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Background: The Dixon-Woods et al. Candidacy Framework, a valuable tool since its 2006 introduction, has been widely utilized to analyze access to various services in diverse contexts, including healthcare. This social constructionist approach examines micro, meso, and macro influences on access, offering concrete explanations for access challenges rooted in socially patterned influences. This study employed the Candidacy Framework to explore the experiences of individuals living with rheumatoid arthritis (RA) and their formal care providers. The investigation extended to assessing supports and innovations in RA diagnosis and management, particularly in primary care., Methods: This systematic review is a Critical Interpretive Synthesis (CIS) of qualitative and mixed methods literature. The CIS aimed to generate theory from identified constructs across the reviewed literature. The study found alignment between the seven dimensions of the Candidacy Framework and key themes emerging from the data. Notably absent from the framework was an eighth dimension, identified as the "embodied relational self." This dimension, central to the model, prompted the proposal of a revised framework specific to healthcare for chronic conditions., Results: The CIS revealed that the eight dimensions, including the embodied relational self, provided a comprehensive understanding of the experiences and perspectives of individuals with RA and their care providers. The proposed Candidacy 2.0 (Chronic Condition (CC)) model demonstrated how integrating approaches like Intersectionality, concordance, and recursivity enhanced the framework when the embodied self was central., Conclusions: The study concludes that while the original Candidacy Framework serves as a robust foundation, a revised version, Candidacy 2.0 (CC), is warranted for chronic conditions. The addition of the embodied relational self dimension enriches the model, accommodating the complexities of accessing healthcare for chronic conditions., Trial Registration: This study did not involve a health care intervention on human participants, and as such, trial registration is not applicable. However, our review is registered with the Open Science Framework at https://doi.org/10.17605/OSF.IO/ASX5C ., (© 2024. The Author(s).)

Objective: The objective was to analyse how the pandemic affected primary care access and comprehensiveness in chronic disease management by comparing primary care patterns before and during the early COVID-19 pandemic., Design: We conducted a quasi-experimental pre-post design cohort study and reported indicators for the 21 months before and after the onset of the COVID-19 pandemic., Setting: We used electronic medical record data from primary care clinics enrolled in the Canadian Primary Care Sentinel Surveillance Network from 1 January 2018 to 31 December 2021., Population: The study population included patients (n=919 928) aged 18 years or older with at least one primary care contact from 12 March 2018 to 12 March 2020, in Canada., Outcome Measures: The study indicators included three indicators measuring access to primary care (encounters, blood pressure measurements and lab tests) and three for comprehensiveness (diagnoses, non-COVID-19 vaccines administered and referrals)., Results: 67.3% of the cohort was aged ≥40 years, 56.4% were female and 53.5% were from Ontario, Canada. Fewer patients received an encounter during the pandemic (91.5% to 81.5%), while the median (IQR) number of encounters remained the same (5 (2-1)) for those with access. Fewer patients received a blood pressure measurement (47.9% to 31.8%), and patients received fewer measurements during the pandemic (2 (1-4) to 1 (0-2))., Conclusions: Encounters with primary care remained consistent during the pandemic, but in-person care, such as lab tests and blood pressure measurements, decreased. In-person care indicators followed temporally to national COVID-19 case counts during the pandemic., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Most antibiotics dispensed by community pharmacies in Canada are prescribed by family physicians, but using the prescribing information contained within primary care electronic medical records (EMRs) for secondary purposes can be challenging owing to variable data quality. We used antibiotic medications as an exemplar to validate a machine-learning approach for cleaning and coding medication data in a pan-Canadian primary care EMR database., Methods: The Canadian Primary Care Sentinel Surveillance Network database contained an estimated 42 million medication records, which we mapped to an Anatomic Therapeutic Chemical (ATC) code by applying a semisupervised classification model developed using reference standard labels derived from the Health Canada Drug Product Database. We validated the resulting ATC codes in a subset of antibiotic records (16 119 unique strings) to determine whether the algorithm correctly classified the medication according to manual review of the original medication record., Results: In the antibiotic subset, the algorithm showed high validity (sensitivity 99.5%, specificity 92.4%, positive predictive value 98.6%, negative predictive value 97.0%) in classifying whether the medication was an antibiotic., Interpretation: Our machine-learning algorithm classified unstructured antibiotic medication data from primary care with a high degree of accuracy. Access to cleaned EMR data can support important secondary uses, including community-based antibiotic prescribing surveillance and practice improvement., Competing Interests: Competing interests: None declared., (© 2023 CMA Impact Inc. or its licensors.)

Background: Since the COVID-19 pandemic began, there have been concerns that interruptions to the health care system may have led to changes in primary care, especially for care of chronic conditions such as diabetes and heart failure. Such changes may have longer term implications for population health., Objective: This study aims to describe the impacts of the COVID-19 pandemic on indicators of primary care access, comprehensiveness, and appropriateness among adult patients, as well as on specific indictors of chronic conditions. Additionally, this study aims to determine whether any identified changes were associated with patient sociodemographic characteristics and multimorbidity., Methods: This is a retrospective, single-arm, pre-post study using Canadian Primary Care Sentinel Surveillance Network (CPCSSN) data. CPCSSN is a research network supported by a primary care electronic medical record database, comprising over 1500 physicians and nearly 2 million patients. We are examining changes in care (eg, frequency of contacts, laboratory tests and investigations, referrals, medications prescribed, etc) among adults. We will also examine indicators specific to evidence-based recommendations for care in patients with diabetes and those with heart failure. We will compare rates of outcomes during key periods of the pandemic between March 13, 2020, and December 31, 2022, with equal time periods before the pandemic. Differences will be examined among specific subgroups of adults, including by decade of age, number of comorbidities, and socioeconomic status. Regression models appropriate to outcome distributions will be used to estimate changes, adjusting for potential confounders. This analysis is part of a mixed-methods study with a qualitative component investigating how patients with diabetes with or without concurrent heart failure perceived the impact of the pandemic on access to primary care and health care-related decisions. This study was approved by the Hamilton Integrated Research Ethics Board (14782-C)., Results: The start date of this study was October 5, 2022, and the prospective end date is January 31, 2024. As of May 2023, the study cohort (n=875,934) is defined, data cleaning is complete, and exploratory analyses have begun. Extended analyses using 2022 data are planned once the new data becomes available. We will disseminate results through peer-reviewed publications and academic conference, as well as creating evidence briefs, infographics, and a video for policy maker and patient audiences., Conclusions: This study will investigate whether the COVID-19 pandemic has resulted in changes in the provision of primary care in Canada and whether these potential changes have led to gaps in care. This study will also identify patient-level characteristics associated with changes in care patterns across the COVID-19 pandemic. Indicators specific to chronic conditions, namely diabetes and heart failure, will also be explored to determine whether there were changes in care of these conditions., Trial Registration: ClinicalTrials.gov NCT05813652; https://clinicaltrials.gov/ct2/show/NCT05813652., International Registered Report Identifier (irrid): RR1-10.2196/49131., (©Michelle Howard, Kris Aubrey-Bassler, Neil Drummond, Marie-Thérèse Lussier, John A Queenan, Meredith Vanstone, Kathryn Nicholson, Amanda Ramdyal, Jennifer Lawson, Shuaib Hafid, Karla Freeman, Rebecca Clark, Dee Mangin. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 21.07.2023.)

Objective: Documenting cannabis use is important for patient care, but no formal requirements for consistent reporting exist in primary care. The objective of this study was to understand how cannabis use is documented in primary care electronic medical record (EMR) data., Results: This was a cross-sectional study using de-identified EMR data from over 398,000 patients and 333 primary care providers in Alberta, Canada. An automated pattern-matching algorithm was developed to identify text and ICD-9 diagnostic codes indicating cannabis use in the EMR. There was a total of 11,724 records indicating cannabis use from 4652 patients, representing approximately 1.2% of the patient sample. Commonly used terms and ICD-9 codes included cannabis, marijuana/marihuana, THC, 304.3 and 305.2. Nabilone was the most frequently prescribed cannabinoid medication. Slightly more males and those with a chronic condition had cannabis use recorded more often. Overall, very few patients have cannabis use recorded in primary care EMR data and this is not captured in a systematic way. We propose several strategies to improve the documentation of cannabis use to facilitate more effective clinical care, research, and surveillance., (© 2023. The Author(s).)

