Search

Purpose of Program: Glomerulonephritis (GN) is a group of rare kidney diseases that is increasingly being managed with higher cost immunosuppressive (IS) agents in Canada. Ontario Health’s Ontario Renal Network (ORN) oversees the management and delivery of GN services in the province. Stakeholder surveys previously conducted by ORN identified that both clinicians and patients do not perceive access to GN medications as comprehensive or timely. The program conducted a focused jurisdictional scan among 7 provinces to inform ORN initiatives to improve access to GN medications. Specifically, the program examined clinician experience with GN access, public drug coverage criteria, and timelines for public coverage for select IS agents (ie, tacrolimus, cyclosporine, mycophenolate mofetil [MMF], mycophenolate sodium, rituximab, and eculizumab) used to manage GN in adults who live in Canada. Methods: For the selected IS agents, a focused jurisdictional scan on medication access was conducted by ORN in 2018 and updated in July 2022. Information was obtained by searching the gray literature and/or credible online sources for public funding policies and eligibility criteria. Findings were supplemented by personal communications with provincial drug programs and consulting GN clinical experts from 7 provinces (ie, Alberta, British Columbia, Saskatchewan, Manitoba, Ontario, Nova Scotia, and Quebec). Key Findings: Clinicians from different provinces prescribe IS agents similarly for GN indications, despite distinctions in public drug funding policies. While patients can obtain public funding for many IS agents, for GN, most provinces rely on case-by-case review processes. In addition, provinces can vary in their funding criteria and which IS agents are listed on the public formulary. For IS agents that require prior authorization or case-by-case review, timelines vary by province with decisions taking a few days to weeks. British Columbia, with a GN-specific drug formulary, had the most integrated and efficient system for patients and prescribers. Limitations: This scan primarily relied on publicly available information for drug coverage criteria and clinician experience with access in their province. Since this scan was conducted, public drug coverage criteria and/or application processes may have changed. Implications: While patients in most provinces have similar needs and nephrologists similar prescribing patterns, gaps still exist for publicly funded GN medications. Interprovincial differences in the drugs funded, funding criteria, and application process may affect timely and equitable access to GN medications across Canada. Given the rarity of GN, a pan-Canadian funding approach may be warranted to improve the current state.

Background: Glomerulonephritis (GN) is a leading cause of kidney failure and accounts for 20% of incident cases of end-stage kidney disease (ESKD) in Canada annually. Reversal of kidney injury and prevention of progression to kidney failure is possible; however, limited knowledge of underlying disease mechanisms and lack of noninvasive biomarkers and therapeutic targets are major barriers to successful therapeutic intervention. Multicenter approaches that link longitudinal clinical and outcomes data with serial biologic specimen collection would help bridge this gap. Objective: To establish a national, patient-centered, multidimensional web-based clinical database and federated virtual biobank to conduct human-based molecular and clinical research in GN in Canada. Design: Multicenter, prospective observational registry, starting in 2019. Setting: Nine participating Canadian tertiary care centers. Patients: Adult patients with a histopathologic pattern of injury consistent with IgA nephropathy, focal and segmental glomerulosclerosis, minimal change disease, membranous nephropathy, C3 glomerulopathy, and membranoproliferative GN recruited within 24 months of biopsy. Measurements: Initial visits include detailed clinical, histopathological, and laboratory data collection, blood, urine, and tonsil swab biospecimen collection, and a self-administered quality of life questionnaire. Follow-up clinical and laboratory data collection, biospecimen collection, and questionnaires are obtained every 6 months thereafter. Methods: Patients receive care as defined by their physician, with study visits scheduled every 6 months. Patients are followed until death, dialysis, transplantation, or withdrawal from the study. Key outcomes include a composite of ESKD or a 40% decline in estimated glomerular filtration rate (eGFR) at 2 years, rate of kidney function decline, and remission of proteinuria. Clinical and molecular phenotypical data will be analyzed by GN subtype to identify disease predictors and discover therapeutic targets. Limitations: Given the relative rarity of individual glomerular diseases, one of the major challenges is patient recruitment. Initial registry studies may be underpowered to detect small differences in clinically meaningful outcomes such as ESKD or death due to small sample sizes and short duration of follow-up in the initial 2-year phase of the study. Conclusions: The Canadian Glomerulonephritis Registry (CGNR) supports national collaborative efforts to study glomerular disease patients and their outcomes. Trial registration: NCT03460054.

