholders should be strengthened.

Abstract Background There is growing interest in the expansion of community health workers programmes in low- and middle-income countries as a cost-effective approach to address shortages of health professionals. However, our understanding of the reception of large-scale programmes and how to improve them remains limited, with knowledge gaps about factors that may promote or discourage equitable access to services. This paper examines the case of the Village Malaria Workers (VMW) programme in Cambodia, an extensive community-based intervention for the management of malaria cases in remote rural areas. Method Fieldwork was conducted in Kampot province, in six case villages characterised by different programme configuration, population size, and distance to the nearest public health facility. In these locations, in-depth interviews (n = 71) with VMWs, village authorities, and residents were conducted to identify facilitators and challenges to service utilisation. Data analysis was informed by a conceptual framework based on five domains of access to services: awareness, accessibility, accommodation, availability, and acceptability. Results Factors that influenced the utilisation of VMW services in our research sites include: the nature of dissemination activities and their ability to reach different population groups; the village topography and the changing road infrastructure; the involvement of VMWs in other community roles and activities; perceptions about the type of disease after the onset of symptoms; the need for comprehensive diagnosis and care; perceptions about the status of VMWs as medical providers; length of VMW appointment. Conclusions This study highlights the complexity and diversity of contextual factors that may influence the uptake of a community health programme. As in other countries, continued use of lay health workers in Cambodia to deliver diagnostic and curative services has the potential for great health and economic impact. However, further consideration should be given to the problem of access in different categories of residents and different contexts of implementation. In addition, a comprehensive mapping of changes in disease epidemiology, road infrastructure and the geography of access to services is crucial to inform policy development in this area.

Abstract Background With the availability of more healthcare courses and an increased intake of nursing students, education institutions are facing challenges to attract school leavers to enter nursing courses. The comparison of career choice influences and perception of nursing among healthcare students can provide information for recruitment strategies. An instrument to compare the influences of healthcare career choice is lacking. The purpose of this study is to develop and evaluate the psychometric properties of an instrument to compare the influences of healthcare career choice with perceptions of nursing as a career choice. Methods The study was conducted in two phases. In phase one, two sets of scales with parallel items that measure the influences of healthcare career choice and perceptions of nursing as a career choice were developed through an earlier qualitative study, literature review, and expert validation. Phase two involved testing the construct validity, concurrent validity and reliability with a convenience sample of 283 first year healthcare students who were recruited at two education institutions in Singapore. Results An exploratory factor analysis revealed 35-parallel items in a six-factor solution (personal interest, prior healthcare exposure, self-efficacy, perceived nature of work, job prospects, and social influences) that explained 59 and 64% of the variance for healthcare career choice and nursing as a career choice respectively. A high correlation (r = 0.76, p

Abstract Background To investigate postural effects on intraocular pressure (IOP) and ocular perfusion pressure (OPP) in patients with non-arteritic ischemic optic neuropathy (NAION). Methods IOP and blood pressure (BP) were measured in 20 patients with unilateral NAION 10 min after changing to each of the following positions sequentially: sitting, supine, right lateral decubitus position (LDP), supine, left LDP, and supine. IOP was measured using a rebound tonometer and OPP was calculated using formulas based on mean BP. The dependent LDP (DLDP) was defined as the position when the eye of interest (affected or unaffected eye) was placed on the dependent side in the LDP. Results IOPs were significantly higher (P = 0.020) and OPPs were significantly lower (P = 0.041) in the affected eye compare with the unaffected eye, with the affected eye in DLDP. Compared with the mean IOP of the unaffected eyes, the mean IOP of the affected eyes increased significantly (+2.9 ± 4.4 versus +0.7 ± 3.1 mmHg, respectively; P = 0.003) and the mean OPP decreased significantly (−6.7 ± 9.4 versus −4.9 ± 8.0 mmHg, respectively; P = 0.022) after changing positions from supine to DLDP. In addition, changing position from supine to DLDP showed significantly larger absolute changes in IOP (4.13 ± 3.19 mmHg versus 2.51 ± 1.92 mmHg, respectively; P = 0.004) and OPP (9.86 ± 5.69 mmHg versus 7.50 ± 5.49 mmHg, respectively; P = 0.009) in the affected eye compared with the unaffected eye. In the affected eye, there was a significant positive correlation between absolute change in IOP and OPP when changing position from supine to DLDP (Rho = 0.512, P = 0.021). Conclusions A postural change from supine to DLDP caused significant fluctuations in IOP and OPP of the affected eye, and may significantly increase IOP and decrease OPP. Posture-induced IOP changes may be a predisposing factor for NAION development.

