Long-term safety and efficacy of garadacimab for preventing hereditary angioedema attacks: Phase 3 open-label extension study.

BACKGROUND: Hereditary angioedema (HAE) is a chronic, unpredictable disease. Long-term prophylactic treatments that offer durable efficacy, safety, and convenience are required to assist patients in achieving complete disease control, per international guidelines. We report an interim analysis of an ongoing phase 3 (VANGUARD) open-label extension (OLE) study evaluating the long-term safety and efficacy of garadacimab for HAE prophylaxis. METHODS: Adults and adolescents aged ≥12 years with HAE previously participating in phase 2 and pivotal phase 3 (VANGUARD) studies were rolled over to an OLE, alongside newly enrolled patients. Patients received garadacimab 200 mg subcutaneously, once monthly for ≥12 months. The primary endpoint was treatment-emergent adverse events (TEAEs) in patients with C1 inhibitor deficiency/dysfunction. RESULTS: At data cut-off (February 13, 2023; N = 161), median (interquartile range) exposure was 13.8 months (11.9-16.3). For the primary endpoint, 133/159 patients experienced ≥1 TEAE (524 events), equivalent to 0.23 events/administration and 2.84 events/patient-year. Garadacimab-related TEAEs (13% of patients, 52 events) were most commonly injection-site reactions (ISRs). No deaths occurred. One patient discontinued treatment due to garadacimab-related moderate ISR. Most TEAEs were mild/moderate; three events were serious (COVID-19, two events; abdominal HAE attack, one event) and not garadacimab related. No abnormal bleeding, thromboembolic, severe hypersensitivity, or anaphylactic events were observed. Mean HAE attack rate decreased by 95% from the run-in period; 60% of patients were attack-free. Almost all patients (93%) rated their response to garadacimab as "good" or "excellent." CONCLUSION: Garadacimab has a favorable safety profile suitable for long-term use and provides durable protection against HAE attacks.

Multi-Stakeholder Validation of an Entrustable Professional Activities Framework for Canadian Geriatrics Residency Programs.

Background: Entrustable Professional Activities (EPAs) have become a cornerstone for an increasing number of competency-based medical education programs. Today, frameworks of EPAs are being used in most, if not all, medical specialties. These frameworks can break a discipline down to its constituting tasks, and structure the training and evaluation of residents. In 2018, The Royal College of Physicians and Surgeons of Canada created an EPA framework for Geriatric Specialty residency programs nationwide. The present study aims to evaluate this EPA framework through focus groups consisting of several stakeholder groups. Methods: Participants were recruited to be part of one of five focus groups-one for each stakeholder group of interest. The five focus groups consisted of: physician faculty, residents, allied health professionals, administrators/managers, and patients. Each focus group met once virtually over ZOOM® for no longer than 90 minutes. Meeting transcripts were iteratively coded based on emerging themes, and were compared for similarities and gaps between stakeholder perspectives. Results: Multi-stakeholder consultation yielded feedback on many specific EPAs, suggestions for new EPAs, and additional input which gave rise to four themes: (i) EPA scope, (ii) Operationalization, (iii) Interprofessional Collaboration, and (iv) Patient Advocacy. Lastly, we received their thoughts on how the framework defines Geriatrics relative to the work of Care of the Elderly physicians in Canada. Conclusions: Consulting a variety of stakeholder groups generates a robust and diverse supply of feedback that holistically augments EPA frameworks to be more practical, appropriate, socially accountable and patient-centred.

The Influence of Vasopressors on Free Flap Outcomes in Head and Neck Cancer Patients.