Background: Kidney biopsy is considered the gold standard for diagnosis of renal disease. It is increasingly performed in cases of diagnostic uncertainty, including in patients with coexistent diabetes and hypertension, for which a presumptive clinical diagnosis can be made. Little is known about the incidence and distribution of biopsy-proven kidney diseases. Changes in the distribution of biopsy diagnoses over time may have significant implications for resource allocation and future research. Objective: We studied the relative frequency of kidney diseases in Southern Alberta over the past 30 years, to determine whether the population-standardized annual biopsy rate and incidence of selected diagnostic categories have changed. We hypothesized an increasing incidence of renal biopsies and a growing proportion of nonglomerular diseases (eg, tubulointerstitial disorders) likely due to evolving indications for biopsy. Given the rise in obesity, diabetes, and aging population with chronic kidney disease (CKD), we anticipated a rise in nephroangiosclerosis and diabetic nephropathy over time. Design: Retrospective population-based cohort study using the Biobank for the Molecular Classification of Kidney Disease (BMCKD). Setting: Southern Alberta, Canada. Patients: All patients who underwent renal biopsy between 1985 and 2015 in our database. Measurements: We used descriptive and quantitative analysis to characterize demographics and biopsy-based diagnoses. Methods: We conducted a retrospective population-based cohort study to analyze all consecutive patients who underwent at least one kidney biopsy over a 30-year period in Southern Alberta (1985-2015). We considered the first adequate biopsy. We described the annual standardized incidence of biopsy-proven kidney diseases over time and summarized associated patient characteristics. We assumed a Poisson distribution for biopsy counts and used provincial demographic information to standardize rates. Results: During the study period, 6434 people (58% male; mean age: 47.9 years) underwent a kidney biopsy. The population-standardized annual biopsy rate increased from 10.8 biopsies per 100 000 person-years in the first 5 years of the study (1985-1989) to 18.2 biopsies per 100 000 person-years in the last 5 years (2010-2014). The mean age at the time of biopsy increased from 42.5 years (1985-1989) to 51.4 years (2010-2014). Glomerular diseases remained the most prevalent histopathological group, with a growing representation of diabetic kidney disease from 3.69% to 16.18%, and a relative decrease in the proportion of other glomerular diseases from 72.32% to 62.92% of glomerular diagnoses. Tubulointerstitial diseases increased from 5.87% to 7.36% of total diagnoses. Limitations: Classification schemes have changed over time, so recently recognized conditions may have been misclassified in earlier data. There was a changing group of pathologists and nephrologists over this period. Variations in interpretation and application of biopsy indications by physician may influence recorded prevalence of certain diagnoses. We do not yet have complete information on indications or patient outcomes linked to the database. Conclusions: In Southern Alberta, kidney biopsy is being utilized more frequently and in older people. Diabetic nephropathy is increasingly diagnosed, which may reflect either or both changes in the prevalence of causative factors and local biopsy practices.

Several case reports suggest that non-steroidal anti-inflammatory drug (NSAID) use is associated with development of thrombotic microangiopathy (TMA). We conducted a matched population-based case-control study using linked administrative healthcare data in Ontario, Canada to assess the relationship between TMA hospitalization and recent exposure to prescription NSAIDs versus acetaminophen (acetaminophen was chosen as the referent drug because it has no known association with TMA). Cases and controls were drawn from a source population of adults who filled a prescription for either NSAIDs or acetaminophen between 1991 and 2015 (restricted to adults with prescription drug benefits [n = 3.6 million]). We identified 44 eligible cases with a hospital admission for incident TMA and a recent prescription for NSAIDs or acetaminophen. We successfully matched 38 cases (1:4) to 152 controls without TMA on demographics, risk factors for TMA, and indications for NSAID use. Cases and controls were similar with respect to age (71 years) and sex (63% women); however, on average, cases had more comorbidities than controls (12 vs. 14; p

Abstract The ongoing evolution of the SARS-CoV-2 virus has led to a move to update vaccine antigens in 2022 and 2023. These updated antigens were chosen and approved based largely on in vitro neutralisation titres against recent SARS-CoV-2 variants. However, unavoidable delays in vaccine manufacture and distribution meant that the updated booster vaccine was no longer well-matched to the circulating SARS-CoV-2 variant by the time of its deployment. Understanding whether the updating of booster vaccine antigens improves immune responses to subsequent SARS-CoV-2 circulating variants is a major priority in justifying future vaccine updates. Here we analyse all available data on the immunogenicity of variants containing SARS-CoV-2 vaccines and their ability to neutralise later circulating SARS-CoV-2 variants. We find that updated booster antigens give a 1.4-fold [95% CI: 1.07–1.82] greater increase in neutralising antibody levels when compared with a historical vaccine immunogen. We then use this to predict the relative protection that can be expected from an updated vaccine even when the circulating variant has evolved away from the updated vaccine immunogen. These findings help inform the rollout of future booster vaccination programmes.