Abstract Background The Government of Cambodia has committed to supporting family care for vulnerable children, including homeless populations. Collecting baseline data on the numbers and characteristics of homeless adolescents was prioritized to illuminate the scope of the issue, mobilize resources and direct the response. Methods Administrative zones across seven cities were purposively selected to cover the main urban areas known to have homeless populations in Cambodia. A complete enumeration of homeless individuals between the ages of 13 and 17 was attempted in the selected areas. In addition, a second independent count was conducted to enable a statistical estimation of completeness based on overlap across counts. This technique is known as capture-recapture. Adolescents were also interviewed about their schooling, health and other circumstances. Results After adjustment by the capture-recapture corrective multipliers (range: 3.53 -27.08), the study yielded an estimate of 2,697 13–17 year old homeless adolescents across all seven cities. The total number of homeless boys counted was significantly greater than homeless girls, especially in older ages. Conclusions To the authors’ knowledge, this is the first time capture-recapture methods have been applied to a homeless estimation of this scale in a resource-limited setting. Findings suggest the number of homeless adolescents in Cambodia is much greater than one would expect if relying on single count data alone and that this population faces many hardships.

Abstract Background The recent dramatic decline in dihydroartemisinin-piperaquine (DHA-PPQ) efficacy in northwestern Cambodia has raised concerns about the rapid spread of piperaquine resistance just as DHA-PPQ is being introduced as first-line therapy in neighbouring countries. Methods Ex vivo parasite susceptibilities were tracked to determine the rate of progression of DHA, PPQ and mefloquine (MQ) resistance from sentinel sites on the Thai–Cambodian and Thai–Myanmar borders from 2010 to 2015. Immediate ex vivo (IEV) histidine-rich protein 2 (HRP-2) assays were used on fresh patient Plasmodium falciparum isolates to determine drug susceptibility profiles. Results IEV HRP-2 assays detected the precipitous emergence of PPQ resistance in Cambodia beginning in 2013 when 40 % of isolates had an IC90 greater than the upper limit of prior years, and this rate doubled to 80 % by 2015. In contrast, Thai–Myanmar isolates from 2013 to 14 remained PPQ-sensitive, while northeastern Thai isolates appeared to have an intermediate resistance profile. The opposite trend was observed for MQ where Cambodian isolates appeared to have a modest increase in overall sensitivity during the same period, with IC50 declining to median levels comparable to those found in Thailand. A significant association between increased PPQ IC50 and IC90 among Cambodian isolates with DHA-PPQ treatment failure was observed. Nearly all Cambodian and Thai isolates were deemed artemisinin resistant with a >1 % survival rate for DHA in the ring-stage assay (RSA), though there was no correlation among isolates to indicate cross-resistance between PPQ and artemisinins. Conclusions Clinical DHA-PPQ failures appear to be associated with declines in the long-acting partner drug PPQ, though sensitivity appears to remain largely intact for now in western Thailand. Rapid progression of PPQ resistance associated with DHA-PPQ treatment failures in northern Cambodia limits drugs of choice in this region, and urgently requires alternative therapy. The temporary re-introduction of artesunate AS-MQ is the current response to PPQ resistance in this area, due to inverse MQ and PPQ resistance patterns. This will require careful monitoring for re-emergence of MQ resistance, and possible simultaneous resistance to all three drugs (AS, MQ and PPQ).

Abstract Background The prevalence of HIV and sexually transmitted infections (STIs) among key populations in Cambodia continues to rise. To address this issue, KHANA, the largest national HIV organization in the country developed and implemented the Sustainable Action against HIV and AIDS in Communities (SAHACOM) project. This study aims to determine the impacts of the SAHACOM on sexual behaviors and the uptake of HIV/STI services among men who have sex with men (MSM) in Cambodia. Methods We compared outcome indicators at midterm (n = 352) and endline (n = 394). Surveys were conducted in 2012 and 2014 in Battambang and Siem Reap provinces. A two-stage cluster sampling method was employed to select the study sample for structured interviews. Results The midterm and endline samples were similar. The average number of sexual partners in the past three months decreased significantly from 6.2 to 4.0 (p = 0.03). The proportion of MSM who reported paying for sex with men in the past three months also decreased significantly from 19.0 % to 9.7 % (OR = 2.0, 95 % CI = 1.3-3.0). No significant change was found in condom and lubricant use in all types of relationships. Regarding STIs, 28.1 % of MSM at midterm reported having at least one STI symptom in the past three months compared to 6.1 % at endline (OR = 4.6, 95 % CI = 2.9–7.4); out of them, 14.1 % of MSM at midterm sought treatment compared to 20.7 % at endline (OR = 2.6, 95 % CI = 1.1–6.9). The proportion of MSM who reported using illicit drugs in the past three months also decreased significantly from 12.2 % to 5.1 % (OR = 2.4, 95 % CI = 1.4–4.2). However, the proportion of MSM who reported having been tested for HIV in the past six months decreased significantly from 94.1 % to 77.1 % (OR = 2.9, 95 % CI = 1.8–3.6). Conclusions Findings from this study indicate that the SAHACOM was effective in improving sexual behaviors and related health outcomes among MSM under the project. However, it could not increase condom use and HIV testing rates among this key population. Tailored intervention programs are needed to improve condom use and HIV testing among MSM in Cambodia.