OBJECTIVE: To compare free flap outcomes between those who received and did not receive vasopressors (VPs) at the time of free flap reconstruction. STUDY DESIGN: This retrospective cohort study includes patients from January 2013 to January 2023. SETTING: This multicenter cohort study utilized data from the TriNetX Research Network which includes 80 health care organizations. METHODS: Head and neck cancer patients older than 18 years who underwent free flap reconstruction were separated into those who received or did not receive VPs on the day of surgery. The primary outcomes were flap failure defined by need for secondary free flap procedures, blood vessel repair, and other flap revision procedures. RESULTS: After propensity score matching, 7446 patients were analyzed. The VP group included 3723 patients (mean age [SD], 62.9 [11.4] years; 2511 males [67.4%]). The non-VP group included 3723 patients (mean age [SD], 63.0 [11.2] years; 2479 males [66.6%]). Free flap outcomes were not statistically different between groups (secondary free flap: 166 [4.5%] VP vs 155 [4.2%] non-VP, P = .04; vessel repair: 314 [8.4%] vs 319 [8.6%], P = .06; other flap revision procedures: 416 [11.2%] vs 449 [12.1%], P = .02). Bony flaps were found to have decreased rates of vessel repair in the VP group (47 [6.1%] vs 69 [9.0%], P = .003]. For secondary outcomes, pneumonia (173 [4.6%] vs 231 [6.2%], P = .0002), urinary tract infection (34 [1.0%] vs 59 [1.6%], P = .0007), and deep vein thrombosis (93 [2.5%] vs 122 [3.3%], P = .004) were significantly different. CONCLUSION: VP use is not significantly associated with free flap complications. These results imply that VP use on the same day as surgery may be safe if clinically necessary.

A call for caution when using network methods to study multimorbidity: an illustration using data from the Canadian Longitudinal Study on Aging.

OBJECTIVES: To examine the impact of two key choices when conducting a network analysis (clustering methods and measure of association) on the number and type of multimorbidity clusters. STUDY DESIGN AND SETTING: Using cross-sectional self-reported data on 24 diseases from 30,097 community-living adults aged 45-85 from the Canadian Longitudinal Study on Aging, we conducted network analyses using 5 clustering methods and 11 association measures commonly used in multimorbidity studies. We compared the similarity among clusters using the adjusted Rand index (ARI); an ARI of 0 is equivalent to the diseases being randomly assigned to clusters, and 1 indicates perfect agreement. We compared the network analysis results to disease clusters independently identified by two clinicians. RESULTS: Results differed greatly across combinations of association measures and cluster algorithms. The number of clusters identified ranged from 1 to 24, with a low similarity of conditions within clusters. Compared to clinician-derived clusters, ARIs ranged from -0.02 to 0.24, indicating little similarity. CONCLUSION: These analyses demonstrate the need for a systematic evaluation of the performance of network analysis methods on binary clustered data like diseases. Moreover, in individual older adults, diseases may not cluster predictably, highlighting the need for a personalized approach to their care.

A Model of Core Emotional Needs and Toxic Experiences: Their Links with Schema Domains, Well-Being, and Ill-Being.

This study examined the second-order schema domains of Early Maladaptive and Adaptive Schemas based on recent trends and compared them with the five theoretical second-order schema domains commonly used in schema therapy. Using six international Eastern and Western community samples-Singapore (n = 628), Malaysia (n = 229), USA (n = 396), South Africa (n = 390), Nigeria (n = 364), India (n = 306)-confirmatory factor analysis showed that the four second-order domains of EMSs and EASs, which ran almost parallel with each other, were the most robust models calling into question the validity of the five domain model. Given the hypothesized links between schemas and needs, these four categories of EMSs and EASs represent four categories of toxic experiences and core emotional needs, respectively. These categories were supported empirically and are useful to parents as well as to clinicians as they approach child rearing and the treatment of clients in schema therapy from the vantage point of needs. These four categories of psychological core emotional needs, as well as toxic experiences, were found, as expected, to be linked with various measures of well-being and ill-being.

Cannabis use in a Canadian long-term care facility: a case study.

BACKGROUND: Following the legalization of cannabis in Canada in 2018, people aged 65 + years reported a significant increase in cannabis consumption. Despite limited research with older adults regarding the therapeutic benefits of cannabis, there is increasing interest and use among this population, particularly for those who have chronic illnesses or are at end of life. Long-term Care (LTC) facilities are required to reflect on their care and policies related to the use of cannabis, and how to address residents' cannabis use within what they consider to be their home. METHODS: Using an exploratory case study design, this study aimed to understand how one LTC facility in western Canada addressed the major policy shift related to medical and non-medical cannabis. The case study, conducted November 2021 to August 2022, included an environmental scan of existing policies and procedures related to cannabis use at the LTC facility, a quantitative survey of Healthcare Providers' (HCP) knowledge, attitudes, and practices related to cannabis, and qualitative interviews with HCPs and administrators. Quantitative survey data were analyzed using descriptive statistics and content analysis was used to analyze the qualitative data. RESULTS: A total of 71 HCPs completed the survey and 12 HCPs, including those who functioned as administrators, participated in the interview. The largest knowledge gaps were related to dosing and creating effective treatment plans for residents using cannabis. About half of HCPs reported providing care in the past month to a resident who was taking medical cannabis (54.9%) and a quarter (25.4%) to a resident that was taking non-medical cannabis. The majority of respondents (81.7%) reported that lack of knowledge, education or information about medical cannabis were barriers to medical cannabis use in LTC. From the qualitative data, we identified four key findings regarding HCPs' attitudes, cannabis access and use, barriers to cannabis use, and non-medical cannabis use. CONCLUSIONS: With the legalization of medical and non-medical cannabis in jurisdictions around the world, LTC facilities will be obligated to develop policies, procedures and healthcare services that are able to accommodate residents' use of cannabis in a respectful and evidence-informed manner.

