Rituximab or cyclosporine a for the treatment of membranous nephropathy: Economic evaluation of the MENTOR trial.

BACKGROUND AND HYPOTHESIS: The MENTOR trial (MEmbranous Nephropathy Trial Of Rituximab) showed that rituximab was noninferior to cyclosporine in inducing complete or partial remission of proteinuria and was superior in maintaining proteinuria remission. However, the cost of rituximab may prohibit first-line use for some patients and health care payers. METHODS: A Markov model was used to determine the incremental cost-effectiveness ratio (ICER) of rituximab compared with cyclosporine for the treatment membranous nephropathy from the perspective of a health care payer with a life-time time horizon. The model was informed by data from the MENTOR trial where possible; additional parameters including cost and utility inputs were obtained from the literature. Sensitivity analyses were performed to evaluate the impact of reduced cost biosimilar rituximab. RESULTS: Rituximab for the treatment of membranous nephropathy was cost-effective (assuming a willingness-to-pay threshold of ${\$}$50 000 per quality adjusted life year (QALY) gained; ${\$}$US 2021) compared with cyclosporine, with an ICER of ${\$}$8 373/QALY over a lifetime time horizon. The incremental cost of rituximab therapy was ${\$}$28 007 with an additional 3.34 QALYs compared with cyclosporine. Lower cost of rituximab biosimilars resulted in a more favourable ICER, and in some cases resulted in rituximab being dominant (lower cost and great benefit) compared to cyclosporine. CONCLUSIONS: Despite the greater cost of rituximab, it may be a cost-effective option for the treatment of membranous nephropathy when compared with cyclosporine. The cost-effectiveness of rituximab is further improved with the use of less expensive biosimilars.

Global trends in chronic kidney disease-related mortality: a systematic review protocol.

INTRODUCTION: In recent decades, all-cause mortality has increased among individuals with chronic kidney disease (CKD), influenced by factors such as aetiology, standards of care and access to kidney replacement therapies (dialysis and transplantation). The recent COVID-19 pandemic also affected mortality over the past few years. Here, we outline the protocol for a systematic review to investigate global temporal trends in all-cause mortality among patients with CKD at any stage from 1990 to current. We also aim to assess temporal trends in the mortality rate associated with the COVID-19 pandemic. METHODS AND ANALYSIS: We will conduct a systematic review of studies reporting mortality for patients with CKD following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We will search electronic databases, national and multiregional kidney registries and grey literature to identify observational studies that reported on mortality associated with any cause for patients with CKD of all ages with any stage of the disease. We will collect data between April and August 2023 to include all studies published from 1990 to August 2023. There will be no language restriction, and clinical trials will be excluded. Primary outcome will be temporal trends in CKD-related mortality. Secondary outcomes include assessing mortality differences before and during the COVID-19 pandemic, exploring causes of death and examining trends across CKD stages, country classifications, income levels and demographics. ETHICS AND DISSEMINATION: A systematic review will analyse existing data from previously published studies and have no direct involvement with patient data. Thus, ethical approval is not required. Our findings will be published in an open-access peer-reviewed journal and presented at scientific conferences. PROSPERO REGISTRATION NUMBER: CRD42023416084.

Geographical Variation In Medication and Health Resource Use In Multiple Sclerosis.

BACKGROUND: Understanding disease-modifying therapy (DMT) use and healthcare resource utilization by different geographical areas among people living with multiple sclerosis (pwMS) may identify care gaps that can be used to inform policies and practice to ensure equitable care. METHODS: Administrative data was used to identify pwMS on April 1, 2017 (index date) in Alberta. DMT use and healthcare resource utilization were compared between those who resided in various geographical areas over a 2-year post-index period; simple logistic regression was applied. RESULTS: Among the cohort (n = 12,338), a higher proportion of pwMS who resided in urban areas (versus rural) received ≥ 1 DMT dispensation (32.3% versus 27.4%), had a neurologist (67.7% versus 63.9%), non-neurologist specialist (88.3% versus 82.9%), ambulatory care visit (87.4% versus 85.3%), and MS tertiary clinic visit (59.2% versus 51.7%), and a lower proportion had an emergency department (ED) visit (46.3% versus 62.4%), and hospitalization (20.4% versus 23.0%). Across the provincial health zones, there were variations in DMT selection, and a higher proportion of pwMS who resided in the Calgary health zone, where care is managed by MS tertiary clinic neurologists, had an outpatient visit to a neurologist or MS tertiary clinic versus those who resided in other zones where delivery of MS-related care is more varied. CONCLUSIONS: Urban/rural inequalities in DMT use and healthcare resource utilization appear to exist among pwMS in Alberta. Findings suggest the exploration of barriers with consequent strategies to increase access to DMTs and provide timely outpatient MS care management, particularly for those pwMS residing in rural areas.

Benzodiazepine use in medical cannabis authorization adult patients from 2013 to 2021: Alberta, Canada.