Abstract Background There is increasing perception that countries cannot work in isolation to militate against the threat of pandemic influenza. In the Greater Mekong Subregion (GMS) of Asia, high socio-economic diversity and fertile conditions for the emergence and spread of infectious diseases underscore the importance of transnational cooperation. Investigation of healthcare resource distribution and inequalities can help determine the need for, and inform decisions regarding, resource sharing and mobilisation. Methods We collected data on healthcare resources deemed important for responding to pandemic influenza through surveys of hospitals and district health offices across four countries of the GMS (Cambodia, Lao PDR, Thailand, Vietnam). Focusing on four key resource types (oseltamivir, hospital beds, ventilators, and health workers), we mapped and analysed resource distributions at province level to identify relative shortages, mismatches, and clustering of resources. We analysed inequalities in resource distribution using the Gini coefficient and Theil index. Results Three quarters of the Cambodian population and two thirds of the Laotian population live in relatively underserved provinces (those with resource densities in the lowest quintile across the region) in relation to health workers, ventilators, and hospital beds. More than a quarter of the Thai population is relatively underserved for health workers and oseltamivir. Approximately one fifth of the Vietnamese population is underserved for beds and ventilators. All Cambodian provinces are underserved for at least one resource. In Lao PDR, 11 percent of the population is underserved by all four resource items. Of the four resources, ventilators and oseltamivir were most unequally distributed. Cambodia generally showed higher levels of inequalities in resource distribution compared to other countries. Decomposition of the Theil index suggests that inequalities result principally from differences within, rather than between, countries. Conclusions There is considerable heterogeneity in healthcare resource distribution within and across countries of the GMS. Most inequalities result from within countries. Given the inequalities, mismatches, and clustering of resources observed here, resource sharing and mobilization in a pandemic scenario could be crucial for more effective and equitable use of the resources that are available in the GMS.

Abstract Background This study was undertaken to evaluate the beneficial effects of a modified prescription of Sutaehwan named Sutaehwan-Gami (SG), created by adding Rhizoma dioscoreae and Carthami semen to Sutaehwan, on menopausal symptoms. Methods To evaluate the estrogenic effect of SG, we first examined estrogen receptor (ER) activation by SG treatment in breast adenocarcinoma cells and confirmed the estrogenic effect of SG in vivo ovariectomized rats. The animals were randomized into four groups: Sham operated group (Sham), saline treated ovariectomized group (OVX), SG treated group (SG) and raloxifene treated group (RLX). Animals were provided with SG at a dose of 500 mg/kg bw/day and RLX at a dose of 5.4 mg/kg bw/day with standard rat pellets for 3 months. Results SG significantly increased ERα phosphorylation, and its downstream effectors, extracellular signal-regulated kinase (ERK) and protein kinase B (Akt) phosphorylation in breast adenocarcinoma cells. Treatment with SG reversed ovariectomy-induced uterine weight reduction and weight gain. Decreases in the levels of GOT and GPT were observed in the SG group. The significantly reduced E2β level in OVX rats was raised by treatment with SG. Moreover, SG significantly increased the phosphorylation levels of ERK and Akt in the uterus. Conclusion Taken together, these data indicate that SG has phytoestrogen-like properties through ERK and Akt activation, implying that it could be protective and beneficial for the management of menopausal symptoms.