Impact of age, comorbidity, and polypharmacy on receipt of systemic therapy in advanced cancers: A retrospective population-based study.

INTRODUCTION: Cancer incidence, comorbidity, and polypharmacy increase with age, but the interplay between these factors on receipt of systemic therapy (ST) in advanced cancer has rarely been studied. MATERIALS AND METHODS: A retrospective cohort study was conducted including patients aged ≥18 years diagnosed from 2004 to 2015 with multiple myeloma (MM) (all stages), lung cancer (stage IV), and stage III-IV non-Hodgkin's lymphoma (NHL), breast, colorectal (CRC), prostate, or ovarian cancer in Manitoba, Canada. Clinical and administrative health data were used to determine demographic and cancer characteristics, treatment history, comorbidity (Charlson Comorbidity Index [CCI] and Resource Utilization Band [RUB]), and polypharmacy (≥6 medications). Multivariable logistic regression was used to evaluate variable associations with receipt of ST and interaction with age. RESULTS: In total, 17,228 patients were diagnosed with advanced cancer. Ages were distributed as follows: 7% <50 years, 16% 50-59 years, 26% 60-69, 26% 70-79, 24% ≥80 years. ST was administered to 50% of patients. Increased age, polypharmacy, and comorbidity each independently decreased the likelihood of receiving ST. Significant interaction effects were found between age at diagnosis with stage of cancer and cancer type. Differences in probability of ST by cancer stage converged as age increased. In multivariable analysis, adjusting for covariates, patients with MM had the highest odds and lung cancer the lowest odds to receive ST. The impact of comorbidity and polypharmacy did not differ meaningfully with increasing age. DISCUSSION: Increased age, polypharmacy, and comorbidity were each independently associated with decreased receipt of ST in people with advanced cancers. The impact of comorbidity and polypharmacy did not differ meaningfully with increasing age, while age meaningfully interacted with stage and cancer type.

An Exploration of Methods to Resolve Inconsistent Self-Reporting of Chronic Conditions and Impact on Multimorbidity in the Canadian Longitudinal Study on Aging.

OBJECTIVES: To quantify inconsistent self-reporting of chronic conditions between the baseline (2011-2015) and first follow-up surveys (2015-2018) in the Canadian Longitudinal Study on Aging (CLSA), and to explore methods to resolve inconsistent responses and impact on multimorbidity. METHODS: Community-dwelling adults aged 45-85 years in the baseline and first follow-up surveys were included (n = 45,184). At each survey, participants self-reported whether they ever had a physician diagnosis of 35 chronic conditions. Identifiable inconsistent responses were enumerated. RESULTS: 32-40% of participants had at least one inconsistent response across all conditions. Illness-related information (e.g., taking medication) resolved most inconsistent responses (>93%) while computer-assisted software asking participants to confirm their inconsistent disease status resolved ≤53%. Using these adjudication methods, multimorbidity prevalence at follow-up increased by ≤1.6% compared to the prevalence without resolving inconsistent responses. DISCUSSION: Inconsistent self-reporting of chronic conditions is common but may not substantially affect multimorbidity prevalence. Future research should validate methods to resolve inconsistencies.

Dual Sensory Impairment and Functional Status in a Prospective Cohort Study.

