Describing primary care patterns before and during the COVID-19 pandemic across Canada: a quasi-experimental pre-post design cohort study using national practice-based research network data.

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.

Using machine learning to standardize medication records in a pan-Canadian electronic medical record database: a data-driven algorithm study focused on antibiotics prescribed in primary care.

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.

Effects of the COVID-19 Pandemic on Primary Health Care for Chronic Conditions in Canada: Protocol for a Retrospective Pre-Post Study Using National Practice-Based Research Network Data.

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.

Documenting cannabis use in primary care: a descriptive cross-sectional study using electronic medical record data in Alberta, Canada.

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.

Older persons living with dementia and their use of acute care services over 2 years in Alberta.

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.

Long-Term Recording of Subthalamic Aperiodic Activities and Beta Bursts in Parkinson's Disease.

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.

Leaving the Walkman and ICD-9 Behind: Modernizing the Disease Classification System Used by Canadian Physicians.

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.

Low Use of Guideline-recommended Cardiorenal Protective Antihyperglycemic Agents in Primary Care: A Cross-sectional Study of Adults With Type 2 Diabetes.

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.

A cross-sectional study evaluating cardiovascular risk and statin prescribing in the Canadian Primary Care Sentinel Surveillance Network database.

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.

Measurement of obesity in primary care practice: chronic conditions matter.

Primary care providers can deliver tailored advice and support to patients who are overweight or have obesity. The 2020 Canadian Adult Obesity Practice Guideline for primary care providers recommended that patients' waist circumference (WC) be measured if their height and weight place them in the overweight or Class I obesity category. The guideline does not recommend how often providers should measure WC nor describe how often this is measured in current practice. We reviewed electronic medical records (EMRs) of 707,819 Canadian adult patients aged 40 and older. Among them, 48.7% had 1 or more body mass index (BMI) recorded; 11.5% had at least 1 waist measurement recorded. Of those with a BMI classified as overweight or having Class I obesity, 23.7% had at least 1 WC measurement recorded, which differed by chronic disease. WC was documented in more patients who had diabetes mellitus (36.8%) than hypertension (26.1%), or osteoarthritis (24.3%). This difference may be reflective of more specific advice in diabetes guidelines. To our knowledge, this is the first study to describe documentation of WC measurement for patients who are overweight or have Class I obesity in Canadian primary care EMRs across obesity-related conditions.

Content of physical activity documentation in Canadian family physicians' electronic medical records.

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.

Fostering trust and sharing responsibility to increase access to dementia care for immigrant older adults.

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.

Epidemiology of dementia onset captured in Canadian primary care 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.

Dementias are conditions that may cause mental symptoms such as forgetfulness, confusion, or disorientation. As the population gradually ages, the number of dementia cases is also increasing. Among people aged 65 and over, the rate of dementia onset increases as people get older. However, among people aged 85 and over, the rate of developing dementia is slower, which might reflect that people who reach the age of 85 are usually healthier in general. Since family practitioners are normally the first contact when patients and their family notice symptoms, primary care plays an important role in diagnosing and managing dementia. Early recognizing dementia for early support is very helpful. According to our study, health-related information recorded in primary care in Canada is sufficient to be used for research. It is a valuable opportunity to study the characteristics of people with dementia, including their health conditions, risks and protective factors that may contribute to the development of the disease.

Risk factors for incidence of dementia in primary care practice: a retrospective cohort study in older adults.

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.

Development of a case definition for hearing loss in community-based older adults: a cross-sectional validation study.

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.

Prevalence of polypharmacy and associated adverse health outcomes in adult patients with chronic kidney disease: protocol for a systematic review and meta-analysis.

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 I2 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 ].

Out-of-Plane Dielectric Susceptibility of Graphene in Twistronic and Bernal Bilayers.

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 αexp = 10.8 Å3 and effective out-of-plane dielectric susceptibility ϵz = 2.5, including their on-layer electron density distribution at zero magnetic field and the interlayer Landau level pinning at quantizing magnetic fields.

Fronto-subthalamic phase synchronization and cross-frequency coupling during conflict processing.

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.