Human Innate Lymphoid Cell Subsets Possess Tissue-Type Based Heterogeneity in Phenotype and Frequency.

Animal models have highlighted the importance of innate lymphoid cells (ILCs) in multiple immune responses. However, technical limitations have hampered adequate characterization of ILCs in humans. Here, we used mass cytometry including a broad range of surface markers and transcription factors to accurately identify and profile ILCs across healthy and inflamed tissue types. High dimensional analysis allowed for clear phenotypic delineation of ILC2 and ILC3 subsets. We were not able to detect ILC1 cells in any of the tissues assessed, however, we identified intra-epithelial (ie)ILC1-like cells that represent a broader category of NK cells in mucosal and non-mucosal pathological tissues. In addition, we have revealed the expression of phenotypic molecules that have not been previously described for ILCs. Our analysis shows that human ILCs are highly heterogeneous cell types between individuals and tissues. It also provides a global, comprehensive, and detailed description of ILC heterogeneity in humans across patients and tissues.

Prepared and highly committed despite the risk of COVID-19 infection: a cross-sectional survey of primary care physicians' concerns and coping strategies in Singapore.

BACKGROUND: Primary care physicians (PCPs) are first points-of-contact between suspected cases and the healthcare system in the current COVID-19 pandemic. This study examines PCPs' concerns, impact on personal lives and work, and level of pandemic preparedness in the context of COVID-19 in Singapore. We also examine factors and coping strategies that PCPs have used to manage stress during the outbreak. METHODS: Two hundred and sixteen PCPs actively practicing in either a public or private clinic were cluster sampled via email invitation from three primary care organizations in Singapore from 6th to 29th March 2020. Participants completed a cross-sectional online questionnaire consisting of items on work- and non-work-related concerns, impact on personal and work life, perceived pandemic preparedness, stress-reduction factors, and personal coping strategies related to COVID-19. RESULTS: A total of 158 questionnaires were usable for analyses. PCPs perceived themselves to be at high risk of COVID-19 infection (89.9%), and a source of risk (74.7%) and concern (71.5%) to loved ones. PCPs reported acceptance of these risks (91.1%) and the need to care for COVID-19 patients (85.4%). Overall perceived pandemic preparedness was extremely high (75.9 to 89.9%). PCPs prioritized availability of personal protective equipment, strict infection prevention guidelines, accessible information about COVID-19, and well-being of their colleagues and family as the most effective stress management factors. CONCLUSIONS: PCPs continue to serve willingly on the frontlines of this pandemic despite the high perception of risk to themselves and loved ones. Healthcare organizations should continue to support PCPs by managing both their psychosocial (e.g. stress management) and professional (e.g. pandemic preparedness) needs.

Shifting care from hospital to community, a strategy to integrate care in Singapore: process evaluation of implementation fidelity.

BACKGROUND: Accessibility to efficient and person-centered healthcare delivery drives healthcare transformation in many countries. In Singapore, specialist outpatient clinics (SOCs) are commonly congested due to increasing demands for chronic care. To improve this situation, the National University Health System (NUHS) Regional Health System (RHS) started an integrated care initiative,the Right-Site Care (RSC) program in 2014. Through collaborations between SOCs at the National University Hospital and primary and community care (PCC) clinics in the western region of the county, the program was designed to facilitate timely discharge and appropriate transition of patients, who no longer required specialist care, to the community. The aim of this study was to evaluate the implementation fidelity of the NUHS RHS RSC program using the modified Conceptual Framework for Implementation Fidelity (CFIF), at three distinct levels; providers, organizational, and system levels to explain outcomes of the program and to inform further development of (similar) programs. METHODS: A convergent parallel mixed methods study using the realist evaluation approach was used. Data were collected between 2016 and 2018 through non-participatory observations, reviews of medical records and program database, together with semi-structured interviews with healthcare providers. Triangulation of data streams was applied guided by the modified CFIF. RESULTS: Our findings showed four out of six program components were implemented with low level of fidelity, and 9112 suitable patients were referred to the program while 3032 (33.3%) declined to be enrolled. Moderating factors found to influence fidelity included: (i) complexity of program, (ii) evolving providers' responsiveness, (iii) facilitation through synergistic partnership, training of PCC providers by specialists and supportive structures: care coordinators, guiding protocols, shared electronic medical record and shared pharmacy, (iv) lack of organization reinforcement, and (v) mismatch between program goals, healthcare financing and providers' reimbursement. CONCLUSION: Functional integration alone is insufficient for a successful right-site care program implementation. Improvement in relationships between providers, organizations, and patients are also warranted for further development of the program.

Implementation fidelity of a strategy to integrate service delivery: learnings from a transitional care program for individuals with complex needs in Singapore.

