Grand River Hospital

In this paper we review a special set of orthonormal functions, namely Zernike polynomials which are widely used in representing the aberrations of optical systems. We give the recurrence relations, relationship to other special functions, as well as scaling and other properties of these important polynomials. Mathematica code for certain operations are given in the Appendix.

BACKGROUND: The clinical utility of molecular profiling of tumor tissue to guide treatment of patients with advanced solid tumors is unknown. Our objectives were to evaluate the frequency of genomic alterations, clinical "actionability" of somatic variants, enrollment in mutation-targeted or other clinical trials, and outcome of molecular profiling for advanced solid tumor patients at the Princess Margaret Cancer Centre (PM). METHODS: Patients with advanced solid tumors aged ≥18 years, good performance status, and archival tumor tissue available were prospectively consented. DNA from archival formalin-fixed paraffin-embedded tumor tissue was tested using a MALDI-TOF MS hotspot panel or a targeted next generation sequencing (NGS) panel. Somatic variants were classified according to clinical actionability and an annotated report included in the electronic medical record. Oncologists were provided with summary tables of their patients' molecular profiling results and available mutation-specific clinical trials. Enrolment in genotype-matched versus genotype-unmatched clinical trials following release of profiling results and response by RECIST v1.1 criteria were evaluated. RESULTS: From March 2012 to July 2014, 1893 patients were enrolled and 1640 tested. After a median follow-up of 18 months, 245 patients (15 %) who were tested were subsequently treated on 277 therapeutic clinical trials, including 84 patients (5 %) on 89 genotype-matched trials. The overall response rate was higher in patients treated on genotype-matched trials (19 %) compared with genotype-unmatched trials (9 %; p < 0.026). In a multi-variable model, trial matching by genotype (p = 0.021) and female gender (p = 0.034) were the only factors associated with increased likelihood of treatment response. CONCLUSIONS: Few advanced solid tumor patients enrolled in a prospective institutional molecular profiling trial were treated subsequently on genotype-matched therapeutic trials. In this non-randomized comparison, genotype-enrichment of early phase clinical trials was associated with an increased objective tumor response rate. TRIAL REGISTRATION: NCT01505400 (date of registration 4 January 2012).

BACKGROUND: Despite advances in treatment of cystic fibrosis (CF), pulmonary exacerbations remain common. The aim of this study was to determine if frequent pulmonary exacerbations are associated with greater declines in lung function, or an accelerated time to death or lung transplantation in adults with CF. METHODS: A 3-year prospective cohort study was conducted on 446 adult patients with CF from Ontario, Canada who could spontaneously produce sputum. Patients enrolled from 2005 to 2008 and were stratified into groups based upon their exacerbation rates over the 3 year study: <1 exacerbation/year (n=140), 1-2 exacerbations/year (n=160) and >2 exacerbations/year (n=146). Exacerbations were defined as acute/subacute worsening of respiratory symptoms severe enough to warrant oral or intravenous antibiotics. Patient-related factors associated with frequent exacerbations were determined, and clinical outcomes were compared among the three exacerbation groups. RESULTS: Patients with frequent exacerbations were more likely to be female, diabetic and have poorer baseline lung function. Patients with >2 exacerbations/year had an increased risk of experiencing a 5% decline from baseline forced expiratory volume in 1 s (FEV(1)); unadjusted HR 1.47 (95% CI 1.07 to 2.01, p=0.02), adjusted HR 1.55 (95% CI 1.10 to 2.18, p=0.01) compared with patients with <1 exacerbation/year. Patients with >2 exacerbations/year also had an increased risk of lung transplant or death over the 3 year study; unadjusted HR 12.74 (95% CI 3.92 to 41.36, p<0.0001), adjusted HR 4.05 (95% CI 1.15 to 14.28, p=0.03). CONCLUSIONS: Patients with CF with frequent exacerbations appear to experience an accelerated decline in lung function, and they have an increased 3 year risk of death or lung transplant.

