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Background: Through medicare, residents in Canada are entitled to medically necessary physician services without paying out of pocket, but still many people struggle to access primary care. We conducted a survey to explore people's experience with and priorities for primary care. Methods: We conducted an online, bilingual survey of adults in Canada in fall 2022. We distributed an anonymous link through diverse channels and a closed link to 122 053 people via a national public opinion firm. We weighted completed responses to mirror Canada's population and adjusted for sociodemographic characteristics using regression models. Results: We analyzed 9279 completed surveys (5.9% response rate via closed link). More than one-fifth of respondents (21.8%) reported having no primary care clinician, and among those who did, 34.5% reported getting a same or next-day appointment for urgent issues. Of respondents, 89.4% expressed comfort seeing another team member if their doctor recommended it, but only 35.9%, 9.5%, and 12.4% reported that their practice had a nurse, social worker, or pharmacist, respectively. The primary care attribute that mattered most was having a clinician who 'knows me as a person and considers all the factors that affect my health.' After we adjusted for respondent characteristics, people in Quebec, the Atlantic region, and British Columbia had lower odds of reporting a primary care clinician than people in Ontario (adjusted odds ratio 0.30, 0.33, and 0.39, respectively; p < 0.001). We also observed large provincial variations in timely access, interprofessional care, and walk-in clinic use. Interpretation: More than 1 in 5 respondents did not have access to primary care, with large variation by province. Reforms should strive to expand access to relationship-based, longitudinal care in a team setting., Research over decades has shown that health systems with strong primary care have better health outcomes, better equity in outcomes, and lower costs. (1,2) Yet, worldwide, countries have struggled with [...]

The term syncretism has had a metamorphic history in terms of its meaning, starting as positive with Plutarch, to being positive and negative during the Reformation, and then becoming neutral and negative after the Reformation to becoming decidedly negative from the 1920s onward. Despite advances in interpreting syncretism in more neutral or positive ways, the word's meaning and function remain imprecise. Central to the fog surrounding the word is its implicit meaning of some type of mixture, whether negative, neutral, or positive. The question then becomes, 'Is mixture a valid central meaning of the word?' More importantly, can the suspicious lens of decolonialism offer insight into redefining it and also give direction as to how it could function? This article studies the development of the term, examines current scholarship within the World Coundl of Churches, and situates syncretism within the larger context of the decolonial discussion in trying to redefine it in light of its original meaning. Keywords syncretism, decolonialism, being, non-being, liminality, ontology, cosmology, epistemohgy, For most of the 20th century, syncretism has been a problem for the church. In some respects, this is partially due to misunderstandings of indigenous cultural practices. In others, this [...]

Background: Variations in primary care practices may explain some differences in health outcomes during the COVID-19 pandemic. We sought to evaluate the characteristics of primary care practices by the proportion of patients unvaccinated against SARS-CoV-2. Methods: We conducted a population-based, cross-sectional cohort study using linked administrative data sets in Ontario, Canada. We calculated the percentage of patients unvaccinated against SARS-CoV-2 enrolled with each comprehensive-care family physician, ranked physicians according to the proportion of patients unvaccinated, and identified physicians in the top 10% (v. the other 90%). We compared characteristics of family physicians and their patients in these 2 groups using standardized differences. Results: We analyzed 9060 family physicians with 10 837 909 enrolled patients. Family physicians with the largest proportion (top 10%) of unvaccinated patients (n = 906) were more likely to be male, to have trained outside of Canada, to be older, and to work in an enhanced fee-for-service model than those in the remaining 90%. Vaccine coverage ([greater than or equal to] 2 doses of SARS-CoV-2 vaccine) was 74% among patients of physicians with the largest proportion of unvaccinated patients, compared with 87% in the remaining patient population. Patients in the top 10% group tended to be younger and live in areas with higher levels of ethnic diversity and immigration and lower incomes. Interpretation: Primary care practices with the largest proportion of patients unvaccinated against SARS-CoV-2 served marginalized communities and were less likely to use team-based care models. These findings can guide resource planning and help tailor interventions to integrate public health priorities within primary care practices., Among people in Canada, concerns about risks and adverse effects are the top reasons for non-intent to receive a SARS-CoV-2 vaccine. (1) These trends are most commonly observed among communities [...]

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For four years, as an increasingly belligerent China breathed down their necks, the United States' allies in Asia quietly endured a torrent of abuse from President Donald Trump. Under President [...]

