Evaluating Cognitive Impairment in a Large Health Care System: The Cognition in Primary Care Program.

Background: The prevalence of Alzheimer's disease and related disorders (ADRD) is rising. Primary care providers (PCPs) will increasingly be required to play a role in its detection but lack the training to do so. Objective: To develop a model for cognitive evaluation which is feasible in primary care and evaluate its implementation in a large health system. Methods: The Cognition in Primary Care Program consists of web-based training together with integrated tools built into the electronic record. We implemented the program among PCPs at 14 clinics in a large health system. We (1) surveyed PCPs to assess the impact of training on their confidence to evaluate cognition, (2) measured the number of cognitive assessments they performed, and (3) tracked the number of patients diagnosed with mild cognitive impairment (MCI). Results: Thirty-nine PCPs completed the training which covered how to evaluate cognition. Survey response rate from those PCPs was 74%. Six months after the end of the training, they reported confidence in assessing cognition (mean 4.6 on 5-point scale). Cognitive assessments documented in the health record increased from 0.8 per month before the training to 2.5 in the six months after the training. Patients who were newly diagnosed with MCI increased from 4.2 per month before the training to 6.0 per month in the six months after the training. Conclusions: This model for cognitive evaluation in a large health system was shown to increase cognitive testing and increase diagnoses of MCI. Such improvements are essential for the timely detection of ADRD.

Topical Steroid Withdrawal is a Targetable Excess of Mitochondrial NAD.

Background: Topical corticosteroids (TCS) are first-line therapies for numerous skin conditions. Topical Steroid Withdrawal (TSW) is a controversial diagnosis advocated by patients with prolonged TCS exposure who report severe systemic reactions upon treatment cessation. However, to date there have been no systematic clinical or mechanistic studies to distinguish TSW from other eczematous disorders. Methods: A re-analysis of a previous survey with eczematous skin disease was performed to evaluate potential TSW distinguishing symptoms. We subsequently conducted a pilot study of 16 patients fitting the proposed diagnostic criteria. We then performed: tissue metabolomics, transcriptomics, and immunostaining on skin biopsies; serum metabolomics and cytokine assessments; shotgun metagenomics on microbiome skin swabs; genome sequencing; followed by functional, mechanistic studies using human skin cell lines and mice. Results: Clinically distinct TSW symptoms included burning, flushing, and thermodysregulation. Metabolomics and transcriptomics both implicated elevated NAD+ oxidation stemming from increased expression of mitochondrial complex I and conversion of tryptophan into kynurenine metabolites. These abnormalities were induced by glucocorticoid exposure both in vitro and in a cohort of healthy controls (N=19) exposed to TCS. Targeting complex I via either metformin or the herbal compound berberine improved outcomes in both cell culture and in an open-label case series for patients with TSW. Conclusion: Taken together, our results suggest that TSW has a distinct dermatopathology. While future studies are needed to validate these results in larger cohorts, this work provides the first mechanistic evaluation into TSW pathology, and offers insights into clinical identification, pharmacogenomic candidates, and directed therapeutic strategies.

Disparities in telemedicine use among Native Hawaiian and Pacific Islander individuals insured through Medicaid.

States have implemented policy changes to increase access to telemedicine services for individuals receiving Medicaid benefits. Native Hawaiian and Pacific Islander (NHPI) individuals experienced disproportionate harms from COVID-19 and have long experienced disparities in health care access compared with other racial and ethnic groups, making the issue of telemedicine access particularly salient for NHPI individuals on Medicaid. Utilizing 100% 2020-2021 Medicaid claims, we compared trends in telemedicine use between NHPI and non-Hispanic White individuals on Medicaid in Washington State and conducted a decomposition analysis to identify drivers of underlying disparities. In both years, NHPI individuals were 38%-39% less likely to use any telemedicine than White individuals after adjusting for patient- and area-level characteristics. Decomposition analysis revealed that most of this difference was due to differential effects of characteristics, rather than group differences in characteristics. Namely, several characteristics that were associated with increased telemedicine use had more muted associations for NHPI vs White individuals, such as English as the primary spoken language and female sex. These findings suggest the presence of limited acceptability of or group-specific barriers to telemedicine for NHPI individuals, including potential discrimination in being offered telemedicine visits. These issues should be understood and mitigated through close collaboration between health care leaders and NHPI communities.