BACKGROUND: Benzodiazepines are a class of medications that are being frequently prescribed in Canada but carry significant risk of harm. There has been increasing clinical interest on the potential "sparing effects" of medical cannabis as one strategy to reduce benzodiazepine use. The objective of this study as to examine the association of medical cannabis authorization with benzodiazepine usage between 2013 and 2021 in Alberta, Canada. METHODS: A propensity score matched cohort study with patients on regular benzodiazepine treatment authorized to use medical cannabis compared to controls who do not have authorization for medical cannabis. A total of 9690 medically authorized cannabis patients were matched to controls. To assess the effect of medical cannabis use on daily average diazepam equivalence (DDE), interrupted time series (ITS) analysis was used to assess the change in the trend of DDE in the 12 months before and 12 months after the authorization of medical cannabis. RESULTS: Over the follow-up period after medical cannabis authorization, there was no overall change in the DDE use in authorized medical cannabis patients compared to matched controls (- 0.08 DDE, 95% CI: - 0.41 to 0.24). Likewise, the sensitivity analysis showed that, among patients consuming ≤5 mg baseline DDE, there was no change immediately after medical cannabis authorization compared to controls (level change, - 0.04 DDE, 95% CI: - 0.12 to 0.03) per patient as well as in the month-to-month trend change (0.002 DDE, 95% CI: - 0.009 to 0.12) per patient was noted. CONCLUSIONS: This short-term study found that medical cannabis authorization had minimal effects on benzodiazepine use. Our findings may contribute ongoing evidence for clinicians regarding the potential impact of medical cannabis to reduce benzodiazepine use. HIGHLIGHTS: • Medical cannabis authorization had little to no effect on benzodiazepine usage among patients prescribed regular benzodiazepine treatment in Alberta, Canada. • Further clinical research is needed to investigate the potential impact of medical cannabis as an alternative to benzodiazepine medication.

Poststroke Care Pathways and Spasticity Treatment: A Retrospective Study in Alberta.

BACKGROUND: Limited evidence exists regarding care pathways for stroke survivors who do and do not receive poststroke spasticity (PSS) treatment. METHODS: Administrative data was used to identify adults who experienced a stroke and sought acute care between 2012 and 2017 in Alberta, Canada. Pathways of stroke care within the health care system were determined among those who initiated PSS treatment (PSS treatment group: outpatient pharmacy dispensation of an anti-spastic medication, focal chemo-denervation injection, or a spasticity tertiary clinic visit) and those who did not (non-PSS treatment group). Time from the stroke event until spasticity treatment initiation, and setting where treatment was initiated were reported. Descriptive statistics were performed. RESULTS: Health care settings within the pathways of stroke care that the PSS (n = 1,079) and non-PSS (n = 22,922) treatment groups encountered were the emergency department (86 and 84%), acute inpatient care (80 and 69%), inpatient rehabilitation (40 and 12%), and long-term care (19 and 13%), respectively. PSS treatment was initiated a median of 291 (interquartile range 625) days after the stroke event, and most often in the community when patients were residing at home (45%), followed by "other" settings (22%), inpatient rehabilitation (18%), long-term care (11%), and acute inpatient care (4%). CONCLUSIONS: To our knowledge, this is the first population based cohort study describing pathways of care among adults with stroke who subsequently did or did not initiate spasticity treatment. Areas for improvement in care may include strategies for earlier identification and treatment of PSS.

Screening for lung cancer with computed tomography: protocol for systematic reviews for the Canadian Task Force on Preventive Health Care.

PURPOSE: Lung cancer is the leading cause of cancer deaths in Canada, and because early cancers are often asymptomatic screening aims to prevent mortality by detecting cancer earlier when treatment is more likely to be curative. These reviews will inform updated recommendations by the Canadian Task Force on Preventive Health Care on screening for lung cancer. METHODS: We will update the review on the benefits and harms of screening with CT conducted for the task force in 2015 and perform de novo reviews on the comparative effects between (i) trial-based selection criteria and use of risk prediction models and (ii) trial-based nodule classification and different nodule classification systems and on patients' values and preferences. We will search Medline, Embase, and Cochrane Central (for questions on benefits and harms from 2015; comparative effects from 2012) and Medline, Scopus, and EconLit (for values and preferences from 2012) via peer-reviewed search strategies, clinical trial registries, and the reference lists of included studies and reviews. Two reviewers will screen all citations (including those in the previous review) and base inclusion decisions on consensus or arbitration by another reviewer. For benefits (i.e., all-cause and cancer-specific mortality and health-related quality of life) and harms (i.e., overdiagnosis, false positives, incidental findings, psychosocial harms from screening, and major complications and mortality from invasive procedures as a result of screening), we will include studies of adults in whom lung cancer is not suspected. We will include randomized controlled trials comparing CT screening with no screening or alternative screening modalities (e.g., chest radiography) or strategies (e.g., CT using different screening intervals, classification systems, and/or patient selection via risk models or biomarkers); non-randomized studies, including modeling studies, will be included for the comparative effects between trial-based and other selection criteria or nodule classification methods. For harms (except overdiagnosis) we will also include non-randomized and uncontrolled studies. For values and preferences, the study design may be any quantitative design that either directly or indirectly measures outcome preferences on outcomes pertaining to lung cancer screening. We will only include studies conducted in Very High Human Development Countries and having full texts in English or French. Data will be extracted by one reviewer with verification by another, with the exception of result data on mortality and cancer incidence (for calculating overdiagnosis) where duplicate extraction will occur. If two or more studies report on the same comparison and it is deemed suitable, we will pool continuous data using a mean difference or standardized mean difference, as applicable, and binary data using relative risks and a DerSimonian and Laird model unless events are rare (< 1%) where we will pool odds ratios using Peto's method or (if zero events) the reciprocal of the opposite treatment arm size correction. For pooling proportions, we will apply suitable transformation (logit or arcsine) depending on the proportions of events. If meta-analysis is not undertaken we will synthesize the data descriptively, considering clinical and methodological differences. For each outcome, two reviewers will independently assess within- and across-study risk of bias and rate the certainty of the evidence using GRADE (Grading of Recommendations Assessment, Development, and Evaluation), and reach consensus. DISCUSSION: Since 2015, additional trials and longer follow-ups or additional data (e.g., harms, specific patient populations) from previously published trials have been published that will improve our understanding of the benefits and harms of screening. The systematic review of values and preferences will allow fulsome insights that will inform the balance of benefits and harms. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022378858.

