Characterizing Proton-Induced Biological Effects in a Mouse Spinal Cord Model: A Comparison of Bragg Peak and Entrance Beam Response in Single and Fractionated Exposures.

PURPOSE: Proton relative biological effectiveness (RBE) is a dynamic variable influenced by factors like linear energy transfer (LET), dose, tissue type, and biological endpoint. The standard fixed proton RBE of 1.1, currently used in clinical planning, may not accurately represent the true biological effects of proton therapy (PT) in all cases. This uncertainty can contribute to radiation-induced normal tissue toxicity in patients. In late-responding tissues such as the spinal cord, toxicity can cause devastating complications. This study investigated spinal cord tolerance in mice subjected to proton irradiation and characterized the influence of fractionation on proton- induced myelopathy at entrance (ENT) and Bragg peak (BP) positions. METHODS AND MATERIALS: Cervical spinal cords of 8-week-old C57BL/6J female mice were irradiated with single- or multi-fractions (18x) using lateral opposed radiation fields at 1 of 2 positions along the Bragg curve: ENT (dose-mean LET = 1.2 keV/µm) and BP (LET = 6.9 keV/µm). Mice were monitored over 1 year for changes in weight, mobility, and general health, with radiation-induced myelopathy as the primary biological endpoint. Calculations of the RBE of the ENT and BP curve (RBEENT/BP) were performed. RESULTS: Single-fraction RBEENT/BP for 50% effect probability (tolerance dose (TD50), grade II paresis, determined using log-logistic model fitting) was 1.10 ± 0.06 (95% CI) and for multifraction treatments it was 1.19 ± 0.05 (95% CI). Higher incidence and faster onset of paralysis were seen in mice treated at the BP compared with ENT. CONCLUSIONS: The findings challenge the universally fixed RBE value in PT, indicating up to a 25% mouse spinal cord RBEENT/BP variation for multifraction treatments. These results highlight the importance of considering fractionation in determining RBE for PT. Robust characterization of proton-induced toxicity, aided by in vivo models, is paramount for refining clinical decision-making and mitigating potential patient side effects.

The Certificate of Added Competence credentialling program in family medicine: a descriptive survey of the family physician perspective of enhanced skill practices in Canada.

Introduction: The College of Family Physicians of Canada (CFPC) offers the Certificate of Added Competence (CAC) program to designate a family physician with enhanced skills. In 2015, the College expanded its program to introduce enhanced certification in four new domains: Palliative Care, Care of the Elderly, Sports and Exercise Medicine, and Family Practice Anesthesia. In this study, we elicited perceptions from Canadian family physicians with and without the CAC on practice impacts associated with the program. Methods: Active family physicians in Canada with and without CACs were surveyed between November 2019 to January 2020. Descriptive statistics were generated to describe the perceptions of family physicians regarding the CAC program and its impacts on practice. Results: Respondents agreed with several benefits of the program including enhancing the capacity to deliver comprehensive care, alleviating the burden of patient travel by increasing the availability of care in rural and remote communities, and providing opportunities to engage in various collaborative care models and new leadership roles. All respondents perceived CAC holders to pursue the certificate to meet both professional interests and community needs. Conclusions: There is a need for strong and continued investment in systemic practice improvements that incentivize the delivery of comprehensive family medicine practice.