Building evidence to advance health equity: a systematic review on care-related outcomes for older, minoritised populations in long-term care homes.

BACKGROUND: Advancing health equity requires more contextualised evidence. OBJECTIVES: To synthesise published evidence using an existing framework on the origins of health disparities and determine care-related outcome disparities for residents of long-term care, comparing minoritised populations to the context-specific dominant population. DESIGN: Systematic review. SUBJECTS: Residents of 24-hour long-term care homes. METHODS: The protocol was registered a priori with PROSPERO (CRD42021269489). Literature published between 1 January 2000 and 26 September 2021, was searched, including studies comparing baseline characteristics and outcomes in minoritised versus dominant populations. Dual screening, two-reviewer verification for extraction, and risk of bias assessments were conducted to ensure rigour. Studies were synthesized using a conceptual framework to contextualise evidence according to multi-level factors contributing to the development of care disparities. RESULTS: Twenty-one of 34 included studies demonstrated disparities in care outcomes for minoritised groups compared to majority groups. Thirty-one studies observed differences in individual-level characteristics (e.g. age, education, underlying conditions) upon entry to homes, with several outcome disparities (e.g. restraint use, number of medications) present at baseline and remaining or worsening over time. Significant gaps in evidence were identified, particularly an absence of literature on provider information and evidence on the experience of intersecting minority identities that contribute to care-related outcome disparities in long-term care. CONCLUSION: This review found differences in minoritised populations' care-related outcomes. The findings provide guidance for future health equity policy and research-supporting diverse and intersectional capacity building in long-term care.

From Compliance to Care: Qualitative Findings from a Survey of Essential Caregivers in Ontario Long-Term Care Homes.

BACKGROUND: The COVID-19 pandemic highlighted the importance of the care provided by family members and close friends to older people living in long-term care (LTC) homes. Our implementation science team helped three Ontario LTC homes to implement an intervention to allow family members to enter the homes during pandemic lockdowns. OBJECTIVE: We used a variety of methods to support the implementation, and this paper reports results from an Ontario-wide survey intended to help us understand the nature of the care provided by family caregivers. METHODS: We administered a survey of essential caregivers in Ontario, and a single open-ended question yielded a substantial qualitative data set that we analysed with a coding and theming procedure that yielded 13 themes. FINDINGS: The 13 themes reveal deficiencies in Ontario's LTC sector, attempts to cope with the deficiencies, and efforts to influence change and improvement. DISCUSSION: Our findings indicate that essential caregivers find it necessary to take on vital roles in order to shore up two significant gaps in the current system: they provide psychosocial and emotional (and sometimes even basic) care to residents, and they play a monitoring and advocacy role to compensate for the failings of the current regulatory compliance regime.

Ascertaining the Francophone population in Ontario: validating the language variable in health data.