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As currently applied, the paired retinol isotope dilution (RID) test, which is used to assess the impact of a vitamin A intervention on vitamin A total body stores (TBS), requires 2 doses of stable isotope-labeled vitamin A.

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Some studies have shown that the incidence of type 2 diabetes increases after a diagnosis of COVID-19, although the evidence is not conclusive. However, the effects of the COVID-19 vaccine on this association, or the effect on other diabetes subtypes, are not clear. We aimed to investigate the association between COVID-19 and incidence of type 2, type 1, gestational and non-specific diabetes, and the effect of COVID- 19 vaccination, up to 52 weeks after diagnosis.

Inadequate vitamin A (VA) intake is common among lactating women in many communities worldwide, but high-dose VA supplementation for postpartum women is not recommended by the World Health Organization as an effective intervention.

Herein, we describe the design and synthesis of γ-secretase modulator (GSM) clinical candidate PF-06648671 (22) for the treatment of Alzheimer’s disease. A key component of the design involved a 2,5-cis-tetrahydrofuran (THF) linker to impart conformational rigidity and lock the compound into a putative bioactive conformation. This effort was guided using a pharmacophore model since crystallographic information was not available for the membrane-bound γ-secretase protein complex at the time of this work. PF-06648671 achieved excellent alignment of whole cell in vitro potency (Aβ42 IC50= 9.8 nM) and absorption, distribution, metabolism, and excretion (ADME) parameters. This resulted in favorable in vivo pharmacokinetic (PK) profile in preclinical species, and PF-06648671 achieved a human PK profile suitable for once-a-day dosing. Furthermore, PF-06648671 was found to have favorable brain availability in rodent, which translated into excellent central exposure in human and robust reduction of amyloid β (Aβ) 42 in cerebrospinal fluid (CSF).

BACKGROUND: Globally, primary care changed dramatically as a result of the coronavirus disease 2019 (COVID-19) pandemic. We aimed to understand the degree to which office and virtual primary care changed, and for which patients and physicians, during the initial months of the pandemic in Ontario, Canada. METHODS: This population-based study compared comprehensive, linked primary care physician billing data from Jan. 1 to July 28, 2020, with the same period in 2019. We identified Ontario residents with at least 1 office or virtual (telephone or video) visit during the study period. We compared trends in total physician visits, office visits and virtual visits before COVID-19 with trends after pandemic-related public health measures changed the delivery of care, according to various patient and physician characteristics. We used interrupted time series analysis to compare trends in the early and later halves of the COVID-19 period. RESULTS: Compared with 2019, total primary care visits between March and July 2020 decreased by 28.0%, from 7.66 to 5.51 per 1000 people/day. The smallest declines were among patients with the highest expected health care use (8.3%), those who could not be attributed to a primary care physician (10.2%), and older adults (19.1%). In contrast, total visits in rural areas increased by 6.4%. Office visits declined by 79.1% and virtual care increased 56-fold, comprising 71.1% of primary care physician visits. The lowest uptake of virtual care was among children (57.6%), rural residents (60.6%) and physicians with panels of [greater than or equal to] 2500 patients (66.0%). INTERPRETATION: Primary care in Ontario saw large shifts from office to virtual care over the first 4 months of the COVID-19 pandemic. Total visits declined least among those with higher health care needs. The determinants and consequences of these major shifts in care require further study., Primary care is considered the cornerstone of most health systems worldwide, and in higher-income countries, primary care visits are about 30 times more frequent than hospital admissions. (1) Health systems [...]