Introduction: Le certificat de compétence additionnelle (CCA) accordé par le Collège des médecins de famille du Canada (CMFC) vise à reconnaître un haut niveau de compétences chez un médecin de famille. En 2015, le Collège a élargi le titre de compétences additionnelles à quatre nouveaux domaines : soins palliatifs, soins aux personnes âgées, médecine du sport et de l'exercice, et anesthésie en médecine familiale. Dans cette étude, nous avons recueilli les perceptions de médecins de famille titulaires et non titulaires d'un CCA sur l'influence de pratiques associées au programme de certification. Méthodes: Des médecins de famille actifs au Canada, titulaires et non titulaires du CCA, ont été interrogés entre novembre 2019 et janvier 2020. Des statistiques descriptives ont été générées pour décrire leurs perceptions concernant le Certificat et ses impacts sur la pratique. Résultats: Les répondants s'entendaient pour reconnaître au CCA plusieurs avantages, notamment le fait d'améliorer la capacité des médecins à fournir des soins complets, de leur offrir la possibilité de s'engager dans divers modèles de soins collaboratifs et de nouveaux rôles de leadership, et d'alléger le fardeau des déplacements des patients en augmentant la disponibilité des soins dans les populations rurales et éloignées. Tous les répondants estiment que les médecins recherchent l'obtention de ce titre de compétence pour répondre à la fois à leurs intérêts professionnels et aux besoins de la collectivité. Conclusions: Il faut investir de manière importante et continue dans des améliorations systémiques qui favoriseront une pratique holistique de la médecine familiale.

Rapid Peroxide Removal Limits the Radiosensitization of Diffuse Intrinsic Pontine Glioma (DIPG) Cells by Pharmacologic Ascorbate.

Diffuse intrinsic pontine gliomas (DIPG) are an aggressive type of pediatric brain tumor with a very high mortality rate. Surgery has a limited role given the tumor's location. Palliative radiation therapy alleviates symptoms and prolongs survival, but median survival remains less than 1 year. There is no clear role for chemotherapy in DIPGs as trials adding chemotherapy to palliative radiation therapy have failed to improve survival compared to radiation alone. Thus, there is a critical need to identify tissue-specific radiosensitizers to improve clinical outcomes for patients with DIPGs. Pharmacologic (high dose) ascorbate (P-AscH-) is a promising anticancer therapy that sensitizes human tumors, including adult high-grade gliomas, to radiation by acting selectively as a generator of hydrogen peroxide (H2O2) in cancer cells. In this study we demonstrate that in contrast to adult glioma models, P-AscH- does not radiosensitize DIPG. DIPG cells were sensitive to bolus of H2O2 but have faster H2O2 removal rates than GBM models which are radiosensitized by P-AscH-. These data support the hypothesis that P-AscH- does not enhance DIPG radiosensitivity, likely due to a robust capacity to detoxify and remove hydroperoxides.

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.

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.

Describing settings of care in the last 100 days of life for cancer decedents: a population-based descriptive study.

BACKGROUND: Few studies have described the settings cancer decedents spend their end-of-life stage, with none considering homecare specifically. We describe the different settings of care experienced in the last 100 days of life by individuals with cancer and how settings of care change as they approached death. METHODS: A retrospective cohort study from January 2013 to December 2017, of decedents whose primary cause of death was cancer, using linked population-level health administrative datasets in Ontario, Canada. RESULTS: Decedents 125,755 were included in our cohort. The average age at death was 73, 46% were female, and 14% resided in rural regions. And 24% died of lung cancer, 7% breast, 7% colorectal, 7% pancreatic, 5% prostate, and 50% other cancers. In the last 100 days of life, decedents spent 25.9 days in institutions, 25.8 days receiving care in the community, and 48.3 days at home without any care. Individuals who died of lung and pancreatic cancers spent the most days at home without any care (52.1 and 52.6 days), while individuals who died of prostate and breast cancer spent the least days at home without any care (41.6 and 45.1 days). Regardless of cancer type, decedents spent fewer days at home and more days in institutions as they approached death, despite established patient preferences for an end-of-life experience at home. CONCLUSIONS: In the last 100 days of life, cancer decedents spent most of their time in either institutions or at home without any care. Improving homecare services during the end-of-life may provide people dying of cancer with a preferred dying experience.

Building Palliative Care Capacity for Generalist Providers in the Community: Results From the Capaciti Pilot Education Program.