BACKGROUND: Language barriers can impact health care and outcomes. Valid and reliable language data is central to studying health inequalities in linguistic minorities. In Canada, language variables are available in administrative health databases; however, the validity of these variables has not been studied. This study assessed concordance between language variables from administrative health databases and language variables from the Canadian Community Health Survey (CCHS) to identify Francophones in Ontario. METHODS: An Ontario combined sample of CCHS cycles from 2000 to 2012 (from participants who consented to link their data) was individually linked to three administrative databases (home care, long-term care [LTC], and mental health admissions). In total, 27,111 respondents had at least one encounter in one of the three databases. Language spoken at home (LOSH) and first official language spoken (FOLS) from CCHS were used as reference standards to assess their concordance with the language variables in administrative health databases, using the Cohen kappa, sensitivity, specificity, positive predictive value (PPV), and negative predictive values (NPV). RESULTS: Language variables from home care and LTC databases had the highest agreement with LOSH (kappa = 0.76 [95%CI, 0.735-0.793] and 0.75 [95%CI, 0.70-0.80], respectively) and FOLS (kappa = 0.66 for both). Sensitivity was higher with LOSH as the reference standard (75.5% [95%CI, 71.6-79.0] and 74.2% [95%CI, 67.3-80.1] for home care and LTC, respectively). With FOLS as the reference standard, the language variables in both data sources had modest sensitivity (53.1% [95%CI, 49.8-56.4] and 54.1% [95%CI, 48.3-59.7] in home care and LTC, respectively) but very high specificity (99.8% [95%CI, 99.7-99.9] and 99.6% [95%CI, 99.4-99.8]) and predictive values. The language variable from mental health admissions had poor agreement with all language variables in the CCHS. CONCLUSIONS: Language variables in home care and LTC health databases were most consistent with the language often spoken at home. Studies using language variables from administrative data can use the sensitivity and specificity reported from this study to gauge the level of mis-ascertainment error and the resulting bias.

The Known and Unknown "Knowns" of Human Susceptibility to Coccidioidomycosis.

Coccidioidomycosis occurs after inhalation of airborne spores of the endemic, dimorphic fungus, Coccidioides. While the majority of individuals resolve the infection without coming to medical attention, the fungus is a major cause of community-acquired pneumonia in the endemic region, and chronic pulmonary and extrapulmonary disease poses significant personal and economic burdens. This review explores the literature surrounding human susceptibility to coccidioidomycosis, including chronic pulmonary and extrapulmonary dissemination. Over the past century of study, themes have emerged surrounding factors impacting human susceptibility to severe disease or dissemination, including immune suppression, genetic susceptibility, sex, pregnancy, and genetic ancestry. Early studies were observational, frequently with small numbers of cases; several of these early studies are highly cited in review papers, becoming part of the coccidioidomycosis "canon". Specific genetic variants, sex, and immune suppression by TNF inhibitors have been validated in later cohort studies, confirming the original hypotheses. By contrast, some risk factors, such as ABO blood group, Filipino ancestry, or lack of erythema nodosum among black individuals, are repeated in the literature despite the lack of supporting studies or biologic plausibility. Using examination of historical reports coupled with recent cohort and epidemiology studies, evidence for commonly reported risk factors is discussed.

Case Report: Profound newborn leukopenia related to a novel RAC2 variant.

We report the case of a 1-week-old male born full-term, who had two inconclusive severe combined immunodeficiency (SCID) newborn screens and developed scalp cellulitis and Escherichia coli bacteremia. He did not pass early confirmatory hearing screens. Initial blood counts and lymphocyte flow cytometry revealed profound neutropenia and lymphopenia with a T-/B-/NK- phenotype. Red blood cell adenosine deaminase 1 activity was within normal limits. A presumptive diagnosis of reticular dysgenesis was considered. Granulocyte colony-stimulating factor was started, but there was no improvement in neutrophil counts. Subsequent lymphocyte flow cytometry at around 4 weeks of age demonstrated an increase in T-, B- and NK-cell numbers, eliminating suspicion for SCID and raising concern for congenital neutropenia and bone marrow failure syndromes. Genetic testing revealed a novel variant in RAC2 [c.181C>A (p.Gln61Lys)] (Q61K). RAC2, a Ras-related GTPase, is the dominant RAC protein expressed in hematopoietic cells and is involved with various downstream immune-mediated responses. Pathogenic RAC2 variants show significant phenotypic heterogeneity (spanning from neutrophil defects to combined immunodeficiency) across dominant, constitutively activating, dominant activating, dominant negative, and autosomal recessive subtypes. Given the identification of a novel variant, functional testing was pursued to evaluate aberrant pathways described in other RAC2 pathogenic variants. In comparison to wild-type RAC2, the Q61K variant supported elevated superoxide production under both basal and PMA-stimulated conditions, increased PAK1 binding, and enhanced plasma membrane ruffling, consistent with other dominant, constitutively active mutations. This case highlights the diagnostic challenge associated with genetic variants identified via next-generation sequencing panels and the importance of functional assays to confirm variant pathogenicity.

