Risk-based lung cancer screening performance in a universal healthcare setting.

Globally, lung cancer is the leading cause of cancer death. Previous trials demonstrated that low-dose computed tomography lung cancer screening of high-risk individuals can reduce lung cancer mortality by 20% or more. Lung cancer screening has been approved by major guidelines in the United States, and over 4,000 sites offer screening. Adoption of lung screening outside the United States has, until recently, been slow. Between June 2017 and May 2019, the Ontario Lung Cancer Screening Pilot successfully recruited 7,768 individuals at high risk identified by using the PLCOm2012noRace lung cancer risk prediction model. In total, 4,451 participants were successfully screened, retained and provided with high-quality follow-up, including appropriate treatment. In the Ontario Lung Cancer Screening Pilot, the lung cancer detection rate and the proportion of early-stage cancers were 2.4% and 79.2%, respectively; serious harms were infrequent; and sensitivity to detect lung cancers was 95.3% or more. With abnormal scans defined as ones leading to diagnostic investigation, specificity was 95.5% (positive predictive value, 35.1%), and adherence to annual recall and early surveillance scans and clinical investigations were high (>85%). The Ontario Lung Cancer Screening Pilot provides insights into how a risk-based organized lung screening program can be implemented in a large, diverse, populous geographic area within a universal healthcare system.

Delivery of Cancer Care in Ontario, Canada, During the First Year of the COVID-19 Pandemic.

Importance: The COVID-19 pandemic has impacted cancer systems worldwide. Quantifying the changes is critical to informing the delivery of care while the pandemic continues, as well as for system recovery and future pandemic planning. Objective: To quantify change in the delivery of cancer services across the continuum of care during the COVID-19 pandemic. Design, Setting, and Participants: This population-based cohort study assessed cancer screening, imaging, diagnostic, treatment, and psychosocial oncological care services delivered in pediatric and adult populations in Ontario, Canada (population 14.7 million), from April 1, 2019, to March 1, 2021. Data were analyzed from May 1 to July 31, 2021. Exposures: COVID-19 pandemic. Main Outcomes and Measures: Cancer service volumes from the first year of the COVID-19 pandemic, defined as April 1, 2020, to March 31, 2021, were compared with volumes during a prepandemic period of April 1, 2019, to March 31, 2020. Results: During the first year of the pandemic, there were a total of 4 476 693 cancer care services, compared with 5 644 105 services in the year prior, a difference of 20.7% fewer services of cancer care, representing a potential backlog of 1 167 412 cancer services. While there were less pronounced changes in systemic treatments, emergency and urgent imaging examinations (eg, 1.9% more parenteral systemic treatments) and surgical procedures (eg, 65% more urgent surgical procedures), major reductions were observed for most services beginning in March 2020. Compared with the year prior, during the first pandemic year, cancer screenings were reduced by 42.4% (-1 016 181 screening tests), cancer treatment surgical procedures by 14.1% (-8020 procedures), and radiation treatment visits by 21.0% (-141 629 visits). Biopsies to confirm cancer decreased by up to 41.2% and surgical cancer resections by up to 27.8% during the first pandemic wave. New consultation volumes also decreased, such as for systemic treatment (-8.2%) and radiation treatment (-9.3%). The use of virtual cancer care increased for systemic treatment and radiation treatment and psychosocial oncological care visits, increasing from 0% to 20% of total new or follow-up visits prior to the pandemic up to 78% of total visits in the first pandemic year. Conclusions and Relevance: In this population-based cohort study in Ontario, Canada, large reductions in cancer service volumes were observed. While most services recovered to prepandemic levels at the end of the first pandemic year, a substantial care deficit likely accrued. The anticipated downstream morbidity and mortality associated with this deficit underscore the urgent need to address the backlog and recover cancer care and warrant further study.

Adherence to guidance for prioritizing higher risk groups for breast cancer screening during the COVID-19 pandemic in the Ontario Breast Screening Program: a descriptive study.