BACKGROUND: To cope with rising demand for healthcare services in Singapore, Regional Health Systems (RHS) comprising of health and social care providers across care settings were set up to integrate service delivery. Tasked with providing care for the western region, in 2012, the National University Health System (NUHS) - RHS developed a transitional care program for elderly patients with complex healthcare needs who consumed high levels of hospital resources. Through needs assessment, development of personalized care plans and care coordination, the program aimed to: (i) improve quality of care, (ii) reduce hospital utilization, and (iii) reduce healthcare-related costs. In this study, recognizing the need for process evaluation in conjunction with outcome evaluation, we aim to evaluate the implementation fidelity of the NUHS-RHS transitional care program to explain the outcomes of the program and to inform further development of (similar) programs. METHODS: Guided by the modified version of the Conceptual Framework for Implementation Fidelity (CFIF), adherence and moderating factors influencing implementation were assessed using non-participatory observations, reviews of medical records and program databases. RESULTS: Most (10 out of 14) components of the program were found to be implemented with low or moderate level of fidelity. The frequency or duration of the program components were observed to vary based on the needs of users, availability of care coordinators (CC) and their confidence. Variation in fidelity was influenced predominantly by: (1) complexity of the program, (2) extent of facilitation through guiding protocols, (3) facilitation of program implementation through CCs' level of training and confidence, (4) evolving healthcare participant responsiveness, and (5) the context of suboptimal capability among community providers. CONCLUSION: This is the first study to assess the context-specific implementation process of a transitional care program in the context of Southeast Asia. It provides important insights to facilitate further development and scaling up of transitional care programs within the NUHS-RHS and beyond. Our findings highlight the need for greater focus on engaging both healthcare providers and users, training CCs to equip them with the relevant skills required for their jobs, and building the capability of the community providers to implement such programs.

The impact of COVID-19 on private and public primary care physicians: A cross-sectional study.

PURPOSE: Primary care physicians (PCP) are at a high risk of contracting COVID-19 as they manage patients with fever or respiratory symptoms, but it is intuitive that private and public practice PCPs may face different challenges during this pandemic. This study compared work- and non-work-related concerns, COVID-19's impact on personal and professional lives, and perceived pandemic preparedness between private and public PCPs in Singapore. METHODS: 216 PCPs who were a registered member of either the National University Polyclinics, National University Health System Primary Care Network or College of Family Physicians Singapore, participated in this online cross-sectional study. The data collection period lasted from 6th March 2020 to 29th March 2020. RESULTS: A final sample of 172 questionnaires were analysed. Private PCPs tended to be older and more experienced. Perceived COVID-19 exposure and overall preparedness was high in both groups. More private PCPs perceived their exposure risk as unacceptable, aOR = 3.96 (1.07, 14.62); that they should not be caring for COVID-19 patients, aOR = 3.55 (1.23, 10.24); and perceived more stigma against their loved ones, aOR = 4.27 (1.74, 10.44). Private PCPs felt less well-trained, aOR = 0.05 (0.01, 0.23); and supported, aOR = 0.14 (0.03, 0.63). CONCLUSIONS: Private PCPs are more likely to be self-employed or work in smaller practices where COVID-19 infection could mean loss of livelihood. As a healthcare system without primary care is crippled in its ability to manage outbreaks, authorities should respond appropriately to the needs of their general practitioners and family physicians.

Characterising and predicting persistent high-cost utilisers in healthcare: a retrospective cohort study in Singapore.

OBJECTIVE: We aim to characterise persistent high utilisers (PHUs) of healthcare services, and correspondingly, transient high utilisers (THUs) and non-high utilisers (non-HUs) for comparison, to facilitate stratifying HUs for targeted intervention. Subsequently we apply machine learning algorithms to predict which HUs will persist as PHUs, to inform future trials testing the effectiveness of interventions in reducing healthcare utilisation in PHUs. DESIGN AND SETTING: This is a retrospective cohort study using administrative data from an Academic Medical Centre (AMC) in Singapore. PARTICIPANTS: Patients who had at least one inpatient admission to the AMC between 2005 and 2013 were included in this study. HUs incurred Singapore Dollar 8150 or more within a year. PHUs were defined as HUs for three consecutive years, while THUs were HUs for 1 or 2 years. Non-HUs did not incur high healthcare costs at any point during the study period. OUTCOME MEASURES: PHU status at the end of the third year was the outcome of interest. Socio-demographic profiles, clinical complexity and utilisation metrics of each group were reported. Area under curve (AUC) was used to identify the best model to predict persistence. RESULTS: PHUs were older and had higher comorbidity and mortality. Over the three observed years, PHUs' expenditure generally increased, while THUs and non-HUs' spending and inpatient utilisation decreased. The predictive model exhibited good performance during both internal (AUC: 83.2%, 95% CI: 82.2% to 84.2%) and external validation (AUC: 79.8%, 95% CI: 78.8% to 80.8%). CONCLUSIONS: The HU population could be stratified into PHUs and THUs, with distinctly different utilisation trajectories. We developed a model that could predict at the end of 1 year, whether a patient in our population will continue to be a HU in the next 2 years. This knowledge would allow healthcare providers to target PHUs in our health system with interventions in a cost-effective manner.