Objective: To characterize transitions to acute and residential care and identify variables associated with specific transitions among community-based persons living with dementia (PLWD)., Design: Retrospective cohort study using primary care electronic medical record data linked with health administrative data., Setting: Alberta., Participants: Adults aged 65 years or older living in the community who had been diagnosed with dementia and who saw a Canadian Primary Care Sentinel Surveillance Network contributor between January 1, 2013, and February 28, 2015., Main Outcome Measures: All emergency department visits, hospitalizations, residential care (supportive living and long-term care) admissions, and deaths within a 2-year follow-up period., Results: In total, 576 PLWD were identified who had a mean (SD) age of 80.4 (7.7) years; 55% were female. In 2 years, 423 (73.4%) had at least 1 transition and, of these, 111 (26.2%) had 6 or more. Emergency department visits, including multiple visits, were common (71.4% had ≥1, 12.1% had ≥4). Of those hospitalized (43.8%), nearly all were admitted from the emergency department; the average (SD) length of stay was 23.6 (35.8) days, and 32.9% had at least 1 alternate level of care day. In total, 19.3% entered residential care, most admitted from hospital. Those admitted to hospital and those admitted to residential care were older and had greater historical health system use, including home care. One-quarter of the sample did not have any transitions (or die) during follow-up; they were typically younger and had limited historical health system use., Conclusion: Older PLWD experienced frequent, and frequently compound, transitions that have implications for them, their family members, and the health system. There was also a large proportion without transitions suggesting that appropriate supports enable PLWD to do well in their own communities. The identification of PLWD who are at risk of or who make frequent transitions may allow for more proactive implementation of community-based supports and smoother transitions to residential care., (Copyright © 2023 the College of Family Physicians of Canada.)

Background: Local field potentials (LFPs) represent the summation of periodic (oscillations) and aperiodic (fractal) signals. Although previous studies showed changes in beta band oscillations and burst characteristics of the subthalamic nucleus (STN) in Parkinson's disease (PD), how aperiodic activity in the STN is related to PD pathophysiology is unknown., Objectives: The study aimed to characterize the long-term effects of STN-deep brain stimulation (DBS) and dopaminergic medications on aperiodic activities and beta bursts., Methods: A total of 10 patients with PD participated in this longitudinal study. Simultaneous bilateral STN-LFP recordings were conducted in six separate visits during a period of 18 months using the Activa PC + S device in the off and on dopaminergic medication states. We used irregular-resampling auto-spectral analysis to separate oscillations and aperiodic components (exponent and offset) in the power spectrum of STN-LFP signals in beta band., Results: Our results revealed a systematic increase in both the exponent and the offset of the aperiodic spectrum over 18 months following the DBS implantation, independent of the dopaminergic medication state of patients with PD. In contrast, beta burst durations and amplitudes were stable over time and were suppressed by dopaminergic medications., Conclusions: These findings indicate that oscillations and aperiodic activities reflect at least partially distinct yet complementary neural mechanisms, which should be considered in the design of robust biomarkers to optimize adaptive DBS. Given the link between increased gamma-aminobutyric acidergic (GABAergic) transmission and higher aperiodic activity, our findings suggest that long-term STN-DBS may relate to increased inhibition in the basal ganglia. © 2022 International Parkinson and Movement Disorder Society., (© 2022 International Parkinson and Movement Disorder Society.)

The International Classification of Diseases, Ninth Revision (ICD-9) was released in the 1970s and adopted in Canada for physician billing claims in 1979 (CIHI n.d.b.; WHO & International Conference for the Ninth Revision of the International Classification of Diseases 1977). ICD-9 is no longer adequate for representing our modern healthcare environment and patient needs. We summarize the findings from a small survey of ICD-9 users across Canada - such as family physicians, researchers and decision makers - who describe the limitations of ICD-9 and the features that they would desire in a new or updated classification system., (Copyright © 2022 Longwoods Publishing.)

Objectives: Glucagon-like peptide-1 receptor agonists (GLP-1 RA) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) have shown cardiorenal benefits independent of their glucose-lowering effects among persons living with type 2 diabetes mellitus (T2DM). In this study, we describe the proportion of persons with T2DM eligible to receive and currently receiving these agents based on their risk criteria for cardiorenal events., Methods: This study was a cross-sectional analysis of primary care electronic medical records, in southern Alberta, of persons with T2DM who had at least 1 encounter with their primary care provider between December 31, 2018, to December 31, 2020. A descriptive and multivariate logistic regression analysis was conducted to examine clinical and demographic determinants of being prescribed one of the new treatments., Results: Our study sample included 11,939 persons living with T2DM, among whom 66.3% had a cardiorenal indication for SGLT2i or GLP-1 RA use. In the secondary and primary prevention subsamples, 19.4% and 16.6% of persons were prescribed SGLT2i or GLP-1 RA, respectively, compared with 20.0% of those with no specific cardiorenal indication. Several person-level characteristics, such as age (odds ratio [OR], 0.96; 95% confidence interval [CI], 0.96 to 0.97), male sex (OR, 1.37; 95% CI, 1.21 to 1.55) and glycated hemoglobin (OR, 1.29; 95% CI, 1.24 to 1.34), were associated with being prescribed SGLT2i or GLP-1 RA., Conclusions: Low rates of SGLT2i or GLP-1 RA use and minimal differences between high-risk and no cardiorenal indication subsamples suggest the presence of barriers to prescribing these medications in a primary care setting. Action to highlight the indications for, and improve access to agents with, cardiorenal benefits will be required to achieve better outcomes for people with T2DM in primary care., (Copyright © 2022 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.)

Background: The dementias are long-term, chronic conditions caused by progressive neurological degeneration. Current literature suggests that cardiovascular disease risk factors may contribute to the onset of dementia; however, evidence of these associations is inconsistent., Objectives: This study aimed to examine the impact of risk factors on dementia onset in older adults diagnosed and managed in Canadian primary care settings., Methods: A retrospective cohort study was employed utilizing electronic medical records data in the Canadian Primary Care Sentinel Surveillance Network (CPCSSN). Patients aged 65+ years with no dementia diagnosis at baseline who were followed from 2009 to 2017 with a run-in year to exclude existing undiagnosed dementia cases. Multivariate Cox proportional hazard models were used to estimate risk., Results: Age was associated with an increased incidence risk of dementia in both examined age groups: 65-79 years (13%) and 80+ years (5%). History of depression increased dementia risk by 38% and 34% in the age groups. There were significant associations with lower social deprivation area quintile, smoking history, osteoarthritis, and diabetes mellitus in patients aged 65-79 years but not in those aged 80+ years. Sex, hypertension, obesity, dyslipidemia, and the use of antihypertensive medications and statins were not associated with risk of incident dementia diagnosis., Conclusions: The association between chronic health conditions and dementia onset is complicated. Primary care electronic medical record data might be useful for research in this topic, though follow-up time is still relatively short to observe a clear causal relationship. Future studies with more complete data may provide evidence for dementia preventive strategies within primary care practice., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Cardiovascular disease (CVD) is a major cause of morbidity and mortality in Canada. Assessment and management of CVD risk is essential in reducing disease burden. This includes both clinical risk factors and socioeconomic factors, though few studies report on socioeconomic status in relation to CVD risk and treatment. The primary objective of this study was to estimate the cardiovascular risk of patients attending primary care practices across Canada; secondly, to evaluate concordance with care indicators suggested by current clinical practice guidelines for statin prescribing according to patients' cardiovascular risk and socioeconomic status., Methods: This cross-sectional observational study used the Canadian Primary Care Sentinel Surveillance Network (CPCSSN) database, which is comprised of clinical data from primary care electronic medical records. Patients aged 35-75y with at least one visit to their primary care provider between 2012 and 2016 were included. Patients were assigned to a CVD risk category (high, medium, low) and a deprivation quintile was calculated for those with full postal code available. Descriptive analyses were used to determine the proportion of patients in each risk category. Logistic regression was used to evaluate the consistency of statin prescribing according to national clinical guidelines by risk category and deprivation quintile., Results: A total of 324,526 patients were included. Of those, 116,947 (36%) of patients were assigned to a high CVD risk category, primarily older adults, males, and those with co-morbidities. There were statistically significant differences between least (quintile 1) and most (quintile 5) deprived socioeconomic quintiles, with those at high CVD risk disproportionately in Q5 (odds ratio 1.4). Overall, 48% of high-risk patients had at least one statin prescription in their record. Patients in the lower socioeconomic groups had a higher risk of statin treatment which deviated from clinical guidelines., Conclusions: Primary care patients who are at high CVD risk are more often male, older, have more co-morbidities and be assigned to more deprived SES quintiles, compared to those at low CVD risk. Additionally, patients who experience more challenging socioeconomic situations may be less likely to receive CVD treatment that is consistent with care guidelines., (© 2022. The Author(s).)

The purpose of this study was to examine the content of physical activity inputs in Canadian family physician electronic medical records. Of 1 225 948 patients aged 18-64 years, a sample of 1535 patients' charts were reviewed. A minority ( n = 148; 9.6%) of patients had at least 1 mention of physical activity at any time. Insufficient information existed to determine physical activity domain (21.6%), purpose (50.0%), or meeting of guidelines (98.1%). Novelty: This study examines the physical activity content of what Canadian family physicians document in their electronic medical records.