A hybrid trapped field magnet lens (HTFML) is a promising device that is able to concentrate a magnetic field higher than the applied field continuously, even after removing an external field, which was conceptually proposed by the authors in 2018. In this study, we propose a new additional advantage of the HTFML, which could be applicable for magnetic levitation and separation. The HTFML device consisting of a GdBaCuO bulk cylinder and a GdBaCuO magnetic lens, after the magnetization process from an applied field, Bapp = 10 T, can generate a maximum trapped field, Bc = 11.4 T, as well as an ultra-high magnetic field gradient product, Bz⋅dBz/dz, over ±3000 T2/m at Ts = 20 K, which is higher than that of existing superconducting magnets and large-scale hybrid magnets. Through detailed numerical simulations, the HTFML device is considered for the magnetic separation of a mixture of precious metal particles (Pt, Au, Ag, and Cu) dispersed in pure water, by exploiting the magneto-Archimedes effect. The HTFML can be realized as a compact and mobile desktop-type superconducting bulk magnet system, and there are a wide range of potential industrial applications, such as in the food and medical industries. [ABSTRACT FROM AUTHOR]

IntroductionMethane production inhibitors included in feed additives are increasingly used to suppress methane production in the rumen. Most products interact with the rumen microbiome and/or component biochemical pathways that scavenge free hydrogen ions (H+) to make methane (CH4 ). The capacity of these agents to inhibit rumen methane production is determined by the ability of the chemical to block methane production pathways, the amount of agent delivered to the rumen (i.e. the dose) and the absorption, distribution, metabolism and excretion (i.e. the pharmacokinetic) characteristics of the chemical that contribute to removal from the site of action (the rumen). The intrinsic inhibitory capacity of an agent determines the maximum rate of methane suppression. This maximal rate may reduce according to pharmacokinetic effects arising from dose rate and frequency. Most studies of additive methane reduction efficacy use total mixed ration (TMR; with the additive included into the ration) feeding systems and estimate methane reduction (absolute or relative) across a 24-hour period. Few studies report critical pharmacokinetic parameters, making it difficult to extrapolate findings into non-TMR systems (such as grazing) where differing doses and dose frequencies apply.MethodsWe consider the likely behaviour of a rumen-acting oral additive to reduce methane production applying basic pharmacokinetic principles to propose an analytical approach to data from multiple field studies employing different dose rates and dose frequencies to estimate methane suppression responses. This is based upon a logistic transformation of relative efficacy (percentage reduction in methane comparing treatment with control groups) as the dependent variable and includes total dose, dose frequency, quadratic and interaction terms between total dose and dose frequency as independent variables that potentially capture any pharmacokinetic effects on performance. The model was tested using simulation and verified against real data (cattle 3-nitrooxypropanol (3-NOP) methane-reduction studies).ResultsGood fit between predicted and observed methane suppression was obtained.DiscussionWe propose use of the general form of this logistic model with dose and dose frequency components included that address basic pharmacological impacts on methane suppression as the standard approach to meta-analysis.

Bulk high-temperature superconducting materials can trap magnetic fields up to an order of magnitude larger than conventional permanent magnets. Recent advances in pulsed field magnetization (PFM) techniques now provide a fast and cost-effective method to magnetize bulk superconductors to fields of up to 5 T. We have developed a portable, desktop bulk high-temperature superconducting magnet system by combining advanced PFM techniques with state-of-the-art cryocooler technology and single-grain, REâ€"Baâ€"Cuâ€"O [(RE)BCO, where RE is a rare-earth element or yttrium] bulk superconducting materials. The base temperature of the system is 41 K and it takes about 1 h for the system to cool down to 50 K from room temperature. A capacitor bank, combined with easily-interchangeable, solenoid- or split-type copper magnetizing coils and an insulated bipolar gate transistor acting as a high-speed switch, allows magnetic pulses to be generated with different pulse profiles. The system is capable of trapping magnetic fields of up to ∼3 T. In this work, we report the results of the magnetization of a range of single-grain Yâ€"Baâ€"Cuâ€"O, Euâ€"Baâ€"Cuâ€"O and Gdâ€"Baâ€"Cuâ€"O (GdBCO), bulk superconducting discs using this system. A higher trapped field was recorded using a split coil incorporating iron yokes at temperatures of 65 K and above, whereas at lower temperatures, a higher trapped field was obtained using the solenoid coil. The GdBCO sample achieved the highest trapped field for both single-pulse (SP) and two-stage-multi-pulse (TSMP) methods using the solenoid coil. Maximum trapped fields of 2.26 T at 55 K and 2.85 T at 49 K were recorded at the centre of the top surface of the GdBCO sample for the SP and TSMP methods, respectively. The PFM process is substantially an adiabatic process so, therefore, the thermal contact between the sample and sample holder is of critical importance for cooling the bulk sample during application of the pulse. The design of the sample holder can be modified easily to enhance the thermal stability of the sample in order to achieve a higher trapped field. [ABSTRACT FROM AUTHOR]