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Background The prognostic and pathophysiologic significance of the biliary microbiota in pancreaticobiliary malignancies is little understood. Our goal was to find malignancy-related microbiomic fingerprints in bile samples taken from patients with benign and malignant pancreaticobiliary diseases. Methods Bile specimens were collected from consenting patients during routine endoscopic retrograde cholangiopancreatography. We used PowerViral RNA/DNA Isolation kit to extract DNA from bile specimens. The Illumina 16S Metagenomic Sequencing Library Preparation guide was used to amplify the bacterial 16S rRNA gene and create libraries. QIIME (Quantitative Insights Into Microbial Ecology), Bioconductor phyloseq, microbiomeSeq, and mixMC packages were used for post-sequencing analysis. Results Of 46 enrolled patients, 32 patients had pancreatic cancers, 6 had cholangiocarcinoma and 1 had gallbladder cancer. Rest of the patients had benign diseases including gallstones, and acute and chronic pancreatitis. We used multivariate approach in mixMC to classify Operational Taxonomic Units (OTUs). Doing this, we found a predominance of genera Dickeya (p = 0.00008), [Eubacterium] hallii group (p = 0.0004), Bacteroides (p = 0.0006), Faecalibacterium (p = 0.006), Escherichia-Shigella (p = 0.008), and Ruminococcus 1 (p = 0.008) in bile samples from pancreaticobiliary cancers as compared to benign diseases. Additionally, bile samples from patients with pancreatic cancer exhibited a predominance of genus Rothia (p = 0.008) as compared to those with cholangiocarcinoma, whereas bile samples from patients with cholangiocarcinoma exhibited a predominance of genera Akkermansia (p = 0.031) and Achromobacter (p = 0.031) as compared to those with pancreatic cancers. Conclusions Both benign and malignant pancreaticobiliary diseases have distinct microbiomic fingerprints. The relative abundance of OTUs in bile samples varies between patients with benign and malignant pancreaticobiliary diseases, as well as between cholangiocarcinoma and pancreatic cancer. Our data suggest that either these OTUs play a role in carcinogenesis or that benign disease-specific microenvironmental changes differ from cancer-specific microenvironmental changes, resulting to a clear separation of OTU clusters. We need more research to confirm and expand on our findings.

This research proposes a simulation-based assessment of outdoor thermal and acoustic comfort for a planned business urban district in Singapore for retail planning using a customized OpenFOAM-centric multi-physics environmental simulation platform called the Integrated Environmental Modeller (IEM). IEM was employed to simulate the coupled impacts of solar radiation on wind and air temperature and wind and air temperature effects on traffic noise propagation in the district on the equinox and solstice day of the hottest period. Using IEM simulation results, we computed the thermal and acoustic comfort acceptability indicators derived from local field studies’ results. The spatial distribution of environmental comfort acceptability indicators in the worst-case scenario can be used to distinguish the zones exposed to thermal or noise influence. The noise-affected zones are near the main roads and overlap a part of the thermal-affected area. The thermal-affected area is almost everywhere in the studied sites in the worst-case scenario. Having outdoor retail spaces with both poor thermal and acoustic comfort is not recommended if the thermal and acoustic comfort cannot be improved simultaneously. For the high-level retail planning, a simplified parametric analysis considering solar irradiance blockage and wind speed enhancements, is provided. Considering the worst-case scenario, ≥50% thermal acceptability can be achieved by blocking 54%-68% solar irradiance among the pedestrian thoroughfares and the retail spaces. Coupled together, blocking the solar irradiance and enhancing the wind speed can further improve thermal comfort locally. These results can guide the retail mix (e.g., al fresco restaurants, pop-up kiosks etc.) near high footfall areas and provide reference for future plans combining landscape and infrastructure, (e.g., trees with shelter walkaways, green walls with outdoor ventilation fans etc.) taking into account the environmental acceptability of people working in or visiting the tropical urban district.

This study evaluated the knowledge of diabetes mellitus and predictors of the level of diabetes knowledge among the general public of Singapore. Confirmatory factor analysis and exploratory factor analysis were used to evaluate the fit of different factor models for the diabetes knowledge questionnaire. Multiple linear regressions were performed to determine the sociodemographic characteristics associated with diabetes knowledge. The final factor model identified three domains for diabetes knowledge: general knowledge, diabetes specific knowledge and causes of diabetes, and complications of untreated diabetes. Overall knowledge scores were 23.8 ± 2.4 for general diabetes knowledge, 2.3 ± 0.8 for diabetes specific knowledge, 2.3 ± 1.2 for causes, and 5.2 ± 1.2 for complications of untreated diabetes. Patients with diabetes were more knowledgeable than adults without diabetes in the population. While the general public in Singapore has adequate knowledge of diabetes, misconceptions were identified in both groups which underscores the need to tailor specific educational initiatives to reduce these diabetes knowledge gaps.