Disease-modifying therapy use and health resource utilisation associated with multiple sclerosis over time: A retrospective cohort study from Alberta, Canada.

BACKGROUND: Estimating multiple sclerosis (MS) prevalence and incidence, and assessing the utilisation of disease-modifying therapies (DMTs) and healthcare resources over time is critical to understanding the evolution of disease burden and impacts of therapies upon the healthcare system. METHODS: A retrospective population-based study was used to determine MS prevalence and incidence (2003-2019), and describe utilisation of DMTs (2009-2019) and healthcare resources (1998-2019) among people living with MS (pwMS) using administrative data in Alberta. RESULTS: Prevalence increased from 259 (95% confidence interval [CI]: 253-265) to 310 (95% CI: 304, 315) cases per 100,000 population, and incidence decreased from 21.2 (95% CI: 19.6-22.8) to 12.7 (95% CI: 11.7-13.8) cases per 100,000 population. The proportion of pwMS who received ≥1 DMT dispensation increased (24% to 31% annually); use of older platform injection therapies decreased, and newer oral-based, induction, and highly-effective therapies increased. The proportion of pwMS who had at least one MS-related physician, ambulatory, or tertiary clinic visits increased, and emergency department visits and hospitalizations decreased. CONCLUSIONS: Alberta has one of the highest rates of MS globally. The proportion of pwMS who received DMTs and had outpatient visits increased, while acute care visits decreased over time. The landscape of MS care appears to be rapidly evolving in response to changes in disease burden and new highly-effective therapies.

Risk Factors for Developing Low Estimated Glomerular Filtration Rate and Albuminuria in Living Kidney Donors.

Rationale & Objective: Chronic kidney disease is associated with significant morbidity and mortality in the general population, but little is known about the incidence and risk factors associated with developing low estimated glomerular filtration rate (eGFR) and moderate-severe albuminuria in living kidney donors following nephrectomy. Study Design: Retrospective, population-based cohort study. Setting & Participants: Kidney donors in Alberta, Canada. Exposure: Donor nephrectomy between May 2001 and December 2017. Outcome: Two eGFR measurements <45 mL/min/1.73 m2 or 2 measurements of moderate or severe albuminuria from 1-year postdonation onwards that were at least 90 days apart. Analytical Approach: Associations between potential risk factors and the primary outcome were assessed using Cox proportional hazard regression analyses. Results: Over a median follow-up period of 8.6 years (IQR, 4.7-12.6 years), 47 of 590 donors (8.0%) developed sustained low eGFR or moderate-severe albuminuria with an incidence rate of 9.2 per 1,000 person-years (95% confidence interval, 6.6-11.8). The median time for development of this outcome beyond the first year after nephrectomy was 2.9 years (IQR, 1.4-8.0 years). Within the first 4 years of follow-up, a 5 mL/min/1.73 m2 lower predonation eGFR increased the hazard of developing postdonation low eGFR or moderate-severe albuminuria by 26% (adjusted HR, 1.26; 95% CI, 1.10-1.44). Furthermore, donors were at higher risk of developing low eGFR or albuminuria if they had evidence of predonation hypertension (adjusted HR, 2.52; 95% CI, 1.28-4.96) or postdonation diabetes (adjusted HR, 4.72; 95% CI, 1.54-14.50). Limitations: We lacked data on certain donor characteristics that may affect long-term kidney function, such as race, smoking history, and transplant-related characteristics. Conclusions: A proportion of kidney donors at an incidence rate of 9.2 per 1,000 person-years will develop low eGFR or albuminuria after donation. Donors with lower predonation eGFR, predonation hypertension, and postdonation diabetes are at increased risk of developing this outcome.