Objective: Primary care providers play an important role in providing early palliative care, however they often lack practical supports to operationalize this approach in practice. CAPACITI is a virtual training program aimed at providing practical tips, strategies, and action plans to help primary care providers offer an early palliative approach to care. The CAPACITI pilot program consisted of 10 facilitated, monthly training sessions, covering identification and assessment, communication, and engaging caregivers and specialists. We present the findings of an evaluation of the pilot program. Method: We conducted a single cohort study of primary care providers who participated in CAPACITI. Study outcomes were the change in the percentage of caseload reported as requiring palliative care and improved confidence in competencies measured on a 20-item, study-created survey. Pre and post survey data were analyzed using paired t-tests. Results: Twenty-two teams representing 127 care providers (including 36 physicians and 28 Nurse Practitioners) completed CAPACITI. Paired comparisons showed a moderate improvement in confidence across the competencies covered (.6 to 1.3 mean improvement across items using seven-point scales, all P < .05). Pre-CAPACITI, clinician prescribers (N = 32) identified a mean of 1.2% of their caseload requiring a palliative approach to care, which increased to 1.6% post-program (P = .02). Said differently, the total group of paired clinician prescribers identified 338 patients as requiring palliative care in their caseloads at baseline vs 482 patients following the intervention, for an overall increase of 144 patients in their collective caseloads. Conclusion: CAPACITI improved self-assessed palliative care identification and provider confidence in core competencies. The program demonstrated potential for building palliative care capacity in primary care teams.

Continuity of physician care over the last year of life for different cause-of-death categories: a retrospective population-based study.

BACKGROUND: The mix of care provided by family physicians, specialists and palliative care physicians can vary by the illnesses leading to death, which may result in disruptions of continuity of care at the end of life. We measured continuity of outpatient physician care in the last year of life across differing causes of death and assessed factors associated with higher continuity. METHODS: We conducted a retrospective descriptive study of adults who died in Ontario between 2013 and 2018, using linked provincial health administrative data. We calculated 3 measures of continuity (usual provider, Bice-Boxerman and sequential continuity), which range from 0 to 1, from outpatient physician visits over the last year of life for terminal illness, organ failure, frailty, sudden death and other causes of death. We used multivariable logistic regression models to evaluate associations between characteristics and a continuity score of 0.5 or greater. RESULTS: Among the 417 628 decedents, we found that mean usual provider, Bice-Boxerman and sequential continuity indices were 0.37, 0.30 and 0.37, respectively, with continuity being the lowest for those with terminal illness (0.27, 0.23 and 0.33, respectively). Higher number of comorbidities, higher neighbourhood income quintile and all non-sudden death categories were associated with lower continuity. INTERPRETATION: We found that continuity of physician care in the last year of life was low, especially in those with cancer. Further research is needed to validate measures of continuity against end-of-life health care outcomes.

Inpatient Palliative Care Is Associated with the Receipt of Palliative Care in the Community after Hospital Discharge: A Retrospective Cohort Study.

Background: For hospitalized patients with palliative care needs, there is little evidence on whether postdischarge outcomes differ if inpatient palliative care was delivered by a palliative care specialist or nonspecialist/generalist. Objective: To evaluate relationships between inpatient palliative care involvement and physician-delivered palliative care in the community after hospital discharge among individuals with limited life expectancy. Design: Population-based retrospective cohort study using administrative health data. Settings/Subjects: Adults with a predicted median survival of six months or less admitted to acute care hospitals in Ontario, Canada, between April 1, 2013, and March 31, 2017, and discharged to the community. Measurements: Inpatient palliative care involvement was classified as high (e.g., palliative care unit), medium (e.g., palliative care specialist consult), low (e.g., generalist-delivered palliative care), or none. Community palliative care included outpatient and home and clinic visits three weeks postdischarge. Results: Among 3660 hospitalized adults, 82 (2.2%) received inpatient palliative care with high level of involvement, 462 (12.6%) with medium level of involvement, 525 (14.3%) with low level of involvement, and 2591 (70.8%) had no inpatient palliative care. Patients who received inpatient palliative care were more likely to receive community palliative care after discharge than those who received no inpatient palliative care. These associations were stronger among patients who received high/medium palliative care involvement than patients who received low palliative care involvement. Conclusions: Inpatient palliative care, including that delivered by generalists, is associated with an increased likelihood of community palliative care after discharge. Increased inpatient generalist palliative care may help support patients' palliative care needs.