Objective: To examine the impact of visual impairment, hearing impairment, and dual sensory impairment (DSI) on functional status in older adults. Methods: Secondary analysis of the Manitoba Health and Aging Study, a population-based cohort study of 1751 adults age 65+. Data were collected from 1991 to 1992 (Time 1), with follow-up five years later (Time 2). Vision and hearing were self-reported. Functional status was measured using the Older Americans Resource and Services (OARS). Logistic regression models were constructed to assess functional status at both Time 1 and Time 2. Results: Dual sensory impairment (DSI) at Time 1 predicted poor functional status at both Time 1 and Time 2. The adjusted odds ratios (OR; 95% confidence interval [CI]) for poor functional status at Time 1 for those with only hearing impairment was 1.74 (1.25, 2.44) for visual impairment was 2.95 (2.19, 3.98), and for DSI was 3.58 (2.58, 4.95). At Time 2, the adjusted ORs for poor functional status for those with only hearing impairment was 1.32 (0.86, 2.03), for visual impairment was 1.63 (1.05, 2.52), and for DSI was 2.61 (1.54, 4.40). Conclusions: DSI is associated with lower functional status, but the effect of visual impairment is more pronounced than hearing impairment.

Aberrations in ion channels interacting with lipid metabolism and epithelial-mesenchymal transition in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is the most prevalent malignant gastrointestinal tumor. Ion channels contribute to tumor growth and progression through interactions with their neighboring molecules including lipids. The dysregulation of membrane ion channels and lipid metabolism may contribute to the epithelial-mesenchymal transition (EMT), leading to metastatic progression. Herein, transcriptome profiles of patients with ESCC were analyzed by performing differential gene expression and weighted gene co-expression network analysis to identify the altered ion channels, lipid metabolism- and EMT-related genes in ESCC. A total of 1,081 differentially expressed genes, including 113 ion channels, 487 lipid metabolism-related, and 537 EMT-related genes, were identified in patients with ESCC. Thereafter, EMT scores were correlated with altered co-expressed genes. The altered co-expressed genes indicated a correlation with EMT signatures. Interactions among 22 ion channels with 3 hub lipid metabolism- and 13 hub EMT-related proteins were determined using protein-protein interaction networks. A pathway map was generated to depict deregulated signaling pathways including insulin resistance and the estrogen receptor-Ca2+ signaling pathway in ESCC. The relationship between potential ion channels and 5-year survival rates in ESCC was determined using Kaplan-Meier plots and Cox proportional hazard regression analysis. Inositol 1,4,5-trisphosphate receptor type 3 (ITPR3) was found to be associated with poor prognosis of patients with ESCC. Additionally, drugs interacting with potential ion channels, including GJA1 and ITPR3, were identified. Understanding alterations in ion channels with lipid metabolism and EMT in ESCC pathophysiology would most likely provide potential targets for the better treatment of patients with ESCC.

Developing a question prompt list for family caregivers concerning the progression and palliative care needs of nursing home residents living with dementia.

Objective: Communication around a palliative approach to dementia care often is problematic or occurs infrequently in nursing homes (NH). Question prompt lists (QPLs), are evidence-based lists designed to improve communication by facilitating discussions within a specific population. This study aimed to develop a QPL concerning the progression and palliative care needs of residents living with dementia. Methods: A mixed-methods design in 2 phases. In phase 1, potential questions for inclusion in the QPL were identified using interviews with NH care providers, palliative care clinicians and family caregivers. An international group of experts reviewed the QPL. In phase 2, NH care providers and family caregivers reviewed the QPL assessing the clarity, sensitivity, importance, and relevance of each item. Results: From 127 initial questions, 30 questions were included in the first draft of the QPL. After review by experts, including family caregivers, the QPL was finalized with 38 questions covering eight content areas. Conclusion: Our study has developed a QPL for persons living with dementia in NHs and their caregivers to initiate conversations to clarify questions they may have regarding the progression of dementia, end of life care, and the NH environment. Further work is needed to evaluate its effectiveness and determine optimal use in clinical practice. Innovation: This unique QPL is anticipated to facilitate discussions around dementia care, including self-care for family caregivers.

Efficacy, pharmacokinetics, and safety of subcutaneous C1-esterase inhibitor as prophylaxis in Japanese patients with hereditary angioedema: Results of a Phase 3 study.