The purpose of this study was to understand the risk of developing kidney disease in living kidney donors after donation. We followed 590 donors in Alberta, Canada for almost 9 years. Approximately 8% of donors developed reduced kidney function (low estimated glomerular filtration rate) or increased protein in the urine (albuminuria). Donors with lower kidney function before donation, hypertension before donation, or diabetes after donation had a higher likelihood of experiencing these kidney outcomes. This research provides important insights to patients and health care providers to better support the long-term kidney health of living kidney donors.

The impact of the Starting dialysis on Time, At home on the Right Therapy (START) project on the use of peritoneal dialysis.

BACKGROUND: Peritoneal dialysis (PD) is actively promoted, but increasing PD utilisation is difficult. The objective of this study was to determine if the Starting dialysis on Time, At Home, on the Right Therapy (START) project was associated with an increase in the proportion of dialysis patients receiving PD within 6 months of starting therapy. METHODS: Consecutive patients over age 18, with end-stage kidney failure, who started dialysis between 1 April 2015 and 31 March 2018 in the province of Alberta, Canada. Programmes were provided with high-quality data about the individual steps in the process of care that drive PD utilisation that were used to identify problem areas, design and implement interventions to address them, and then evaluate whether those interventions had impact. The primary outcome was the proportion of patients receiving PD within 6 months of starting dialysis. Secondary outcomes included hospitalisation, death or probability of transfer to haemodialysis (HD). Interrupted time series methodology was used to evaluate the impact of the quality improvement initiative on the primary and secondary outcomes. RESULTS: A total of 1962 patients started dialysis during the study period. Twenty-seven per cent of incident patients received PD at baseline, and there was a 5.4% (95% confidence interval: 1.5-9.2) increase in the use of PD in the province immediately after implementation. There were no changes in the rates of hospitalisation, death or probability of transfer to HD after the introduction of START. CONCLUSIONS: The approach used in the START project was associated with an increase in the use of PD in a setting with high baseline utilisation.

Sodium-glucose co-transporter-2 inhibitors are associated with kidney benefits at all degrees of albuminuria: A retrospective cohort study of adults with diabetes.

AIM: To estimate the real-world effectiveness of sodium-glucose co-transporter-2 inhibitors (SGLT2is) versus dipeptidyl peptidase-4 inhibitors (DPP4is) at reducing loss of kidney function and adverse kidney events in adults with varying levels of albuminuria. MATERIALS AND METHODS: In this retrospective cohort study using administrative data, we matched new SGLT2i users 1:2 to DPP4i users on diabetes therapy, chronic kidney disease (CKD) stage, albuminuria and time-conditional propensity score. Albuminuria was defined by spot urine albumin or equivalent as mild, moderate or severe. Linear regression was used to model the estimated glomerular filtration rate (eGFR), and Poisson regression for a composite kidney outcome (> 40% loss of eGFR, kidney replacement therapy or death from kidney causes) and all-cause mortality. RESULTS: SGLT2i users (n = 19 238, median age 57.9 years, female 40.9%) had mostly nil/mild albuminuria (70.7%). SGLT2is were associated with a 1.36 (95% CI 0.98-1.74) mL/min/1.73m2 (P < .001) acute (≤ 60 days) decline in eGFR, relative to DPP4is. Thereafter, SGLT2is were associated with 1.04 (95% CI 0.93-1.15) mL/min/1.73m2 (P < .001) less annual eGFR loss. SGLT2i users had fewer adverse kidney outcomes (incidence rate ratio [IRR] 0.58 [0.47-0.71]; P < .001), but not all-cause mortality (IRR 0.82 [0.66-1.01]; P = .06). Outcomes were similar considering only those with nil/mild albuminuria. CONCLUSIONS: SGLT2is may prevent eGFR decline and reduce the risk of adverse kidney events in adults with diabetes and nil or non-severe albuminuria.

Degree of Albuminuria is Associated With Increased Risk of Fragility Fractures Independent of Estimated GFR.

Introduction: Fragility fractures are common in persons with chronic kidney disease (CKD); however, the association between fragility fractures and albuminuria is not well-studied. The primary objective of this study is to determine the association of albuminuria with incident risk of fragility fractures. The secondary objective is to examine the risk of fragility fracture by estimated glomerular filtration rate (eGFR) and Kidney Disease Improving Global Outcomes (KDIGO) risk categories. Methods: Community dwelling adults residing in Alberta, Canada who had at least 1 creatinine and albuminuria measurement between April 1, 2008 and March 31, 2019 participated in the study (N = 2.72 million). Incident fragility fractures were identified using Canadian Chronic Disease Surveillance Systems Osteoporosis Working Group algorithms. Albuminuria was categorized as none/mild (albumin-to-creatinine ratio [ACR] <30 mg/g, protein-to-creatinine ratio [PCR] <150 mg/g, trace/negative dipstick); moderate (ACR 30-300 mg/g, PCR 150-500 mg/g, 1+ dipstick) or severe (ACR >300 mg/g, PCR >500 mg/g, ≥2+ dipstick). Multivariable analysis controlled for 42 variables. Results: Patients with severe albuminuria had an increased risk of hip fracture (odds ratio [OR] = 1.37; 95% confidence interval [CI] 1.28, 1.47]), vertebral fracture (OR = 1.31; 95% CI 1.21, 1.41) and any-type fracture (OR = 1.22; 95% CI 1.17, 1.28) compared with patients with none/mild albuminuria. Patients in the most severe KDIGO risk category had an increased risk of hip fracture (OR = 1.22; 95% CI 1.16, 1.29), vertebral fracture (OR = 1.18; 95% CI 1.09, 1.26) and any type of fracture (OR = 1.25; 95% CI 1.21, 1.30). Conclusion: This study demonstrates the important role of albuminuria as a risk factor for fragility fractures in CKD and may help inform risk stratification and prevention strategies in this high-risk population category.