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BACKGROUND: Indigenous people worldwide are disproportionately affected by diabetes and its complications. We aimed to assess the monitoring, treatment and control of blood glucose and lipids in First Nations people in Ontario. METHODS: We conducted a longitudinal population-based study using administrative data for all people in Ontario with diabetes, stratified by First Nations status. We assessed age- and sex-specific rates of completion of recommended monitoring for low-density lipoprotein (LDL) and glycated hemoglobin ([A.sub.1c]) from 2001/02 to 2014/15. We used data from 2014/15 to conduct a cross-sectional analysis of rates of achievement of [A.sub.1c] and LDL targets and use of glucose-lowering medications. RESULTS: The study included 22 240 First Nations people and 1319503 other people in Ontario with diabetes. Rates of monitoring according to guidelines were 20%-50% for [A.sub.1c] and 30%-70% for lipids and were lowest for younger First Nations men. The mean age- and sex-adjusted [A.sub.1c] level was higher among First Nations people than other people (7.59 [95% confidence interval (CI) 7.57 to 7.61] v. 7.03 [95% CI 7.02 to 7.03]). An [A.sub.1c] level of 8.5% or higher was observed in 24.7% (95% CI 23.6 to 25.0) of First Nations people, compared to 12.8% (95% CI 12.1 to 13.5) of other people in Ontario. An LDL level of 2.0 mmol/L or less was observed in 60.3% (95% CI 59.7 to 61.6) of First Nations people, compared to 52.0% (95% CI 51.1 to 52.9) of other people in Ontario. Among those aged 65 or older, a higher proportion of First Nations people than other Ontarians were using insulin (28.1% v. 15.1%), and fewer were taking no medications (28.3% v. 40.1%). INTERPRETATION: As of 2014/15, monitoring and achievement of glycemic control in both First Nations people and other people in Ontario with diabetes remained suboptimal. Interventions to support First Nations patients to reach their treatment goals and reduce the risk of complications need further development and study., Diabetes and its related complications are major contributors to morbidity and mortality worldwide. (1-3) Indigenous populations in Canada and around the world are disproportionately affected by diabetes owing to the [...]

BACKGROUND: Diabetes mellitus is an established health concern in First Nations communities and is associated with complex influences of colonization. This study, a partnership between First Nations and academic researchers, was undertaken to determine patterns of diabetes prevalence, incidence and mortality in Ontario. METHODS: Using health services and population data from Ontario for 1995 to 2014, linked with the federal Indian Register, we calculated age- and sex-adjusted annual estimates of diabetes prevalence, incidence and mortality for First Nations people (living within and outside First Nations communities) and other people in Ontario. We also examined age- and sex-specific crude diabetes prevalence. RESULTS: Between 1995 and 2014, the prevalence of diabetes increased and the incidence decreased somewhat in all populations. Both prevalence and incidence were substantially higher among First Nations people than among other people in Ontario. In particular, First Nations women had higher prevalence than other women (4.2% v. 1.6% for ages 20-34 yr and 17.6% v. 6.0% for ages 35-49 yr). The lifetime risk of diabetes was higher among First Nations people than among other people in Ontario (57.0%, 95% confidence interval [CI] 56.3%-57.6% v. 44.5%, 95% CI 44.4%-44.6%). Over time, all-cause mortality for those with diabetes declined but remained consistently higher for First Nations people than for other people in Ontario. INTERPRETATION: Diabetes is more common among First Nations people than among other people in Ontario, particularly at younger ages and in women. First Nations-led approaches to address the high prevalence of diabetes in younger First Nations women have the potential to improve metabolic health across generations., Diabetes mellitus is an established health concern for First Nations in Canada (1,2) and is associated with other chronic conditions, increased risk of death and higher health care use. (3,4) [...]

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BACKGROUND: Rates of cardiovascular disease among people with diabetes have declined over the last 20-30 years. To determine whether First Nations people have experienced similar declines, we compared time trends in rates of cardiac event and disease management among First Nations people with diabetes and other people with diabetes in Ontario, Canada. METHODS: We conducted a retrospective cohort study of patients aged 20 to 105 years with diabetes between 1996 and 2015, using linked health administrative databases. Outcomes compared were the annual incidence of each admission to hospital for myocardial infarction and heart failure, and death owing to ischemic heart disease. Management indicators were coronary revascularization and prescription rates for cardioprotective medications. Overall rates and annual percent changes were compared using Poisson regression. RESULTS: Incidence rates for all cardiac outcomes decreased over the study period. The greatest relative annual decline among First Nations men and women were observed in ischemic heart disease death (4.4%, 95% confidence interval [CI] 3.0 to 5.9) and heart failure (5.4%, 95% CI 4.5 to 6.4), respectively. Among other men and women, the greatest annual declines were seen in ischemic heart disease death (6.3%, 95% CI 6.1 to 6.5 and 7.3%, 95% CI 7.1 to 7.6, respectively). However, all absolute cardiac event rates were higher among First Nations people (p < 0.001). Coronary artery revascularization procedures and prescriptions for cardioprotective medications increased among First Nations people, while only prescriptions increased among other people. INTERPRETATION: Over the last 20 years, the incidence of cardiac events has declined among First Nations people with diabetes, but remains higher than other people with diabetes in Ontario. For continued reductions in incidence, future efforts need to recognize First Nations people's unique social and cultural determinants of health., Cardiovascular disease is a major cause of premature morbidity and mortality among people with diabetes, developing 15 years earlier and being associated with poorer prognoses after an event than among [...]