Objectives Occupation is a poorly characterised risk factor for cardiovascular disease (CVD) with females and indigenous populations under-represented in most research. This study assessed associations between occupation and ischaemic heart disease (IHD) in males and females of the general and Māori (indigenous people of NZ) populations of New Zealand (NZ). Methods Two surveys of the NZ adult population (NZ Workforce Survey (NZWS); 2004–2006; n = 3003) and of the Māori population (NZWS Māori; 2009–2010; n = 2107) with detailed occupational histories were linked with routinely collected health data and followed-up until December 2018. Cox regression was used to calculate hazard ratios (HR) for IHD and “ever-worked” in any of the nine major occupational groups or 17 industries. Analyses were controlled for age, deprivation and smoking, and stratified by sex and survey. Results ‘Plant/machine operators and assemblers’ and ‘elementary occupations’ were positively associated with IHD in female Māori (HR 2.2, 95%CI 1.2–4.1 and HR 2.0, 1.1–3.8, respectively) and among NZWS males who had been employed as ‘plant/machine operators and assemblers’ for 10+ years (HR 1.7, 1.2–2.8). Working in the ‘manufacturing’ industry was also associated with IHD in NZWS females (HR 1.9, 1.1–3.7), whilst inverse associations were observed for ‘technicians and associate professionals’ (HR 0.5, 0.3–0.8) in NZWS males. For ‘clerks’, a positive association was found for NZWS males (HR 1.8, 1.2–2.7), whilst an inverse association was observed for Māori females (HR 0.4, 0.2–0.8). Conclusion Associations with IHD differed significantly across occupational groups and were not consistent across males and females or for Māori and the general population, even within the same occupational groups, suggesting that current knowledge regarding the association between occupation and IHD may not be generalisable across different population groups.

Multimorbidity, common in the primary care setting, has diverse implications for both the patient and the healthcare system. However, there is no consensus on the definition of multimorbidity globally. Thus, we aimed to conduct a Delphi study to gain consensus on the definition of multimorbidity, the list and number of chronic conditions used for defining multimorbidity in the Singapore primary care setting. Our Delphi study comprised three rounds of online voting from purposively sampled family physicians in public and private settings. Delphi round 1 included open-ended questions for idea generation. The subsequent two rounds used questions with pre-selected options. Consensus was achieved based on a pre-defined criteria following an iterative process. The response rates for the three rounds were 61.7% (37/60), 86.5% (32/37) and 93.8% (30/32), respectively. Among 40 panellists who responded, 46.0% were 31–40 years old, 64.9% were male and 73.0% were from the public primary healthcare setting. Based on the findings of rounds 1, 2 and 3, consensus on the definition of a chronic condition, multimorbidity and finalised list of chronic conditions were achieved. For a condition to be chronic, it should last for six months or more, be recurrent or persistent, impact patients across multiple domains and require long-term management. The consensus-derived definition of multimorbidity is the presence of three or more chronic conditions from a finalised list of 23 chronic conditions. We anticipate that our findings will inform multimorbidity conceptualisation at the national level, standardise multimorbidity measurement in primary care and facilitate resource allocation for patients with multimorbidity.

Background Post-acute coronary syndrome (ACS) depression is a common but not well understood complication experienced by ACS patients. Research on the effectiveness of various therapies remains limited. Hence, we sought to conduct a network meta-analysis to assess the efficacy of different interventions for post-ACS depression in improving patient outcomes. Methods and findings Three electronic databases were searched for randomised controlled trials describing different depression treatment modalities in post-ACS patients. Each article was screened based on inclusion criteria and relevant data were extracted. A bivariate analysis and a network meta-analysis was performed using risk ratios (RR) and standardized mean differences (SMD) for binary and continuous outcomes, respectively. A total of 30 articles were included in our analysis. Compared to standard care, psychosocial therapy was associated with the greatest reduction in depression scores (SMD:-1.21, 95% CI: -1.81 to -0.61, p Conclusion This network meta-analysis found that the treatment effect of the various psychological modalities on depression severity were similar. Future trials on psychological interventions assessing clinical outcomes and improvement in adherence to ACS-specific interventions are needed.