Associations of Estradiol With Mortality and Health Outcomes in Patients Undergoing Hemodialysis: A Prospective Cohort Study.

Background: Both lower and higher estradiol (E2) levels have been associated with increased mortality among women with kidney failure. However, robust data are still lacking. Objective: We investigated the interaction of diabetes and age on linear and nonlinear associations between E2 levels, adverse outcomes, and health-related quality of life (HRQOL) in Canadian women undergoing hemodialysis (HD). Design: Population-based cohort study; data from Canadian Kidney Disease Cohort Study (CKDCS). Setting & patients: A total of 427 women undergoing HD enrolled in the CKDCS. Measurements: Baseline E2 (in pmol/L) and E2 tertiles (<38 pmol/L, 38-95 pmol/L, >95 pmol/L). Methods: Cox-proportional hazards used for all-cause and cardiovascular disease (CVD) mortality. Fine-Gray models used for incident CVD. Mixed models used for Health Utilities Index Mark 3 (HUI3), Kidney Disease Quality of Life Physical Component Scores (KDQOL12-PCS), and Mental Component Scores (KDQOL12-MCS). Results: Over a median follow-up of 3.6 (interquartile range [IQR]: 1.6-7.5) years, 250 (58.6%) participants died; 74 deaths (29.6%) were CV-related. Among 234 participants without prior CV events, 80 (34.2%) had an incident CVD event. There were no significant linear associations between E2 and all-cause mortality, CVD mortality, and incident CVD. However, E2 showed a significant concave association with all-cause mortality, but not with CVD mortality and incident CVD. Among patients aged ≥63 years, higher E2 levels were associated with lower HUI3 scores, mean difference (MD) = -0.062 per 1 - SD pmol/L, 95% confidence interval (CI) = -0.112 to -0.012, but the opposite was observed in younger patients (<63 years) in whom higher E2 levels were associated with higher HUI3 scores (MD = 0.032 per 1 - SD pmol/L, 95% CI = 0.008-0.055), Pinteraction = .045. No associations were observed among E2, KDQOL12-PCS (MD = -0.15 per 1 - SD pmol/L, 95% CI = -1.15 to 0.86), and KDQOL12-MCS (MD = -0.63 per 1 - SD pmol/L, 95% CI = -1.82 to 0.57). Limitations: Unmeasured confounding and small sample size. Conclusions: The association between E2 and all-cause mortality may be nonlinear, while no association was observed for CVD mortality, incident CVD, KDQOL12-PCS, and KDQOL12-MCS. Furthermore, the association between serum E2 and HUI3 was modified by age: Higher levels were associated with higher utility among women aged <63 years and the converse observed among older women.

