Kidney Failure Risk Equation in vascular access planning: a population-based study supporting value in decision making.

Background: The Kidney Failure Risk Equation (KFRE) can play a better role in vascular access (VA) planning in patients with chronic kidney disease (CKD) requiring hemodialysis (HD). We described the VA creation and utilization pattern under existing estimated glomerular filtration rate (eGFR)-based referral, and investigated the utility of KFRE score as an adjunct variable in VA planning. Methods: Patients with CKD aged ≥18 years with eGFR <20 mL/min/1.73 m2 who chose HD as dialysis modality from January 2010 to August 2020 were included from a population-based database in British Columbia, Canada. Modality selection date was the index date. Exposures were categorized as (i) current eGFR-based referral, (ii) eGFR-based referral plus KRFE 2-year risk score on index date (KFRE-2) >40% and (iii) eGFR-based referral plus KFRE-2 ≤40%. We estimated the proportion of patients who started HD on arteriovenous fistula/graft (AVF/G) within 2 years, indicating timely pre-emptive creation, and the proportion of patients in whom AVF/G was created but did not start HD within 2 years, indicating too-early creation. Results: Study included 2581 patients, median age 71 years, 60% male. Overall, 1562(61%) started HD and 276 (11%) experienced death before HD initiation within 2 years. Compared with current referral, the proportion of patients who started HD on AVF/G was significantly higher when KFRE-2 was considered in addition to current referral (49% vs 58%, P-value <.001). Adjunct KFRE-2 significantly reduced too-early creation (31% vs 18%, P-value <.001). Conclusions: KFRE in addition to existing eGFR-based referral for VA creation has the potential to improve VA resource utilization by ensuring more patients start HD on AVF/G and may minimize too-early/unnecessary creation. Prospective research is necessary to validate these findings.

Oral Nutritional Supplement Prescription and Patient-Reported Symptom Burden Among Patients With Late-Stage Non-Dialysis Chronic Kidney Disease.

Background: Malnutrition and protein-energy wasting (PEW) are nutritional complications of advanced chronic kidney disease (CKD) that contribute to morbidity, mortality, and decreased quality of life. No previous studies have assessed the effect of oral nutritional supplements (ONSs) on patient-reported symptom burden among patients with non-dialysis CKD (CKD-ND) who have or are at risk of malnutrition/PEW. Objective: The objective of this study was (1) to quantify the associations between baseline nutritional parameters and patient-reported symptom scores for wellbeing, tiredness, nausea, and appetite and (2) to compare the change in symptom scores among patients prescribed ONS with patients who did not receive ONS in a propensity-score-matched analysis. Design: This study conducted observational cohort analysis using provincial registry data. Setting: This study was done in multidisciplinary CKD clinics in British Columbia. Patients: Adult patients >18 years of age with CKD-ND entering multidisciplinary CKD clinics between January 1, 2010-July 31, 2019 who had at least 2 Edmonton Symptom Assessment System Revised: Renal (ESASr:Renal) assessments. Measurements: The measurements include nutrition-related parameters such as body mass index (BMI), serum albumin, serum phosphate, serum bicarbonate, neutrophil-to-lymphocyte ratio (NLR), and ESASr:Renal scores (overall and subscores for wellbeing, tiredness, nausea, and appetite). Methods: Multivariable linear regression was applied to assess associations between nutritional parameters and ESASr:Renal scores. Propensity-score matching using the greedy method was used to match patients prescribed ONS with those not prescribed ONS using multiple demographic, comorbidity, health care utilization, and temporal factors. Linear regression was used to assess the association between first ONS prescription and change in ESASr:Renal overall score and subscores for wellbeing, tiredness, nausea, and appetite. Results: Of total, 2076 patients were included. Higher baseline serum albumin was associated with lower overall ESASr:Renal score (-0.20, 95% confidence interval [CI] = -0.40 to -0.01 per 1 g/L increase in albumin), lower subscores for tiredness (-0.04, 95% CI = -0.07 to -0.01), nausea (-0.03, 95% CI = -0.04 to -0.01), and appetite (-0.03, 95% CI = -0.06 to -0.01). Higher BMI was associated with higher overall ESASr:Renal score (0.32, 95% CI = 0.16 to 0.48 per 1 kg/m2 increase in BMI), higher symptom subscores for wellbeing (0.02, 95% CI = 0.00 to 0.04) and tiredness (0.05, 95% CI = 0.02 to 0.07). Higher baseline NLR was associated with higher overall score (0.21, 95% CI = 0.03 to 0.39 per 1 unit increase in NLR), higher symptom subscores for wellbeing (0.03, 95% CI = 0.01 to 0.05) and nausea (0.03, 95% CI = 0.02 to 0.05). In the propensity-score-matched analysis, there were no statistically significant associations between ONS prescription and change in overall ESASr:Renal (beta coefficient for change in ESASr:Renal = 0.17, 95% CI = -2.64 to 2.99) or for subscores for appetite, tiredness, nausea, and wellbeing. Limitations: Possible residual confounding. The ESASr:Renal assessments were obtained routinely only in patients with G5 CKD-ND and/or experiencing significant CKD-related symptoms. Conclusions: This exploratory observational analysis of patients with advanced non-dialysis CKD demonstrated BMI, serum albumin, and NLR were modestly associated with patient-reported symptoms, but we did not observe an association between ONS use and change in ESASr:Renal scores.

