Clinical activities that contributed to the effectiveness of a cardiologist-pharmacist collaborative care model in managing diabetes.

OBJECTIVES: The primary objectives of this study were to evaluate the change in glycated haemoglobin (HbA1c) and its association to clinical activities. The secondary objective was to elucidate moderators of the relationship between pharmacist-involved collaborative care (PCC) and change in HbA1c. METHODS: This study was a retrospective cohort study conducted in a tertiary hospital over 12 months. Individuals with Type 2 diabetes, aged ≥21 years with established cardiovascular diseases were included while individuals with incomplete care documentation or missing data related to cardiovascular diseases were excluded. Individuals under the care of PCC were matched 1:1 based on baseline HbA1c with an eligible person who received care from the cardiologists (CC). Changes in mean HbA1c were analysed using linear mixed model. Linear regression was used to determine clinical activities that associated with improvement in HbA1c. Moderation analyses were conducted using the MacArthur framework. KEY FINDINGS: A total of 420 participants (PCC:210, CC:210) were analysed. The mean age of the participants was 65.6 ± 11.1 years, with the majority being male and Chinese. The mean HbA1c among participants in the PCC group decreased significantly after 6 months (PCC: -0.4% versus CC: -0.1%, P = 0.016), with maintenance of improvement at 12 months (PCC: -0.4% versus CC: -0.2%, P < 0.001). Frequencies of lifestyle counselling, reinforcement of visits to healthcare providers, health education, resolution of drug-related problems, emphasis on medication adherence, dose adjustments and advice on self-care techniques were significantly higher in the intervention group (P < 0.001). CONCLUSION: Improvements in HbA1c were associated with the provision of health education and medication adjustments.

Heterogeneous vs homogenous photocatalysis: what dominates in the degradation of methyl orange and methylene blue mixtures?

Photocatalysis has been oft proposed as a green solution for pollution remediation, however, majority of the existing literature only studies the degradation of solitary analytes. The degradation of mixtures of organic contaminants is inherently more complicated due to a variety of photochemical processes that occur in parallel. Here, we describe a model system comprised of methylene blue and methyl orange dyes whose degradation carried out by two common photocatalysts, P25 TiO2 and g-C3N4. With P25 TiO2 as the catalyst, the degradation rate of methyl orange slowed by 50% when degraded in a mixture compared to when alone. Control experiments with radical scavengers showed this to occur due to competition between the dyes for oxidative photogenerated species. In the presence of g-C3N4, methyl orange's degradation rate in the mixture increased by 2300% due to two homogeneous photocatalysis processes sensitized by methylene blue. Homogenous photocatalysis was found to be fast relative to heterogeneous photocatalysis by g-C3N4 but slow relative to photocatalysis by P25 TiO2 and explains the change observed between the two catalysts. Changes in dye adsorption to the catalyst when in a mixture were also explored but not found to coincide with changes in degradation rate.

Injectable thermosensitive hydrogel to modulate tolerogenic dendritic cells under hyperglycemic condition.

Hyperglycemia associated with diabetes mellitus is a significant risk factor for periodontitis and it polarizes the immune cells towards an inflammatory state. Specific biomaterials can deliver therapeutic or immunomodulatory agents to regulate the excessive periodontal inflammation. Dendritic cells (DCs) bridge the innate and adaptive immune systems and are crucially involved in periodontitis. Thus, targeting DCs is an attractive treatment option for diabetic periodontitis, which, by modulating the downstream adaptive immune cells could regulate the host immune responses. In this study, a chitosan-based thermosensitive injectable self-assembled hydrogel (TISH) was developed to modulate DCs towards a tolerogenic phenotype, which can induce regulatory T-cells to attenuate inflammation and promote healing. Granulocyte-macrophage colony-stimulating factor (GM-CSF) and resveratrol were loaded into TISH (TISH(G + R)) and were sustainably released. TISH demonstrated good biocompatibility and cell penetration in its porous structure. DCs grown in TISH(G + R) under an in vitro hyperglycemic condition showed reduced maturation and activation markers such as CD80, CD83 and CD86, while simultaneously upregulated tolerogenic genes such as FOXP3, SOCS3, TGFß and IL10. Co-culture of these tolerogenic DCs with naïve T-cells induced regulatory T-cells differentiation, evidenced by elevated gene expressions of FOXP3, TGFß and IL-10. In vivo subcutaneous injection of TISH (G + R) into the mice showed significant infiltration of DCs and regulatory T-cells. In conclusion, TISH was developed and optimized as an injectable hydrogel to modulate DCs towards the tolerogenic phenotype and induce regulatory T-cells under hyperglycemia. TISH has promising potential to improve periodontal parameters in diabetic periodontitis.