Background: Dementia is an increasing concern in many countries, especially in those experiencing rapid growth in the proportion of older adults in their population., Objective: This study aims to describe trends and demographic characteristics of incident dementia cases in community-dwelling older adults managed by primary care physicians., Methods: We used electronic medical records from the Canadian Primary Care Sentinel Surveillance Network database to conduct a retrospective analysis to determine the number of, and trends for, incident diagnoses of dementia. Age-standardized annual incidence rates were calculated. Participants in our cohort are Canadian community dwelling seniors aged 65+ years who were not diagnosed with dementia before baseline with at least six years of record at their primary care clinics., Results: The cohort consisted of 39 067 patients of whom 57% were females; the mean (SD) follow-up was 8.4 (1.5) years. During follow-up, 4935 patients were diagnosed with dementia. The risk for dementia diagnosis increased with increasing age but decreased in the last four years among people aged 80 and older at baseline (P < 0.001). People with dementia were more likely to be females (P = 0.001) and urban residents (P < 0.001), they are less likely to be classified into the least deprived group (P = 0.012)., Conclusions: The incidence of dementia diagnosis increased with age except in the oldest old in both sexes. This may be attributed to the effect of mortality competing risk. Future research on the association between risk factors and dementia should consider studying dementia among the oldest old separately to minimize bias., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved.For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: This paper explores the role of immigrant-serving agencies in facilitating access to dementia services and supports provided by dementia service agencies (particularly the health authority and local chapters of the Alzheimer Society) through their propensity to develop trusting relationships between staff and clients. Design: Our research is a qualitative case study of Punjabi and Korean speakers living in the Lower Mainland of BC, Canada. Data are drawn from interviews with 15 dyads of persons with dementia and their family caregivers (10 Punjabi, 5 Korean), six focus groups (one focus group with each of 8-10 older men, older women, and mixed gender working age adults in each community). We also interviewed 20 managerial and frontline staff of dementia service agencies, i.e. the health authority and the local Alzheimer Society ( n  = 11) and two immigrant-serving agencies ( n  = 9), each dedicated to either Punjabi or Korean-speaking clients. We adopted the Candidacy framework for understanding access to dementia services and supports and the concept of trust as guiding precepts in this study. Results: Families of persons with dementia are pivotal to identification of a problem requiring professional help, navigation to appropriate services and acceptance of services offered. However, trust in family members should not be taken for granted, since family dynamics are complex. Alternative sources of trusted support are therefore needed. Immigrant-serving agencies are more often instrumental in establishing trusted relationships between their staff and clients, but they often lack detailed knowledge about heath conditions, their treatment and management, and they lack power to implement statutory care. Conclusions: Partnerships between mainstream mental health/dementia services and the community sector have proven successful in increasing the accessibility of specialized resources, while maximizing their combined trustworthiness, accessibility and effectiveness. Such partnerships should become fundamental components of health service strategy and provision for vulnerable and underserved immigrant older adults.

Growing evidence suggests that both the medial prefrontal cortex (mPFC) and the subthalamic nucleus (STN) play crucial roles in conflict processing, but how these two structures coordinate their activities remains poorly understood. We simultaneously recorded electroencephalogram from the mPFC and local field potentials from the STN using deep brain stimulation electrodes in 13 Parkinson's disease patients while they performed a Stroop task. Both mPFC and STN showed significant increases in theta activities (2-8 Hz) in incongruent trials compared to the congruent trials. The theta activity in incongruent trials also demonstrated significantly increased phase synchronization between mPFC and STN. Furthermore, the amplitude of gamma oscillation was modulated by the phase of theta activity at the STN in incongruent trials. Such theta-gamma phase-amplitude coupling (PAC) was much stronger for incongruent trials with faster reaction times than those with slower reaction times. Elevated theta-gamma PAC in the STN provides a novel mechanism by which the STN may operationalize its proposed "hold-your-horses" role. The co-occurrence of mPFC-STN theta phase synchronization and STN theta-gamma PAC reflects a neural substrate for fronto-subthalamic communication during conflict processing. More broadly, it may be a general mechanism for neuronal interactions in the cortico-basal ganglia circuits via a combination of long-range, within-frequency phase synchronization and local cross-frequency PAC., Competing Interests: Declaration of Competing of Interest The authors declare no competing financial interests., (Copyright © 2021. Published by Elsevier Inc.)

Background: Research based in primary care suggests that hearing loss may be underreported as well as inconsistently recorded in patient histories. In this study, we aimed to develop and validate a case definition for hearing loss among older adults in primary care, using electronic medical records., Methods: We used data from adult patients aged 55 years and older from 13 practices in the Southern Alberta Primary Care Research Network database, part of the Canadian Primary Care Sentinel Surveillance Network (CPCSSN), from Dec. 1, 2014, to Dec. 31, 2016. We developed a hearing loss case definition that was translated into an electronic algorithm. A record review was undertaken as the reference standard, followed by application of the algorithm to the sample. Validation metrics included sensitivity, specificity, positive predictive value and negative predictive value, as well as prevalence. We assessed risk factors using the Fisher exact test and odds ratios., Results: The sample included 1000 patients; 496 (49.6%) were female and the mean age was 67.5 (standard deviation 9.6) years. Sensitivity of the case definition algorithm was determined to be 87.3% (95% confidence interval [CI] 76.5%-94.4%) with specificity valued at 94.8% (95% CI 93.1%-96.1%). Positive and negative predictive values were 52.9% (95% CI 42.8%-62.8%) and 99.1% (95% CI 98.2%-99.6%), respectively. The prevalence of hearing loss within the sample was 6.3% (95% CI 4.9%-7.9%). Older age was a significant risk factor for hearing loss ( t = 4.98, 95% CI 3.76-8.65). Men had greater odds of hearing loss than women (odds ratio 1.65, 95% CI 0.98-2.79)., Interpretation: The validated case definition for hearing loss in community-based older adults had high sensitivity and specificity. It may be applied to surveillance and future epidemiologic research within the CPCSSN database., Competing Interests: Competing interests: None declared., (© 2021 CMA Joule Inc. or its licensors.)

We describe how the out-of-plane dielectric polarizability of monolayer graphene influences the electrostatics of bilayer graphene-both Bernal (BLG) and twisted (tBLG). We compare the polarizability value computed using density functional theory with the output from previously published experimental data on the electrostatically controlled interlayer asymmetry potential in BLG and data on the on-layer density distribution in tBLG. We show that monolayers in tBLG are described well by polarizability α exp = 10.8 Å 3 and effective out-of-plane dielectric susceptibility ϵ z = 2.5, including their on-layer electron density distribution at zero magnetic field and the interlayer Landau level pinning at quantizing magnetic fields.

Background: Polypharmacy, often defined as the concomitant use of ≥ 5 medications, has been identified as a significant global public health threat. Aging and multimorbidity are key drivers of polypharmacy and have been linked to a broad range of adverse health outcomes and mortality. Patients with chronic kidney disease (CKD) are particularly at high risk of polypharmacy and use of potentially inappropriate medications given the numerous risk factors and complications associated with CKD. The aim of this systematic review will be to assess the prevalence of polypharmacy among adult patients with CKD, and the potential association between polypharmacy and adverse health outcomes within this population., Methods/design: We will search empirical databases such as MEDLINE, Embase, Cochrane Library, CINAHL, Web of Science, and PsycINFO and grey literature from inception onwards (with no language restrictions) for observational studies (e.g., cross-sectional or cohort studies) reporting the prevalence of polypharmacy in adult patients with CKD (all stages including dialysis). Two reviewers will independently screen all citations, full-text articles, and extract data. Potential conflicts will be resolved through discussion. The study methodological quality will be appraised using an appropriate tool. The primary outcome will be the prevalence of polypharmacy. Secondary outcomes will include any adverse health outcomes (e.g., worsening kidney function) in association with polypharmacy. If appropriate, we will conduct random effects meta-analysis of observational data to summarize the pooled prevalence of polypharmacy and the associations between polypharmacy and adverse outcomes. Statistical heterogeneity will be estimated using Cochran's Q and I 2 index. Additional analyses will be conducted to explore the potential sources of heterogeneity (e.g., sex, kidney replacement therapy, multimorbidity)., Discussion: Given that polypharmacy is a major and a growing public health issue, our findings will highlight the prevalence of polypharmacy, hazards associated with it, and medication thresholds associated with adverse outcomes in patients with CKD. Our study will also draw attention to the prognostic importance of improving medication practices as a key priority area to help minimize the use of inappropriate medications in patients with CKD., Systematic Review Registration: PROSPERO registration number: [ CRD42020206514 ].