BACKGROUND: Hereditary angioedema (HAE) is a rare and potentially life-threatening genetic disorder characterized by recurrent attacks of angioedema. HAE types I and II result from deficient or dysfunctional C1-esterase inhibitor (C1-INH). This Phase 3 study assessed the efficacy, pharmacokinetics (PK), and safety of subcutaneous (SC) C1-INH in Japanese patients with HAE. METHODS: The prospective, open-label, multicenter, single-arm Phase 3 study recruited patients with HAE types I or II to an initial run-in period, followed by a 16-week treatment period where patients received 60 IU/kg C1-INH (SC) twice weekly. The two primary endpoints were the time-normalized number of HAE attacks per month and C1-INH functional activity at Week 16. RESULTS: Nine patients entered the treatment period and completed the study. Treatment with C1-INH (SC) significantly reduced the mean monthly attack rate from 3.7 during the run-in period to 0.3 during treatment (exploratory p value of within-patient comparison = 0.004). After the last dose of C1-INH (SC) at Week 16, the mean trough concentration of C1-INH was 59.8%, and the mean area under the plasma concentration-time curve to the end of the dosing period and to the last sample were 5317.1 and 13,091.5 h•%, respectively. During the study, there were no deaths, serious adverse events, or adverse events leading to study discontinuation. CONCLUSIONS: C1-INH (SC) (60 IU/kg twice weekly) was efficacious and well tolerated as a prophylaxis against HAE attacks in Japanese patients with HAE types I or II, which was supported by the increased and maintained C1-INH functional activity. EudraCT Number 2019-003921-99; JapicCTI-205273.

Effect of the COVID-19 pandemic on adolescent mental health and substance use up to March, 2022, in Iceland: a repeated, cross-sectional, population-based study.

BACKGROUND: Poor mental health in the first year of the COVID-19 pandemic has been well documented in adolescents; however, less is known about the longer-term effect of the pandemic. We aimed to examine adolescent mental health and substance use as well as covariates associated with these outcomes 1 year or more into the pandemic. METHODS: A nationwide sample of adolescents aged 13-18 years enrolled in school in Iceland were invited to complete surveys administered during October-November or February-March, 2018, October-November, 2020, February-March or October-November, 2021, and February-March 2022. The survey was in Icelandic for all administrations and offered to adolescents aged 13-15 years in English in 2020 and 2022 and in Polish in 2022. Surveys assessed depressive symptoms (Symptom Checklist-90); mental wellbeing (Short Warwick Edinburgh Mental Wellbeing Scale); and the frequency of cigarette smoking, e-cigarette use, and alcohol intoxication. Covariates comprised age, gender, and migration status as determined by language spoken at home, level of social restrictions based on residency, parental social support, and sleep duration (≥8 h nightly). Weighted mixed-effect models were used to determine the effect of time and the covariates on mental health and substance use. The main outcomes were assessed in all participants with more than 80% of the necessary data, and multiple imputation was used to handle missing data. Bonferroni corrections were used to adjust for multiple testing and analyses were considered significant at a p value of <0·0017. FINDINGS: 64 071 responses were submitted and analysed between 2018 and 2022. Elevated depressive symptoms and worsened mental wellbeing across girls and boys aged 13-18 years were observed to have been maintained up to 2 years into the pandemic (p>0·0017). Alcohol intoxication initially decreased during the pandemic but increased again as social restrictions eased (p<0·0001). No changes were observed in cigarette smoking and e-cigarette use during the COVID-19 pandemic. Higher levels of parental social support and an average sleep duration of 8 h or more per night were associated with mental health better outcomes and less substance use (p<0·0001). Social restrictions and migration background were inconsistently associated with the outcomes. INTERPRETATION: Population-level prevention targeting adolescent depressive symptoms should be prioritised in health policy in the wake of COVID-19. FUNDING: Icelandic Research Fund.

Findings in percutaneous trans-hepatic cholecysto-cholangiography in neonates and infants presenting with conjugated hyperbilirubinemia: emphasis on differential diagnosis and cholangiographic patterns.