BACKGROUND: Breast cancer screening in Ontario, Canada, was deferred during the first wave of the COVID-19 pandemic, and a prioritization framework to resume services according to breast cancer risk was developed. The purpose of this study was to assess the impact of the pandemic within the Ontario Breast Screening Program (OBSP) by comparing total volumes of screening mammographic examinations and volumes of screening mammographic examinations with abnormal results before and during the pandemic, and to assess backlogs on the basis of adherence to the prioritization framework. METHODS: A descriptive study was conducted among women aged 50 to 74 years at average risk and women aged 30 to 69 years at high risk, who participated in the OBSP. Percentage change was calculated by comparing observed monthly volumes of mammographic examinations from March 2020 to March 2021 with 2019 volumes and proportions by risk group. We plotted estimates of backlog volumes of mammographic examinations by risk group, comparing pandemic with prepandemic screening practices. Volumes of mammographic examinations with abnormal results were plotted by risk group. RESULTS: Volumes of mammographic examinations in the OBSP showed the largest declines in April and May 2020 (> 99% decrease) and returned to prepandemic levels as of March 2021, with an accumulated backlog of 340 876 examinations. As of March 2021, prioritization had reduced the backlog volumes of screens for participants at high risk for breast cancer by 96.5% (186 v. 5469 expected) and annual rescreens for participants at average risk for breast cancer by 13.5% (62 432 v. 72 202 expected); there was a minimal decline for initial screens. Conversely, the backlog increased by 7.6% for biennial rescreens (221 674 v. 206 079 expected). More than half (59.4%) of mammographic examinations with abnormal results were for participants in the higher risk groups. INTERPRETATION: Prioritizing screening for those at higher risk for breast cancer may increase diagnostic yield and redirect resources to minimize potential long-term harms caused by the pandemic. This further supports the clinical utility of risk-stratified cancer screening.

Measuring the impact of the COVID-19 pandemic on organized cancer screening and diagnostic follow-up care in Ontario, Canada: A provincial, population-based study.

It is essential to quantify the impacts of the COVID-19 pandemic on cancer screening, including for vulnerable sub-populations, to inform the development of evidence-based, targeted pandemic recovery strategies. We undertook a population-based retrospective observational study in Ontario, Canada to assess the impact of the pandemic on organized cancer screening and diagnostic services, and assess whether patterns of cancer screening service use and diagnostic delay differ across population sub-groups during the pandemic. Provincial health databases were used to identify age-eligible individuals who participated in one or more of Ontario's breast, cervical, colorectal, and lung cancer screening programs from January 1, 2019-December 31, 2020. Ontario's screening programs delivered 951,000 (-41%) fewer screening tests in 2020 than in 2019 and volumes for most programs remained more than 20% below historical levels by the end of 2020. A smaller percentage of cervical screening participants were older (50-59 and 60-69 years) during the pandemic when compared with 2019. Individuals in the oldest age groups and in lower-income neighborhoods were significantly more likely to experience diagnostic delay following an abnormal breast, cervical, or colorectal cancer screening test during the pandemic, and individuals with a high probability of living on a First Nation reserve were significantly more likely to experience diagnostic delay following an abnormal fecal test. Ongoing monitoring and management of backlogs must continue. Further evaluation is required to identify populations for whom access to cancer screening and diagnostic care has been disproportionately impacted and quantify impacts of these service disruptions on cancer incidence, stage, and mortality. This information is critical to pandemic recovery efforts that are aimed at achieving equitable and timely access to cancer screening-related care.

Prescription Patterns in Dialysis Patients: Differences Between Hemodialysis and Peritoneal Dialysis Patients and Opportunities for Deprescription.