Painting and Poetry From a Bereaved Family and the Caring Physician.

This is a case description and personal account shared by a palliative care physician whose team provided specialist palliative care support to a patient who attempted immolation. This case depicts a family at risk of complicated grief due to the violent nature of self-inflicted burns and the lingering social stigmatization of suicide. Here, we explore important psycho-emotional considerations and share our experience using art and poetry to build therapeutic connections with the grieving family.

"Building palliative care capacity in cancer treatment centres: a participatory action research".

INTRODUCTION: There is a significant lack of palliative care access and service delivery in the Indian cancer institutes. In this paper, we describe the development, implementation, and evaluation of a palliative care capacity-building program in Indian cancer institutes. METHODS: Participatory action research method was used to develop, implement and evaluate the outcomes of the palliative care capacity-building program. Participants were healthcare practitioners from various cancer institutes in India. Training and education in palliative care, infrastructure for palliative care provision, and opioid availability were identified as key requisites for capacity-building. Researchers developed interventions towards capacity building, which were modified and further developed after each cycle of the capacity-building program. Qualitative content analysis was used to develop an action plan to build capacity. Descriptive statistics were used to measure the outcomes of the action plan. RESULTS: Seventy-three healthcare practitioners from 31 cancer treatment centres in India were purposively recruited between 2016 and 2020. The outcome indicators of the project were defined a priori, and were audited by an independent auditor. The three cycles of the program resulted in the development of palliative care services in 23 of the 31 institutes enrolled in the program. Stand-alone palliative care outpatient services were established in all the 23 centres, with the required infrastructure and manpower being provided by the organization. Morphine availability improved and use increased in these centres, which was an indication of improved pain management skills among the participants. The initiation and continuation of education, training, and advocacy activities in 20 centres suggested that healthcare providers continued to remain engaged with the program even after the cessation of their training cycle. CONCLUSION: This program illustrates how a transformational change at the organizational and individual level can lead to the development of sustained provision of palliative care services in cancer institutes.

PDMS hydrogel-coated tissue culture plates for studying the impact of substrate stiffness on dendritic cell function.

The mechanical properties of polydimethylsiloxane hydrogels can be tuned to mimic physiological tensions, an underappreciated environmental parameter in immunology studies. We describe a workflow to prepare PDMS-coated tissue culture plates with biologically relevant substrate stiffness, and the use of these hydrogel plates to condition isolated primary splenic CD11c+ dendritic cells (DC). Finally, we suggest downstream applications to study the impact of substrate stiffness on DC function and metabolism. The protocol could be adapted to study other mechanosensitive immune cell subsets. For complete details on the use and execution of this protocol, please refer to Chakraborty et al. (2021).

Cross Country Comparison of Expert Assessments of the Quality of Death and Dying 2021.

CONTEXT: Few efforts have attempted to quantify how well countries deliver end-of-life (EOL) care. OBJECTIVES: To score, grade, and rank countries (and Hong Kong and Taiwan) on the quality of EOL care based on assessments from country experts using a novel preference-based scoring algorithm. METHODS: We fielded a survey to country experts around the world, asking them to assess the performance of their country on 13 key indicators of EOL care. Results were combined with preference weights from caregiver-proxies of recently deceased patients to generate a preference-weighted summary score. The scores were then converted to grades (from A-F) and a ranking was created for all included countries. RESULTS: The final sample included responses from 181 experts representing 81 countries with 2 or more experts reporting. The 6 countries who received the highest assessment scores and a grade of A were United Kingdom, Ireland, Taiwan, Australia, Republic of Korea, and Costa Rica. Only Costa Rica (upper middle) is not a high income country. Not until Uganda (ranked 31st) does a low-income country appear on the ranking. Based on the assessment scores, twenty-one countries received a failing grade, with only two - Czech Republic (66th), and Portugal (75th) - being high income countries. CONCLUSION: This study provides an example of how a preference-based scoring algorithm and input from key stakeholders can be used to assess EOL health system performance. Results highlight the large disparities in assessments of the quality of EOL care across countries, and especially between the highest income countries and others.

Preparedness to Face the COVID-19 Pandemic in Hospice and Palliative Care Services in the Asia-Pacific Region: A Rapid Online Survey.