Abstract Background Health care planning for pandemic influenza is a challenging task which requires predictive models by which the impact of different response strategies can be evaluated. However, current preparedness plans and simulations exercises, as well as freely available simulation models previously made for policy makers, do not explicitly address the availability of health care resources or determine the impact of shortages on public health. Nevertheless, the feasibility of health systems to implement response measures or interventions described in plans and trained in exercises depends on the available resource capacity. As part of the AsiaFluCap project, we developed a comprehensive and flexible resource modelling tool to support public health officials in understanding and preparing for surges in resource demand during future pandemics. Results The AsiaFluCap Simulator is a combination of a resource model containing 28 health care resources and an epidemiological model. The tool was built in MS Excel© and contains a user-friendly interface which allows users to select mild or severe pandemic scenarios, change resource parameters and run simulations for one or multiple regions. Besides epidemiological estimations, the simulator provides indications on resource gaps or surpluses, and the impact of shortages on public health for each selected region. It allows for a comparative analysis of the effects of resource availability and consequences of different strategies of resource use, which can provide guidance on resource prioritising and/or mobilisation. Simulation results are displayed in various tables and graphs, and can also be easily exported to GIS software to create maps for geographical analysis of the distribution of resources. Conclusions The AsiaFluCap Simulator is freely available software (http://www.cdprg.org) which can be used by policy makers, policy advisors, donors and other stakeholders involved in preparedness for providing evidence based and illustrative information on health care resource capacities during future pandemics. The tool can inform both preparedness plans and simulation exercises and can help increase the general understanding of dynamics in resource capacities during a pandemic. The combination of a mathematical model with multiple resources and the linkage to GIS for creating maps makes the tool unique compared to other available software.

Abstract Background Salmonella enterica serovar Typhi (S. Typhi) is a human-specific pathogen that causes typhoid fever, and remains a global health problem especially in developing countries. Its pathogenesis is complex and host response is poorly understood. In Africa, typhoid fever can be a major cause of morbidity in young infected children. The onset of the illness is insidious and clinical diagnosis is often unreliable. Gold standard blood culture diagnostic services are limited, thus rapid, sensitive, and affordable diagnostic test is essential in poor-resourced clinical settings. Routine typhoid fever vaccination is highly recommended but currently licensed vaccines provide only 55-75% protection. Recent epidemiological studies also show the rapid emergence of multi-drug resistant S. Typhi strains. High-throughput molecular technologies, such as microarrays, can dissect the molecular mechanisms of host responses which are S. Typhi-specific to provide a comprehensive genomic component of immunological responses and suggest new insights for diagnosis and treatment. Methods Global transcriptional profiles of S. Typhi-infected young Nigerian children were obtained from their peripheral blood and compared with that of other bacteremic infections using Agilent gene expression microarrays. The host-response profiles of the same patients in acute vs. convalescent phases were also determined. The top 96-100 differentially-expressed genes were identified and four genes were validated by quantitative real-time PCR. Gene clusters were obtained and functional pathways were predicted by DAVID (Database for Annotation, Visualization and Integrated Discovery). Results Transcriptional profiles from S. Typhi-infected children could be distinguished from those of other bacteremic infections. Enriched gene clusters included genes associated with extracellular peptides/components such as lipocalin (LCN2) and systemic immune response which is atypical in bacterial invasion. Distinct gene expression profiles can also be obtained from acute vs. convalescent phase during typhoid fever infection. We found novel down-regulation of ABC (ATP-binding cassette) transporters genes such as ABCA7, ABCC5, and ABCD4 and ATPase activity as the highest enriched pathway. Conclusions We identified unique extracellular components and ABC transporters gene enrichments in typhoid fever-infected Nigerian children, which have never been reported. These enriched gene clusters may represent novel targeted pathways to improve diagnostic, prognostic, therapeutic and next-generation vaccine strategies for typhoid fever in Africa.