The efficacy of convalescent plasma for coronavirus disease 2019 (COVID-19) is unclear. Although most randomized controlled trials have shown negative results, uncontrolled studies have suggested that the antibody content could influence patient outcomes. We conducted an open-label, randomized controlled trial of convalescent plasma for adults with COVID-19 receiving oxygen within 12 d of respiratory symptom onset ( NCT04348656 ). Patients were allocated 2:1 to 500 ml of convalescent plasma or standard of care. The composite primary outcome was intubation or death by 30 d. Exploratory analyses of the effect of convalescent plasma antibodies on the primary outcome was assessed by logistic regression. The trial was terminated at 78% of planned enrollment after meeting stopping criteria for futility. In total, 940 patients were randomized, and 921 patients were included in the intention-to-treat analysis. Intubation or death occurred in 199/614 (32.4%) patients in the convalescent plasma arm and 86/307 (28.0%) patients in the standard of care arm-relative risk (RR) = 1.16 (95% confidence interval (CI) 0.94-1.43, P = 0.18). Patients in the convalescent plasma arm had more serious adverse events (33.4% versus 26.4%; RR = 1.27, 95% CI 1.02-1.57, P = 0.034). The antibody content significantly modulated the therapeutic effect of convalescent plasma. In multivariate analysis, each standardized log increase in neutralization or antibody-dependent cellular cytotoxicity independently reduced the potential harmful effect of plasma (odds ratio (OR) = 0.74, 95% CI 0.57-0.95 and OR = 0.66, 95% CI 0.50-0.87, respectively), whereas IgG against the full transmembrane spike protein increased it (OR = 1.53, 95% CI 1.14-2.05). Convalescent plasma did not reduce the risk of intubation or death at 30 d in hospitalized patients with COVID-19. Transfusion of convalescent plasma with unfavorable antibody profiles could be associated with worse clinical outcomes compared to standard care.

Lung cancer is the leading cause of cancer death in Canada and a significant cause of morbidity for patients and their loved ones. There have been rapid advances in preventing, screening and treating this disease. Here, we present a contemporary review of treatment of non-small cell lung cancer in Canada based on current best practices. The focus of this review is to highlight recent data in screening for lung cancer, management of patients with early and locally-advanced non-small cell lung cancer, as well as management of patients with metastatic disease. There is a special focus on the incorporation of immunotherapy into practice and its associated toxicities.

BACKGROUND: Preclinical and observational studies suggest that exercise may improve cancer outcomes. However, definitive level 1 evidence is lacking. METHODS: In this phase 3, randomized trial conducted at 55 centers, we assigned patients with resected colon cancer who had completed adjuvant chemotherapy to participate in a structured exercise program (exercise group) or to receive health-education materials alone (health-education group) over a 3-year period. The primary end point was disease-free survival. RESULTS: From 2009 through 2024, a total of 889 patients underwent randomization to the exercise group (445 patients) or the health-education group (444 patients). At a median follow-up of 7.9 years, disease-free survival was significantly longer in the exercise group than in the health-education group (hazard ratio for disease recurrence, new primary cancer, or death, 0.72; 95% confidence interval [CI], 0.55 to 0.94; P = 0.02). The 5-year disease-free survival was 80.3% in the exercise group and 73.9% in the health-education group (difference, 6.4 percentage points; 95% CI, 0.6 to 12.2). Results support longer overall survival in the exercise group than in the health-education group (hazard ratio for death, 0.63; 95% CI, 0.43 to 0.94). The 8-year overall survival was 90.3% in the exercise group and 83.2% in the health-education group (difference, 7.1 percentage points; 95% CI, 1.8 to 12.3). Musculoskeletal adverse events occurred more often in the exercise group than in the health-education group (in 18.5% vs. 11.5% of patients). CONCLUSIONS: A 3-year structured exercise program initiated soon after adjuvant chemotherapy for colon cancer resulted in significantly longer disease-free survival and findings consistent with longer overall survival. (Funded by the Canadian Cancer Society and others; CHALLENGE ClinicalTrials.gov number, NCT00819208.).

BACKGROUND: Providing patients with access to their electronic health records offers great promise to improve patient health and satisfaction with their care, as well to improve professional and organizational approaches to health care. Although many benefits have been identified, there are many questions about best practices for the implementation of patient accessible Electronic Health Records (EHRs). OBJECTIVES: To develop recommendations to assist health care organizations in providing patients with access to EHRs in a meaningful, responsible, and responsive manner. METHODS: A Patient Accessible Electronic Health Record (PAEHR) Workshop was held with nationally and internationally renowned experts to explore issues related to providing patient access to the EHR and managing institutional change. RESULTS: The PAEHR Workshop was attended by 45 participants who discussed recommendations for the implementation of patient accessible EHRs. Recommendations were discussed under four subject domains: (1) providing patient access to the EHR, (2) maintaining privacy and confidentiality related to the PAEHR, (3) patient education and navigation of the PAEHR, and (4) strategies for managing institutional change. The discussion focused on the need for national infrastructure, clear definitions for privacy, security and confidentiality, flexible, interoperable solutions, and patient and professional education. In addition, there was a strong call for research into all domains of patient accessible EHRs to ensure the adoption of evidence-based practices. CONCLUSIONS: Patient access to personal health information is a fundamental issue for patient engagement and empowerment. Health care professionals and organizations should consider the potential benefits and risks of patient access when developing EHR strategies. Flexible, standardized, and interoperable solutions must be integrated with outcomes-based research to activate effectively patients as partners in their health care.