Contexte: La malnutrition et la dénutrition protéino-énergétique (DPÉ) sont des complications nutritionnelles de l'insuffisance rénale chronique (IRC) de stade avancé qui contribuent à la morbidité, à la mortalité et à la diminution de la qualité de vie associées à la maladie. Aucune étude n'a évalué l'effet des suppléments nutritionnels administrés par voie orale (SNO) sur le fardeau des symptômes autodéclarés par les patients non dialysés atteints d'IRC (IRC-ND) et souffrant de malnutrition/DPÉ ou risquant d'en souffrir. Objectifs: (1) Quantifier les associations entre les paramètres nutritionnels initiaux et les scores des symptômes autodéclarés en lien avec le bien-être, la fatigue, les nausées et l'appétit. (2) Comparer, dans une analyse des scores de propension appariés, la variation des scores associés aux symptômes des patients ayant reçu une ordonnance de SNO par rapport aux patients n'en ayant pas reçu. Conception: Analyse de cohorte observationnelle à partir des données du registre provincial. Cadre: Cliniques multidisciplinaires d'IRC en Colombie-Britannique. Sujets: Des patients adultes atteints d'IRC-ND admis entre le 1er janvier 2010 et le 31 juillet 2019 dans des cliniques multidisciplinaires d'IRC avec au moins deux évaluations selon l'Échelle d'évaluation Edmonton pour l'insuffisance rénale (ESASr:renal­Edmonton Symptom Assessment System Revised: Renal). Mesures: Les paramètres liés à la nutrition: indice de masse corporelle (IMC), albumine sérique, phosphate sérique, bicarbonate sérique, rapport neutrophiles/lymphocytes (RNL), ainsi que les scores ESASr:renal (scores globaux et scores secondaires pour le bien-être, la fatigue, les nausées et l'appétit). Méthodologie: La régression linéaire multivariable a servi à évaluer les associations entre les paramètres nutritionnels et les scores ESASr:renal. Une correspondance des scores de propension par la méthode Greedy a été utilisée pour apparier des patients ayant reçu ordonnance de SNO avec des patients n'en ayant pas reçu selon plusieurs facteurs démographiques, les comorbidités, l'utilisation des soins de santé et des facteurs temporels. La régression linéaire a servi à évaluer l'association entre la première ordonnance de SNO et la variation des scores globaux et des scores secondaires de l'ESASr:renal pour le bien-être, la fatigue, les nausées et l'appétit. Résultats: Au total, 2 076 patients ont été inclus à l'étude. Un taux d'albumine sérique plus élevé à l'inclusion était associé à un score ESASr:rénal global plus faible (-0,20 [IC 95 %: -0,40 à -0,01 pour 1 g/L d'augmentation de l'albumine]) et à des scores secondaires plus faibles pour la fatigue (-0,04 [IC 95 %: -0,07 à -0,01]), les nausées (-0,03 [IC 95 %: -0,04 à 0,01]) et l'appétit (0,03 [IC 95 %: -0,06 à -0,01]). Un IMC plus élevé était associé à un score ESASr:renal global plus élevé (0,32 [IC 95 %: 0,16 à 0,48 par augmentation de 1 kg/m2 de l'IMC]), des scores secondaires de symptômes plus élevés pour le bien-être (0,02 [IC 95 %: 0,00 à 0,04]) et la fatigue (0,05 [IC 95 %: 0,02 à 0,07]). Un RNL initial plus élevé était associé à un score ESASr:renal global plus élevé (0,21 [IC 95 %: 0,03 à 0,39 par unité d'augmentation du RNL]), des scores secondaires de symptômes plus élevés pour le bien-être (0,03 [IC 95 %: 0,01 à 0,05]) et les nausées (0,03 [IC 95 %: 0,02 à 0,05]). Dans l'analyse des scores de propension appariés, aucune association statistiquement significative n'a été observée entre une ordonnance de SNO et une variation significative dans les scores globaux de l'ESASr:renal (coefficient bêta de variation de l'ESASr:rénal: 0,17 [IC 95 %: -2,64 ­ à 2,99]) ou les scores secondaires pour l'appétit, la fatigue, les nausées et le bien-être. Limites: Possibilité de facteurs de confusion résiduels. Les évaluations ESASr:renal ont été effectuées de routine uniquement pour les patients atteints d'IRC-ND G5 et/ou présentant des symptômes importants liés à l'IRC. Conclusion: Cette analyse observationnelle exploratoire portant sur des patients atteints d'IRC avancée non dialysés a démontré que l'IMC, l'albumine sérique et le RNL étaient associés de façon modeste aux symptômes autodéclarés. Toutefois, aucune association n'a été observée entre une ordonnance de SNO et une variation des scores ESASr:renal.