BACKGROUND: Patients treated with maintenance dialysis are at high risk of polypharmacy given their many comorbidities as well as complications from their disease state and treatment. The prescribing patterns and burden of polypharmacy in patients treated with maintenance dialysis, and specifically the difference between hemodialysis (HD) and peritoneal dialysis (PD) prescribing, are not well characterized. OBJECTIVES: The objectives of this study were to review the prescribing patterns for patients treated with maintenance dialysis, to compare prescribing pattern between HD and PD, and to identify opportunities for deprescription. DESIGN: This is a retrospective cohort study. SETTING: This study was conducted in all dialysis centers in British Columbia, Canada. PATIENTS: Patients who were receiving chronic dialysis (>120 days on the same dialysis modality) between June 3 and October 1, 2015, and registered in the British Columbia (BC) Renal Patient Records and Outcomes Management Information System. MEASUREMENTS: Patient demographics as well as both prescription and non-prescription medications were collected. Comparison of discrete and continuous variables was made by chi-square analysis and independent t test, respectively. All statistical tests were 2-sided, and a P value of <.05 was considered statistically significant. METHODS: Medications were classified by indication: (1) management of renal complications, (2) cardiovascular (CV) medications, (3) diabetes medications, or (4) management of symptoms, and then classified as to whether they were a "potentially inappropriate medication" (PIM) or not. Ethics approval was granted from the University of British Columbia Research and Ethics Board. RESULTS: In total, 3017 patients met inclusion criteria (2243 HD, 774 PD). The mean age was 66.2 ± 14.8 years. The HD group had more patients over 80 years old (22.1% vs 12.5%) and more patients with diabetes and CV disease. The mean number (standard deviation [SD]) of discrete prescribed medications was 17.71 (5.72) overall with more medications in the HD group versus the PD group. The mean number of medications increased with dialysis vintage in both groups. HD patients were on more medications for renal complications and management of symptoms than PD patients. Of the total number of medications prescribed, 5.02 (2.78) were classified as a PIM, with the number of PIMs higher in HD vs PD patients: 5.37 (2.83) versus 4.02 (2.37). LIMITATIONS: In BC, some of the medications are prescribed through standardized protocols and may not be comparable with other Canadian provinces. We report here prescribing patterns, not utilization patterns, as we are not able to ascertain actual consumption of prescribed medication. CONCLUSION: This study reviews and characterizes both the prescription and non-prescription medication prescribed to HD patients and PD patients in BC. Pill burden in both groups is high, as is the prescription of PIMs. Patients receiving maintenance HD receive more overall medications and more PIMs. These results highlight areas of opportunities for future systematic and patient-informed deprescription initiatives in both patient groups.

CONTEXTE: Les patients sous dialyse à long terme, en raison de leurs nombreuses comorbidités et des complications inhérentes à leur état de santé et à leur traitement, s'exposent à un plus grand risque de polypharmacie. On en sait toutefois peu sur le fardeau qu'elle représente pour ces patients et sur leurs profils de prescription, particulièrement sur les possibles différences entre les patients traités par hémodialyse ou par dialyse péritonéale. OBJECTIFS: Comparer les profils de prescription des patients traités par hémodialyse (HD) et par dialyse péritonéale (DP), et cerner les possibilités de déprescription. TYPE D'ÉTUDE: Étude de cohorte rétrospective. CADRE: Tous les centres de dialyse de la Colombie-Britannique (Canada). SUJETS: Les patients sous dialyse chronique (plus de 120 jours avec la même modalité) entre le 3 juin et le 1er octobre 2015, et inscrits dans la base de données Renal Patient Records and Outcomes Management Information System de Colombie-Britannique. MESURES: Les caractéristiques démographiques des patients et la liste des médicaments, prescrits ou non. Une analyse du chi-carré (variables discontinues) et un test t indépendant (variables continues) ont été employés pour comparer les différentes variables. Tous les tests statistiques étaient bilatéraux. Une valeur de P inférieure à 0,05 a été jugée significative. MÉTHODOLOGIE: Les médicaments ont été classés par indication : (1) traitement des complications rénales, (2) contre les maladies cardiovasculaires (3) contre le diabète et (4) traitement des symptômes. Ils ont ensuite été classés comme étant ou non un « médicament potentiellement inapproprié ¼ (MPI). L'approbation déontologique a été octroyée par le comité d'éthique de la recherche de l'Université de la Colombie-Britannique. RÉSULTATS: Un total de 3 017 patients, dont l'âge moyen était de 66,2 ± 14,8 ans, satisfaisaient les critères d'inclusion (2243 HD, 774 DP). Le groupe HD comportait davantage de patients âgés de plus de 80 ans (22,1 % contre 12,5 %) et de patients souffrant de diabète et de maladies cardiovasculaires. Le nombre moyen de prescriptions (écart-type) s'élevait à 17,71 (5,72) avec des nombres globaux plus élevés dans le groupe HD. Le nombre moyen de médicaments augmentait avec le temps passé en dialyse dans les deux groupes. Les patients HD prenaient davantage de médicaments pour traiter les symptômes et les complications rénales que les patients DP. Dans l'ensemble, une moyenne de 5,02 (2,78) médicaments ont été classés MPI, et leur nombre était plus élevé dans le groupe HD que dans le groupe DP (5,37 [2,83] contre 4,02 [2,37]). LIMITES: En C.-B., certains médicaments sont prescrits selon des protocoles standardisés, et ceci pourrait ne pas être comparable aux autres provinces canadiennes. L'article présente des profils de prescription et non des schémas de prise de médicaments, car nous ne pouvions vérifier la consommation réelle des médicaments prescrits. CONCLUSION: Cette étude examine et caractérise les médicaments sous ordonnance et en vente libre qui sont prescrits aux patients britanno-colombiens traités par HD et DP. La charge médicamenteuse est élevée dans les deux groupes, de même que le nombre d'ordonnances de MPI. Les patients traités par HD se voient prescrire davantage de médicaments et de MPI. Ces résultats montrent que des initiatives de déprescription systématiques et informées sont possibles pour ces deux groupes de patients.