Background: Parkinson's disease (PD) is a common neurodegenerative disorder that results in movement-related dysfunction and has variable cognitive impairment. Deep brain stimulation (DBS) of the dorsal subthalamic nucleus (STN) has been shown to be effective in improving motor symptoms; however, cognitive impairment is often unchanged, and in some cases, worsened particularly on tasks of verbal fluency. Traditional DBS strategies use high frequency gamma stimulation for motor symptoms (∼130 Hz), but there is evidence that low frequency theta oscillations (5-12 Hz) are important in cognition., Methods: We tested the effects of stimulation frequency and location on verbal fluency among patients who underwent STN DBS implantation with externalized leads. During baseline cognitive testing, STN field potentials were recorded and the individual patients' peak theta frequency power was identified during each cognitive task. Patients repeated cognitive testing at five different stimulation settings: no stimulation, dorsal contact gamma (130 Hz), ventral contact gamma, dorsal theta (peak baseline theta) and ventral theta (peak baseline theta) frequency stimulation., Results: Acute left dorsal peak theta frequency STN stimulation improves overall verbal fluency compared to no stimulation and to either dorsal or ventral gamma stimulation. Stratifying by type of verbal fluency probes, verbal fluency in episodic categories was improved with dorsal theta stimulation compared to all other conditions, while there were no differences between stimulation conditions in non-episodic probe conditions., Conclusion: Here, we provide evidence that dorsal STN theta stimulation may improve verbal fluency, suggesting a potential possibility of integrating theta stimulation into current DBS paradigms to improve cognitive outcomes., Competing Interests: Declaration of competing interest Dr. De Vloo reports grants from Helaers Foundation. Dr. Fasano reports personal fees and other from Abbott, grants and personal fees from Boston Scientific, personal fees from Brainlab, personal fees from Ceregate, grants, personal fees, non-financial support and other from Medtronic. Dr. Chen reports grants from Canadian Institutes of Health Research, during the conduct of the study; personal fees from Allergan, personal fees from Merz, personal fees from Ipsen. Dr. Kalia reports other support from Medtronic. Dr. Lozano reports other support from Medtronic, other from Abbott, other from Boston Scientific, other from Insightec, other from Functional Neuromodulation, during the conduct of the study., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Chronic obstructive pulmonary disease (COPD) is a complex disease that is predicted to be the third most common cause of death by 2030. In Canada, the care and management of chronic conditions is largely provided by primary care providers. Although there is emerging research and initiatives that describe the prevalence of COPD in Canadian primary care settings, to our knowledge, there have been no efforts to use a large pan-Canadian database to analyze COPD as a risk factor for other common chronic conditions managed in primary care. We report the risk of developing comorbidities after the onset of COPD, that is, the extent to which COPD is a risk factor for developing common chronic conditions (heart failure, depression, anxiety, coronary artery disease, diabetes, anemia, hypertension, ischemic heart disease, underweight, and osteoporosis). After adjusting for age, sex, urban vs rural residence, and smoking status, the relative risks for patients with COPD at baseline were significantly higher for subsequent incidence of anemia, anxiety, diabetes, depression, heart failure, ischemic heart disease, lung cancer, osteoporosis, sleep apnea, underweight, and hypertension than patients without COPD. Using a cut-point of a 200% increase in relative risk as indicative of particular clinical relevance, COPD has a statistically and clinically significant association with developing lung cancer, becoming underweight, and developing heart failure.

The interconnection of the angular gyrus of right posterior parietal cortex (PPC) and the left motor cortex (LM1) is essential for goal-directed hand movements. Previous work with transcranial magnetic stimulation (TMS) showed that right PPC stimulation increases LM1 excitability, but right PPC followed by left PPC-LM1 stimulation (LPPC-LM1) inhibits LM1 corticospinal output compared with LPPC-LM1 alone. It is not clear if right PPC-mediated inhibition of LPPC-LM1 is due to inhibition of left PPC or to combined effects of right and left PPC stimulation on LM1 excitability. We used paired-pulse TMS to study the extent to which combined right and left PPC stimulation, targeting the angular gyri, influences LM1 excitability. We tested 16 healthy subjects in five paired-pulsed TMS experiments using MRI-guided neuronavigation to target the angular gyri within PPC. We tested the effects of different right angular gyrus (RAG) and LM1 stimulation intensities on the influence of RAG on LM1 and on influence of left angular gyrus (LAG) on LM1 (LAG-LM1). We then tested the effects of RAG and LAG stimulation on LM1 short-interval intracortical facilitation (SICF), short-interval intracortical inhibition (SICI), and long-interval intracortical inhibition (LICI). The results revealed that RAG facilitated LM1, inhibited SICF, and inhibited LAG-LM1. Combined RAG-LAG stimulation did not affect SICI but increased LICI. These experiments suggest that RAG-mediated inhibition of LAG-LM1 is related to inhibition of early indirect (I)-wave activity and enhancement of GABA B receptor-mediated inhibition in LM1. The influence of RAG on LM1 likely involves ipsilateral connections from LAG to LM1 and heterotopic connections from RAG to LM1. NEW & NOTEWORTHY Goal-directed hand movements rely on the right and left angular gyri (RAG and LAG) and motor cortex (M1), yet how these brain areas functionally interact is unclear. Here, we show that RAG stimulation facilitated right hand motor output from the left M1 but inhibited indirect (I)-waves in M1. Combined RAG and LAG stimulation increased GABA B , but not GABA A , receptor-mediated inhibition in left M1. These findings highlight unique brain interactions between the RAG and left M1.

Background: Hypertension is a common chronic condition affecting nearly a quarter of Canadians. Hypertension surveillance in Canada typically relies on administrative data and/or national surveys. Routinely-captured data from primary care electronic medical records (EMRs) are a complementary source for chronic disease surveillance, with longitudinal patient-level details such as sociodemographics, blood pressure, weight, prescribed medications, and behavioural risk factors. As EMR data are generated from patient care and administrative tasks, assessing data quality is essential before using for secondary purposes. This study evaluated the quality of primary care EMR data from one province in Canada within the context of hypertension surveillance., Methods: We conducted a cross-sectional, descriptive study using primary care EMR data collected by two practice-based research networks in Alberta, Canada. There were 48,377 adults identified with hypertension from 53 clinics as of June 2018. Summary statistics were used to examine the quality of data elements considered relevant for hypertension surveillance., Results: Patient year of birth and sex were complete, but other sociodemographic information (ethnicity, occupation, education) was largely incomplete and highly variable. Height, weight, body mass index and blood pressure were complete for most patients (over 90%), but a small proportion of outlying values indicate data inaccuracies were present. Most patients had a relevant laboratory test present (e.g. blood glucose/glycated hemoglobin, lipid profile), though a very small proportion of values were outside a biologically plausible range. Details of prescribed antihypertensive medication, such as start date, strength, dose, frequency, were mostly complete. Nearly 80% of patients had a smoking status recorded, though only 66% had useful information (i.e. categorized as current, past, or never), and less than half had their alcohol use described; information related to amount, frequency or duration was not available., Conclusions: Blood pressure and prescribed medications in primary care EMR data demonstrated good completeness and plausibility, and contribute valuable information for hypertension epidemiology and surveillance. The use of other clinical, laboratory, and sociodemographic variables should be used carefully due to variable completeness and suspected data errors. Additional strategies to improve these data at the point of entry and after data extraction (e.g. statistical methods) are required.

The relative contributions of reticulospinal versus corticospinal pathways for movement production are thought to be dependent on the type of response involved. For example, unilateral distal movements involving the hand and finger have been thought to be primarily driven by corticospinal output, whereas bilateral responses are considered to have greater reticulospinal drive. The current study investigated whether a difference in the relative contribution of reticulospinal drive to a bimanual versus unimanual finger movement could be assessed using a StartReact protocol. The StartReact effect refers to the early and involuntary initiation of a prepared movement when a startle reflex is elicited. A decreased response latency on loud stimulus trials where a startle reflex is observed in sternocleidomastoid (SCM+ trials) confirms the StartReact effect, which is attributed to increased reticulospinal drive associated with engagement of the startle reflex circuitry. It was predicted that a StartReact effect would be absent for the predominantly corticospinal-mediated unimanual finger movement but present for the bimanual finger movement due to stronger reticulospinal drive. Results supported both predictions as reaction time was statistically equivalent for SCM+ and SCM- trials during unimanual finger movements but significantly shorter for SCM+ trials during bimanual finger movements. These results were taken as strong and novel evidence for increased reticulospinal output for bimanual finger movements. NEW & NOTEWORTHY The relative contributions of reticulospinal and corticospinal pathways to movement initiation are relatively unknown but appear to depend on the involved musculature. Here, we show that unimanual finger movements, which are predominantly initiated via corticospinal pathways, are not triggered at short latency by a startling acoustic stimulus (SAS), while bimanual finger movements are triggered by the SAS. This distinction is attributed to increased reticulospinal drive for bilateral responses.

Recent progress in targeted interrogation of basal ganglia structures and networks with deep brain stimulation in humans has provided insights into the complex functions the subthalamic nucleus (STN). Beyond the traditional role of the STN in modulating motor function, recognition of its role in cognition was initially fueled by side effects seen with STN DBS and later revealed with behavioral and electrophysiological studies. Anatomical, clinical, and electrophysiological data converge on the view that the STN is a pivotal node linking cognitive and motor processes. The goal of this review is to synthesize the literature to date that used DBS to examine the contributions of the STN to motor and non-motor cognitive functions and control. Multiple modalities of research have provided us with an enhanced understanding of the STN and reveal that it is critically involved in motor and non-motor inhibition, decision-making, motivation and emotion. Understanding the role of the STN in cognition can enhance the therapeutic efficacy and selectivity not only for existing applications of DBS, but also in the development of therapeutic strategies to stimulate aberrant circuits to treat non-motor symptoms of Parkinson's disease and other disorders., Competing Interests: Declaration of Competing Interest The authors declared no potential conflicts of interest with respect to the research, authorship, and publication of this article., (Copyright © 2020. Published by Elsevier Inc.)