Anti-Interleukin-23 Autoantibodies in Adult-Onset Immunodeficiency.

BACKGROUND: Autoantibodies against interleukin-12 (anti-interleukin-12) are often identified in patients with thymoma, but opportunistic infections develop in only some of these patients. Interleukin-12 (with subunits p40 and p35) shares a common subunit with interleukin-23 (subunits p40 and p19). In a patient with disseminated Burkholderia gladioli infection, the identification of both anti-interleukin-23 and anti-interleukin-12 prompted further investigation. METHODS: Among the patients (most of whom had thymoma) who were known to have anti-interleukin-12, we screened for autoantibodies against interleukin-23 (anti-interleukin-23). To validate the potential role of anti-interleukin-23 with respect to opportunistic infection, we tested a second cohort of patients with thymoma as well as patients without either thymoma or known anti-interleukin-12 who had unusual infections. RESULTS: Among 30 patients with anti-interleukin-12 who had severe mycobacterial, bacterial, or fungal infections, 15 (50%) also had autoantibodies that neutralized interleukin-23. The potency of such neutralization was correlated with the severity of these infections. The neutralizing activity of anti-interleukin-12 alone was not associated with infection. In the validation cohort of 91 patients with thymoma, the presence of anti-interleukin-23 was associated with infection status in 74 patients (81%). Overall, neutralizing anti-interleukin-23 was detected in 30 of 116 patients (26%) with thymoma and in 30 of 36 patients (83%) with disseminated, cerebral, or pulmonary infections. Anti-interleukin-23 was present in 6 of 32 patients (19%) with severe intracellular infections and in 2 of 16 patients (12%) with unusual intracranial infections, including Cladophialophora bantiana and Mycobacterium avium complex. CONCLUSIONS: Among patients with a variety of mycobacterial, bacterial, or fungal infections, the presence of neutralizing anti-interleukin-23 was associated with severe, persistent opportunistic infections. (Funded by the National Institute of Allergy and Infectious Diseases and others.).

Estimated mortality risk and use of palliative care services among home care clients during the last 6 months of life: a retrospective cohort study.

BACKGROUND: In Canada, only 15% of patients requiring palliative care receive such services in the year before death. We describe health care utilization patterns among home care users in their last 6 months of life to inform care planning for older people with varying mortality risks and evolving care needs as they decline. METHODS: Using population health administrative data from Ontario, we performed a retrospective cohort study involving home care clients aged 50 years and older who received at least 1 interRAI (Resident Assessment Instrument) Home Care assessment between April 2018 and September 2019. We report the proportion of clients who used acute care, long-term care, and palliative home care services within 6 months of their assessment, stratified by their predicted 6-month mortality risk using a prognostic tool called the Risk Evaluation for Support: Predictions for Elder-life in their Communities Tool (RESPECT) and vital status. RESULTS: The cohort included 247 377 adults, 11.9% of whom died within 6 months of an assessment. Among decedents, 50.6% of those with a RESPECT-estimated median survival of fewer than 3 months received at least 1 nonphysician palliative home care visit before death. This proportion declined to 38.7% and 29.5% among decedents with an estimated median survival between 3 and 6 months and between 6 and 12 months, respectively. INTERPRETATION: Many older adults in Ontario do not receive any palliative home care before death. Prognostic tools such as RESPECT may improve recognition of reduced life expectancies and palliative care needs of individuals in their final years of life.

Clinical and functional spectrum of RAC2-related immunodeficiency.