Predicting kidney failure risk after acute kidney injury among people receiving nephrology clinic care.

BACKGROUND: Outcomes after acute kidney injury (AKI) are well described, but not for those already under nephrology clinic care. This is where discussions about kidney failure risk are commonplace. We evaluated whether the established kidney failure risk equation (KFRE) should account for previous AKI episodes when used in this setting. METHODS: This observational cohort study included 7491 people referred for nephrology clinic care in British Columbia in 2003-09 followed to 2016. Predictors were previous Kidney Disease: Improving Global Outcomes-based AKI, age, sex, proteinuria, estimated glomerular filtration rate (eGFR) and renal diagnosis. Outcomes were 5-year kidney failure and death. We developed cause-specific Cox models (AKI versus no AKI) for kidney failure and death, stratified by eGFR (

Evaluating a New International Risk-Prediction Tool in IgA Nephropathy.

Importance: Although IgA nephropathy (IgAN) is the most common glomerulonephritis in the world, there is no validated tool to predict disease progression. This limits patient-specific risk stratification and treatment decisions, clinical trial recruitment, and biomarker validation. Objective: To derive and externally validate a prediction model for disease progression in IgAN that can be applied at the time of kidney biopsy in multiple ethnic groups worldwide. Design, Setting, and Participants: We derived and externally validated a prediction model using clinical and histologic risk factors that are readily available in clinical practice. Large, multi-ethnic cohorts of adults with biopsy-proven IgAN were included from Europe, North America, China, and Japan. Main Outcomes and Measures: Cox proportional hazards models were used to analyze the risk of a 50% decline in estimated glomerular filtration rate (eGFR) or end-stage kidney disease, and were evaluated using the R2D measure, Akaike information criterion (AIC), C statistic, continuous net reclassification improvement (NRI), integrated discrimination improvement (IDI), and calibration plots. Results: The study included 3927 patients; mean age, 35.4 (interquartile range, 28.0-45.4) years; and 2173 (55.3%) were men. The following prediction models were created in a derivation cohort of 2781 patients: a clinical model that included eGFR, blood pressure, and proteinuria at biopsy; and 2 full models that also contained the MEST histologic score, age, medication use, and either racial/ethnic characteristics (white, Japanese, or Chinese) or no racial/ethnic characteristics, to allow application in other ethnic groups. Compared with the clinical model, the full models with and without race/ethnicity had better R2D (26.3% and 25.3%, respectively, vs 20.3%) and AIC (6338 and 6379, respectively, vs 6485), significant increases in C statistic from 0.78 to 0.82 and 0.81, respectively (ΔC, 0.04; 95% CI, 0.03-0.04 and ΔC, 0.03; 95% CI, 0.02-0.03, respectively), and significant improvement in reclassification as assessed by the NRI (0.18; 95% CI, 0.07-0.29 and 0.51; 95% CI, 0.39-0.62, respectively) and IDI (0.07; 95% CI, 0.06-0.08 and 0.06; 95% CI, 0.05-0.06, respectively). External validation was performed in a cohort of 1146 patients. For both full models, the C statistics (0.82; 95% CI, 0.81-0.83 with race/ethnicity; 0.81; 95% CI, 0.80-0.82 without race/ethnicity) and R2D (both 35.3%) were similar or better than in the validation cohort, with excellent calibration. Conclusions and Relevance: In this study, the 2 full prediction models were shown to be accurate and validated methods for predicting disease progression and patient risk stratification in IgAN in multi-ethnic cohorts, with additional applications to clinical trial design and biomarker research.