Objective: To describe the process for linking electronic medical record (EMR) and administrative data in Alberta and examine the advantages and limitations of utilising linked data for hypertension surveillance., Methods: De-identified EMR data from 323 primary care providers contributing to the Canadian Primary Care Sentinel Surveillance Network (CPCSSN) in Alberta were used. Mapping files from each contributing provider were generated from their EMR to facilitate linkage to administrative data within the provincial health data warehouse. Deterministic linkage was conducted using valid personal healthcare number (PHN) with age and/or sex. Characteristics of patients and providers in the linked cohort were compared with population-level sources. Criteria used to define hypertension in both sources were examined., Results: Data were successfully linked for 6307 hypertensive patients (96.2% of eligible patients) from 49 contributing providers. Non-linkages from invalid PHN (n=246) occurred more for deceased patients and those with fewer primary care encounters, with differences due to type of EMR and patient EMR status. The linked cohort had more patients who were female, >60 years and residing in rural areas compared to the provincial healthcare registry. Family physicians were more often female and medically trained in Canada compared to all physicians in Alberta. Most patients (>97%) had ≥1 record in the registry, pharmacy, emergency/ambulatory care and claims databases; 44.3% had ≥1 record in the hospital discharge database., Conclusion: EMR-administrative data linkage has the potential to enhance hypertension surveillance. The current linkage process in Alberta is limited and subject to selection bias. Processes to address these deficiencies are under way., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Although asthma is one of the most common chronic conditions affecting Canadians, its epidemiologic characteristics and burden in primary care contexts are poorly understood. The aim of this study was to develop and validate a case definition to identify adults with asthma who consult family physicians and to estimate the prevalence of asthma in that setting in Canada. This validation study utilized a database of electronic medical records (EMRs) from the Southern Alberta Primary Care Research Network, a node of the Canadian Primary Care Sentinel Surveillance Network (SAPCReN-CPCSSN). The population included patients over age 17y of any gender and health status who had visited an SAPCReN-CPCSSN primary care provider during the period December 1, 2014-December 31, 2016. The validation of the case definition involved comparing a case-finding algorithm to caseness determined by an expert physician review of the records of 1000 patient in the CPCSSN database. The case definition, which included the ICD-9 code 493 and asthma-related text words, had 83.33% sensitivity (95% CI: 63.61-93.88%), 99.28% specificity (95% CI: 98.51-99.67%), a positive predictive value of 74.07% (95% CI: 55.03-87.14%), and a negative predictive value of 99.59% (95% CI: 98.93-99.86%). The prevalence of adult asthma in CPCSSN primary care practices in southern Alberta was 4.20% (95% CI: 4.09-4.31). The strong validation metrics suggest that this case definition is valid for both clinical and research purposes. The validated case definition may be used to improve patient care and improve understanding of the prevalence and burden of asthma in primary care in Canada.

Background: To date, there has been no validated method to identify cases of pelvic floor disorders in primary care electronic medical record (EMR) data. We aimed to develop and validate symptom-based case definitions for urinary incontinence, fecal incontinence and pelvic organ prolapse in women, for use in primary care epidemiologic or clinical research., Methods: Our retrospective study used EMR data from the Southern Alberta Primary Care Research Network (SAPCReN) and the Canadian Primary Care Sentinel Surveillance Network (CPCSSN) in southern Alberta. Trained researchers remotely reviewed a random sample of EMR charts of women aged 18 years or older from 6 rural and urban clinics to validate case definitions for urinary incontinence, fecal incontinence and pelvic organ prolapse. We calculated sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV), and estimated SAPCReN prevalence as appropriate., Results: Charts of 900 women were included. Sensitivity was 81.9% (95% confidence interval [CI] 75.1-87.2) for urinary incontinence, 61.2% (95% CI 46.2-74.5) for fecal incontinence, and 51.8% (95% CI 40.6-62.8) for pelvic organ prolapse. Corresponding specificity values were 71.9% (95% CI 68.4-75.1), 99.2% (95% CI 98.2-99.6) and 98.8% (95% CI 97.7-99.4), PPVs 40.6% (95% CI 35.4-46.0), 81.1% (95% CI 64.3-91.4) and 81.1% (95% CI 67.6-90.1), and NPVs 94.4% (95% CI 92.1-96.1), 97.8% (95% CI 96.5-98.6) and 95.3% (95% CI 93.6-96.6). The SAPCReN-observed prevalence for urinary incontinence was 29.7% (95% CI 29.3-30.0), but the adjusted prevalence was 2.97%., Interpretation: The case definition for urinary incontinence met our standard for validity (sensitivity and specificity > 70%), and the case definitions for fecal incontinence and pelvic organ prolapse had PPVs greater than 80%. The urinary incontinence definition may be used in epidemiologic research, and those for fecal incontinence and pelvic organ prolapse may be used in quality-improvement studies or creation of disease registries. Our symptom-based case definitions could also be adapted for research in other EMR settings., Competing Interests: Competing interests: None declared., (Copyright 2020, Joule Inc. or its licensors.)

Background: Primary care electronic medical record (EMR) data are emerging as a useful source for secondary uses, such as disease surveillance, health outcomes research, and practice improvement. These data capture clinical details about patients' health status, as well as behavioural risk factors, such as smoking. While the importance of documenting smoking status in a healthcare setting is recognized, the quality of smoking data captured in EMRs is variable. This study was designed to test methods aimed at improving the quality of patient smoking information in a primary care EMR database., Methods: EMR data from community primary care settings extracted by two regional practice-based research networks in Alberta, Canada were used. Patients with at least one encounter in the previous 2 years (2016-2018) and having hypertension according to a validated definition were included (n = 48,377). Multiple imputation was tested under two different assumptions for missing data (smoking status is missing at random and missing not-at-random). A third method tested a novel pattern matching algorithm developed to augment smoking information in the primary care EMR database. External validity was examined by comparing the proportions of smoking categories generated in each method with a general population survey., Results: Among those with hypertension, 40.8% (n = 19,743) had either no smoking information recorded or it was not interpretable and considered missing. Those with missing smoking data differed statistically by demographics, clinical features, and type of EMR system used in the clinic. Both multiple imputation methods produced fully complete smoking status information, with the proportion of current smokers estimated at 25.3% (data missing at random) and 12.5% (data missing not-at-random). The pattern-matching algorithm classified 18.2% of patients as current smokers, similar to the population-based survey (18.9%), but still resulted in missing smoking information for 23.6% of patients. The algorithm was estimated to be 93.8% accurate overall, but varied by smoking status category., Conclusion: Multiple imputation and algorithmic pattern-matching can be used to improve EMR data post-extraction but the recommended method depends on the purpose of secondary use (e.g. practice improvement or epidemiological analyses).

Objective: To validate a case definition for speech and language disorders in community-dwelling older adults and to determine the prevalence of speech and language disorders in a primary care population., Design: This is a combined case definition validation and cross-sectional prevalence study. Chart review was considered the reference standard and was used to estimate prevalence. This study used de-identified electronic medical record data from participating SAPCReN-CPCSSN (Southern Alberta Primary Care Research Network-Canadian Primary Care Sentinel Surveillance Network) primary care clinics., Setting: Southern Alberta., Participants: Men and women aged 55 years and older who had visited a SAPCReN-CPCSSN physician or nurse practitioner at least once in the 2 years before the beginning of the study., Main Outcome Measures: Validation analysis included estimation of sensitivity, specificity, positive predictive value, and negative predictive value. Prevalence was the other main outcome measure., Results: The prevalence of speech and language disorders within the sample of 1384 patients was 1.2%. The case definition had a favourable specificity (99.9%, 95% CI 99.6% to 100.0%), positive predictive value (75.6%, 95% CI 25.4% to 96.6%), and negative predictive value (99.0%, 95% CI 98.8% to 99.2%). Sensitivity was not sufficient for validity (18.8%, 95% CI 4.05% to 45.6%)., Conclusion: The case definition did not meet an acceptable standard for validity and thus cannot be used for future epidemiologic research. However, owing to the case definition's high positive predictive value, it might be useful for clinical purposes and for cohort studies. Finally, while the case definition did not prove valid, this study has provided a conservative estimate of prevalence (1.2%) given the case definition's high specificity., (Copyright© the College of Family Physicians of Canada.)