ABSTRACT: Mutations in the small Rho-family guanosine triphosphate hydrolase RAC2, critical for actin cytoskeleton remodeling and intracellular signal transduction, are associated with neonatal severe combined immunodeficiency (SCID), infantile neutrophilic disorder resembling leukocyte adhesion deficiency (LAD), and later-onset combined immune deficiency (CID). We investigated 54 patients (23 previously reported) from 37 families yielding 15 novel RAC2 missense mutations, including one present only in homozygosity. Data were collected from referring physicians and literature reports with updated clinical information. Patients were grouped by presentation: neonatal SCID (n = 5), infantile LAD-like disease (n = 5), or CID (n = 44). Disease correlated to RAC2 activity: constitutively active RAS-like mutations caused neonatal SCID, dominant-negative mutations caused LAD-like disease, whereas dominant-activating mutations caused CID. Significant T- and B-lymphopenia with low immunoglobulins were seen in most patients; myeloid abnormalities included neutropenia, altered oxidative burst, impaired neutrophil migration, and visible neutrophil macropinosomes. Among 42 patients with CID with clinical data, upper and lower respiratory infections and viral infections were common. Twenty-three distinct RAC2 mutations, including 15 novel variants, were identified. Using heterologous expression systems, we assessed downstream effector functions including superoxide production, p21-activated kinase 1 binding, AKT activation, and protein stability. Confocal microscopy showed altered actin assembly evidenced by membrane ruffling and macropinosomes. Altered protein localization and aggregation were observed. All tested RAC2 mutant proteins exhibited aberrant function; no single assay was sufficient to determine functional consequence. Most mutants produced elevated superoxide; mutations unable to support superoxide formation were associated with bacterial infections. RAC2 mutations cause a spectrum of immune dysfunction, ranging from early onset SCID to later-onset combined immunodeficiencies depending on RAC2 activity. This trial was registered at www.clinicaltrials.gov as #NCT00001355 and #NCT00001467.

Nurse practitioner and physician end-of-life home visits and end-of-life outcomes.

OBJECTIVES: Physicians and nurse practitioners (NPs) play critical roles in supporting palliative and end-of-life care in the community. We examined healthcare outcomes among patients who received home visits from physicians and NPs in the 90 days before death. METHODS: We conducted a retrospective cohort study using linked data of adult home care users in Ontario, Canada, who died between 1 January 2018 and 31 December 2019. Healthcare outcomes included medications for pain and symptom management, emergency department (ED) visits, hospitalisations and a community-based death. We compared the characteristics of and outcomes in decedents who received a home visit from an NP, physician and both to those who did not receive a home visit. RESULTS: Half (56.9%) of adult decedents in Ontario did not receive a home visit from a provider in the last 90 days of life; 34.5% received at least one visit from a physician, 3.8% from an NP and 4.9% from both. Compared with those without any visits, having at least one home visit reduced the odds of hospitalisation and ED visits, and increased the odds of receiving medications for pain and symptom management and achieving a community-based death. Observed effects were larger in patients who received at least one visit from both. CONCLUSIONS: Beyond home care, receiving home visits from primary care providers near the end of life may be associated with better outcomes that are aligned with patients' preferences-emphasising the importance of NPs and physicians' role in supporting people near the end of life.

Protocol for a living evidence synthesis on variants of concern and COVID-19 vaccine effectiveness.

BACKGROUND: It is evident that COVID-19 will remain a public health concern in the coming years, largely driven by variants of concern (VOC). It is critical to continuously monitor vaccine effectiveness as new variants emerge and new vaccines and/or boosters are developed. Systematic surveillance of the scientific evidence base is necessary to inform public health action and identify key uncertainties. Evidence syntheses may also be used to populate models to fill in research gaps and help to prepare for future public health crises. This protocol outlines the rationale and methods for a living evidence synthesis of the effectiveness of COVID-19 vaccines in reducing the morbidity and mortality associated with, and transmission of, VOC of SARS-CoV-2. METHODS: Living evidence syntheses of vaccine effectiveness will be carried out over one year for (1) a range of potential outcomes in the index individual associated with VOC (pathogenesis); and (2) transmission of VOC. The literature search will be conducted up to May 2023. Observational and database-linkage primary studies will be included, as well as RCTs. Information sources include electronic databases (MEDLINE; Embase; Cochrane, L*OVE; the CNKI and Wangfang platforms), pre-print servers (medRxiv, BiorXiv), and online repositories of grey literature. Title and abstract and full-text screening will be performed by two reviewers using a liberal accelerated method. Data extraction and risk of bias assessment will be completed by one reviewer with verification of the assessment by a second reviewer. Results from included studies will be pooled via random effects meta-analysis when appropriate, or otherwise summarized narratively. DISCUSSION: Evidence generated from our living evidence synthesis will be used to inform policy making, modelling, and prioritization of future research on the effectiveness of COVID-19 vaccines against VOC.