Introduction Cambodia aims to eliminate malaria by 2025, however tackling Plasmodium vivax (P.v) presents multiple challenges. The prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency has prevented the deployment of 8-aminoquinolones for “radical cure”, due to the risk of severe haemolysis. Patients with P. vivax have therefore continued to experience recurrent relapses leading to cumulative health and socioeconomic burden. The recent advent of point of care testing for G6PD deficiency has made radical cure a possibility, however at the time of the study lack of operational experience and guidance meant that they had not been introduced. This study therefore aimed to design, implement and evaluate a new care pathway for the radical cure of P.vivax. Methods This implementation study took place in Pursat province, Western Cambodia. The interventions were co-developed with key stakeholders at the national, district, and local level, through a continuous process of consultations as well as formal meetings. Mixed methods were used to evaluate the feasibility of the intervention including its uptake (G6PD testing rate and the initiation of primaquine treatment according to G6PD status); adherence (self-reported); and acceptability, using quantitative analysis of primary and secondary data as well as focus group discussions and key informant interviews. Results The co-development process resulted in the design of a new care pathway with supporting interventions, and a phased approach to their implementation. Patients diagnosed with P.v infection by Village Malaria Workers (VMWs) were referred to local health centres for point-of-care G6PD testing and initiation of radical cure treatment with 14-day or 8-week primaquine regimens depending on G6PD status. VMWs carried out follow-up in the community on days 3, 7 and 14. Supporting interventions included training, community sensitisation, and the development of a smartphone and tablet application to aid referral, follow-up and surveillance. The testing rate was low initially but increased rapidly over time, reflecting the deliberately cautious phased approach to implementation. In total 626 adults received G6PD testing, for a total of 675 episodes. Of these 555 occurred in patients with normal G6PD activity and nearly all (549/555, 98.8%) were initiated on PQ14. Of the 120 with deficient/intermediate G6PD activity 61 (50.8%) were initiated on PQ8W. Self-reported adherence was high (100% and 95.1% respectively). No severe adverse events were reported. The pathway was found to be highly acceptable by both staff and patients. The supporting interventions and gradual introduction were critical to success. Challenges included travel to remote areas and mobility of P.v patients. Conclusion The new care pathway with supporting interventions was highly feasible with high levels of uptake, adherence and acceptability in this setting where high prevalence of G6PD deficiency is high and there is a well-established network of VMWs. Scaling up of the P.v radical cure programme is currently underway in Cambodia and a decline in reduction in the burden of malaria is being seen, bringing Cambodia a step closer to elimination.

ObjectivesFamily caregivers play a fundamental role in the care of the older blunt trauma patient. We aim to identify risk factors for negative and positive experiences of caregiving among family caregivers.DesignProspective, nationwide, multi-center cohort study.Setting and participants110 family caregivers of Singaporeans aged≥55 admitted for unintentional blunt trauma with an Injury Severity Score (ISS) or New Injury Severity Score (NISS)≥10 were assessed for caregiving-related negative (disturbed schedule and poor health, lack of family support, lack of finances) and positive (esteem) experiences using the modified-Caregiver Reaction Assessment (m-CRA) three months post-injury.MethodsThe association between caregiver and patient factors, and the four m-CRA domains were evaluated via linear regression.ResultsCaregivers of retired patients and caregivers of functionally dependent patients (post-injury Barthel score Conclusions and implicationsNegative and positive experiences of caregiving among caregivers of older blunt trauma patients are associated with pre-injury disability and certain patient and caregiver demographics. These factors should be considered when planning the post-discharge support of older blunt trauma patients.

Main objective There is limited information on how patient outcomes have changed during the COVID-19 pandemic. This study characterizes changes in mortality, intubation, and ICU admission rates during the first 20 months of the pandemic. Study design and methods University of Wisconsin researchers collected and harmonized electronic health record data from 1.1 million COVID-19 patients across 21 United States health systems from February 2020 through September 2021. The analysis comprised data from 104,590 adult hospitalized COVID-19 patients. Inclusion criteria for the analysis were: (1) age 18 years or older; (2) COVID-19 ICD-10 diagnosis during hospitalization and/or a positive COVID-19 PCR test in a 14-day window (+/- 7 days of hospital admission); and (3) health system contact prior to COVID-19 hospitalization. Outcomes assessed were: (1) mortality (primary), (2) endotracheal intubation, and (3) ICU admission. Results and significance The 104,590 hospitalized participants had a mean age of 61.7 years and were 50.4% female, 24% Black, and 56.8% White. Overall risk-standardized mortality (adjusted for age, sex, race, ethnicity, body mass index, insurance status and medical comorbidities) declined from 16% of hospitalized COVID-19 patients (95% CI: 16% to 17%) early in the pandemic (February-April 2020) to 9% (CI: 9% to 10%) later (July-September 2021). Among subpopulations, males (vs. females), those on Medicare (vs. those on commercial insurance), the severely obese (vs. normal weight), and those aged 60 and older (vs. younger individuals) had especially high mortality rates both early and late in the pandemic. ICU admission and intubation rates also declined across these 20 months. Conclusions Mortality, intubation, and ICU admission rates improved markedly over the first 20 months of the pandemic among adult hospitalized COVID-19 patients although gains varied by subpopulation. These data provide important information on the course of COVID-19 and identify hospitalized patient groups at heightened risk for negative outcomes. Trial registration ClinicalTrials.gov Identifier: NCT04506528 (https://clinicaltrials.gov/ct2/show/NCT04506528).