Humoral Response Following 3 Doses of mRNA COVID-19 Vaccines in Patients With Non-Dialysis-Dependent CKD: An Observational Study.

Background: Chronic kidney disease (CKD) is associated with a lower serologic response to vaccination compared to the general population. There is limited information regarding the serologic response to coronavirus disease 2019 (COVID-19) vaccination in the non-dialysis-dependent CKD (NDD-CKD) population, particularly after the third dose and whether this response varies by estimated glomerular filtration rate (eGFR). Methods: The NDD-CKD (G1-G5) patients who received 3 doses of mRNA COVID-19 vaccines were recruited from renal clinics within British Columbia and Ontario, Canada. Between August 27, 2021, and November 30, 2022, blood samples were collected serially for serological testing every 3 months within a 9-month follow-up period. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) anti-spike, anti-receptor binding domain (RBD), and anti-nucleocapsid protein (NP) levels were determined by enzyme-linked immunosorbent assay (ELISA). Results: Among 285 NDD-CKD patients, the median age was 67 (interquartile range [IQR], 52-77) years, 58% were men, 48% received BNT162b2 as their third dose, 22% were on immunosuppressive treatment, and COVID-19 infection by anti-NP seropositivity was observed in 37 of 285 (13%) patients. Following the third dose, anti-spike and anti-RBD levels peaked at 2 months, with geometric mean levels at 1131 and 1672 binding antibody units per milliliter (BAU/mL), respectively, and seropositivity rates above 93% and 85%, respectively, over the 9-month follow-up period. There was no association between eGFR or urine albumin-creatinine ratio (ACR) with mounting a robust antibody response or in antibody levels over time. The NDD-CKD patients on immunosuppressive treatment were less likely to mount a robust anti-spike response in univariable (odds ratio [OR] 0.43, 95% confidence interval [CI]: 0.20, 0.93) and multivariable (OR 0.52, 95% CI: 0.25, 1.10) analyses. An interaction between age, immunoglobulin G (IgG) antibody levels, and time was observed in both unadjusted (anti-spike: P = .005; anti-RBD: P = .03) and adjusted (anti-spike: P = .004; anti-RBD: P = .03) models, with older individuals having a more pronounced decline in antibody levels over time. Conclusion: Most NDD-CKD patients were seropositive for anti-spike and anti-RBD after 3 doses of mRNA COVID-19 vaccines and we did not observe any differences in the antibody response by eGFR.