Contexte: Les taux faibles comme les taux élevés d'estradiol (E2) ont été associés à une mortalité accrue chez les femmes souffrant d'insuffisance rénale. Les données fiables à ce sujet font cependant encore défaut. Objectif: Nous avons étudié l'incidence du diabète et de l'âge sur les associations linéaires et non linéaires entre les niveaux d'E2, les issues défavorables et la qualité de vie liée à la santé (QVLS) chez les Canadiennes suivant des traitements d'hémodialyse (HD). Conception: Étude de cohorte en population réalisée à partir des données de la Canadian Kidney Disease Cohort Study (CKDCS). Sujets et cadre de l'étude: 427 femmes sous HD inscrites à la CKDCS. Mesures: Le taux d'E2 initial (pmol/L) et les taux d'E2 tertiles (<38 pmol/L; 38-95 pmol/L; >95 pmol/L). Méthodologie: Des modèles à risques proportionnels de Cox ont été utilisés pour mesurer la mortalité toutes causes confondues et la mortalité liée aux maladies cardiovasculaires (MCV). Des modèles Fine-Gray ont été utilisés pour mesurer les MCV incidentes; et des modèles mixtes ont été utilisés pour calculer l'indice Health Utilities Index Mark 3 (HUI3) et les scores des composantes physique (KDQOL12-PCS [Physical Component Score]) et mentale (KDQOL12-MCS [Mental Component Score])) du questionnaire sur la qualité de vie (KDQOL). Résultats: Au cours d'un suivi médian de 3,6 ans (intervalle interquartile [IIQ]: 1,6 à 7,5 ans), 250 participantes (58,6 %) sont décédées; 74 décès (29,6 %) étaient liés à un événement CV. Parmi les 234 participantes sans événements cardiovasculaires antérieurs, 80 (34,2 %) ont vécu un événement incident de MCV. Aucune association linéaire significative n'a été observée entre le taux d'E2 et la mortalité toutes causes confondues, la mortalité par MCV ou les MCV incidentes. Le taux d'E2 a cependant montré une association concave significative avec la mortalité toutes causes confondues, mais pas avec la mortalité par MCV ni avec les MCV incidentes. Chez les patientes âgées de 63 ans et plus, des taux élevés d'E2 ont été associés à des scores HUI3 plus faibles (différence moyenne [DM] = -0,062 par 1-SD pmol/L; intervalle de confiance à 95 % [IC95]: -0,112 à 0,012); alors qu'on a observé le contraire chez les patientes plus jeunes (< 63 ans), où des taux élevés d'E2 étaient plutôt associés à des scores plus élevés d'HUI3 (DM = 0,032 par 1-SD pmol/L; IC95: 0,008 à 0,055; p=0,045). Aucune association n'a été observée entre le taux d'E2, le KDQOL12-PCS (DM = -0,15 par 1-SD pmol/L; IC 95: -1,15 à 0,86) et le KDQOL12-MCS (DM = -0,63 par 1-SD pmol/L; IC95: -1,82 à 0,57). Limites: Facteurs de confusion non mesurés; échantillon de petite taille. Conclusion: Il pourrait exister une association non linéaire entre le taux d'E2 et la mortalité toutes causes confondues. Aucune association n'a toutefois été observée entre le taux d'E2 et la mortalité par MCV, les MCV incidentes, le KDQOL12-PCS et le KDQOL12-MCS. En outre, l'association entre le taux sérique d'E2 et l'HUI3 a été modifiée par l'âge: des taux plus élevés d'E2 ont été associés à un indice de santé plus élevé (HUI) chez les femmes âgées de moins de 63 ans, alors que l'inverse a été observé chez les femmes plus âgées.

Multidisciplinary Support To Access living donor Kidney Transplant (MuST AKT): A Clinical Research Protocol for a Pilot Randomized Controlled Trial to Increase Living Kidney Donation.

Background: Living donor kidney transplantation (LDKT) is the optimal treatment for eligible patients with kidney failure, although it is underutilized. Contextually tailored patient- and family-centered interventions may be effective to increase LDKT. Objective: We outline a protocol to test the feasibility of the Multidisciplinary Support To Access living donor Kidney Transplant (MuST AKT) intervention designed to increase LDKT. Design: Non-blinded single-center pilot randomized controlled trial with a qualitative interview component. Setting: Academic transplant referral center in Northern Alberta Region with a population of more than 2 million in its catchment area. Patients: English-speaking patients of the age range 18 to 75 years who are referred for kidney transplantation are eligible to participate. Measurements: Feasibility will be assessed by indicators of recruitment, retention, and completion rates, treatment fidelity, adherence to intervention, engagement in intervention, and acceptability. Methods: Participants will be randomly assigned 1:1 to either standard care (control) or the experimental group who receive standard care plus the MuST AKT intervention, a person-centered program designed to assist and enable the kidney transplant candidate to achieve what is required to receive an LDKT. The intervention consists of an introductory session and 4 intervention sessions delivered in-person or virtually. Limitations: Inferences cannot be drawn regarding the efficacy/effectiveness of the MuST AKT intervention. This study is non-blinded. Conclusions: This pilot study is the first step in our broader initiative to increase LDKT in our health care jurisdiction. The results of this study will be used to inform the development of a future definitive randomized controlled trial. Trial registration number: NCT04666545.

Contexte: Bien qu'elle soit encore sous-utilisée, la transplantation d'un rein provenant d'un donneur vivant (TRDV) constitue le traitement optimal pour les patients atteints d'insuffisance rénale qui sont admissibles. Des interventions personnalisées, axées sur le patient et la famille, pourraient s'avérer efficaces pour favoriser la TRDV. Objectif: Nous décrivons un protocole examinant la faisabilité de l'intervention MuST AKT (Multidisciplinary Support To Access living donor Kidney Transplant), laquelle vise l'augmentation des TRDV. Conception: Essai clinique pilote unicentrique, sans insu, comportant une composante d'entretiens qualitatifs. Cadre: Un center universitaire pour les transplantations du Nord de l'Alberta, situé dans une zone de référence comptant plus de deux millions de personnes. Sujets: Seront admissibles tous les patients anglophones âgés de 18 à 75 ans aiguillés pour une transplantation rénale. Mesures: La faisabilité sera évaluée par des indicateurs du taux de recrutement, de rétention et d'achèvement, de même que par la fidélité au traitement, l'adhésion à l'intervention, l'engagement dans l'intervention et l'acceptabilité. Méthodologie: Les sujets seront répartis aléatoirement 1:1 dans le groupe témoin, qui recevra les soins habituels, ou dans le groupe expérimental, qui recevra les soins habituels et l'intervention MuST AKT. Ce program axé sur le patient est conçu pour aider les candidats à une greffe rénale à réaliser les étapes nécessaires pour recevoir une TRDV. L'intervention est constituée d'une séance d'introduction et de quatre séances d'intervention réalisées en personne ou virtuellement. Limites: Nous ne serons pas en mesure de tirer des conclusions quant à l'efficacité de l'intervention MuST AKT. Cette étude n'est pas menée en aveugle. Conclusion: Cette étude pilote constitue la première étape d'une initiative plus vaste qui vise à accroître la TRDV dans notre région sanitaire. Les résultats de cette étude seront utilisés pour guider l'élaboration d'un futur essai clinique définitif.