BACKGROUND: Older adults with acute myeloid leukemia (AML) represent a vulnerable population in whom disease-based and clinical risk factors, patient goals, prognosis, and practitioner- and patient-perceived treatment risks and benefits influence treatment recommendations. OBJECTIVE: These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in their decisions about management of AML in older adults. METHODS: ASH formed a multidisciplinary guideline panel that included specialists in myeloid leukemia, geriatric oncology, patient-reported outcomes and decision-making, frailty, epidemiology, and methodology, as well as patients. The McMaster Grading of Recommendations Assessment, Development and Evaluation (GRADE) Centre supported the guideline-development process, including performing systematic evidence reviews (up to 24 May 2019). The panel prioritized clinical questions and outcomes according to their importance to patients, as judged by the panel. The panel used the GRADE approach, including GRADE's Evidence-to-Decision frameworks, to assess evidence and make recommendations, which were subject to public comment. RESULTS: The panel agreed on 6 critical questions in managing older adults with AML, mirroring real-time practitioner-patient conversations: the decision to pursue antileukemic treatment vs best supportive management, the intensity of therapy, the role and duration of postremission therapy, combination vs monotherapy for induction and beyond, duration of less-intensive therapy, and the role of transfusion support for patients no longer receiving antileukemic therapy. CONCLUSIONS: Treatment is recommended over best supportive management. More-intensive therapy is recommended over less-intensive therapy when deemed tolerable. However, these recommendations are guided by the principle that throughout a patient's disease course, optimal care involves ongoing discussions between clinicians and patients, continuously addressing goals of care and the relative risk-benefit balance of treatment.

Abstract Lead is commonly used in medical radiology departments as a shielding material. Lead‐based protective materials are also used by clinical personnel during X‐ray image‐guided interventional radiology (IVR) procedures. However, lead is extremely toxic and prolonged exposure to it can result in serious health concerns. Polymer composites, on the other hand, can be designed to be lead‐free in addition to being lightweight, conformable, cost effective, and potentially capable of significantly attenuating X‐rays. Nanomaterials have unique material properties that can be exploited to develop novel lead‐free radiation‐protection materials. In this study, polydimethylsiloxane (PDMS) nanocomposites were fabricated using different weight percentages (wt %) of bismuth oxide (BO) nanopowder. The attenuation properties of the nanocomposites were characterized using diagnostic X‐ray energies from 40 to 150 kV tube potential and were compared to the attenuation characteristics of 0.25‐mm‐thick pure lead sheet. The PDMS/BO nanocomposite (44.44 wt% of BO and 3.73‐mm thick) was capable of attenuating all the scattered X‐rays generated at a tube potential of 60 kV, which is the beam energy commonly employed in IVR. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2013

IMPORTANCE: Patients with colorectal cancer with liver metastases undergo hepatic resection with curative intent. Positron emission tomography combined with computed tomography (PET-CT) could help avoid noncurative surgery by identifying patients with occult metastases. OBJECTIVES: To determine the effect of preoperative PET-CT vs no PET-CT (control) on the surgical management of patients with resectable metastases and to investigate the effect of PET-CT on survival and the association between the standardized uptake value (ratio of tissue radioactivity to injected radioactivity adjusted by weight) and survival. DESIGN, SETTING, AND PARTICIPANTS: A randomized trial of patients older than 18 years with colorectal cancer treated by surgery, with resectable metastases based on CT scans of the chest, abdomen, and pelvis within the previous 30 days, and with a clear colonoscopy within the previous 18 months was conducted between 2005 and 2013, involving 21 surgeons at 9 hospitals in Ontario, Canada, with PET-CT scanners at 5 academic institutions. INTERVENTIONS: Patients were randomized using a 2 to 1 ratio to PET-CT or control. MAIN OUTCOMES AND MEASURES: The primary outcome was a change in surgical management defined as canceled hepatic surgery, more extensive hepatic surgery, or additional organ surgery based on the PET-CT. Survival was a secondary outcome. RESULTS: Of the 263 patients who underwent PET-CT, 21 had a change in surgical management (8.0%; 95% CI, 5.0%-11.9%). Specifically, 7 patients (2.7%) did not undergo laparotomy, 4 (1.5%) had more extensive hepatic surgery, 9 (3.4%) had additional organ surgery (8 of whom had hepatic resection), and the abdominal cavity was opened in 1 patient but hepatic surgery was not performed and the cavity was closed. Liver resection was performed in 91% of patients in the PET-CT group and 92% of the control group. After a median follow-up of 36 months, the estimated mortality rate was 11.13 (95% CI, 8.95-13.68) events/1000 person-months for the PET-CT group and 12.71 (95% CI, 9.40-16.80) events/1000 person-months for the control group. Survival did not differ between the 2 groups (hazard ratio, 0.86 [95% CI, 0.60-1.21]; P = .38). The standardized uptake value was associated with survival (hazard ratio, 1.11 [90% CI, 1.07-1.15] per unit increase; P < .001). The C statistic for the model including the standardized uptake value was 0.62 (95% CI, 0.56-0.68) and without it was 0.50 (95% CI, 0.44-0.56). The difference in C statistics is 0.12 (95% CI, 0.04-0.21). The low C statistic suggests that the standard uptake value is not a strong predictor of overall survival. CONCLUSIONS AND RELEVANCE: Among patients with potentially resectable hepatic metastases of colorectal adenocarcinoma, the use of PET-CT compared with CT alone did not result in frequent change in surgical management. These findings raise questions about the value of PET-CT scans in this setting. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00265356.