BACKGROUND: Hospice and palliative care services provision for COVID-19 patients is crucial to improve their life quality. There is limited evidence on COVID-19 preparedness of such services in the Asia-Pacific region. AIM: To evaluate the preparedness and capacity of hospice and palliative care services in the Asia-Pacific region to respond to the COVID-19 pandemic. METHOD: An online cross-sectional survey was developed based on methodology guidance. Asia-Pacific Hospice and Palliative Care Network subscribers (n = 1551) and organizational members (n = 185) were emailed. Descriptive analysis was undertaken. RESULTS: Ninety-seven respondents completed the survey. Around half of services were hospital-based (n = 47, 48%), and public-funded (n = 46, 47%). Half of services reported to have confirmed cases (n = 47, 49%) and the majority of the confirmed cases were patients (n = 28, 61%). Staff perceived moderate risk of being infected by COVID-19 (median: 7/10). > 85% of respondents reported they had up-to-date contact list for staff and patients, one-third revealed challenges to keep record of relatives who visited the services (n = 30, 31%), and of patients visited in communities (n = 29, 30%). Majority of services (60%) obtained adequate resources for infection control except face mask. More than half had no guidance on Do Not Resuscitate orders (n = 59, 66%) or on bereavement care for family members (n = 44, 51%). CONCLUSION: Recommendations to strengthen the preparedness of palliative care services include: 1) improving the access to face mask; 2) acquiring stress management protocols for staff when unavailable; 3) reinforcing the contact tracing system for relatives and visits in the community and 4) developing guidance on patient and family care during patient's dying trajectory.

Biomaterial Properties Modulating Bone Regeneration.

Biomaterial scaffolds have been gaining momentum in the past several decades for their potential applications in the area of tissue engineering. They function as three-dimensional porous constructs to temporarily support the attachment of cells, subsequently influencing cell behaviors such as proliferation and differentiation to repair or regenerate defective tissues. In addition, scaffolds can also serve as delivery vehicles to achieve sustained release of encapsulated growth factors or therapeutic agents to further modulate the regeneration process. Given the limitations of current bone grafts used clinically in bone repair, alternatives such as biomaterial scaffolds have emerged as potential bone graft substitutes. This review summarizes how physicochemical properties of biomaterial scaffolds can influence cell behavior and its downstream effect, particularly in its application to bone regeneration.

Mechanical Stiffness Controls Dendritic Cell Metabolism and Function.

Stiffness in the tissue microenvironment changes in most diseases and immunological conditions, but its direct influence on the immune system is poorly understood. Here, we show that static tension impacts immune cell function, maturation, and metabolism. Bone-marrow-derived and/or splenic dendritic cells (DCs) grown in vitro at physiological resting stiffness have reduced proliferation, activation, and cytokine production compared with cells grown under higher stiffness, mimicking fibro-inflammatory disease. Consistently, DCs grown under higher stiffness show increased activation and flux of major glucose metabolic pathways. In DC models of autoimmune diabetes and tumor immunotherapy, tension primes DCs to elicit an adaptive immune response. Mechanistic workup identifies the Hippo-signaling molecule, TAZ, as well as Ca2+-related ion channels, including potentially PIEZO1, as important effectors impacting DC metabolism and function under tension. Tension also directs the phenotypes of monocyte-derived DCs in humans. Thus, mechanical stiffness is a critical environmental cue of DCs and innate immunity.

Glucose oxidase kinetics using MnO2 nanosheets: confirming Michaelis-Menten kinetics and quantifying decreasing enzyme performance with increasing buffer concentration.

MnO2 nanosheets and ultraviolet-visible (UV-Vis) absorbance spectroscopy are used to study glucose oxidase (GOx) kinetics. Glucose oxidation by GOx produces H2O2, which rapidly decomposes the nanosheets and reduces their absorption. This direct approach for monitoring glucose oxidation enables simpler, real time kinetics analysis compared to methods that employ additional enzymes. Using this approach, the present study confirms that GOx kinetics is consistent with the Michaelis-Menten (MM) model, and reveals that the MM constant increases by an order of magnitude with increasing buffer concentration. Since larger MM constants imply higher enzyme substrate concentrations are required to achieve the same rate of product formation, increasing MM constants imply decreasing enzyme performance. These results demonstrate the facility of using MnO2 nanosheets to study GOx kinetics and, given the widespread applications of enzymes with buffers, the important sensitivity of enzyme-buffer systems on buffer concentration.