At the Epicentre of the COVID-19 Pandemic in Canada: Experiences and Recommendations of Family Care Partners of an Older Person Living in a Long-Term Care Home.

The roles of family care partners of older persons living in long-term care homes (LTCH) were severely disrupted during the coronavirus disease (COVID-19) pandemic. Our aim was to describe their experiences and to solicit their recommendations for supportive actions. We conducted a critical ethnography with 24 care partners who cared or had cared for an older person living in an LTCH in Québec during the COVID-19 pandemic. We collected data during interviews and used Spradley's method to analyse them. Care partners experienced a forced separation from the older persons they cared for, which resulted in significant distress. Care, including post-mortem care, was considered inadequate and sometimes even inhumane. Communication was inconsistent, and this variability was also noted in visitation rules. Care partners perceived LTCHs as a neglected community. Supportive actions were recommended. The results illustrated the essential contribution of care partners, and the supportive actions they recommended must be a catalyst for change toward more humane care in LTCH settings.

Physician continuity of care in the last year of life in community-dwelling adults: retrospective population-based study.

OBJECTIVE: To describe the timing of involvement of various physician specialties over the last year of life across different levels of primary care physician continuity for differing causes of death. METHODS: We conducted a retrospective cohort study of adults who died in Ontario, Canada, between 1 January 2013 and 31 December 2018, using linked population level health administrative data. Outcomes were median days between death and first and last outpatient palliative care specialist encounter, last outpatient encounter with other specialists and with the usual primary care physician. These were calculated by tertile of score on the Usual Provider Continuity Index, defined as the proportion of outpatient physician encounters with the patient's primary care physician. RESULTS: Patients' (n=395 839) mean age at death was 76 years. With increasing category of usual primary care physician continuity, a larger proportion were palliative care generalists, palliative care specialist involvement decreased in duration and was concentrated closer to death, the primary care physician was involved closer to death, and other specialist physicians ceased involvement earlier. For patients with cancer, palliative care specialist involvement was longer than for other patients. CONCLUSIONS: Compared with patients with lower continuity, those with higher usual provider continuity were more likely to have a primary care physician involved closer to death providing generalist palliative care.

Exploring COVID-19 education to support vaccine confidence amongst the general adult population with special considerations for healthcare and long-term care staff: A scoping review.

Background: Despite the demonstrated efficacy of approved COVID-19 vaccines, high levels of hesitancy were observed in the first few months of the COVID-19 vaccines' rollout. Factors contributing to vaccine hesitancy are well-described in the literature. Among the various strategies for promoting vaccine confidence, educational interventions provide a foundationally and widely implemented set of approaches for supporting individuals in their vaccine decisions. However, the evidence around the measurable impact of various educational strategies to improve vaccine confidence is limited. We conducted a scoping review with the aim of exploring and characterizing educational interventions delivered during the pandemic to support COVID-19 vaccine confidence in adults. Methods: We developed a search strategy with a medical information scientist and searched five databases, including Ovid MEDLINE and Web of Science, as well as grey literature. We considered all study designs and reports. Interventions delivered to children or adolescents, interventions on non-COVID-19 vaccines, as well as national or mass vaccination campaigns without documented interaction(s) between facilitator(s) and a specific audience were excluded. Articles were independently screened by three reviewers. After screening 4602 titles and abstracts and 174 full-text articles across two rounds of searches, 22 articles met our inclusion criteria. Ten additional studies were identified through hand searching. Data from included studies were charted and results were described narratively. Results: We included 32 studies and synthesized their educational delivery structure, participants (i.e., facilitators and priority audience), and content. Formal, group-based presentations were the most common type of educational intervention in the included studies (75%). A third of studies (34%) used multiple strategies, with many formal group-based presentations being coupled with additional individual-based interventions (29%). Given the novelty of the COVID-19 vaccines and the unique current context, studies reported personalized conversations, question periods, and addressing misinformation as important components of the educational approaches reviewed. Conclusions: Various educational interventions were delivered during the COVID-19 pandemic, with many initiatives involving multifaceted interventions utilizing both formal and informal approaches that leveraged community (cultural, religious) partnerships when developing and facilitating COVID-19 vaccine education. Train-the-trainer approaches with recognized community members could be of value as trust and personal connections were identified as strong enablers throughout the review.