The objectives of this prospective study were to calculate incidence rates for fall-related hospitalization, to compare the effect of risk factors among benzodiazepine (BZD) users and unexposed controls, and to examine variations in risks according to length of time following a BZD prescription. Data were derived from Saskatchewan Health linked data bases, leading to information on 468 hospitalizations for injury due to falls among a study population of 321422. Incidence rates per 10000 within 28 days of the prescription fill date were 26.2, 12.1 and 9.0 for BZD sedative users, BZD tranquillizer users and for unexposed controls, respectively. Incidence rates increased with age, and were higher for women than for men. Results from multivariate logistic regression models also showed a greater risk of falling for BZD users but the odds ratio was higher for men than for women. A history of treatment for alcohol abuse was a very strong risk factor for falls among both men (odds ratio, 10.7) and women (odds ratio, 4.3). The highest risk of serious injury due to falls was within 15 days of filling the prescription, with an odds ratio of 3.6 for BZD sedatives and 2.6 for BZD tranquillizers. Risk decreased with further increase of time after the BZD fill date. For the individual BZD, flurazepam and triazolam showed the highest increase in risk with odds ratios of 3.4 and 2.7, respectively, while oxazepam, lorazepam and diazepam showed odds ratios of 2.2, 2.0 and 1.8 (all odds ratios mentioned are statistically significant at p < 0.05).