The role of palliative medicine in ICU bed allocation in COVID-19: a joint position statement of the Singapore Hospice Council and the Chapter of Palliative Medicine Physicians.

Facing the possibility of a surge of COVID-19-infected patients requiring ventilatory support in Intensive Care Units (ICU), the Singapore Hospice Council and the Chapter of Palliative Medicine Physicians forward its position on the guiding principles that ought to drive the allocation of ICU beds and its role in care of these patients and their families.

End of life experiences of patients with advanced cancer in Myanmar: Results from the APPROACH study.

BACKGROUND: Access to palliative care services is essential for attaining universal health coverage for patients with a terminal cancer. Despite this, many patients with advanced cancer in low-income countries, such as Myanmar, suffer at the end of life (EOL) due to little or no access to palliative care. However, actual evidence on EOL experiences of cancer patients in Myanmar is lacking. This paper aims to describe various dimensions of EOL experiences among patients with an advanced cancer from the largest public hospital in Myanmar. METHODS: We surveyed 195 patients with stage IV cancer seeking care from outpatient oncology clinics to assess their quality of life, pain severity, pain medications taken, quality of communication with doctors, nursing care and health care coordination, and desire to end life sooner. We assessed socioeconomic status (SES) differences in each patient outcome using separate multivariate linear/logistic regressions. RESULTS: Forty-one percent of the patients in our sample reported that they wish their life would end sooner. Low SES cancer patients had significantly worse quality of life, reported poor health care coordination and were more likely to report severe pain compared to high SES cancer patients visiting the same hospital. CONCLUSION: To improve quality of life and pain management and to reduce EOL distress among patients with advanced cancer, there is a pressing need to develop and invest in hospital and community-level palliative care services in Myanmar.

Redefining Palliative Care-A New Consensus-Based Definition.

CONTEXT: The International Association for Hospice and Palliative Care developed a consensus-based definition of palliative care (PC) that focuses on the relief of serious health-related suffering, a concept put forward by the Lancet Commission Global Access to Palliative Care and Pain Relief. OBJECTIVE: The main objective of this article is to present the research behind the new definition. METHODS: The three-phased consensus process involved health care workers from countries in all income levels. In Phase 1, 38 PC experts evaluated the components of the World Health Organization definition and suggested new/revised ones. In Phase 2, 412 International Association for Hospice and Palliative Care members in 88 countries expressed their level of agreement with the suggested components. In Phase 3, using results from Phase 2, the expert panel developed the definition. RESULTS: The consensus-based definition is as follows: Palliative care is the active holistic care of individuals across all ages with serious health-related suffering due to severe illness and especially of those near the end of life. It aims to improve the quality of life of patients, their families and their caregivers. The definition includes a number of bullet points with additional details as well as recommendations for governments to reduce barriers to PC. CONCLUSION: Participants had significantly different perceptions and interpretations of PC. The greatest challenge faced by the core group was trying to find a middle ground between those who think that PC is the relief of all suffering and those who believe that PC describes the care of those with a very limited remaining life span.

Ensuring and Restoring Balance on Access to Controlled Substances for Medical and Scientific Purposes: Joint Statement from Palliative Care Organizations.

The central principle of "balance" represents the dual obligation of governments to establish a system of control that ensures the adequate availability of controlled substances for medical and scientific purposes while simultaneously preventing their nonmedical use, diversion, and trafficking, two primary goals of the international control system. On the one hand, although strong opioids, including morphine, are absolutely necessary for the relief of severe pain, legitimate access to opioids for pain treatment and palliative care is lacking in the majority of the world's countries. On the other hand, in a few high-income countries with higher consumption of prescription opioids, diversion and nonmedical use are increasingly prevalent. This report presents examples of unbalanced systems and a joint statement from global and regional palliative care organizations to promote development of balanced systems for optimal public health outcomes. Although nonmedical use of controlled substances poses a risk to society, the system of control is not intended to be a barrier to their availability for medical and scientific purposes, nor to interfere in their legitimate medical use for patient care. As representatives of palliative care organizations, we urge heads of state to act and to take measures to ensure and restore balanced systems in their countries and call on public health leaders and regulators to work together.

Incidence of thromboembolic and bleeding events in patients with newly diagnosed nonvalvular atrial fibrillation: An Asian multicenter retrospective cohort study in Singapore.