Two distinct interstitial macrophage populations coexist across tissues in specific subtissular niches.

Macrophages are a heterogeneous cell population involved in tissue homeostasis, inflammation, and various pathologies. Although the major tissue-resident macrophage populations have been extensively studied, interstitial macrophages (IMs) residing within the tissue parenchyma remain poorly defined. Here we studied IMs from murine lung, fat, heart, and dermis. We identified two independent IM subpopulations that are conserved across tissues: Lyve1loMHCIIhiCX3CR1hi (Lyve1loMHCIIhi) and Lyve1hiMHCIIloCX3CR1lo (Lyve1hiMHCIIlo) monocyte-derived IMs, with distinct gene expression profiles, phenotypes, functions, and localizations. Using a new mouse model of inducible macrophage depletion (Slco2b1 flox/DTR), we found that the absence of Lyve1hiMHCIIlo IMs exacerbated experimental lung fibrosis. Thus, we demonstrate that two independent populations of IMs coexist across tissues and exhibit conserved niche-dependent functional programming.

Assessing the influence of health systems on Type 2 Diabetes Mellitus awareness, treatment, adherence, and control: A systematic review.

BACKGROUND: Type 2 Diabetes Mellitus (T2DM) is reported to affect one in 11 adults worldwide, with over 80% of T2DM patients residing in low-to-middle-income countries. Health systems play an integral role in responding to this increasing global prevalence, and are key to ensuring effective diabetes management. We conducted a systematic review to examine the health system-level factors influencing T2DM awareness, treatment, adherence, and control. METHODS AND FINDINGS: A protocol for this study was published on the PROSPERO international prospective register of systematic reviews (PROSPERO 2016: CRD42016048185). Studies included in this review reported the effects of health systems factors, interventions, policies, or programmes on T2DM control, awareness, treatment, and adherence. The following databases were searched on 22 February 2017: Medline, Embase, Global health, LILACS, Africa-Wide, IMSEAR, IMEMR, and WPRIM. There were no restrictions on date, language, or study designs. Two reviewers independently screened studies for eligibility, extracted the data, and screened for risk of bias. Thereafter, we performed a narrative synthesis. A meta-analysis was not conducted due to methodological heterogeneity across different aspects of included studies. 93 studies were included for qualitative synthesis; 7 were conducted in LMICs. Through this review, we found two key health system barriers to effective T2DM care and management: financial constraints faced by the patient and limited access to health services and medication. We also found three health system factors that facilitate effective T2DM care and management: the use of innovative care models, increased pharmacist involvement in care delivery, and education programmes led by healthcare professionals. CONCLUSIONS: This review points to the importance of reducing, or possibly eliminating, out-of-pocket costs for diabetes medication and self-monitoring supplies. It also points to the potential of adopting more innovative and integrated models of care, and the value of task-sharing of care with pharmacists. More studies which identify the effect of health system arrangements on various outcomes, particularly awareness, are needed.

Macro-thyrotropin: a case report and review of literature.

CONTEXT: Isolated elevation of TSH in the absence of thyroid symptoms can be very rarely caused by a macromolecule formed between TSH and Ig (macro-TSH), confounding the interpretation of thyroid function test results. OBJECTIVE: We described the use of several commonly available laboratory-based approaches to investigate an isolated TSH elevation [232 mIU/liter; free T(4), 10 pmol/liter (reference interval, 10.0-23.0 pmol/liter), Vitros platform] in a clinically euthyroid elderly gentleman, which led to the diagnosis of macro-TSH. METHODS AND RESULTS: TSH concentration of the patient was significantly lower (122 mIU/liter) when measured on the Advia Centaur platform. Serial dilution of the patient's sample showed a nonlinear increase in TSH recovery at increasing dilution (nonlinearity). Polyethylene glycol precipitation and mixing the patient's sample with a hypothyroid patient sample showed reduced TSH recovery, suggesting the presence of a high molecular weight interfering substance and excess TSH binding capacity, respectively. Heterophile blocking tube studies and rheumatoid factors were negative. Gel filtration chromatography demonstrated a TSH peak fraction that approximated the molecular size of IgG; together with the excess TSH binding capacity, this indicated the presence of TSH-IgG macro-TSH. A review of 12 macro-TSH case reports showed that samples with macro-TSH produce over-recovery with dilution, return negative results on anti-animal and anti-heterophile blocking studies, and commonly have recovery of less than 20% when subjected to polyethylene glycol precipitation. CONCLUSION: Macro-TSH is an underrecognized laboratory interference. Routine laboratory techniques described above can help diagnose this rare entity. A close dialogue between the physician and the laboratory is important in approaching such cases.