Abstract Background There is a significant increase in survival for HIV-infected children who have early access to diagnosis and treatment. The goal of this multi-country review was to examine when and where HIV-exposed infants and children are being diagnosed, and whether the EID service is being maximally utilized to improve health outcomes for HIV-exposed children. Methods In four countries across Africa and Asia existing documents and data were reviewed and key informant interviews were conducted. EID testing data was gathered from the central testing laboratories and was then complemented by health facility level data extraction which took place using a standardized and validated questionnaire Results In the four countries reviewed from 2006 to 2009 EID sample volumes rose dramatically to an average of >100 samples per quarter in Cambodia and Senegal, >7,000 samples per quarter in Uganda, and >2,000 samples per quarter in Namibia. Geographic coverage of sites also rapidly expanded to 525 sites in Uganda, 205 in Namibia, 48 in Senegal, and 26 in Cambodia in 2009. However, only a small proportion of testing was done at lower-level health facilities: in Uganda Health Center IIs and IIIs comprised 47% of the EID collection sites, but only 11% of the total tests, and in Namibia 15% of EID sites collected >93% of all samples. In all countries except for Namibia, more than 50% of the EID testing was done after 2 months of age. Few sites had robust referral mechanisms between EID and ART. In a sub-sample of children, we noted significant attrition of infants along the continuum of care post testing. Only 22% (Senegal), 37% (Uganda), and 38% (Cambodia) of infants testing positive by PCR were subsequently initiated onto treatment. In Namibia, which had almost universal EID coverage, more than 70% of PCR-positive infants initiated ART in 2008. Conclusions While EID testing has expanded dramatically, a large proportion of PCR- positive infants are initiated on treatment. As EID services continue to scale-up, more programmatic attention and support is needed to retain HIV-exposed infants in care and ensure that those testing positive initiate treatment in a timely manner. Namibia's experience demonstrates that it is feasible for a rural, low-income country to achieve high national coverage of infant testing and treatment.

Abstract Background Since 2003, Asia-Pacific, particularly Southeast Asia, has received substantial attention because of the anticipation that it could be the epicentre of the next pandemic. There has been active investment but earlier review of pandemic preparedness plans in the region reveals that the translation of these strategic plans into operational plans is still lacking in some countries particularly those with low resources. The objective of this study is to understand the pandemic preparedness programmes, the health systems context, and challenges and constraints specific to the six Asian countries namely Cambodia, Indonesia, Lao PDR, Taiwan, Thailand, and Viet Nam in the prepandemic phase before the start of H1N1/2009. Methods The study relied on the Systemic Rapid Assessment (SYSRA) toolkit, which evaluates priority disease programmes by taking into account the programmes, the general health system, and the wider socio-cultural and political context. The components under review were: external context; stewardship and organisational arrangements; financing, resource generation and allocation; healthcare provision; and information systems. Qualitative and quantitative data were collected in the second half of 2008 based on a review of published data and interviews with key informants, exploring past and current patterns of health programme and pandemic response. Results The study shows that health systems in the six countries varied in regard to the epidemiological context, health care financing, and health service provision patterns. For pandemic preparation, all six countries have developed national governance on pandemic preparedness as well as national pandemic influenza preparedness plans and Avian and Human Influenza (AHI) response plans. However, the governance arrangements and the nature of the plans differed. In the five developing countries, the focus was on surveillance and rapid containment of poultry related transmission while preparation for later pandemic stages was limited. The interfaces and linkages between health system contexts and pandemic preparedness programmes in these countries were explored. Conclusion Health system context influences how the six countries have been preparing themselves for a pandemic. At the same time, investment in pandemic preparation in the six Asian countries has contributed to improvement in health system surveillance, laboratory capacity, monitoring and evaluation and public communications. A number of suggestions for improvement were presented to strengthen the pandemic preparation and mitigation as well as to overcome some of the underlying health system constraints.

Abstract Background Chromophobe renal cell carcinoma (chRCC) and renal oncocytoma are two distinct but closely related entities with strong morphologic and genetic similarities. While chRCC is a malignant tumor, oncocytoma is usually regarded as a benign entity. The overlapping characteristics are best explained by a common cellular origin, and the biologic differences between chRCC and oncocytoma are therefore of considerable interest in terms of carcinogenesis, diagnosis and clinical management. Previous studies have been relatively limited in terms of examining the differences between oncocytoma and chromophobe RCC. Methods Gene expression profiling using the Affymetrix HGU133Plus2 platform was applied on chRCC (n = 15) and oncocytoma specimens (n = 15). Supervised analysis was applied to identify a discriminatory gene signature, as well as differentially expressed genes. High throughput single-nucleotide polymorphism (SNP) genotyping was performed on independent samples (n = 14) using Affymetrix GeneChip Mapping 100 K arrays to assess correlation between expression and gene copy number. Immunohistochemical validation was performed in an independent set of tumors. Results A novel 14 probe-set signature was developed to classify the tumors internally with 93% accuracy, and this was successfully validated on an external data-set with 94% accuracy. Pathway analysis highlighted clinically relevant dysregulated pathways of c-erbB2 and mammalian target of rapamycin (mTOR) signaling in chRCC, but no significant differences in p-AKT or extracellular HER2 expression was identified on immunohistochemistry. Loss of chromosome 1p, reflected in both cytogenetic and expression analysis, is common to both entities, implying this may be an early event in histogenesis. Multiple regional areas of cytogenetic alterations and corresponding expression biases differentiating the two entities were identified. Parafibromin, aquaporin 6, and synaptogyrin 3 were novel immunohistochemical markers effectively discriminating the two pathologic entities. Conclusions Gene expression profiles, high-throughput SNP genotyping, and pathway analysis effectively distinguish chRCC from oncocytoma. We have generated a novel transcript predictor that is able to discriminate between the two entities accurately, and which has been validated both in an internal and an independent data-set, implying generalizability. A cytogenetic alteration, loss of chromosome 1p, common to renal oncocytoma and chRCC has been identified, providing the opportunities for identifying novel tumor suppressor genes and we have identified a series of immunohistochemical markers that are clinically useful in discriminating chRCC and oncocytoma.