The BC Glomerulonephritis Network: Improving Access and Reducing the Cost of Immunosuppressive Treatments for Glomerular Diseases.

Glomerulonephritis (GN) is a common cause of end-stage renal disease in Canada and worldwide, and results in significant health care resource utilization and patient morbidity. However, GN has not been a traditional priority of provincial renal health care organizations, despite the known benefits to health services delivery and patient outcomes from integrated provincial care in other types of chronic kidney disease. To address this deficiency, the British Columbia (BC) Provincial Renal Agency created the BC GN Network in 2013 to coordinate provincial GN health services delivery informed by robust population-level data capture on all GN patients in the province via the BC GN Registry. This report describes the use of the BC GN Network infrastructure to systematically develop and evaluate a provincial GN drug formulary to improve patient and physician access to evidence-based immunosuppressive treatments for GN in a cost-efficient manner that successfully halted historical trends of increasing medication costs. An example is provided of using the provincial infrastructure to implement and subsequently evaluate an evidence-informed health policy of converting brand to generic tacrolimus for the treatment of GN. The BC GN Network, including the provincial drug formulary and data infrastructure, is an example of the benefits of expanding the mandate of provincial renal health administrative organizations to include the care of patients with GN, and constitutes a viable health delivery model that can be implemented in other Canadian provinces to achieve similar goals.

La glomérulonéphrite (GN) est une cause courante de néphropathie terminale à l'échelle canadienne et mondiale. Elle est liée à une forte exploitation de ressources en santé et à un taux de morbidité élevé. La GN demeure toutefois négligée par les organismes provinciaux en santé rénale, bien que les effets bénéfiques d'un système de soins provincial intégré sur la prestation des services et l'état de santé des patients soient démontrés dans le cas d'autres types de néphropathie chronique. Pour combler cette lacune, la Provincial Renal Agency de Colombie-Britannique a fondé, en 2013, le GN Network. Ce réseau vise une coordination provinciale des services de prise en charge de la GN basée sur des données rigoureuses à l'échelle populationnelle, recueillies sur tous les patients atteints de GN de la province et colligées dans le GN Registry. Le présent article décrit comment on a utilisé l'infrastructure du GN Network pour mettre en place et évaluer systématiquement une liste provinciale de médicaments remboursables pour le traitement de la GN. On a dressé cette liste pour faciliter aux patients et aux médecins l'accès à des traitements immunosuppresseurs de la GN dont l'efficacité a été démontrée, et ce, de manière économiquement viable, permettant ainsi de mettre fin à la hausse historique du coût de ces médicaments. Nous décrivons ici un exemple d'utilisation de l'infrastructure provinciale pour établir et ensuite évaluer une politique de santé étayée par des données probantes qui encadre la substitution du tacrolimus d'origine par la version générique pour le traitement de la GN. Le GN Network, par son infrastructure de données et sa liste provinciale de médicaments remboursables, démontre les avantages d'un élargissement du mandat des organismes administratifs provinciaux en santé rénale qui inclut la prise en charge de la GN. Il constitue un modèle de prestation des services de santé qui peut être viable et transposable à d'autres provinces canadiennes.

The population-level costs of immunosuppression medications for the treatment of glomerulonephritis are increasing over time due to changing patterns of practice.