End-of-life interventions in patients with cancer.

OBJECTIVES: To describe variations in the receipt of potentially inappropriate interventions in the last 100 days of life of patients with cancer according to patient characteristics and cancer site. METHODS: We conducted a population-based retrospective cohort study of cancer decedents in Ontario, Canada who died between 1 January 2013 and 31 December 2018. Potentially inappropriate interventions, including chemotherapy, major surgery, intensive care unit admission, cardiopulmonary resuscitation, defibrillation, dialysis, percutaneous coronary intervention, mechanical ventilation, feeding tube placement, blood transfusion and bronchoscopy, were captured via hospital discharge records. We used Poisson regression to examine associations between interventions and decedent age, sex, rurality, income and cancer site. RESULTS: Among 151 618 decedents, 81.3% received at least one intervention, and 21.4% received 3+ different interventions. Older patients (age 95-105 years vs 19-44 years, rate ratio (RR) 0.36, 95% CI 0.34 to 0.38) and women (RR 0.94, 95% CI 0.93 to 0.94) had lower intervention rates. Rural patients (RR 1.09, 95% CI 1.08 to 1.10), individuals in the highest area-level income quintile (vs lowest income quintile RR 1.02, 95% CI 1.01 to 1.04), and patients with pancreatic cancer (vs colorectal cancer RR 1.10, 95% CI 1.07 to 1.12) had higher intervention rates. CONCLUSIONS: Potentially inappropriate interventions were common in the last 100 days of life of cancer decedents. Variations in interventions may reflect differences in prognostic awareness, healthcare access, and care preferences and quality. Earlier identification of patients' palliative care needs and involvement of palliative care specialists may help reduce the use of these interventions at the end of life.

Somatic mutational landscape of hereditary hematopoietic malignancies caused by germline variants in RUNX1, GATA2, and DDX41.

Individuals with germ line variants associated with hereditary hematopoietic malignancies (HHMs) have a highly variable risk for leukemogenesis. Gaps in our understanding of premalignant states in HHMs have hampered efforts to design effective clinical surveillance programs, provide personalized preemptive treatments, and inform appropriate counseling for patients. We used the largest known comparative international cohort of germline RUNX1, GATA2, or DDX41 variant carriers without and with hematopoietic malignancies (HMs) to identify patterns of genetic drivers that are unique to each HHM syndrome before and after leukemogenesis. These patterns included striking heterogeneity in rates of early-onset clonal hematopoiesis (CH), with a high prevalence of CH in RUNX1 and GATA2 variant carriers who did not have malignancies (carriers-without HM). We observed a paucity of CH in DDX41 carriers-without HM. In RUNX1 carriers-without HM with CH, we detected variants in TET2, PHF6, and, most frequently, BCOR. These genes were recurrently mutated in RUNX1-driven malignancies, suggesting CH is a direct precursor to malignancy in RUNX1-driven HHMs. Leukemogenesis in RUNX1 and DDX41 carriers was often driven by second hits in RUNX1 and DDX41, respectively. This study may inform the development of HHM-specific clinical trials and gene-specific approaches to clinical monitoring. For example, trials investigating the potential benefits of monitoring DDX41 carriers-without HM for low-frequency second hits in DDX41 may now be beneficial. Similarly, trials monitoring carriers-without HM with RUNX1 germ line variants for the acquisition of somatic variants in BCOR, PHF6, and TET2 and second hits in RUNX1 are warranted.