Abstract Background Klotho was originally characterized as an anti-aging gene that predisposed Klotho-deficient mice to a premature aging-like syndrome. Recently, KLOTHO was reported to function as a secreted Wnt antagonist and as a tumor suppressor. Epigenetic gene silencing of secreted Wnt antagonists is considered a common event in a wide range of human malignancies. Abnormal activation of the canonical Wnt pathway due to epigenetic deregulation of Wnt antagonists is thought to play a crucial role in cervical tumorigenesis. In this study, we examined epigenetic silencing of KLOTHO in human cervical carcinoma. Results Loss of KLOTHO mRNA was observed in several cervical cancer cell lines and in invasive carcinoma samples, but not during the early, preinvasive phase of primary cervical tumorigenesis. KLOTHO mRNA was restored after treatment with either the DNA demethylating agent 2'-deoxy-5-azacytidine or histone deacetylase inhibitor trichostatin A. Methylation-specific PCR and bisulfite genomic sequencing analysis of the promoter region of KLOTHO revealed CpG hypermethylation in non-KLOTHO-expressing cervical cancer cell lines and in 41% (9/22) of invasive carcinoma cases. Histone deacetylation was also found to be the major epigenetic silencing mechanism for KLOTHO in the SiHa cell line. Ectopic expression of the secreted form of KLOTHO restored anti-Wnt signaling and anti-clonogenic activity in the CaSki cell line including decreased active β-catenin levels, suppression of T-cell factor/β-catenin target genes, such as c-MYC and CCND1, and inhibition of colony growth. Conclusions Epigenetic silencing of KLOTHO may occur during the late phase of cervical tumorigenesis, and consequent functional loss of KLOTHO as the secreted Wnt antagonist may contribute to aberrant activation of the canonical Wnt pathway in cervical carcinoma.

Abstract Background While several molecular markers of bladder cancer prognosis have been identified, the limited value of current prognostic markers has created the need for new molecular indicators of bladder cancer outcomes. The aim of this study was to identify genetic signatures associated with disease prognosis in bladder cancer. Results We used 272 primary bladder cancer specimens for microarray analysis and real-time reverse transcriptase polymerase chain reaction (RT-PCR) analysis. Microarray gene expression analysis of randomly selected 165 primary bladder cancer specimens as an original cohort was carried out. Risk scores were applied to stratify prognosis-related gene classifiers. Prognosis-related gene classifiers were individually analyzed with tumor invasiveness (non-muscle invasive bladder cancer [NMIBC] and muscle invasive bladder cancer [MIBC]) and prognosis. We validated selected gene classifiers using RT-PCR in the original (165) and independent (107) cohorts. Ninety-seven genes related to disease progression among NMIBC patients were identified by microarray data analysis. Eight genes, a progression-related gene classifier in NMIBC, were selected for RT-PCR. The progression-related gene classifier in patients with NMIBC was closely correlated with progression in both original and independent cohorts. Furthermore, no patient with NMIBC in the good-prognosis signature group experienced cancer progression. Conclusions We identified progression-related gene classifier that has strong predictive value for determining disease outcome in NMIBC. This gene classifier could assist in selecting NMIBC patients who might benefit from more aggressive therapeutic intervention or surveillance.