Importance: Although patients with chronic kidney disease (CKD) are routinely managed in primary care settings, no nationally representative study has assessed the quality of care received by these patients in Canada., Objective: To evaluate the current state of CKD management in Canadian primary care practices to identify care gaps to guide development and implementation of national quality improvement initiatives., Design, Setting, and Participants: This cross-sectional study leveraged Canadian Primary Care Sentinel Surveillance Network data from January 1, 2010, to December 31, 2015, to develop a cohort of 46 162 patients with CKD managed in primary care practices. Data analysis was performed from August 8, 2018, to July 31, 2019., Main Outcomes and Measures: The study examined the proportion of patients with CKD who met a set of 12 quality indicators in 6 domains: (1) detection and recognition of CKD, (2) testing and monitoring of kidney function, (3) use of recommended medications, (4) monitoring after initiation of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs), (5) management of blood pressure, and (6) monitoring for glycemic control in those with diabetes and CKD. The study also analyzed associations of divergence from these quality indicators., Results: The cohort comprised 46 162 patients (mean [SD] age, 69.2 [14.0] years; 25 855 [56.0%] female) with stage 3 to 5 CKD. Only 4 of 12 quality indicators were met by 75% or more of the study cohort. These indicators were receipt of an outpatient serum creatinine test within 18 months after confirmation of CKD, receipt of blood pressure measurement at any time during follow-up, achieving a target blood pressure of 140/90 mm Hg or lower, and receiving a hemoglobin A1c test for monitoring diabetes during follow-up. Indicators in the domains of detection and recognition of CKD, testing and monitoring of kidney function (specifically, urine albumin to creatinine ratio testing), use of recommended medications, and appropriate monitoring after initiation of treatment with ACEIs or ARBs were not met. Only 6529 patients (18.4%) with CKD received a urine albumin test within 6 months of CKD diagnosis, and 3954 (39.4%) had a second measurement within 6 months of an abnormal baseline urine albumin level. Older age (≥85 years) and CKD stage 5 were significantly associated with not satisfying the criteria for the quality indicators across all domains. Across age categories, younger patients (aged 18-49 years) and older patients (≥75 years) were less likely to be tested for albuminuria (314 of 1689 patients aged 18-49 years [18.5%], 1983 of 11 919 patients aged 75-84 years [61.6%], and 614 of 5237 patients aged ≥85 years [11.7%] received the urine albumin to creatinine ratio test within 6 months of initial estimated glomerular filtration rate <60 mL/min per 1.73 m2; P < .001). Patients aged 18 to 49 years were less commonly prescribed recommended medications (222 of 2881 [7.7%]), whereas patients aged 75 to 84 years were prescribed ACEIs or ARBs most frequently (2328 of 5262 [44.2%]; P < .001)., Conclusions and Relevance: The findings suggest that management of CKD across primary care practices in Canada varies according to quality indicator. This study revealed potential priority areas for quality improvement initiatives in Canadian primary care practices.

Objective: To determine the stability of warfarin anticoagulation using a nationally representative sample of Canadian primary care patients and providers., Design: Prospective cohort study., Setting: Primary care practices associated with the Canadian Primary Care Sentinel Surveillance Network., Participants: Adult warfarin users with 7 or more evaluable international normalized ratio (INR) readings., Main Outcomes Measures: International normalized ratio time in therapeutic range (TTR) determined using the Rosendaal method; TTR above 75% was considered good INR control and TTR below 60% was considered poor INR control. The primary outcome was the proportion of all warfarin users (using an INR target range of 2.0 to 3.5) with good INR control during their first year taking warfarin who have poor INR control the following year. Secondary outcomes included the TTR using an INR target of 2.0 to 3.0 when restricted to patients with known atrial fibrillation (AF) or venous thromboembolism (VTE); and the proportion of INR values below the target of 2.0 and above the targets of 3.0 and 3.5 in the year before the availability of other oral anticoagulants., Results: Among 18 303 adult warfarin users (mean age of 71.0 years, 46.6% female), the median TTR (INR target range of 2.0 to 3.5) was 77.4% (interquartile range of 64.6% to 86.4%). The TTR was above 75% in 56.0% of patients and below 60% in 19.3% of patients. Of those exhibiting good INR control in year 1 of anticoagulation therapy, only 10.2% had poor control the following year. When restricted to patients with known AF or VTE (89.7% with AF and 13.5% with VTE), and assuming an INR target range of 2.0 to 3.0, the TTR was 67.8% (interquartile range of 54.8% to 77.9%). Of these patients, 27.9% had INR values below 2.0, and 19.4% and 8.6% had values above 3.0 and 3.5, respectively., Conclusion: Primary care warfarin management produces a TTR comparable to that in randomized trials, with out-of-range INR values 3 times more likely to predispose to thrombosis (INR of < 2.0) than to hemorrhage (INR of > 3.5). A history of good INR control does predict future INR stability and meaningfully informs decisions to switch established warfarin users onto newer agents., (Copyright© the College of Family Physicians of Canada.)

Background: A risk-based model of care for managing patients with chronic kidney disease (CKD) using the Kidney Failure Risk Equation (KFRE) has been successfully integrated into nephrology care pathways in several jurisdictions. However, as most patients with CKD can be managed in primary care, the next pertinent steps would be to integrate the KFRE into primary care pathways., Objective: Using a risk-based approach for guiding CKD care in the primary care setting, the objective of the study is to develop, implement, and evaluate tools that can be used by patients and providers., Design: This study is a multicenter cluster randomized control trial., Setting: Thirty-two primary care clinics belonging to the Canadian Primary Care Sentinel Surveillance Network (CPCSSN) across Manitoba and Alberta., Patients: All patients at least 18 years old or older with CKD categories G3-G5 attending the participating clinics; we estimate each clinic will have an average of 185 patients with CKD., Methods: Thirty-two primary care clinics will be randomized to receive either an active knowledge translation intervention or no intervention. The intervention involves the addition of the KFRE and decision aids to clinics' Data Presentation Tool (DPT), as well as patient-facing visual aids, a medical detailing visit, and sentinel feedback reports. Control clinics will only be exposed to current guidelines for CKD management, without active dissemination., Measurements: Data from the CPCSSN repository will be used to assess whether a risk-based care approach affected management of CKD. Primary outcomes are as follows: the proportion of patients with measured urine albumin-to-creatinine ratio, and the proportion of patients being appropriately treated with angiotensin-converting enzyme inhibitor or angiotensin receptor blockers. Secondary outcomes are as follows: the optimal management of diabetes (hemoglobin A1C <8.5%, and the use of sodium-glucose cotransporter-2 inhibitors in CKD G3 patients), hypertension (office blood pressure <130/80 for patients with diabetes, 140/90 for those without), and cardiovascular risk (statin prescription); prescriptions of nonsteroidal anti-inflammatory drugs; and decline in estimated glomerular filtration rate (eGFR). In addition, in a substudy, we will measure CKD-specific health literacy and trust in physician care via surveys administered in the clinic post-visit. At the provider level, we will measure satisfaction with the risk prediction tools. Lastly, at the health system level, outcomes include cost of CKD care, and appropriate referrals for patients at high risk of kidney failure based on provincial guidelines. Primary and secondary outcomes will be measured at the patient level and enumerated at the clinic level 1 year after the intervention implementation, except for decline in eGFR, which will be measured 2 years postintervention., Limitations: Limitations include scalability of the proposal in other health care systems., Conclusions: If successful, this intervention has the potential to improve the management of patients with CKD within Canadian primary care settings, leading to health and economic benefits, and influencing practice guidelines., Trial Registration: ClinicalTrials.gov identifier: NCT03365063., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Identifying cases of disease in primary care electronic medical records (EMRs) is important for surveillance, research, quality improvement and clinical care. We aimed to develop and validate a case definition for type 1 diabetes mellitus using EMRs., Methods: For this exploratory study, we used EMR data from the Southern Alberta Primary Care Network within the Canadian Primary Care Sentinel Surveillance Network (CPCSSN), for the period 2008 to 2016. For patients identified as having diabetes mellitus according to the existing CPCSSN case definition, we asked family physicians to confirm the diabetes subtype, to create the reference standard. We used 3 decision-tree classification algorithms and least absolute shrinkage and selection operator logistic regression to identify variables that correctly distinguished between type 1 and type 2 diabetes cases., Results: We identified a total of 1309 people with type 1 or type 2 diabetes, 110 of whom were confirmed by their physicians as having type 1 diabetes. Two machine learning algorithms were useful in identifying these cases in the EMRs. The first algorithm used "type 1" text words or age less than 22 years at time of initial diabetes diagnosis; this algorithm had sensitivity 42.7% (95% confidence interval [CI] 33.5%-52.5%), specificity 99.3% (95% CI 98.6%-99.7%), positive predictive value 85.5% (95% CI 72.8%-93.1%) and negative predictive value 94.9% (95% CI 93.5%-96.1%). The second algorithm used a combination of free-text terms, insulin prescriptions and age; it had sensitivity 87.3% (95% CI 79.2%-92.6%), specificity 85.4% (95% CI 83.2%-87.3%), positive predictive value 35.6% (95% CI 29.9%-41.6%) and negative predictive value 98.6% (95% CI 97.7%-99.2%)., Interpretation: We used machine learning to develop and validate 2 case definitions that achieve different goals in distinguishing between type 1 and type 2 diabetes in CPCSSN data. Further validation and testing with a larger and more diverse sample are recommended., Competing Interests: Competing interests: None declared., (Copyright 2019, Joule Inc. or its licensors.)