PEER simplified lipid guideline 2023 update: Prevention and management of cardiovascular disease in primary care.

OBJECTIVE: To update the 2015 clinical practice guideline and provide a simplified approach to lipid management in the prevention of cardiovascular disease (CVD) for primary care. METHODS: Following the Institute of Medicine's Clinical Practice Guidelines We Can Trust, a multidisciplinary, pan-Canadian guideline panel was formed. This panel was represented by primary care providers, free from conflicts of interest with industry, and included the patient perspective. A separate scientific evidence team performed evidence reviews on statins, ezetimibe, proprotein convertase subtilisin-kexin type 9 inhibitors, fibrates, bile acid sequestrants, niacin, and omega-3 supplements (docosahexaenoic acid with eicosapentaenoic acid [EPA] or EPA ethyl ester alone [icosapent]), as well as on 11 supplemental questions. Recommendations were finalized by the guideline panel through use of the Grading of Recommendations Assessment, Development and Evaluation methodology. RECOMMENDATIONS: All recommendations are presented in a patient-centred manner designed with the needs of family physicians and other primary care providers in mind. Many recommendations are similar to those published in 2015. Statins remain first-line therapy for both primary and secondary CVD prevention, and the Mediterranean diet and physical activity are recommended to reduce cardiovascular risk (primary and secondary prevention). The guideline panel recommended against using lipoprotein a, apolipoprotein B, or coronary artery calcium levels when assessing cardiovascular risk, and recommended against targeting specific lipid levels. The team also reviewed new evidence pertaining to omega-3 fatty acids (including EPA ethyl ester [icosapent]) and proprotein convertase subtilisin-kexin type 9 inhibitors, and outlined when to engage in informed shared decision making with patients on interventions to lower cardiovascular risk. CONCLUSION: These updated evidence-based guidelines provide a simplified approach to lipid management for the prevention and management of CVD. These guidelines were created by and for primary health care professionals and their patients.

Lignes directrices simplifiées de PEER sur les lipides : actualisation 2023: Prévention et prise en charge des maladies cardiovasculaires en soins primaires.

OBJECTIF: Actualiser le guide de pratique clinique de 2015 et présenter une approche simplifiée de la prise en charge des lipides dans la prévention des maladies cardiovasculaires (MCV) en première ligne. MÉTHODES: Conformément aux recommandations de l'Institute of Medicine dans Clinical Practice Guidelines We Can Trust, un panel pancanadien d'experts multidisciplinaires en lignes directrices a été formé. Ce panel était représentatif des cliniciens en soins primaires, libre de tout conflit d'intérêts avec l'industrie, et il tenait compte des points de vue des patients. Une équipe distincte, responsable des données probantes scientifiques, a passé en revue l'information sur les statines, l'ézétimibe, les inhibiteurs de la proprotéine convertase subtilisine-kexine de type 9, les fibrates, les chélateurs des acides biliaires, la niacine et les suppléments d'omega-3 (acide docosahexaénoïque avec acide eicosapentaénoïque [EPA] ou ester éthylique de l'EPA seul [icosapent]), ainsi que sur la réponse à 11 questions supplémentaires. Le panel des lignes directrices a finalisé les recommandations en utilisant la méthodologie GRADE (Grading of Recommendations Assessment, Development and Evaluation). RECOMMANDATIONS: Toutes les recommandations sont présentées de manière à être centrées sur le patient et conçues en ayant à l'esprit les besoins des médecins de famille et des autres cliniciens des soins primaires. De nombreuses recommandations sont semblables à celles publiées en 2015. Les statines demeurent le traitement de première intention pour la prévention tant primaire que secondaire des MCV, et le régime méditerranéen et l'activité physique sont recommandés pour réduire le risque cardiovasculaire (en prévention primaire et secondaire). Le panel des lignes directrices a recommandé de ne pas utiliser le dosage des lipoprotéines a, des apolipoprotéines B ou le score calcique coronarien (SCC) dans l'évaluation du risque cardiovasculaire, et de ne pas cibler de seuils précis de taux lipidiques. L'équipe a aussi passé en revue de nouvelles données concernant les acides gras omega-3 (y compris l'ester éthylique d'EAP [icosapent]) et les inhibiteurs de la proprotéine convertase subtilisine-kexine de type 9, et a précisé les moments où il convient de procéder à une prise de décision partagée avec les patients sur les interventions pour diminuer le risque cardiovasculaire. CONCLUSION: Ces lignes directrices actualisées et fondées sur des données probantes présentent une approche simplifiée de la prise en charge des lipides pour la prévention et le traitement des MCV. Ce guide de pratique clinique a été conçu par et pour des professionnels de la santé en soins primaires et leurs patients.