Abstract Background S100 calcium binding protein A8 (S100A8) has been implicated as a prognostic indicator in several types of cancer. However, previous studies are limited in their ability to predict the clinical behavior of the cancer. Here, we sought to identify a molecular signature based on S100A8 expression and to assess its usefulness as a prognostic indicator of disease progression in non-muscle invasive bladder cancer (NMIBC). Methods We used 103 primary NMIBC specimens for microarray gene expression profiling. The median follow-up period for all patients was 57.6 months (range: 3.2 to 137.0 months). Various statistical methods, including the leave-one-out cross validation method, were applied to identify a gene expression signature able to predict the likelihood of progression. The prognostic value of the gene expression signature was validated in an independent cohort (n = 302). Results Kaplan-Meier estimates revealed significant differences in disease progression associated with the expression signature of S100A8-correlated genes (log-rank test, P < 0.001). Multivariate Cox regression analysis revealed that the expression signature of S100A8-correlated genes was a strong predictor of disease progression (hazard ratio = 15.225, 95% confidence interval = 1.746 to 133.52, P = 0.014). We validated our results in an independent cohort and confirmed that this signature produced consistent prediction patterns. Finally, gene network analyses of the signature revealed that S100A8, IL1B, and S100A9 could be important mediators of the progression of NMIBC. Conclusions The prognostic molecular signature defined by S100A8-correlated genes represents a promising diagnostic tool for the identification of NMIBC patients that have a high risk of progression to muscle invasive bladder cancer.

Abstract Background There is little information about influenza disease among the Cambodian population. To better understand the dynamics of influenza in Cambodia, the Cambodian National Influenza Center (NIC) was established in August 2006. To continuously monitor influenza activity, a hospital based sentinel surveillance system for ILI (influenza like illness) with a weekly reporting and sampling scheme was established in five sites in 2006. In addition, hospital based surveillance of acute lower respiratory infection (ALRI) cases was established in 2 sites. Methods The sentinel sites collect weekly epidemiological data on ILI patients fulfilling the case definition, and take naso-pharyngeal specimens from a defined number of cases per week. The samples are tested in the Virology Unit at the Institut Pasteur in Phnom Penh. From each sample viral RNA was extracted and amplified by a multiplex RT-PCR detecting simultaneously influenza A and influenza B virus. Influenza A viruses were then subtyped and analyzed by hemagglutination inhibition assay. Samples collected by the ALRI system were tested with the same approach. Results From 2006 to 2008, influenza circulation was observed mainly from June to December, with a clear seasonal peak in October shown in the data from 2008. Conclusion Influenza activity in Cambodia occurred during the rainy season, from June to December, and ended before the cool season (extending usually from December to February). Although Cambodia is a tropical country geographically located in the northern hemisphere, influenza activity has a southern hemisphere transmission pattern. Together with the antigenic analysis of the circulating strains, it is now possible to give better influenza vaccination recommendation for Cambodia.

Abstract Background Injection overuse and unsafe injection practices facilitate transmission of bloodborne pathogens such as hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV). Anecdotal reports of unsafe and unnecessary therapeutic injections and the high prevalence of HBV (8.0%), HCV (6.5%), and HIV (2.6%) infection in Cambodia have raised concern over injection safety. To estimate the magnitude and patterns of such practices, a rapid assessment of injection practices was conducted. Methods We surveyed a random sample of the general population in Takeo Province and convenience samples of prescribers and injection providers in Takeo Province and Phnom Penh city regarding injection-related knowledge, attitudes, and practices. Injection providers were observed administering injections. Data were collected using standardized methods adapted from the World Health Organization safe injection assessment guidelines. Results Among the general population sample (n = 500), the overall injection rate was 5.9 injections per person-year, with 40% of participants reporting receipt of ≥ 1 injection during the previous 6 months. Therapeutic injections, intravenous infusions, and immunizations accounted for 74%, 16% and 10% of injections, respectively. The majority (>85%) of injections were received in the private sector. All participants who recalled their last injection reported the injection was administered with a newly opened disposable syringe and needle. Prescribers (n = 60) reported that 47% of the total prescriptions they wrote included a therapeutic injection or infusion. Among injection providers (n = 60), 58% recapped the syringe after use and 13% did not dispose of the used needle and syringe appropriately. Over half (53%) of the providers reported a needlestick injury during the previous 12 months. Ninety percent of prescribers and injection providers were aware HBV, HCV, and HIV were transmitted through unsafe injection practices. Knowledge of HIV transmission through "dirty" syringes among the general population was also high (95%). Conclusion Our data suggest that Cambodia has one of the world's highest rates of overall injection usage, despite general awareness of associated infection risks. Although there was little evidence of reuse of needles and syringes, support is needed for interventions to address injection overuse, healthcare worker safety and appropriate waste disposal.