Background: Immunosuppression (IS) is the main treatment for most types of glomerulonephritis (GN). Quantifying the cost of IS is necessary to ensure equitable access to therapies and optimal health outcomes, but the real-world cost of IS treatment for GN is largely unknown. We examined temporal changes in the population-level IS medication costs for GN over a 14-year period in a large Canadian province. Methods: We linked a provincial pathology database (containing all GN cases from 2000 to 2012) with renal and medication administrative databases to capture clinical characteristics and IS medications, with follow-up until 2013. The primary outcome (mean IS medication cost per treated patient each year) was evaluated for trends over time. Results: The cohort included 2983 GN patients followed for a mean of 5.7 years. The yearly per-patient medication cost increased 6.8-fold from $205 to $1394 (P < 0.001), with significant increases of 3.5-11.7-fold in anti-neutrophil cytoplasmic antibody (ANCA) vasculitis, focal segmental glomerulosclerosis, lupus nephritis, minimal change disease and membranous nephropathy (P ≤ 0.004), but no change in immunoglobulin A (IgA) nephropathy. The cost of mycophenolate mofetil, calcineurin inhibitors and rituximab increased significantly (P < 0.001) such that in 2000 they accounted for 17.6% of medication costs and were used by 2.2% of patients, which increased to 94.5% and 44.6%, respectively, in 2013. The costs of azathioprine, cyclophosphamide and prednisone increased only slightly or decreased. Patterns of drug use and contribution to cost varied by type of GN. Conclusions: These are the first population-level estimates of the IS treatment costs for GN, and demonstrate a striking increase due to changing practice patterns from older, cheaper medications to newer, more expensive therapies. These results provide important information to guide future health policy strategies and cost-effectiveness research in glomerular diseases.

Femoral Arteriovenous Grafts for Hemodialysis: Retrospective Comparison With Upper Extremity Grafts and Fistulas.

BACKGROUND: Femoral arteriovenous grafts are rarely used to provide vascular access for dialysis patients. This is likely due, in part, to historically high rates of graft loss from infection and thrombosis. However, for selected patients who have exhausted all access options in the upper extremity, femoral grafts can provide additional sites for access creation and may be preferred over central venous catheters. OBJECTIVE: We sought to demonstrate that femoral grafts can provide a reliable and safe alternative to central venous catheters for selected patients. METHODS: A single-center retrospective review in Vancouver, Canada, from April 1, 2008, to March 31, 2012, was conducted. All patients with new arteriovenous access (grafts and fistulas) created during the study period were included in the study population and followed for a minimum of 2 years. Comparisons of patency (primary, secondary, and functional) and complications (infectious and noninfectious) were made between the different access types. RESULTS: Thirteen patients with femoral grafts were compared with 22 patients with arm grafts and 384 patients with fistulas. Femoral grafts had higher rates of thrombosis (46% with a thrombotic event) and a higher requirement for interventions (1.3 angioplasties and 0.12 thrombolytic procedures per patient per year). However, compared with arm grafts, femoral grafts had superior secondary and functional patency. No difference in patency was seen when comparing femoral grafts with upper extremity fistulas. Only 2 patients with femoral grafts required antibiotics for infection, and no grafts were lost to infection. CONCLUSIONS: For patients with limited access options remaining, femoral grafts may provide an additional form of vascular access before resorting to catheter use. Our study shows that with appropriate patient selection, femoral grafts have low infection rates and patency that is comparable with other access types.