Short Graphic Values History Tool for decision making during serious illness.

OBJECTIVES: To develop and validate a values clarification tool, the Short Graphic Values History Tool (GVHT), designed to support person-centred decision making during serious illness. METHODS: The development phase included input from experts and laypersons and assessed acceptability with patients/family members. In the validation phase, we recruited additional participants into a before-after study. Our primary validation hypothesis was that the tool would reduce scores on the Decisional Conflict Scale (DCS) at 1-2 weeks of follow-up. Our secondary validation hypotheses were that the tool would improve values clarity (reduce scores) more than other DCS subscales and increase engagement in advance care planning (ACP) processes related to identification and discussion of one's values. RESULTS: In the development phase, the tool received positive overall ratings from 22 patients/family members in hospital (mean score 4.3; 1=very poor; 5=very good) and family practice (mean score 4.5) settings. In the validation phase, we enrolled 157 patients (mean age 71.8 years) from family practice, cancer clinic and hospital settings. After tool completion, decisional conflict decreased (-6.7 points, 95% CI -11.1 to -2.3, p=0.003; 0-100 scale; N=100), with the most improvement seen in the values clarity subscale (-10.0 points, 95% CI -17.3 to -2.7, p=0.008; N=100), and the ACP-Values process score increased (+0.4 points, 95% CI 0.2 to 0.6, p=0.001; 1-5 scale; N=61). CONCLUSIONS: The Short GVHT is acceptable to end users and has some measure of validity. Further study to evaluate its impact on decision making during serious illness is warranted.

Palliative care physicians' motivations for models of practicing in the community: A qualitative descriptive study.

BACKGROUND: Internationally, both primary care providers and palliative care specialists are required to address palliative care needs of our communities. Clarity on the roles of primary and specialist-level palliative care providers is needed in order to improve access to care. This study examines how community-based palliative care physicians apply their roles as palliative care specialists, what motivates them, and the impact that has on how they practice. DESIGN: A qualitative descriptive study using semi-structured virtual interviews of community-based palliative care specialists. We asked participants to describe their care processes and the factors that influence how they work. SETTING/PARTICIPANTS: A qualitative descriptive study using semi-structured virtual interviews of community-based palliative care physicians in Ontario, Canada was undertaken between March and June 2020. At interview end, participants indicated whether their practice approaches aligned with one or more models depicted in a conceptual framework that includes consultation (specialist provides recommendations to the family physician) and takeover (palliative care physician takes over all care responsibility from the family physician) models. RESULTS: Of the 14 participants, 4 worked in a consultation model, 8 in a takeover model, and 2 were transitioning to a consultation model. Different motivators were found for the two practice models. In the takeover model, palliative care physicians were primarily motivated by their relationships with patients. In the consultation model, palliative care physicians were primarily motivated by their relationships with primary care. These differing motivations corresponded to differences in the day-to-day processes and outcomes of care. CONCLUSIONS: The physician's personal or internal motivators were drivers in their practice style of takeover versus consultative palliative care models. Awareness of these motivations can aid our understanding of current models of care and help inform strategies to enhance consultative palliative care models.

Nursing Home Resident Admission Characteristics and Potentially Preventable Emergency Department Transfers.