BACKGROUND: Biliary atresia (BA) is one of the causes of conjugated hyperbilirubinemia in infants which if untreated leads to end-stage liver disease and death. Percutaneous Trans-hepatic Cholecysto-Cholangiography (PTCC) is a minimally invasive study which can be utilized in the diagnostic work-up of these patients. This study's purpose is to describe the experience with PTCC in neonates, the imaging findings encountered, and the abnormal patterns which warrant further investigation. METHODS: A 16-year single-center retrospective study of patients with persistent neonatal cholestasis (suspected BA) undergoing PTCC. Patient demographics, laboratory values, PTCC images, pathology and surgical reports were reviewed. RESULTS: 73 patients underwent PTCC (68% male, mean age 8.7 weeks, mean weight 4.0 Kg). The majority of studies were normal (55%). Abnormal patterns were identified in 33 cases, 79% were diagnosed with BA and 12% with Alagille syndrome. Non-opacification of the common hepatic duct with a narrowed common bile duct (42%) and isolated small gallbladder (38%) were the most common patterns in BA. CONCLUSION: PTCC is a minimally invasive study in the diagnostic work-up of infants presenting with conjugated hyperbilirubinemia (suspected BA). Further invasive investigations or surgery can be avoided when results are normal.

Life Course Predictors of Young Men Surviving to Age 90 in a Cohort Study: The Manitoba Follow-up Study.

The purpose of this study was to identify factors at various time points in life that are associated with surviving to age 90. Data from men enrolled in a cohort study since 1948 were considered in 12-year intervals. Logistic regression models were constructed with the outcome of surviving to age 90. Factors were: childhood illness, blood pressure (BP), body mass index (BMI), chronic diseases, and electrocardiogram (ECG) findings. After 1996, the Short Form-36 was added. A total of 3,976 men were born in 1928 or earlier, and hence by the end of our study window in 2018, each had the opportunity of surviving to age 90. Of these, 721 did live to beyond his 90th birthday.The factors in 1948 which predicted surviving were: lower diastolic BP, lower BMI, and not smoking. In 1960, these factors were: lower BP, lower BMI, not smoking, and no major ECG changes. In 1972, these factors were lower BP, not smoking, and fewer disease states. In 1984, these factors were lower systolic BP, not smoking, ECG changes, and fewer disease states. In 1996, the factors were fewer disease states and higher physical and mental health functioning. In 2008, only higher physical functioning predicted survival to the age of 90. In young adulthood, risk factors are important predictors of surviving to age 90; in mid-life, chronic illnesses emerge, and in later life, functional status becomes predominant.

Positive Schemas: Replication, Associations With Negative Schemas, and the Dark Triad.

The purpose of the current study was to replicate the factor structure of the 14 positive schemas identified in the earlier study by Louis et al. (2018). Using confirmatory factor analysis (CFA), and Multi-group CFA, the 14 positive schemas were found to be robust across four new non-clinical English-speaking community samples - USA (n = 396), South Africa (n = 390), Nigeria (n = 364), and India (n = 306). Further, results from CFA, and chi square tests showed that positive and negative schemas were independent but related constructs, and that they do not reflect bipolarity. Using hierarchical regression and Pearson's correlations the negative schemas of Entitlement, Approval Seeking and Mistrust, and the positive schema of Empathic Consideration were found to be associated positively and negatively respectively with Machiavellianism, narcissism, and psychopathy of the Dark Triad scale in all four worldwide samples. Implications of this finding in Schema Therapy treatment were discussed.

Polypharmacy and Potentially Inappropriate Medication Use in Older Adults With Systemic Lupus Erythematosus.