While debate over the appropriate scope and goals of COVID-19 lockdowns has raged, all public health agencies have been clear on one matter: older adults have the highest rates of mortality (Comas-Herrera et al., 2020) and should be isolated (Public Health Agency of Canada, 2020). Older adults and individuals with complex health conditions are most vulnerable to the virus. Yet, social isolation contributes to the onset and intensifies depression, feelings of despair and, in older adults with dementia, further cognitive decline. Older adults living in long-term care (LTC) facilities comprise 79% of the COVID-19 death toll in Canada (Rothan & Byrareddy, 2020; Walsh & Semeniuk, 2020). While our failure to protect long-term care (LTC) facilities has been made apparent both by this high mortality and a shocking recent Canadian Armed Forces Report (Mialkowski, 2020), the singular focus on mortality has overshadowed any attention to morbidity – particularly the effects of physical distancing on health, quality of life, and autonomy. Annual mortality in LTC facilities exceeds 25%, approaching 50% in some jurisdictions (Tanuseputro et al., 2015). This suggests that if physical distancing measures are extended for months or years until either herd immunity or a vaccination, a shocking proportion of LTC residents are likely to die under a 'new normal' of isolation that few would choose. Many in Canada were deeply troubled by the recent news of family members being turned away from the windows of Ontario LTC facilities as they attempted to visit loved ones while respecting physical distancing recommendations (Pringle, 2020). Equally troubling stories have emerged detailing the challenges that LTC residents have faced including restrictions on visitors and volunteers, elimination of the interactions residents enjoyed with their families (Armitage & Nellums, 2020; Gardner, States, & Bagley, 2020), and limitations on physical and social activities (Bains, 2020; Flint, Bingham, & Iaboni, 2020; Harden, 2020; Kingdon, 2020; Liebermen, 2020; Steinman, Perry, & Perissinotto, 2020; United Nations, 2020). Recent changes to LTC visitation policies allow loved ones to visit in-person but continue to be overly restrictive: visits could only be 30-minute long, outdoors, physically distanced while wearing personal protective equipment (PPE), and the visitor needed to attest to a COVID-19 negative test (Ontario Ministry of Long-term Care, 2020). The impracticalities of such visits are obvious: spouses of residents are often older adults themselves and face mobility challenges getting tested, residents have hearing and vision loss making communicating during a physically distanced visit outdoors challenging, and covering visitor faces with masks is not helpful or comforting for residents with memory loss. Some residents have been socially isolated for over 3 months due to COVID-19 outbreaks, spending all day and every meal trapped alone in their rooms; held hostage by ill-conceived policies (Bercovici, 2020). Such policies are out of touch with the needs of residents and are causing emotional distress. Given the World Health Organization's holistic definition of health (WHO, 2020) and the impact of social isolation on the psychosocial well-being of older adults, any public health response is morally obligated to mitigate the impact of isolation as a policy consequence. Social isolation is defined as an objective lack of a social network, relates to loneliness (the subjective, negative experience that results from social isolation), and a lack of meaningful, supportive relationships with family and friends (Hernández-Ascanio et al., 2020). More older adults living alone as the population ages (National Seniors Council, 2017), contributing to a social isolation epidemic among older adults long before physical distancing became a key policy priority. Before the COVID-19 pandemic, approximately 50% of Canadians over the age of 80 reported feelings of loneliness, particularly those with physical or mental illness, cognitive deficits, members of marginalized groups, and those experiencing life transitions such as loss of employment, a spouse, or access to a vehicle. Those most at risk for social isolation face the greatest number of barriers to support (National Seniors Council, 2013, 2017). Such isolation increases the risk of cardiovascular disease, obesity, and stroke (Tomás, Pinazo-Hernandis, Oliver, Donio-Bellegarde, & Tomás-Aguirre, 2019) and correlates with anxiety, depression, and cognitive decline (Barbosa Neves, Sanders, & Kokanović, 2019; Hernández-Ascanio et al., 2020). Frail older adults and those with cognitive deficits may also depend on caregivers for their activities of daily living (ADLs), orientation and safety (Steinman et al., 2020). While social isolation has become ubiquitous for older adults during the COVID-19 pandemic, its experience is simultaneously unique to each person (Machielse, 2015). It generates a positive feedback loop, magnifying and being magnified by a multitude of chronic conditions (Barbosa Neves et al., 2019; Kirkevold, Moyle, Wilkinson, Meyer, & Hauge, 2013; Wong, Chau, Fang, & Woo, 2017). While correlation does not indicate causation, the relationship between social isolation and medical illness suggests that the dangers of social isolation pose a significant counterweight to the threat of COVID-19. Our society must confront the toll and trauma that COVID-19 countermeasures have taken on older adults residing in LTC facilities and their families. The public has generated several solutions to increase the quality of life for older adults during the pandemic. These include the use of mobile devices to engage remotely with older adults. Teleconferencing applications such as Skype, Facetime, or Zoom (Canadian Frailty Network, 2020a; Klein, 2020; Lorinc, 2020), allowing users to interact virtually. Conventional telephone calls and written letters provide a familiar form of communication (Holtby, 2020) that can remind older adults of their support network (Canadian Frailty Network, 2020b; Ireland, 2020). Written letter campaigns have emerged to combat the isolation experienced by many older adults during the crisis (Field, 2020) and before it (Harris, 2020). In these campaigns, strangers write letters to LTC residents, including photographs, poetry, and uplifting messages, to remind them that they are valued. While such solutions are helpful, many older adults either lack the access to remote communication; most LTC facilities have a limited number of iPads to share between residents, constraining their access to their loved ones. Another problem is that many LTC residents lack the dexterity to hold a tablet steady. Family members end up looking at the ceiling, instead of the face of their loved one (CBC News, 2020). Many older adults also lack the technical proficiency to use such devices (Klein, 2020), particularly those with limited cognition (Bains, 2020). Some homes have hired more staff solely to help residents make video calls rather than purchasing tablets for every resident – highlighting a patchwork solution to the real problem of technology that is not well designed for older adult users. There is room for innovation and improvement. In particular, making technology easier to use and understand for older adults. User-centred design approaches would be suitable to generate technology focused on the needs of older adults and healthcare providers in LTC. The need for innovative collaboration between researchers, developers, older adults, and their family members has never been made more clear than during this pandemic. Our current broad strokes approach assumes the priorities of older adults to be largely homogeneous and views LTC residents as passive recipients of care, without any particular desires or preferences. That view is paternalistic and antithetical to a person-centred approach that is so central to nursing. Implicit to this discussion is the recognition that older adults are valued by their loved ones and community. We must not value incautiously quantity of life over quality of life. Little attention has been paid to autonomy and individual acceptance of risk. Any pandemic response must balance these risks and recognize that morbidity may be as important as mortality. In this case, it means calculating if and when residents and their families should have the latitude to make autonomous decisions concerning theirwell-being. In absence of allowing residents the dignity of choice, there are widespread reports of increased suicide rates and of residents preferring death over isolation in their rooms, referring to their treatment as being 'held like a prisoner' (Aronson, 2020). LTC facilities must collaborate with residents and families to ideate creative solutions and help them understand the risks associated with each solution, as well as establishing a care plan that is centred on the physical and psychosocial well-being of the resident. Additionally, it is a clinical reality that residents will likely experience their end of life in LTC. The unknown duration of isolation means that over one-third of LTC residents could die without seeing their loved ones for months or even years (Jayaraman and Joseph 2013). Thus, the questions surrounding quality and manner of death are intensely important ones. Dignity should be paramount when older adults must experience the end of their lives in hospitals and LTC facilities alone, barred from visits. Dying alone has become a hallmark of COVID-19. Some final moments are immortalized on social media with screenshots of video calls capturing the grief, pain, and trauma of close family watching their loved ones pass. These are deeply disturbing scenarios which should deeply trouble most of us and is not what residents, families, or staff want. Nurses are the primary clinicians responsible for leading and coordinating care in LTC facilities referred to as 'ground zero' of COVID-19 (Barnett & Grabowski, 2020). From a policy perspective, nurses are advocating for more staffing and appropriate resources to be diverted into LTC (Registered Nurses' Association of Ontario, 2020). This advocacy should come as no surprise as nurses have been always been revolutionaries during times of infectious diseases for which there were no effective medical interventions. Nurses can prepare for future outbreaks by organizing and advocating for health policy reform and investment into LTC, ensuring homes can effectively respond to outbreaks while meeting the physical and psychosocial needs of residents. Furthermore, this pandemic is an opportunity for nurses in LTC to refocus care on the resident and reintroduce person-centred care into countermeasures. Nurse can lead the innovation in LTC to address key issues, especially in anticipation for a 'second wave'. This means welcoming and advocating for innovation, user-friendly digital technologies that promote connections to loved ones, and leveraging their close relationships with residents to advocate for more person-centred policies. Policy makers and nurse leaders need to enable nurses to work to the top of their scope of practice in LTC and provide the resources to support nurses working in their full capacity. COVID-19 countermeasures like physical distancing involves a balance of risks for older adults living in LTC facilities. The COVID-19 epidemic has upended many assumptions about the safety, health, and well-being of older adults and revealed numerous areas for collaboration, innovation, and improvement. Within this crisis lies an opportunity for nurses to start a deeper conversation about autonomy and values and how to restore person-centred care in LTC facilities. CC: Conceptualization, Writing, Reviewing and Editing, and Supervision. SDW: Writing, Reviewing, and Editing. CD: Conceptualization, Writing, Reviewing, and Editing. None The authors have no conflicts of interests to declare. CC is funded by the Alzheimer Society of Canada New Investigator Award. No funding to declare.