OBJECTIVES: To determine which nursing home (NH) resident-level admission characteristics are associated with potentially preventable emergency department (PPED) transfers. DESIGN: We conducted a population-level retrospective cohort study on NH resident data collected using the Resident Assessment Instrument-Minimum Data Set Version 2.0 and linked to the National Ambulatory Care Reporting System for ED transfers. SETTING: We used all NH resident admission assessments from January 1, 2017, to December 31, 2018, in Ontario. PARTICIPANTS: The cohort included the admission assessment of 56,433 NH residents. METHODS: PPED transfers were defined based on the International Classification of Disease, Version 10 (Canadian) We used logistic regression with 10-fold cross-validation and computed average marginal effects to identify the association between resident characteristics at NH admission and PPED transfers within 92 days after admission. RESULTS: Overall, 6.2% of residents had at least 1 PPED transfer within 92 days of NH admission. After adjustment, variables that had a prevalence of 10% or more that were associated with a 1% or more absolute increase in the risk of a PPED transfer included polypharmacy [of cohort (OC) 84.4%, risk difference (RD) 2.0%], congestive heart failure (OC 29.0%, RD 3.0%), and renal failure (OC 11.6%, RD 1.2%). Female sex (OC 63.2%, RD -1.3%), a do not hospitalize directive (OC 24.4%, RD -2.6%), change in mood (OC 66.9%, RD -1.2%), and Alzheimer's or dementia (OC 62.1%, RD -1.2%) were more than 10% prevalent and associated with a 1% or more absolute decrease in the risk of a PPED. CONCLUSIONS AND IMPLICATIONS: Though many routinely collected resident characteristics were associated with a PPED transfer, the absence of sufficiently discriminating characteristics suggests that emergency department visits by NH residents are multifactorial and difficult to predict. Future studies should assess the clinical utility of risk factor identification to prevent transfers.

Assessing the application of continuity of care indices in the last year of life: a retrospective population-based study.

Context: Most people spend the majority of their last year of life at home or in a home-like setting, receiving outpatient healthcare. Increasing numbers of physicians and teams, including palliative care providers, may become involved in care in addition to a usual provider such as a family physician. Continuity of care (CoC) near the end of life, although considered a marker of quality of care, may be interrupted despite the provision of high-quality care. Objective: To describe continuity of outpatient physician care in the last 12 months of life and determine patient and illness-related factors associated with high continuity. Study Design: Retrospective cohort study. Datasets: Linked population-based health administrative databases for Ontario, Canada, held at ICES. Population: Decedents aged 19 years or older, who died between January 1, 2013, and December 31, 2017. Outcome Measures: Continuity of care scores for the last 12 months of life, using the Usual Provider continuity (UPC), Bice-Boxerman continuity (CoC), and Sequential Continuity (SECON) indices. Multivariate models were used to determine factors associated with higher continuity scores (>= 0.75). Results: Decedents (n=322,445) were on average 76.3 years of age, 47.8% were female, and 13.2% resided in rural regions. Decedents had a mean of 16.2 outpatient physician encounters in the last year of life, from a mean of 3.8 different physician specialties. Mean continuity indices' scores (1 being perfect) were low: UPC= 0.36, CoC= 0.31, and SECON= 0.37. Proportions of decedents with high continuity were: UPC= 12.6%, CoC= 9.6%, and SECON= 12.9%. Decedents who experienced a terminal illness (i.e., cancer) end-of-life trajectory were least likely to experience high UPC (OR= 0.32; 95% CI= 0.30, 0.34). Having six or more comorbidities (OR= 0.65; 95% CI= 0.63, 0.66), and being in the highest quintile of outpatient physician encounters (i.e., >22 visits) (OR= 0.28; 95% CI= 0.27, 0.29) were also negatively associated with high UPC. Results were similar for other indices. Conclusions: Decedents experience low continuity of outpatient physician care in the last year of life, especially those with cancer, comorbidities, and frequent physician visits. Modifications to existing indices may be needed to serve as end-of-life care quality indicators.

Has Lockdown and COVID-19 Led to a Change in the Characteristics of Deep Vein Thrombosis and Patients Who Are Afflicted With It?