Corticospinal output pathways have typically been considered to be the primary driver for voluntary movements of the hand/forearm; however, more recently, reticulospinal drive has also been implicated in the production of these movements. Although both pathways may play a role, the reticulospinal tract is thought to have stronger connections to flexor muscles than to extensors. Similarly, movements involuntarily triggered via a startling acoustic stimulus (SAS) are believed to receive greater reticular input than voluntary movements. To investigate a differential role of reticulospinal drive depending on movement type or acoustic stimulus, corticospinal drive was transiently interrupted using high-intensity transcranial magnetic stimulation (TMS) applied during the reaction time (RT) interval. This TMS-induced suppression of cortical drive leads to RT delays that can be used to assess cortical contributions to movement. Participants completed targeted flexion and extension movements of the wrist in a simple RT paradigm in response to a control auditory go signal or SAS. Occasionally, suprathreshold TMS was applied over the motor cortical representation for the prime mover. Results revealed that TMS significantly increased RT in all conditions. There was a significantly longer TMS-induced RT delay seen in extension movements than in flexion movements and a greater RT delay in movements initiated in response to control stimuli compared with SAS. These results suggest that the contribution of reticulospinal drive is larger for wrist flexion than for extension. Similarly, movements triggered involuntarily by an SAS appear to involve greater reticulospinal drive, and relatively less corticospinal drive, than those that are voluntarily initiated. NEW & NOTEWORTHY Through the use of the transcranial magnetic stimulation-induced silent period, we provide novel evidence for a greater contribution of reticulospinal drive, and a relative decrease in corticospinal drive, to movements involuntarily triggered by a startle compared with voluntary movements. These results also provide support for the notion that both cortical and reticular structures are involved in the neural pathway underlying startle-triggered movements. Furthermore, our results indicate greater reticulospinal contribution to wrist flexion than extension movements.

Background: The trajectory of dementia through time is characterized by common transitions which are difficult for persons with dementia (PWDs) and their families and friends. Our study sought to identify determinants for the quality of transition outcomes., Method: A 24-month, prospective, longitudinal design identified specific transitions as they occurred in 108 person-with-dementia/caregiver dyads, and assessed the perceived transition quality from the perspective of the caregiver and what we denote as the 'summative' transition quality outcome variable (as explained in the Data Processing section under Methods)., Results: Among caregivers and during the authors' deliberations of the summative transition quality outcomes, good transition quality was associated with the PWD's baseline Disability Assessment for Dementia (OR 1.04, 95% CI 1.02-1.06 per increase in percent score based on summative assessments), and with the PWD's higher baseline quality of life scores (OR 1.11, 95% CI 1.05-1.18 per increase in unit of score in QOL-AD based on summative assessments). Caregiver-perceived better outcome quality was associated with lower caregiver burden, (OR 0.97, 95% CI 0.95-0.99 per unit CBI score increase)., Conclusion: Identifying determinants of successful transitions is feasible and may be translated into practical guidance for use in clinical encounters. Those with worse prior quality of life or worse performance in activities of daily living appear to require specific support during transitions, as do those whose caregivers report higher levels of burden., Competing Interests: CONFLICT OF INTEREST DISCLOSURES The author declares that no conflicts of interest exist.

Introduction: Surveillance systems enable optimal care delivery and appropriate resource allocation, yet Canada lacks a dedicated surveillance system for chronic kidney disease (CKD). Using data from the Canadian Primary Care Sentinel Surveillance Network (CPCSSN), a national chronic disease surveillance system, this study describes the geographic, sociodemographic, and clinical variations in CKD prevalence in the Canadian primary care context., Methods: This cross-sectional study included 559,745 adults in primary care in 5 provinces across Canada from 2010 through 2015. Data were analyzed by geographic (urban or rural residence), sociodemographic (age, sex, deprivation index), and clinical (medications prescribed, comorbid conditions) factors, using data from CPCSSN and the Canadian Deprivation Index. CKD stage 3 or higher was defined as 2 estimated glomerular filtration rate (eGFR) values of <60 ml/min per 1.73 m 2 more than 90 days apart as of January 1, 2015., Results: Prevalence of CKD was 71.9 per 1000 individuals and varied by geography, with the highest prevalence in rural settings compared with urban settings (86.2 vs. 68.4 per 1000). CKD was highly prevalent among individuals with 3 or more other chronic diseases (281.7 per 1000). Period prevalence of CKD indicated a slight decline over the study duration, from 53.4 per 1000 in 2010 to 46.5 per 1000 in 2014., Conclusion: This is the first study to estimate the prevalence of CKD in primary care in Canada at a national level. Results may facilitate further research, prioritization of care, and quality improvement activities to identify gaps and improvement in CKD care.

Response preparation in simple reaction time (RT) tasks has been modeled as an increase in neural activation to a sub-threshold level, which is maintained until the go-signal. However, the amount of time required for response preparation following a warning signal (WS) is currently unclear, as experiments typically employ long foreperiods to ensure maximal preparation. The purpose of the present experiments was to examine the time course of motor preparation in a simple RT task when given a limited amount of time to engage in preparatory processing. In Experiment 1, participants completed wrist extension movements in a simple RT paradigm with a short (500 ms) fixed foreperiod, and a long (8.5-10.5 s) inter-trial interval. To probe response preparation, a startling acoustic stimulus (SAS), which involuntarily triggers the release of sufficiently prepared responses, was randomly presented during the foreperiod at one of six equally spaced time points between 0 and 500 ms prior to the go-signal. Results showed that the long inter-trial interval was not always effective at preventing participants from engaging in preparatory processing between trials; thus, in Experiment 2 participants performed wrist flexion or extension movements in an instructed delay paradigm, where the required movement was cued by the WS. Results showed that the proportion of startle trials where the intended response was elicited by the SAS at short latency significantly increased until 100 ms prior to the go-signal, indicating response preparation can take up to 300-400 ms following the WS in a simple RT task with a short fixed foreperiod., (Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.)

Objective: To use data from the Canadian Primary Care Sentinel Surveillance Network (CPCSSN) to evaluate the prevalence of antidepressant and antipsychotic prescriptions among patients with no previous depression or psychosis diagnoses, and to identify the factors associated with the use of these drugs in this population., Design: Retrospective cohort study using data derived from CPCSSN., Setting: Primary care practices associated with CPCSSN., Participants: Patients who were born before 1949; who were associated with a CPCSSN primary care practitioner between October 1, 2007, and September 30, 2013; and whose electronic medical records contained data from at least 6 months before and 12 months after the date of dementia diagnosis., Main Outcome Measures: Prescription for an antidepressant or antipsychotic medication in the absence of a depression or psychosis diagnosis. Multivariable models were fitted to determine estimated odds ratios (ORs) and were adjusted for age and sex., Results: Of the 3252 patients without a depression diagnosis, 8.5% received a new prescription for an antidepressant in the 12 months following their diagnosis of dementia. Prescribing was reduced in association with older age (OR of 0.86 per 5-year age increase, P =.001) and male sex (OR=0.77, P =.056), and prescribing increased in association with prescription of cholinesterase inhibitor medications (OR=1.57, P =.003). Of the 4262 patients without a diagnosis of psychosis, 6.1% received a new prescription for an antipsychotic in the 12 months following their diagnosis of dementia. Higher rates of antipsychotic prescriptions were reported in men (OR=1.31, P =.046), those receiving a prescription for steroids (OR=1.90, P =.037), and those diagnosed with Parkinson disease (OR 1.58, P =.051)., Conclusion: A substantial number of patients with dementia are being prescribed antidepressant or antipsychotic medications by their primary care practitioners without evidence of depression or psychosis in their electronic medical records., (Copyright© the College of Family Physicians of Canada.)