CONTEXTE: De manière générale, les greffons artérioveineux fémoraux sont rarement utilisés pour fournir des accès vasculaires aux patients dialysés, très probablement en raison des taux historiquement élevés de perte du greffon due à une infection ou à une thrombose. Toutefois, pour certains patients ayant épuisé toutes les options d'accès dans les membres supérieurs, les greffons fémoraux peuvent fournir des sites supplémentaires pour la création d'un accès vasculaire et peuvent être préférés aux cathéters veineux centraux. OBJECTIF DE L'ÉTUDE: Nous avons voulu démontrer que les greffons fémoraux peuvent fournir une solution de rechange fiable et sûre aux cathéters veineux centraux chez certains patients. MÉTHODOLOGIE: Il s'agit d'une étude rétrospective qui s'est tenue dans un centre hospitalier de Vancouver, au Canada, entre le 1er avril 2008 et le 31 mars 2012. Tous les patients chez qui on a procédé à un nouvel accès artérioveineux (greffons ou fistules) au cours de la période d'étude ont été inclus. Les patients recrutés ont été suivis sur une période minimale de deux ans. La perméabilité vasculaire (primaire, secondaire et fonctionnelle) et les complications rapportées (infectieuses et non infectieuses) ont été comparées entre les différents types d'accès. RÉSULTATS: Pour cette étude, treize patients avec greffons artérioveineux fémoraux ont été comparés à 22 patients avec greffons artérioveineux brachiaux et 384 patients avec fistules. Les greffons fémoraux ont présenté des taux plus élevés de thrombose (46% des patients ont subi un événement thrombotique) et nécessité davantage d'interventions (moyenne de 1,3 angioplastie et de 0,12 procédure thrombolytique par patient par année). Toutefois, lorsque comparés aux greffons brachiaux, les greffons fémoraux présentaient des valeurs de perméabilité secondaire et fonctionnelle supérieures. Aucune différence de perméabilité n'a cependant été observée lors de la comparaison des greffons fémoraux et des fistules des membres supérieurs. Seuls deux patients avec un greffon artérioveineux fémoral ont dû être traités aux antibiotiques pour soigner une infection, et aucune perte de greffon en raison d'une infection n'a été observée au cours de l'étude. CONCLUSIONS: Pour les patients dont les possibilités d'accès vasculaire sont limitées, le recours à un greffon artérioveineux fémoral peut s'avérer une option supplémentaire avant de devoir recourir à une sonde. Notre étude montre qu'en portant une attention particulière à la sélection des patients, les greffons artérioveineux fémoraux présentent de faibles taux d'infections et une perméabilité comparable à celle des autres types d'accès vasculaires.

The MEST score provides earlier risk prediction in lgA nephropathy.

The Oxford Classification of IgA nephropathy (IgAN) includes the following four histologic components: mesangial (M) and endocapillary (E) hypercellularity, segmental sclerosis (S) and interstitial fibrosis/tubular atrophy (T). These combine to form the MEST score and are independently associated with renal outcome. Current prediction and risk stratification in IgAN requires clinical data over 2 years of follow-up. Using modern prediction tools, we examined whether combining MEST with cross-sectional clinical data at biopsy provides earlier risk prediction in IgAN than current best methods that use 2 years of follow-up data. We used a cohort of 901 adults with IgAN from the Oxford derivation and North American validation studies and the VALIGA study followed for a median of 5.6 years to analyze the primary outcome (50% decrease in eGFR or ESRD) using Cox regression models. Covariates of clinical data at biopsy (eGFR, proteinuria, MAP) with or without MEST, and then 2-year clinical data alone (2-year average of proteinuria/MAP, eGFR at biopsy) were considered. There was significant improvement in prediction by adding MEST to clinical data at biopsy. The combination predicted the outcome as well as the 2-year clinical data alone, with comparable calibration curves. This effect did not change in subgroups treated or not with RAS blockade or immunosuppression. Thus, combining the MEST score with cross-sectional clinical data at biopsy provides earlier risk prediction in IgAN than our current best methods.

Identifying the ideal metric of proteinuria as a predictor of renal outcome in idiopathic glomerulonephritis.