Incidence and prevalence, and medication use among adults living with dermatomyositis: an Alberta, Canada population-based cohort study.

Dermatomyositis is a rare disease characterized by progressive muscle weakness and skin rashes. Estimates of incidence and prevalence are fundamental measures in epidemiology, but few studies have been conducted on dermatomyositis. To address this knowledge gap, we conducted a population-based study to determine the contemporary incidence (between 2013 and 2019) and prevalence (2019) of adults living with dermatomyositis using administrative health data in Alberta, Canada. We also described disease-related medication use, as there are very few approved medications for the treatment of dermatomyositis, and no Canadian therapeutic guidelines. The average age- and sex-standardized annual incidence of dermatomyositis was 2.8-3.0 cases per 100,000 adults, and prevalence was 28.6 cases per 100,000 adults, which is greater than reported in other cohorts. Dermatomyositis-related medication use decreased from 73% in the first year to 46% in the eighth year after diagnosis. Glucocorticoids were the most commonly used drug class, often taken concurrently with various immunomodulatory agents; this medication use aligns with empirically-based recommendations and the few therapeutic guidelines for dermatomyositis. Considering that Alberta may have one of the highest rates of dermatomyositis among adults, further research on the burden of disease is warranted for planning within the health care system.

Health care cost of severe obesity and obesity-related comorbidities: A retrospective cohort study from Alberta, Canada.

BACKGROUND: Estimates of health care costs associated with severe obesity, and those attributable to specific health conditions among adults living with severe obesity are needed. METHODS: Administrative data was used to identify adults who previously received a procedure, and had (investigational cohort) or did not have (control cohort) a body mass index ≥ 35 kg/m2. Two-part models were used to estimate the incremental health care cost of severe obesity and related health conditions during a 1-year observation period. RESULTS: Adjusting for potential confounders, the total health care cost ratio was higher in the investigational (n = 220,190) versus control (n = 1,955,548) cohort (1.32 [95 % CI: 1.32, 1.33]) with a predicted incremental cost of $2221 (95 % CI $2184, $22,265) per person-year; costs were less when obesity-related health conditions were controlled for (1.13 [95 % CI: 1.13, 1.14]; $1097 [95 % CI: $1084, $1110] per person-year). Among those living with severe obesity, incremental costs associated with specific health conditions ranged from $737 (95 % CI: $747, $728) lower (dyslipidemia) to $12,996 (95 % CI: $12,512, $13,634) higher (peripheral vascular disease) per person-year. CONCLUSIONS: Adults living with severe obesity had greater costs than those without, largely driven by obesity-related health conditions. For the Alberta adult population with a severe obesity prevalence of 11 %, severe obesity may account for an estimated additional $453-918 million in health care costs per year. Findings of this study provide rationale for resources and strategies to prevent and manage obesity and its complications.

Trajectory of health care resources among adults stopping or reducing treatment frequency of botulinum toxin for chronic migraine treatment in Alberta, Canada.

OBJECTIVE: Understand health resource, medication use, and cost of adults with chronic migraine who received guideline-recommended onabotulinumtoxinA (botulinum toxin) treatment frequency and then continued or reduced/stopped. BACKGROUND: Botulinum toxin may be a beneficial treatment for chronic migraine; the trajectory of health resources utilization among those with continued or reduced/stopped use is unclear. METHODS: A retrospective population-based cohort study utilizing administrative data from Alberta, Canada (2012-2020), was performed. A cohort of adults who received ≥5 botulinum toxin treatment cycles for chronic migraine over 18 months (6-month run-in; 1-year pre-index period) were grouped into those who (1) continued use (≥3 treatments/year), or (2) stopped or reduced use (stopped for 6 months then received 0 or 1-2 treatments/year, respectively) over a 1-year post-index period. Health resources and medication use were described, and pre-post costs were assessed. A second cohort that received ≥3 treatments/year immediately followed by 1 year of stopped or reduced use was considered in sensitivity analysis. RESULTS: Pre-post health resource, medication use, and costs were similar among those with continued use (n = 3336). Among those who stopped or reduced use (n = 1099; 756 stopped, 343 reduced), health resource, medication use, and costs were lower in the post- (total median per-person cost [IQR]: all-cause $4851 [$8090]; migraine-related $835 [$1915]) versus pre- (all-cause $6096 [$7207]; migraine-related $2995 [$1950]) index period (estimated cost ratios [95% CI]: total all-cause 0.86 [0.79, 0.95]; total migraine-related 0.44 [0.40, 0.48]). In the second cohort (n = 3763), return to continued use (≥3 treatments/year) occurred in up to 70.4% in those with reduced use. CONCLUSIONS: Of adults treated with botulinum toxin for chronic migraine, 75.2% had continued use, stable health resource and medication use, and costs over a 2 year period. In those that stopped/reduced use, the observed lower health resource and migraine medication use may indicate improved symptom control, but the resumption of guideline-recommended treatment intervals after reduced use was common.