BACKGROUND: There is growing evidence identifying coronavirus disease 2019 (COVID-19) as a significant risk factor for thrombosis in inpatients. However, it remains uncertain if patients in the community have been influenced during the COVID-19 pandemic and national lockdown. This study, across four centres in the United Kingdom (UK), reviewed outpatients with deep vein thrombosis (DVT). AIM: This study aims to find out whether lockdown and COVID-19 led to a change in the characteristics of DVT and patients who are afflicted with it, alongside a review of DVT service. METHODS: Data was collected retrospectively from electronic patient records system for the following periods: April 1 to June 30, 2019, and April 1 to June 30, 2020. These were the key months during the first national lockdown in UK. Data were analysed for patient demographics, risk factors, characteristics of DVT, management, and DVT reoccurrence. Statistical analyses were performed using GraphPad Prism 8 (Dotmatics, Boston, Massachusetts, United States). RESULTS: During the study periods, 227 outpatients from the community sustained DVT in 2019 and 211 in 2020. Of these patients, 13 in 2020 were COVID-19 positive. There was a difference in gender distribution with 128 males and 99 females in 2019, and 93 males and 118 females in 2020 (p= 0.0128). No significant difference was noted in the incidence of thrombophilia with nine in 2019 and three in 2020 (p=0.1437). Fewer long-haul journeys were made in 2020 (only two), compared to 16 in 2019 (p=0.012). Fewer patients had immobility as a risk factor in 2020 (n=55) compared to 2019 (n=79) (p=0.0494). However, there were more patients using oral contraceptive pills, with one in 2019 and nine in 2020 (p=0.0086) . CONCLUSION: There is no significant difference in the characteristics, extent, and management of DVT prior to and during the COVID-19 lockdown. National lockdowns do not affect DVT in the community; however, it is important to highlight the surrounding inpatient numbers.

Impacts of the Certificates of Added Competence credentialling program: a qualitative case study of enhanced-skill family medicine practice across Canada.

BACKGROUND: In 2015, the College of Family Physicians of Canada (CFPC) expanded its Certificates of Added Competence (CAC) program to include enhanced-skill certification in Care of Elderly, Family Practice Anesthesia, Palliative Care, and Sports and Exercise Medicine. We aimed to describe the impact of these 4 CACs on the provision of comprehensive care in Canada, while also identifying the factors of influence that foster these impacts. METHODS: Between September 2018 and June 2019, we conducted qualitative case studies of 6 family medicine practices across Canada, sampled to represent geographic, population and practice arrangement diversity. We developed a framework of relevant factors and their relations to CAC-mediated comprehensive care delivery. We took an exploratory approach to the first 4 case studies, guided by theoretical propositions based on a literature review, and the CFPC's 4 principles of family medicine and goals for practice. The emerging theory was confirmed and adapted through the final 2 explanatory case studies. Data were obtained through semistructured qualitative interviews with enhanced-skill and generalist physicians, specialists, trainees and administrators associated with these cases. We performed a descriptive content analysis, within and across cases. RESULTS: Interviews with 48 participants showed considerable variation in the way CACs are operationalized related to the specific domain of care, the community, relationships among practitioners, motivations of the practitioner and needs of the patient population. The presence of CAC holders in communities expands the scope of available services, reduces the need for patients to travel and encourages continuity of care; however, comprehensive care may be negatively affected when CAC holders develop enhanced-skill practices according to clinical interests rather than community needs. Factors associated with collaborative care models, practice requirements, remuneration structure, community culture and individual aspirations interact to reinforce or undermine the effectiveness of enhanced-skill practices. INTERPRETATION: Holders of CACs have a positive impact when they work in collaborative models that align with the needs of communities and that support local generalist family physicians. Health care policies should incentivize CAC activities that contribute to planned care delivery at the practice and community levels.

Impact of physician-based palliative care delivery models on health care utilization outcomes: A population-based retrospective cohort study.