Considerable burden is reported by informal caregivers of older individuals with cognitive impairment. Significant progress in the understanding of determinants of this burden has been achieved. However, further progress could be attained if we considered important methodological issues that may have limited our understanding of caregiver burden. These issues include subgroups of care recipients and caregivers, measurement issues, research design, and statistical techniques. Fifty-three studies published between 1980 and 1997 (inclusive) that focused on caregiver burden were abstracted to determine the extent to which the methodological issues discussed above were considered. Overall, we found considerable variability among the studies surveyed. Further understanding of the caregiving process and reductions in caregiver burden will depend on the attention to methodological issues and understanding of burden across the whole caregiving career.

Recent studies have suggested that platelets have a crucial role in enhancing the survival of circulating tumor cells in the bloodstream and aggravating cancer metastasis. The main function of platelets is to bind to the sites of the damaged vessels to stop bleeding. However, in cancer patients, activated platelets adhere to circulating tumor cells and exacerbate metastatic spreading. Several hypotheses have been proposed about the platelet-cancer cell interactions, but the underlying mechanisms of these interactions are not completely understood yet. In this work, we quantitatively investigated the interactions between circulating tumor cells, red blood cells, platelets, plasma flow and microvessel walls via computational modelling at the cellular scale. Our highly detailed computational model allowed us to understand and quantitatively explain the role of platelets in deformation, adhesion and survival of tumor cells in their active arrest to the endothelium.