Palm pressed fibre (PPF) is a lignocellulose biomass generated from palm oil mill that is rich in cellulose. The present work aimed to combine acid hydrolysis followed by high-pressure homogenisation (HPH) to produce nanocrystal cellulose (CNC) with enhanced physicochemical properties from PPF. PPF was alkaline treated, bleached, acid hydrolysed and homogenised under high pressure condition to prepare CNC. The effects of homogenisation pressure (10, 30, 50, 70 MPa) and cycles (1, 3, 5, 7) on the particle size, zeta potential and rheological properties of CNC produced were investigated. HPH was capable of producing CNC with better stability. Results revealed that utilizing 1 cycle of homogenisation at a pressure of 50 MPa resulted in CNC with the smallest dimension, highest aspect ratio, moderate viscosity and exceptionally high zeta potential. Subsequently, 0.15% (CNC 0.15 -PE) and 0.30% (CNC 0.30 -PE) of CNC was used to stabilise oil-in-water emulsions and their stability was evaluated against different pH, temperature and ionic strength. All the CNC-stabilised emulsions demonstrated good thermal stability. CNC 0.30 -PE exhibited larger droplets but higher stability than CNC 0.15 -PE. In short, CNC with gel like structure has a promising potential to serve as a natural Pickering emulsifier to stabilise oil-in-water emulsion in various food applications.

Insects hold considerable ecological and agricultural importance making it vital to understand the factors impacting their reproductive output. Environmental stressors are examples of such factors which have a substantial and significant influence on insect reproductive fitness. Insects are also ectothermic and small in size which makes them even more susceptible to environmental stresses. The present study assesses the consequence of desiccation on the mating latency and copulations duration in tropical Drosophila melanogaster. We tested flies for these reproductive behavioral parameters at varying body water levels and with whole metabolome analysis in order to gain a further understanding of the physiological response to desiccation. Our results showed that the duration of desiccation is positively correlated with mating latency and mating failure, while having no influence on the copulation duration. The metabolomic analysis revealed three biological pathways highly affected by desiccation: starch and sucrose metabolism, galactose metabolism, and phenylalanine, tyrosine and tryptophan biosynthesis. These results are consistent with carbohydrate metabolism providing an energy source in desiccated flies and also suggests that the phenylalanine biosynthesis pathway plays a role in the reproductive fitness of the flies. Desiccation is a common issue with smaller insects, like Drosophila and other tropical insects, and our findings indicate that this lack of ambient water can immediately and drastically affect the insect reproductive behaviour, which becomes more crucial because of unpredictable and dynamic weather conditions.

Background Older adults aged 65 years and above have a disproportionately higher utilization of emergency healthcare, of which Emergency Department (ED) visits are a key component. They experience higher degree of multimorbidity and mobility issues compared to younger patients, and are consequently more likely to experience a health event which requires an ED visit. During their visit, older adults tend to require more extensive workup, therefore spending a greater amount of time in the ED. Compared to the younger population, older adults are more susceptible to adverse events following discharge. Considering these factors, investigating the determinants of ED utilisation would be valuable. In this paper, we present a protocol for a systematic review of the determinants of ED utilisation among communitydwelling older adults aged 65 years and above, applying Andersen and Newman’s model of healthcare utilisation. Furthermore, we aim to present other conceptual frameworks for healthcare utilisation and propose a holistic approach for understanding the determinants of ED utilisation by older persons. Methods The protocol is developed in accordance with the standards of Campbell Collaboration guidelines for systematic reviews, with reference to the Cochrane Handbook for Systematic Review of Interventions. Medline, Embase and Scopus will be searched for studies published from 2000 to 2020. Studies evaluating more than one determinant for ED utilisation among older adults aged 65 years and above will be included. Search process and selection of studies will be presented in a PRISMA flow chart. Statistically significant (p < 0.05) determinants of ED utilisation will be grouped according to individual and societal determinants. Quality of the studies will be assessed using Newcastle Ottawa Scale (NOS). Discussion In Andersen and Newman’s model, individual determinants include predisposing factors, enabling and illness factors, and societal determinants include technology and social norms. Additional conceptual frameworks for healthcare utilisation include Health Belief Model, Social Determinants of Health and Big Five personality traits. By incorporating the concepts of these models, we hope to develop a holistic approach of conceptualizing the factors that influence ED utilisation among older people. Systematic review registration This protocol is registered on 8 May 2021 with PROSPERO’s International Prospective Register of Systematic Reviews (CRD42021253770).