BACKGROUND: Increasing involvement of palliative care generalists may improve access to palliative care. It is unknown, however, if their involvement with and without palliative care specialists are associated with different outcomes. AIM: To describe physician-based models of palliative care and their association with healthcare utilization outcomes including: emergency department visits, acute hospitalizations and intensive care unit (ICU) admissions in last 30 days of life; and, place of death. DESIGN: Population-based retrospective cohort study using linked health administrative data. We used descriptive statistics to compare outcomes across three models (generalist-only palliative care; consultation palliative care, comprising of both generalist and specialist care; and specialist-only palliative care) and conducted a logistic regression for community death. SETTING/PARTICIPANTS: All adults aged 18-105 who died in Ontario, Canada between April 1, 2012 and March 31, 2017. RESULTS: Of the 231,047 decedents who received palliative services, 40.3% received generalist, 32.3% consultation and 27.4% specialist palliative care. Across models, we noted minimal to modest variation for decedents with at least one emergency department visit (50%-59%), acute hospitalization (64%-69%) or ICU admission (7%-17%), as well as community death (36%-40%). In our adjusted analysis, receipt of a physician home visit was a stronger predictor for increased likelihood of community death (odds ratio 9.6, 95% confidence interval 9.4-9.8) than palliative care model (generalist vs consultation palliative care 2.0, 1.9-2.0). CONCLUSION: The generalist palliative care model achieved similar healthcare utilization outcomes as consultation and specialist models. Including a physician home visit component in each model may promote community death.

Dosimetric Assessment of a High Precision System for Mouse Proton Irradiation to Assess Spinal Cord Toxicity.

The uncertainty associated with the relative biological effectiveness (RBE) in proton therapy, particularly near the Bragg peak (BP), has led to the shift towards biological-based treatment planning. Proton RBE uncertainty has recently been reported as a possible cause for brainstem necrosis in pediatric patients treated with proton therapy. Despite this, in vivo studies have been limited due to the complexity of accurate delivery and absolute dosimetry. The purpose of this investigation was to create a precise and efficient method of treating the mouse spinal cord with various portions of the proton Bragg curve and to quantify associated uncertainties for the characterization of proton RBE. Mice were restrained in 3D printed acrylic boxes, shaped to their external contour, with a silicone insert extending down to mold around the mouse. Brass collimators were designed for parallel opposed beams to treat the spinal cord while shielding the brain and upper extremities of the animal. Up to six animals may be accommodated for simultaneous treatment within the restraint system. Two plans were generated targeting the cervical spinal cord, with either the entrance (ENT) or the BP portion of the beam. Dosimetric uncertainty was measured using EBT3 radiochromic film with a dose-averaged linear energy transfer (LETd) correction. Positional uncertainty was assessed by collecting a library of live mouse scans (n = 6 mice, two independent scans per mouse) and comparing the following dosimetric statistics from the mouse cervical spinal cord: Volume receiving 90% of the prescription dose (V90); mean dose to the spinal cord; and LETd. Film analysis results showed the dosimetric uncertainty to be ±1.2% and ±5.4% for the ENT and BP plans, respectively. Preliminary results from the mouse library showed the V90 to be 96.3 ± 4.8% for the BP plan. Positional uncertainty of the ENT plan was not measured due to the inherent robustness of that treatment plan. The proposed high-throughput mouse proton irradiation setup resulted in accurate dose delivery to mouse spinal cords positioned along the ENT and BP. Future directions include adapting the setup to account for weight fluctuations in mice undergoing fractionated irradiation.

Frequency of providing a palliative approach to care in family practice: a chart review and perceptions of healthcare practitioners in Canada.

BACKGROUND: Most patients nearing the end of life can benefit from a palliative approach in primary care. We currently do not know how to measure a palliative approach in family practice. The objective of this study was to describe the provision of a palliative approach and evaluate clinicians' perceptions of the results. METHODS: We conducted a descriptive study of deceased patients in an interprofessional team family practice. We integrated conceptual models of a palliative approach to create a chart review tool to capture a palliative approach in the last year of life and assessed a global rating of whether a palliative approach was provided. Clinicians completed a questionnaire before learning the results and after, on perceptions of how often they believed a palliative approach was provided by the team. RESULTS: Among 79 patients (mean age at death 73 years, 54% female) cancer and cardiac diseases were the top conditions responsible for death. One-quarter of patients were assessed as having received a palliative approach. 53% of decedents had a documented discussion about goals of care, 41% had nurse involvement, and 15.2% had a discussion about caregiver well-being. These indicators had the greatest discrimination between a palliative approach or not. Agreement that elements of a palliative approach were provided decreased significantly on the clinician questionnaire from before to after viewing the results. CONCLUSIONS: This study identified measurable indicators of a palliative approach in family practice, that can be used as the basis for quality improvement.