UNLABELLED: The pi3k/Akt/mtor (phosphatidylinositol 3 kinase/ Akt/mammalian target of rapamycin) signalling pathway is an established driver of oncogenic activity in human malignancies. Therapeutic targeting of this pathway holds significant promise as a treatment strategy. Everolimus, an mtor inhibitor, is the first of this class of agents approved for the treatment of hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer. Everolimus has been associated with significant improvements in progression-free survival; however, it is also associated with increased toxicity related to its specific mechanism of action. METHODS: A comprehensive review of the literature conducted using a focused medline search was combined with a search of current trials at http://ClinicalTrials.gov/. Summary tables of the toxicities of the various classes of pi3k/Akt/mtor inhibitors were created. A broad group of Canadian health care professionals was assembled to review the data and to produce expert opinion and summary recommendations for possible best practices in managing the adverse events associated with these pathway inhibitors. RESULTS: Differing toxicities are associated with the various classes of pi3k/Akt/mtor pathway inhibitors. The most common unique adverse events observed in everolimus clinical trials in breast cancer include stomatitis (all grades: approximately 60%), noninfectious pneumonitis (15%), rash (40%), hyperglycemia (15%), and immunosuppression (40%). To minimize grades 3 and 4 toxicities and to attempt to attain optimal outcomes, effective management of those adverse events is critical. Management should be interdisciplinary and should use approaches that include education, early recognition, active intervention, and potentially prophylactic strategies. DISCUSSION: Everolimus likely represents the first of many complex oral targeted therapies for the treatment of breast cancer. Using this agent as a template, it is essential to establish best practices involving and integrating multiple disciplines for the management of future pi3k/Akt/mtor signalling pathway inhibitors.

PURPOSE: A systematic review was conducted to evaluate the effectiveness of workplace rehabilitation interventions for injured workers with low back pain (LBP). METHOD: MEDLINE, CINAHL (Cumulative Index to Nursing and Allied Health Literature), EMBASE, and AMED (Allied and Complementary Medicine) were searched from 1982 to 2005 for peer-reviewed studies of rehabilitation interventions that were provided at the workplace to workers with musculoskeletal work-related LBP. Methodological quality appraisal and data extraction were conducted by five reviewers. RESULTS: Of a total of 1,224 articles that were identified by the search, 15 articles, consisting of 10 studies, were of sufficient quality to be included in the review. The best evidence was that clinical interventions with occupational interventions as well as early return to work/modified work interventions were effective in returning workers to work faster, reducing pain and disability, and decreasing the rate of back injuries. Ergonomic interventions also were found to be effective workplace interventions. CONCLUSION: The need for further research in this area is necessary to reduce the burden of back pain on employees and their families, employers, and the health care system.

Venous invasion (VI) is an independent prognostic indicator in colorectal cancer and may prompt consideration for adjuvant chemotherapy in patients with stage II tumors. Recent evidence suggests that VI is underreported in colorectal cancer and that detection may be enhanced by an elastin stain. This study aimed (1) to determine the impact of an elastin stain on VI detection and on interobserver agreement between gastrointestinal (GI) and non-GI pathologists, and (2) to identify factors associated with increased VI detection. Forty hematoxylin and eosin (H&E)-stained slides were circulated to 6 GI and 6 non-GI pathologists who independently assessed the VI status as positive, negative, or equivocal. Six weeks later, 40 corresponding Movat-stained slides were recirculated together with the original H&E slides and reassessed for VI status. Detection of VI was >2-fold higher with a Movat stain compared with an H&E stain alone (46.4% vs. 19.6%, P=0.001). GI pathologists detected VI more frequently than non-GI pathologists on both H&E (30.0% vs. 9.2%, P=0.029) and Movat (58.3% vs. 34.6%, P=0.018) stains. There was higher interobserver agreement in the case of a Movat stain, particularly for extramural VI (H&E: κ=0.23 vs. Movat: κ=0.41). A poststudy survey indicated that GI pathologists and non-GI pathologists applied similar diagnostic criteria but that GI pathologists more frequently applied "orphan arteriole" and "protruding tongue" signs as diagnostic clues to VI. This study confirms that VI is underdetected on H&E and highlights the role of elastin staining in improving VI detection and interobserver agreement. Strategies to improve VI detection are warranted.

The benefit of adding rituximab to standard treatment in nonsplenectomized patients with primary immune thrombocytopenia (ITP) is uncertain. We performed a pilot randomized trial to determine the feasibility of recruitment, protocol adherence, and blinding of a larger trial of rituximab versus placebo; and to evaluate the potential efficacy of adjuvant rituximab in ITP. Nonsplenectomized adults with newly diagnosed or relapsed ITP who were receiving standard ITP therapy for a platelet count below 30 × 10(9)/L were randomly allocated to receive 4 weekly infusions of 375 mg/m(2) rituximab or saline placebo. Sixty patients were recruited over 46 months, which was slower than anticipated. Protocol adherence and follow-up targets were achieved, and blinding was successful for research staff but not for patients. After 6 months, there was no difference between rituximab and placebo groups for the composite outcome of any platelet count below 50 × 10(9)/L, significant bleeding or rescue treatment once standard treatment was stopped (21/32 [65.6%] vs 21/26 [80.8%]; relative risk = 0.81, 95% confidence intervals, 0.59%-1.11%). Timely accrual poses a challenge to the conduct of a large randomized trial of rituximab for presplenectomy ITP. No difference in the frequency of the composite outcome was observed in this pilot trial (registered at www.clinicaltrials.gov NCT00372892).