BACKGROUND: Real-world effectiveness and safety of antithrombotics in nonvalvular atrial fibrillation (NVAF) patients in Singapore has not been thoroughly studied. HYPOTHESIS: Users of various antithrombotics experience a significantly different risk of stroke and major bleed compared with warfarin users. METHODS: This multicenter retrospective cohort study included patients age ≥ 21 years newly diagnosed with NVAF between July 2012 and September 2015. Using electronic medical records, data on patients' demographics, antithrombotics prescribed, and CHA2 DS2 -VASc and HAS-BLED risk factors were collected. Patients were followed for 1 year from diagnosis for the primary effectiveness and safety endpoints of incident stroke or systemic embolism and major bleed, respectively. The secondary safety endpoint was overall bleed. Hazard ratios (HR) were determined from Cox regression. RESULTS: Of 743 patients included, 224 were on warfarin, 156 on direct oral anticoagulants (DOACs), 277 on single antiplatelet therapy (SAPT), 28 on dual antiplatelet therapy (DAPT), and 58 on no therapy. Mean age (±SD) was 68.7 ± 13.0 years. Compared with warfarin users, SAPT (adjusted [adj.] HR: 3.70, 95% confidence interval [CI]: 1.21-11.3) and DAPT users (adj. HR: 10.1, 95% CI: 1.51-67.2) were more likely to develop thromboembolic outcomes. Also, DOAC users (adj. HR: 0.304, 95% CI: 0.158-0.585), SAPT users (adj. HR: 0.142, 95% CI: 0.0680-0.295), and DAPT users (adj. HR: 0.112, 95% CI: 0.0146-0.857) were less likely to experience any bleed compared with warfarin users. CONCLUSIONS: SAPT and DAPT are less effective than warfarin in NVAF patients. DOACs may be considered in view of lower risk of overall bleed.

Controlled hierarchical assembly of gold nanoparticles in macroscopic films: from densely packed monolayers to networks of micropores and nanobundles.

The present study demonstrates the ability of excess, weakly amphiphilic n-alkanethiols (n = 4, 12, 18) and solvent composition to tune through a wide range of large-scale, macroscopic architectures formed by alkanethiol-capped Au nanoparticles (NPs). Both the alkanethiols and NPs are significantly hydrophobic species and compete for surface area at an air-water interface. When solutions of the two species are spread on a large (50 cm2) water surface in a Teflon well, a thin film forms and exhibits co-existing macroscopic regions with various distinct NP self-assembled architectures, namely a close packed monolayer, a network phase characterized by micron-sized pores (micropores) surrounded by quasi-linear bundles of nanoparticles, and finally aggregates. We hypothesize that the co-existence of various NP architectures results from fast, non-uniform evaporation across the large water surface. When solutions are instead deposited on a smaller (5 cm2) water surface contained within a Teflon ring to control the water surface curvature and the evaporation rate is slowed, we show for the first time that NPs form macroscopically uniform self-assemblies whose architectures can be tuned from monolayers → monolayers with micropores → extended micropore/NP bundle networks by varying excess alkanethiol concentration and solvent composition. We propose that competition between NPs and excess alkanethiols for water surface area, and alkanethiol self-assembly as well as solvent dewetting play important roles in the formation of the network phase, and discuss a potential mechanism for its formation.

Palliative care development in the Asia-Pacific region: an international survey from the Asia Pacific Hospice Palliative Care Network (APHN).

BACKGROUND: Although palliative care is an important public healthcare issue worldwide, the current situation in the Asia-Pacific region has not been systematically evaluated. OBJECTIVES: This survey aimed to clarify the current status of palliative care in the Asia-Pacific region. METHODS: Questionnaires were sent to a representative physician of each member country/region of the Asia Pacific Hospice Palliative Care Network (APHN). The questionnaire examined palliative care service provision, information regarding physician certification in palliative care, the availability of essential drugs for palliative care listed by the International Association for Hospice and Palliative Care (IAHPC) and the regulation of opioid-prescribing practice. RESULTS: Of the 14 member countries/regions of the APHN, 12 (86%) responded. Some form of specialist palliative care services had developed in all the responding countries/regions. Eight member countries/regions had physician certifications for palliative care. Most essential drugs for palliative care listed by the IAHPC were available, whereas hydromorphone, oxycodone and transmucosal fentanyl were unavailable in most countries/regions. Six member countries/regions required permission to prescribe and receive opioids. CONCLUSIONS: The development of palliative care is in different stages across the surveyed countries/regions in the Asia-Pacific region. Data from this survey can be used as baseline data for monitoring the development of palliative care in this region.