Inhibition of ATM Induces Hypersensitivity to Proton Irradiation by Upregulating Toxic End Joining.

Proton Bragg peak irradiation has a higher ionizing density than conventional photon irradiation or the entrance of the proton beam profile. Whether targeting the DNA damage response (DDR) could enhance vulnerability to the distinct pattern of damage induced by proton Bragg peak irradiation is currently unknown. Here, we performed genetic or pharmacologic manipulation of key DDR elements and evaluated DNA damage signaling, DNA repair, and tumor control in cell lines and xenografts treated with the same physical dose across a radiotherapy linear energy transfer spectrum. Radiotherapy consisted of 6 MV photons and the entrance beam or Bragg peak of a 76.8 MeV spot scanning proton beam. More complex DNA double-strand breaks (DSB) induced by Bragg peak proton irradiation preferentially underwent resection and engaged homologous recombination (HR) machinery. Unexpectedly, the ataxia-telangiectasia mutated (ATM) inhibitor, AZD0156, but not an inhibitor of ATM and Rad3-related, rendered cells hypersensitive to more densely ionizing proton Bragg peak irradiation. ATM inhibition blocked resection and shunted more DSBs to processing by toxic ligation through nonhomologous end-joining, whereas loss of DNA ligation via XRCC4 or Lig4 knockdown rescued resection and abolished the enhanced Bragg peak cell killing. Proton Bragg peak monotherapy selectively sensitized cell lines and tumor xenografts with inherent HR defects, and the repair defect induced by ATM inhibitor coadministration showed enhanced efficacy in HR-proficient models. In summary, inherent defects in HR or administration of an ATM inhibitor in HR-proficient tumors selectively enhances the relative biological effectiveness of proton Bragg peak irradiation. SIGNIFICANCE: Coadministration of an ATM inhibitor rewires DNA repair machinery to render cancer cells uniquely hypersensitive to DNA damage induced by the proton Bragg peak, which is characterized by higher density ionization.See related commentary by Nickoloff, p. 3156.

Transitioning From Hospital to Palliative Care at Home: Patient and Caregiver Perceptions of Continuity of Care.

CONTEXT: Continuity of care is important at improving the patient experience and reducing unnecessary hospitalizations when transitioning across care settings, especially at the end of life. OBJECTIVE: To explore patient and caregiver understanding and valuation of "continuity of care" while transitioning from an in-hospital to a home-based palliative care team. METHODS: Longitudinal qualitative design using semistructured interviews conducted with patients and their caregivers before and after transitioning from hospital to palliative care at home. Interviews were audio-recorded and transcribed verbatim. Data were analyzed using thematic analysis within a postpositivist framework. Thirty-nine participants (18 patients, seven caregivers, and seven patient-caregiver dyads) were recruited from two acute care hospitals, wherein they received care from an inpatient palliative care consultation team and transitioned to home-based palliative care. RESULTS: Patients had a mean age of 68 years, 60% were female and 60% had a diagnosis of cancer. Caregivers had a mean age of 62 years and 50% were female. Participants perceived continuity of care to occur in three ways, depending on which stage they were at in their hospital-to-home transition. In hospital, continuity of care was experienced, as consistency of information exchanged between providers. During the transition from hospital to home, continuity of care was experienced as consistency of treatments. When receiving home-based palliative care, continuity of care was experienced as having consistent providers. CONCLUSION: Patients' and their caregivers' valuation of continuity of care was dependent on their stage of the hospital-to-home transition. Optimizing continuity of care requires an integrated network of providers with reliable information transfer and communication.