The majority of our insight about glomerulonephritis (GN) is from observational research. Because proteinuria is an important element of outcome in GN, the validity of observational analyses is dependent on the metric used to model proteinuria. Previous metrics of proteinuria included the value at baseline, the average of all values over the entire follow-up (time-averaged), the instantaneous value at each time point (time-varying), or the average of all values prior to each time point, and each of these standardized to body surface area. It was not known which of these metrics best accounts for the risk of renal outcome and should be used in GN research. To address this, we studied 1351 adult patients with IgA nephropathy, focal segmental glomerulosclerosis, and membranous nephropathy from the Toronto GN Registry. Cox regression models for the risk of end-stage renal disease or a halving of estimated glomerular filtration rate included each proteinuria metric and were compared using model fit and discrimination. Proteinuria did not need to be standardized to body surface area. Time-varying proteinuria was the best metric to account for the prognostic effects of proteinuria over time, especially in focal segmental glomerulosclerosis and IgA nephropathy over the majority of follow-up, and in membranous nephropathy earlier in the disease course. Using alternate proteinuria metrics biased analyses up to 30.3%. These findings can improve the validity and design of future observational and prediction modeling studies in GN.

The need for improved uptake of the KDIGO glomerulonephritis guidelines into clinical practice in Canada: a survey of nephrologists.

BACKGROUND: The lack of glomerulonephritis (GN) guidelines has historically contributed to substantial variability in the treatment of GN. We hypothesize that there are barriers to GN guideline implementation leading to incomplete translation of the 2012 KDIGO GN guidelines into patient care, and that current practice patterns deviate from guideline recommendations. METHODS: Adult nephrologists in Canada (N = 390) were surveyed using a web-based tool. The survey of 40 questions captured physician demographics, self-reported GN case load, treatment approaches and barriers to guideline implementation. RESULTS: The response rate was 44%. Physicians report seeing six (IQR 4,10) new cases of idiopathic GN every 6 months. The majority treat ANCA GN according to guidelines, but 9-37% treat nephrotic focal segmental glomerulosclerosis or membranous nephropathy with non-recommended immunosuppression and 6-9% do not treat with any immunotherapy, whereas 26% treat subnephrotic disease with immunosuppression. The majority indicated that standardized care tools would improve patient care, but they were only available to 25-44%. Patient education tools and nursing support are unavailable to 87 and 67%, respectively; insurance coverage for immune therapies is poorly accessible to 84%, yet 86% feel this would improve care and 96% of physicians support comparing their practice with benchmarks from provincial GN registries. CONCLUSIONS: We show that 2 years after the publication of the KDIGO GN guidelines, 15-46% of Canadian nephrologists report treatment strategies not in keeping with guideline recommendations. We identify barriers to guideline implementation and widespread physician support for initiatives that address these barriers to improve patient care.

Bayesian adjustment for measurement error in continuous exposures in an individually matched case-control study.

BACKGROUND: In epidemiological studies explanatory variables are frequently subject to measurement error. The aim of this paper is to develop a Bayesian method to correct for measurement error in multiple continuous exposures in individually matched case-control studies. This is a topic that has not been widely investigated. The new method is illustrated using data from an individually matched case-control study of the association between thyroid hormone levels during pregnancy and exposure to perfluorinated acids. The objective of the motivating study was to examine the risk of maternal hypothyroxinemia due to exposure to three perfluorinated acids measured on a continuous scale. Results from the proposed method are compared with those obtained from a naive analysis. METHODS: Using a Bayesian approach, the developed method considers a classical measurement error model for the exposures, as well as the conditional logistic regression likelihood as the disease model, together with a random-effect exposure model. Proper and diffuse prior distributions are assigned, and results from a quality control experiment are used to estimate the perfluorinated acids' measurement error variability. As a result, posterior distributions and 95% credible intervals of the odds ratios are computed. A sensitivity analysis of method's performance in this particular application with different measurement error variability was performed. RESULTS: The proposed Bayesian method to correct for measurement error is feasible and can be implemented using statistical software. For the study on perfluorinated acids, a comparison of the inferences which are corrected for measurement error to those which ignore it indicates that little adjustment is manifested for the level of measurement error actually exhibited in the exposures. Nevertheless, a sensitivity analysis shows that more substantial adjustments arise if larger measurement errors are assumed. CONCLUSIONS: In individually matched case-control studies, the use of conditional logistic regression likelihood as a disease model in the presence of measurement error in multiple continuous exposures can be justified by having a random-effect exposure model. The proposed method can be successfully implemented in WinBUGS to correct individually matched case-control studies for several mismeasured continuous exposures under a classical measurement error model.