OBJECTIVE: To assess the prevalence and potential risk factors for polypharmacy and prescribing of the potentially inappropriate medications, opioids and benzodiazepines/Z-drugs, in older adults with systemic lupus erythematosus (SLE). METHODS: The study population comprised adults age ≥50 years meeting American College of Rheumatology or Systemic Lupus International Collaborating Clinics classification criteria followed at a tertiary care rheumatology clinic. Information on prescriptions filled in the 4 months preceding chart review was obtained from the Manitoba Drug Program Information Network. Clinical data, including age, sex, Charlson Comorbidity Index (CCI) score, Systemic Lupus Erythematosus Disease Activity Index 2000 score, prednisone use, SLE duration, and rural residence were abstracted from electronic medical records. Logistic regression analyses were performed to assess any association between polypharmacy (using 2 definitions: ≥5 and ≥10 medications), potentially inappropriate medication use, and clinical features. RESULTS: A total of 206 patients (mean age 62 years, 91% female, 36% rural) were included: 148 (72%) filled ≥5 medications, 71 (35%) filled ≥10 medications, 63 (31%) used benzodiazepines/Z-drugs, and 50 (24%) used opioids. Among the 77 patients age ≥65 years, 57 (74%) filled ≥5 medications, and 26 (34%) filled ≥10 medications, compared to 30% and 4%, respectively, of Manitobans age ≥65 years (National Prescription Drug Utilization Information System, 2016). The odds of polypharmacy were greater with prednisone use (adjusted odds ratio [OR] 3.70 [95% confidence interval (95% CI) 1.40-9.79] for ≥5 medications), CCI score (adjusted OR 1.62 [95% CI 1.20-2.17]), and rural residence (adjusted OR 2.05 [95% CI 1.01-4.18]). Odds of benzodiazepine/Z-drug use were increased with polypharmacy (adjusted OR 4.35 [95% CI 1.69-11.22]), and odds of opioid use were increased with polypharmacy (adjusted OR 6.75 [95% CI 1.93-23.69]) and CCI score (adjusted OR 1.29 [95% CI 1.08-1.54]). CONCLUSION: The prevalence of polypharmacy in this SLE cohort was higher than in the general Manitoban population. Polypharmacy is a strong marker for use of prescription benzodiazepines/Z-drugs and opioids.

Multimorbidity and depressive symptoms in older adults and the role of social support: Evidence using Canadian Longitudinal Study on Aging (CLSA) data.

BACKGROUND: The rising prevalence of multimorbidity poses challenges to health systems globally. The objectives of this study were to investigate: 1) the association between multimorbidity and depressive symptoms; and 2) whether social support plays a protective role in this association. METHODS: A prospective population-based cohort study was conducted to analyze baseline and 3-year follow-up data of 16,729 community dwelling participants aged 65 and above in the Canadian Longitudinal Study of Aging (CLSA). Multimorbidity was defined as having three or more chronic conditions. The 10-item Center for Epidemiologic Studies Depression scale (CESD-10) was used to measure depressive symptoms. The 19-item Medical Outcomes Study (MOS) Social Support Survey was employed to assess perceived social support. Multivariate logistic regression models were used to examine the association between multimorbidity, social support and depressive symptoms. RESULTS: Multimorbidity was very common among participants with a prevalence of 70.6%. Fifteen percent of participants had depressive symptoms at baseline. Multimorbidity was associated with increased odds of having depressive symptoms at 3-year follow-up (adjusted odds ratio, aOR = 1.51, 95% CI 1.33, 1.71), and developing depressive symptoms by follow-up among those with no depressive symptoms at baseline (aOR = 1.65, 95% CI 1.42, 1.92). Social support was consistently associated with decreased odds of depressive symptoms, regardless of level of multimorbidity. CONCLUSION: Multimorbidity was positively associated with depressive symptoms over time, but social support served as a protective factor. As a modifiable, protective factor, emphasis should be placed in clinical practice to assess social support and refer patients to appropriate services, such as support groups. Similarly, health policy should focus on ensuring that older adults have access to social support opportunities as a way to promote mental health among older adults. Community organizations that offer social activities or support groups play a key role in this respect and should be adequately supported (e.g., with funding).

Multi-stakeholder validation of entrustable professional activities for a family medicine care of the elderly residency program: a focus group study.

Entrustable Professional Activities (EPAs) have become widely used within Competency-Based Medical Education (CBME) for the training and evaluation of residents. Little is known about the effectiveness of incorporating multiple stakeholder groups in the validation of EPAs. Here, we seek to validate an EPA framework developed for the University of Manitoba Care of the Elderly Enhanced Skills program using online focus groups consisting of five stakeholder groups. Participants were recruited to take part in one of five online focus groups, one for each stakeholder group (physician faculty, residents, non-physician healthcare professionals, administrators/managers, and patients). Each group met one time for 90 minutes over ZOOM®. The themes arising from stakeholder feedback suggest that successful EPAs must neither be too specific nor too expansive in scope, clearly delineate appropriate means of evaluation, and indicate specific clinical settings in which each EPA should be evaluated. Cross-cutting themes included requiring trainees to collaborate with other professionals when it would optimize patient care, and preparing trainees to advocate for their patients' health (Advocacy). The present study demonstrates that multi-stakeholder analysis yields diverse feedback that can help make EPAs more clear, easier to use in evaluation, and more socially accountable.