Abstract Background Non-Hodgkin lymphoma (NHL) has been identified as a significant contributor to the cancer burden. This study investigates the incidence, mortality, and survival trends of NHL cancer in Brunei Darussalam from 2011 to 2020. Methods This is a registry-based retrospective study using de-identified data from the Brunei Darussalam Cancer Registry on patients diagnosed with NHL from 2011 to 2020 based on the ICD-10 codes C82-86. Statistical methods include descriptive statistics, age-specific and age-standardised incidence (ASIR) and mortality rates (ASMR), and joinpoint regression for trend analysis. Survival analysis was conducted using Kaplan-Meier plots, log-rank test, and Cox Proportional Hazards regression. Results From 2011 to 2020, 330 patients were diagnosed with NHL. The majority of patients were males (51.8%) and of Malay descent (82.7%). The age group most diagnosed was 55–74 years (42.3%), with a mean age at diagnosis being 55.1 years. The ASIRs were 12.12 for males and 10.39 per 100,000 for females; ASMRs were 6.11 for males and 4.76 per 100,000 for females. Diffuse large B-cell lymphoma was the most prevalent subtype, accounting for 39.1% of cases. The overall 5-year survival rate was 61.2%, with lower rates observed in older patients and those diagnosed at distant metastasis stage. Furthermore, older age and advanced stage diagnosis significantly increased mortality risk. NHL incidence and mortality rates in Brunei Darussalam remain stable over the period of 10 years, but highlights significant disparities in gender and age. Conclusions The findings emphasize the importance of early detection and tailored treatments, especially for high-risk groups, in managing NHL’s burden. These insights underline the need for focused healthcare strategies and continued research to address NHL’s challenges.

Abstract Background Healthcare Workers (HCWs) are susceptible to hepatitis B virus (HBV) infection and are advised to receive vaccination. However, vaccination rates remain low in developing countries. There is little data concerning Hepatitis B (HepB) vaccination and information regarding HBV knowledge among HCWs in Cambodia. This study aimed to evaluate the knowledge of HBV infection, HepB vaccine, and vaccination status with its associated factors among HCWs in Cambodia. Methods A Cross-sectional study was conducted among HCWs in Kampot and Kep Provinces, Cambodia, from September to October 2023 using a questionnaire survey. A total of 261 HCWs were recruited from 1,309 individuals working in all 83 health facilities using systematic random sampling methods. Statistical analyses including the χ2-test and multivariate logistic regression were conducted to identify factors associated with vaccination among the participants. Results Among 259 participants, 62.9% showed good knowledge of HBV infection, and 65.6% demonstrated good knowledge of the HepB vaccine. 59.8% of the participants had received the HepB vaccine, while 40.2% remained unvaccinated. Analysis showed that HCWs working at Provincial Health Department/Operational Districts and Provincial Referral Hospital/Referral Hospitals were more likely to be vaccinated compared to those at Health Centers [AOR = 6.5; CI = 1.1–39.5, p = 0.0403; AOR = 2.8, CI = 1.0–7.8, p = 0.0412], respectively. Furthermore, individuals with good knowledge of the HBV infection and vaccine were more likely to receive the vaccine compared to those with inadequate knowledge [AOR = 6.3; CI = 3.3–12.3, p

Abstract Background Societal attitudes toward ageing play a significant role in shaping one’s ageing experience, and an age-friendly environment can potentially enhance the life satisfaction of older individuals. The objective of this study is to examine the role of attitudes to ageing as mediators in the association between the perception of an age-friendly city and life satisfaction among middle-aged and older adults. Methods Using the tools of Age-Friendly City (AFC) criteria, Attitudes to Ageing Questionnaire (AAQ) to measure psychosocial loss, psychological growth, and physical change, and Satisfaction with Life Scale (SWLS) to assess the level of life satisfaction among community-dwelling middle-aged and older people in Macao. Multiple mediation analysis was performed to test the mediation effect. Results A total of 543 participants were included in this study. The average score of AFC was 4.25, the total scores of psychosocial loss, physical change, and psychological growth were 24.06, 29.00, and 26.94 respectively. The total score of SWLS was 24.06. There was a partial mediation of attitudes to ageing in the relationship between perception of age-friendly city and life satisfaction. The mediation effect explained 56.1% of the total effect of AFC to life satisfaction. Conclusion The development of an age-friendly city can help improve the public’s view on ageing, and thus improve their life satisfaction. It is important for government to consider the improvement of people’s attitudes to ageing when developing policies regarding AFC.