As well as records, I collect music memorabilia such as flyers, posters and, of course, gig tickets. These are not just bits of paper; they're a collection of a lifetime [...]

Epstein-Barr Virus (EBV) diseases, including EBV-associated post-transplant lymphoproliferative disorder (PTLD) remain important causes of morbidity and mortality in children undergoing solid organ transplantation (SOT) and hematopoietic cell transplantation (HCT). Despite progress in the prevention of EBV disease including PTLD (EBV/PTLD) in HCT, key questions in the prevention, and management of these infectious complications remain unanswered. The goal of this manuscript is to highlight key points and recommendations derived from the consensus guidelines published by the International Pediatric Transplant Association and the European Conference on Infections in Leukemia for children undergoing SOT and HCT, respectively. Additionally, we provide background and guidance on the use of EBV viral load measurement in the prevention and management of these children.

Tumor-infiltrating T cells offer a promising avenue for cancer treatment, yet their states remain to be fully characterized. Here we present a single-cell atlas of T cells from 308,048 transcriptomes across 16 cancer types, uncovering previously undescribed T cell states and heterogeneous subpopulations of follicular helper, regulatory and proliferative T cells. We identified a unique stress response state, TSTR, characterized by heat shock gene expression. TSTRcells are detectable in situ in the tumor microenvironment across various cancer types, mostly within lymphocyte aggregates or potential tertiary lymphoid structures in tumor beds or surrounding tumor edges. T cell states/compositions correlated with genomic, pathological and clinical features in 375 patients from 23 cohorts, including 171 patients who received immune checkpoint blockade therapy. We also found significantly upregulated heat shock gene expression in intratumoral CD4/CD8+cells following immune checkpoint blockade treatment, particularly in nonresponsive tumors, suggesting a potential role of TSTRcells in immunotherapy resistance. Our well-annotated T cell reference maps, web portal and automatic alignment/annotation tool could provide valuable resources for T cell therapy optimization and biomarker discovery.

HTS tape dipole magnets are attractive because one can wind the magnet with a fully insulated without reaction or conductor insulation after winding. Problems with these conductors include; reduction of the conductor critical current in regions with large field components that are perpendicular to the flat face of the tape, large fields due to conductor magnetization at low fields that produce large sextupole and decapole fields when beam is injected into the machine, and the design of the coil ends such that winding stress in reduced to prevent conductor degradation. This paper shows how a dipole can be wound with HTS tapes so that low field magnetization is greatly reduced. The coil conductor current density can be higher, and coil stress can be better managed. The pros and cons of the dipole will be discussed.

You know your height, weight, and current medications. But do you know the results of your last lab test? For many of us, personal health information (PHI) remains siloed in [...]

Lack of a well-functioning institutional feedback culture can undermine acquisition of skills essential for high quality patient care. The objective of this study was to assess feedback culture perceived by resident and fellow trainees, utilizing a mixed methods design.Pediatric fellows and residents completed an anonymous feedback environment survey consisting of 7 constructs: source credibility, feedback quality, feedback delivery, reinforcing feedback, constructive feedback, source availability, and promotion of feedback seeking, using a 7-point Likert scale. Trainee ratings were compared using two-sided Fisher’s exact tests. Multivariable analyses used a linear regression model. For the qualitative study, semistructured interviews of residents were conducted. The constant comparative method was used to incrementally code, categorize data, and derive themes.Fifty-two residents and 21 fellows completed the survey (response rates 65% and 47%, respectively). Scores were more favorable for fellows compared with residents in 6 of 7 feedback constructs (P < .05), including on multivariate analysis. Hispanic ethnicity and female gender were associated with lower scores on source credibility (P = .04) and constructive feedback (P = .03), respectively. Two qualitative themes were identified: expectation of efficiency in patient care compromises the quality and quantity of feedback, and a culture that prioritizes courtesy over candor negatively impacts feedback quality. These themes were more pronounced when residents worked with pediatric subspecialists compared with hospitalists.We described the feedback culture, which was less favorable in the residency program. The need for efficient patient care and a culture of courtesy adversely impacted the quality of feedback, especially among subspecialists.