Physician home visits to rostered patients during their last year of life: a retrospective cohort study.

BACKGROUND: Physician home visits are associated with better health outcomes, yet most patients near the end of life never receive such a visit. Our objectives were to describe the receipt of physician home visits during the last year of life after a referral to home care - an indication that the patient can no longer live independently - and to measure associations between patient characteristics and receipt of a home visit. METHODS: We conducted a retrospective cohort study using linked population-based health administrative databases housed at ICES. We identified adult (aged ≥ 18 yr) decedents in Ontario who died between Mar. 31, 2013, and Mar. 31, 2018, who were receiving primary care and were referred to publicly funded home care services. We described the provision of physician home visits, office visits and telephone management. We used multinomial logistic regression to calculate the odds of receiving home visits from a rostered primary care physician, controlling for referral during the last year of life, age, sex, income quintile, rurality, recent immigrant status, referral by rostered physician, referral during hospital stay, number of chronic conditions and disease trajectory based on the cause of death. RESULTS: Of the 58 753 decedents referred in their last year of life, 3125 (5.3%) received a home visit from their family physician. Patient characteristics associated with higher odds of receiving home visits compared to office-based or telephone-based care were being female (adjusted odds ratio [OR] 1.28, 95% confidence interval [CI] 1.21-1.35), being 85 years of age or older (adjusted OR 2.42, 95% CI 1.80-3.26) and living in a rural area (adjusted OR 1.09, 95% CI 1.00-1.18). Increased odds were associated with home care referrals by the patient's primary care physician (adjusted OR 1.49, 95% CI 1.39-1.58) and referrals occurring during a hospital stay (adjusted OR 1.20, 95% CI 1.13-1.28). INTERPRETATION: A small proportion of patients near the end of life received home-based physician care, and patient characteristics did not explain the low visit rates. Future work on system- and provider-level factors may be critical to improve access to home-based end-of-life primary care.

Perceptions of Palliative and End-Of-Life Care Capacity Among Frontline Staff and Administrators in Long-Term Care Homes During the COVID-19 Pandemic in Ontario, Canada: A Mixed-Methods Evaluation.

OBJECTIVES: The COVID-19 pandemic has greatly affected the morbidity and mortality of residents in long-term care (LTC) homes. However, not much is known about its impact on staff's perception of their capacity to provide palliative and end-of-life (EOL) care for LTC residents over the course of the pandemic. We investigated changes in self-reported confidence among LTC workers and their experience in providing palliative and EOL care to residents before and during the COVID-19 pandemic. DESIGN: Mixed-methods evaluation using a survey (n = 19) and semistructured interviews (n = 28). SETTING AND PARTICIPANTS: Frontline workers from 9 LTC homes who participated in Communication at End-of-Life Program in Ontario, Canada, between August 2019 and March 2020. METHODS: The survey captured LTC staff's confidence level, including attitudes toward death and dying; relationships with residents and families; and participation in palliative and EOL care. The interviews identified facilitators and barriers to providing palliative and EOL care during the pandemic. RESULTS: The COVID-19 pandemic negatively impacted frontline LTC staff's confidence in their role as palliative care providers. Participants also reported notable challenges to providing resident-centered palliative and EOL care. Specifically, visitation restriction has led to increased loneliness and isolation of residents and impeded staff's ability to build supportive relationships with families. Furthermore, staffing shortages due to the single-site work restriction and illness increased workload. Psychological stress caused by a fear of COVID-19 infection and transmission also hindered staff's capacity to provide good palliative and EOL care. CONCLUSIONS AND IMPLICATIONS: Frontline LTC staff-even those who felt competent in their knowledge and skills in providing palliative and EOL care after receiving training-reported notable difficulties in providing resident-centered palliative and EOL care during the COVID-19 pandemic.