Objective: To explore clinical indicators among patients with diabetes in southern Alberta and assess changes over time, and to compare patients with diabetes attending a reference clinic (RC), which had adapted its service model to address the specific needs of the patient population, with patients with diabetes attending comparison clinics (CCs) in the same region., Design: Analysis of longitudinal data from the Canadian Primary Care Sentinel Surveillance Network (CPCSSN)., Setting: Rural southern Alberta., Participants: A community-based family medicine clinic and the 6 other CPCSSN clinics in the same region at the time of the study., Main Outcome Measures: A range of data elements from patients with diabetes within the RC, as well as from patients with diabetes from the CCs, were analyzed by CPCSSN to compare rates of comorbidity and mean body mass index, hemoglobin A 1c levels, and blood pressure, as well as service use and measurement frequency. Rate of change per year was modeled longitudinally for each of the outcomes., Results: The RC had higher proportions of patients with comorbid conditions and a consistently higher mean body mass index. Mean HbA 1c levels varied minimally between the RC and CCs, with both sets worsening slightly. However, the rate of worsening among patients with diabetes in the RC was found to be significantly greater ( P < .05) than for those in the CCs. Blood pressure also varied minimally between the RC and the CCs, with both sets improving; however, the RC had a significantly greater ( P < .001) rate of improvement than the CCs did. Finally, a greater proportion of patients in the RC had complete data for these 3 outcome measures, and RC patients made a greater number of clinic visits compared with the CC patients ( P < .001)., Conclusion: This study describes a team-based comanagement organizational model and might provide useful commentary about organizational effectiveness in primary care. Although improvement in health outcomes cannot be directly attributed to any specific change in clinic organization, some statistically and likely clinically significant benefit was found associated with the service model of the RC in a relatively medically and socially challenged patient population and in a conservative evaluative design., (Copyright© the College of Family Physicians of Canada.)

A new phase V of hydrogen was recently claimed in experiments above 325 GPa and 300 K. Because of the extremely small sample size at such record pressures the measurements were limited to Raman spectroscopy. The experimental data on increase of pressure show decreasing Raman activity and darkening of the sample, which suggests band gap closure and impending molecular dissociation, but no definite conclusions could be reached. Furthermore, the available data are insufficient to determine the structure of phase V, which remains unknown. Introducing saddle-point ab initio random structure searching, we find several new structural candidates of hydrogen which could describe the observed properties of phase V. We investigate hydrogen metallization in the proposed candidate structures, and demonstrate that smaller band gaps are associated with longer bond lengths. We conclude that phase V is a stepping stone towards metallization.

Background: The Canadian Primary Care Sentinel Surveillance Network (CPCSSN) previously carried out a validation study of case definitions for 8 chronic diseases (diabetes mellitus, hypertension, osteoarthritis, depression, dementia, chronic obstructive pulmonary disease, parkinsonism and epilepsy) using direct review of "raw" electronic medical record data. Although effective, this method is time-consuming and can present methodological and organizational challenges. We aimed to determine whether the processed and standardized data contained with the CPCSSN database might function as a reference standard for case definition validation., Methods: Using a traditional validation study design, we compared the case identification results of the chart reviews for the 8 chronic diseases with the results of a manual review of the CPCSSN processed data for the same conditions in the same patient sample. Patients were randomly sampled from the June 30, 2012 CPCSSN database, with oversampling of patients with rare conditions., Results: We analyzed data for 1906 patients. Manual review of the CPCSSN records for case ascertainment yielded sensitivity ranging from 77.5% (95% confidence interval [CI] 73.3%-81.6%) for depression to 97.2% (95% CI 95.4%-99.0%) for diabetes. Specificity was high for all definitions (range 93.1% [95% CI 91.4%-94.7%] to 99.4% [95% CI 99.0%-99.8%]). Positive predictive values and negative predictive values also showed high accuracy of the manual CPCSSN record review relative to review of the raw chart data., Interpretation: The use of CPCSSN records as the reference standard to validate case definitions substantially reduces the burden on sentinel physicians and clinic managers as well as on researchers while offering a reference standard that is a reasonable substitution for chart review., Competing Interests: Competing interests: None declared., (Copyright 2017, Joule Inc. or its licensors.)

Introduction: Effective chronic disease care is dependent on well-organised quality improvement (QI) strategies that monitor processes of care and outcomes for optimal care delivery. Although healthcare is provincially/territorially structured in Canada, there are national networks such as the Canadian Primary Care Sentinel Surveillance Network (CPCSSN) as important facilitators for national QI-based studies to improve chronic disease care. The goal of our study is to improve the understanding of how patients with chronic kidney disease (CKD) are managed in primary care and the variation across practices and provinces and territories to drive improvements in care delivery., Methods and Analysis: The CPCSSN database contains anonymised health information from the electronic medical records for patients of participating primary care practices (PCPs) across Canada (n=1200). The dataset includes information on patient sociodemographics, medications, laboratory results and comorbidities. Leveraging validated algorithms, case definitions and guidelines will help define CKD and the related processes of care, and these enable us to: (1) determine prevalent CKD burden; (2) ascertain the current practice pattern on risk identification and management of CKD and (3) study variation in care indicators (eg, achievement of blood pressure and proteinuria targets) and referral pattern for specialist kidney care. The process of care outcomes will be stratified across patients' demographics as well as provider and regional (provincial/territorial) characteristics. The prevalence of CKD stages 3-5 will be presented as age-sex standardised prevalence estimates stratified by province and as weighted averages for population rates with 95% CIs using census data. For each PCP, age-sex standardised prevalence will be calculated and compared with expected standardised prevalence estimates. The process-based outcomes will be defined using established methods., Ethics and Dissemination: The CPCSSN is committed to high ethical standards when dealing with individual data collected, and this work is reviewed and approved by the Network Scientific Committee. The results will be published in peer-reviewed journals and presented at relevant national and international scientific meetings., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

In a typical go/no-go task a single imperative stimulus is presented each trial, either a go or no-go stimulus. Participants are instructed to initiate a known response upon appearance of the go-signal and withhold the response if the no-go signal is presented. It is unclear whether the go-response is prepared in advance of the imperative stimulus in a go/no-go task. Moreover, it is unclear if inhibitory control processes suppress preparatory go-activation. The purpose of the present experiment was 1) to determine whether the go-response is prepared in advance of stimulus identification with the use of a startling acoustic stimulus (SAS), and 2) investigate the inhibitory role of the right inferior frontal gyrus (rIFG) and pre-supplementary motor area (preSMA) during the performance of a go/no-go task with the use of continuous theta burst stimulation (cTBS). The experiment consisted of three phases; a pre-cTBS phase in which participants completed a go/no-go and simple-RT task, followed by offline cTBS to temporarily deactivate either rIFG or preSMA (with a sham control), then a post-cTBS phase which was identical to the pre-cTBS phase. Results revealed that stimulation to both cortical sites impaired participants' ability to withhold movements during no-go trials. Notably, rIFG or preSMA stimulation did not affect the latency of voluntary go-responses and did not enable the SAS to involuntarily trigger responses. These findings suggest that preparation and initiation of the go-response occurs after the imperative stimulus, with the rIFG and preSMA involved in inhibiting the go-response once the stimulus is identified as a no-go signal., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Increased reaction times (RT) during choice-RT tasks stem from a requirement for additional processing as well as reduced motor-specific preparatory activation. Transcranial direct current stimulation (tDCS) can modulate primary motor cortex excitability, increasing (anodal stimulation) or decreasing (cathodal stimulation) excitability in underlying cortical tissue. The present study investigated whether lateralized differences in choice-RT would result from the concurrent modulation of left and right motor cortices using bi-hemispheric tDCS. Participants completed a choice-RT task requiring either a left or right wrist extension. In forced-choice trials an illuminated target indicated the required response, whereas in free-choice trials participants freely selected either response upon illumination of a central fixation. Following a pre-test trial block, offline bi-hemispheric tDCS (1 mA) was applied over the left and right motor cortices for 10 minutes, which was followed by a post-tDCS block of RT trials. Twelve participants completed three experimental sessions, two with real tDCS (anode right, anode left), as well as a sham tDCS session. Post-tDCS results showed faster RTs for both right and left responses irrespective of tDCS polarity during forced-choice trials, while sham tDCS had no effect. In contrast, no stimulation-related RT or response selection differences were observed in free-choice trials. The present study shows evidence of an effector-independent speeding of response initiation in a forced-choice RT task following bi-hemispheric tDCS and yields novel information regarding the functional effect of bi-hemispheric tDCS.

During a simple reaction time (RT) task, movements can be initiated early and involuntarily through presentation of a loud startling acoustic stimulus (SAS), a phenomenon termed the StartReact effect. In order to infer that activity in startle-related structures led to the early response triggering, it is important to observe a concurrent startle reflex in sternocleidomastoid. It is generally accepted that to consistently elicit a startle reflex, the SAS must be both intense and unpredictable. However, it remains unclear what effect explicit foreknowledge of an impending SAS has on the effectiveness of a SAS to elicit a startle reflex when preparing a motor response. To test this, participants completed two separate blocks of a simple RT task (counterbalanced order), where the control auditory go-signal was replaced with a SAS on 20 % of trials. In an unwarned block, knowledge of the trial type (SAS vs. control) was not provided in advance, while in a warned block, the trial type was forewarned. Results revealed that while foreknowledge of an impending SAS reduced the magnitude of the startle reflex, it did not affect the proportion of startle reflexes elicited or the magnitude of the StartReact effect. An increase in control trial RT was observed during the unwarned block, but only when it was performed first. These results indicate that preparation of a motor response leads to sufficiently increased activation in startle-related neural structures such that even with explicit knowledge of an upcoming SAS, participants are unable to proactively gate the upcoming sensory input.