IMPORTANCE: Unresected locally advanced non-small cell lung cancer (LA-NSCLC) shows poor survival outcomes even after aggressive concurrent chemoradiotherapy. Whether metformin, a diabetes agent that inhibits the mitochondria oxidative phosphorylation chain, could improve radiotherapy and chemotherapy response in LA-NSCLC remains to be studied. OBJECTIVE: To examine whether metformin, given concurrently with chemoradiotherapy and as consolidation treatment, could improve outcomes in patients with LA-NSCLC. DESIGN, SETTING, AND PARTICIPANTS: The Ontario Clinical Oncology Group Advanced Lung Cancer Treatment With Metformin and Chemoradiotherapy (OCOG-ALMERA) study was a multicenter phase 2 randomized clinical trial. Patients were stratified for stage IIIA vs IIIB LA-NSCLC and use of consolidation chemotherapy. The trial was designed to enroll 96 patients with unresected LA-NSCLC who did not have diabetes. The trial was conducted from September 24, 2014, to March 8, 2019. INTERVENTIONS: Patients were randomized to platinum-based chemotherapy, concurrent with chest radiotherapy (60-63 Gy), with or without consolidation chemotherapy or the same treatment plus metformin, 2000 mg/d, during chemoradiotherapy and afterward for up to 12 months. MAIN OUTCOMES AND MEASURES: The primary outcome was the proportion of patients who experienced a failure event (ie, locoregional disease progression, distant metastases, death, and discontinuation of trial treatment or planned evaluations for any reason within 12 months). Proportions were compared using a 2-sided Fisher exact test. Conventional progression-free and overall survival were estimated using the Kaplan-Meier method. Adverse events were graded with Common Terminology Criteria for Adverse Events, version 4.03. All randomized patients were included in an intention-to-treat analysis. RESULTS: The trial was stopped early due to slow accrual. Between 2014 and 2019, 54 patients were randomized (26 in experimental arm and 28 in control arm). Participants included 30 women (55.6%); mean (SD) age was 65.6 (7.6) years. Treatment failure was detected in 18 patients (69.2%) receiving metformin within 1 year vs 12 (42.9%) control patients (P = .05). The 1-year progression-free survival rate was 34.8% (95% CI, 16.6%-53.7%) in the metformin arm and 63.0% (95% CI, 42.1%-78.1%) in the control arm (hazard ratio, 2.42; 95% CI, 1.14-5.10) The overall survival rates were 47.4% (95% CI, 26.3%-65.9%) in the metformin arm and 85.2% (95% CI, 65.2%-94.2%) in the control arm (hazard ratio, 3.80; 95% CI, 1.49-9.73). More patients in the experimental arm vs control arm (53.8% vs 25.0%) reported at least 1 grade 3 or higher adverse event. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, the addition of metformin to chemoradiotherapy was associated with worse treatment efficacy and increased toxic effects compared with combined modality therapy alone. Metformin is not recommended in patients with LA-NSCLC who are candidates for chemoradiotherapy. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02115464.

BACKGROUND: Access to personal health information through the electronic health record (EHR) is an innovative means to enable people to be active participants in their own health care. Currently this is not an available option for consumers of health. The absence of a key technology, the EHR, is a significant obstacle to providing patient accessible electronic records. To assess the readiness for the implementation and adoption of EHRs in Canada, a national scan was conducted to determine organizational readiness and willingness for patient accessible electronic records. METHODS: A survey was conducted of Chief Executive Officers (CEOs) of Canadian public and acute care hospitals. RESULTS: Two hundred thirteen emails were sent to CEOs of Canadian general and acute care hospitals, with a 39% response rate. Over half (54.2%) of hospitals had some sort of EHR, but few had a record that was predominately electronic. Financial resources were identified as the most important barrier to providing patients access to their EHR and there was a divergence in perceptions from healthcare providers and what they thought patients would want in terms of access to the EHR, with providers being less willing to provide access and patients desire for greater access to the full record. CONCLUSION: As the use of EHRs becomes more commonplace, organizations should explore the possibility of responding to patient needs for clinical information by providing access to their EHR. The best way to achieve this is still being debated.