Are patients with primary glomerular disease at increased risk of malignancy?

Over the past decade, several observational studies and case series have provided evidence suggesting a connection between glomerular diseases (GN) and the development of malignancies, with an estimated risk ranging from 5%-11%. These malignancies include solid organ tumors as well as hematologic malignancies such as lymphoma and leukemia. However, these risk estimates are subject to several sources of bias, including unmeasured confounding from inadequate exploration of risk factors, inclusion of GN cases that were potentially secondary to an underlying malignancy, misclassification of GN type, and ascertainment bias arising from an increased likelihood of physician encounters compared to the general population. Consequently, population-based studies that accurately evaluate the cancer risk in GN populations are lacking. While it is speculated that long-term use of immunosuppressive medications and GN disease activity measured by proteinuria and estimated glomerular filtration rate may be associated with cancer risk in patients with GN, the independent role of these risk factors remains largely unknown. The presence of these knowledge gaps could lead to (i) lack of awareness of cancer as a potential chronic complication of GN, (ii) under-utilization of routine screening practices in clinical care that allow early diagnosis and treatment of malignancies, and (iii) under-recognition of modifiable risk factors to decrease the risk of de novo malignancies over time. This review summarizes the current evidence on the risk of cancer in patients with GN, explores the limitations of prior studies, and discusses methodological challenges and potential solutions for obtaining accurate estimates of cancer risk and identifying modifiable risk factors unique to GN populations.

Messaging preferences for the role of pharmacists in pharmacy education recruitment material.

INTRODUCTION: Applications to pharmacy programs are declining worldwide. Previous research suggests that positioning of recruitment material according to prospective students' preferences may increase interest in the profession and entry-to-practice programs. The aim of this study was to determine messaging preferences for the role of the pharmacist. METHODS: This was a best-worst choice survey conducted at one institution in one country. Participants included prospective students, current pharmacy students, and others representing the general public. Thirteen statements (plus one control) describing the role of the pharmacist were extracted from pharmacy program websites. Survey participants completed the best-worst choice analysis, and a conditional logit model was used to estimate statement preference coefficients. RESULTS: A total of 150 complete survey responses were collected. The top ranked statement was, "Pharmacists are health care professionals who are experts in medicines" and the least ranked statement was the control statement, "Pharmacists are experts in dispensing medications and counting tablets." No differences were observed between the different groups of survey respondents. Other highly ranked statements spoke to the expertise of the pharmacist and promoted a well-defined role. Catchy statements, such as "Pharmacists are medicines superheroes," were not ranked highly. CONCLUSIONS: This study found that current and prospective pharmacy students preferred descriptive and explicit messages that align with pharmacists' professional identity for promotion of the pharmacist's role.

COVID-19 Vaccine Effectiveness Among Patients With Maintenance Dialysis; Observations From Population Level Cohort Studies in 2 Large Canadian Provinces.

Background: It was unknown if the effectiveness of COVID-19 vaccines could vary between regions. Objective: To explore key differences in COVID-19 pandemics in British Columbia (BC) and Ontario (ON) and to investigate if the vaccine effectiveness (VE) among maintenance dialysis population could vary between these 2 provinces. Study Design: Retrospective cohort. Setting and Patients: This retrospective cohort study included patients from population-level registry in BC who were on maintenance dialysis from December 14, 2020, to December 31, 2021. The COVID-19 VE among BC patients were compared to the previously published VE among similar patient population in ON. Two-sample t-test for unpaired data were used to investigate if the VE estimates from BC and ON were statistically significantly different. Exposure: Exposure to COVID-19 vaccines (BNT162b2, ChAdOx1nCoV-19, mRNA-1273) was modeled in a time-dependent fashion. Outcome: Reverse transcription polymerase chain reaction (RT-PCR) confirmed COVID-19 infection and related severe outcome defined by hospitalization or death. Analytical Approach: Time-dependent Cox regression analysis. Results: This study using BC data included 4284 patients. Median age was 70 years and 61% was male. Median follow-up time was 382 days. 164 patients developed COVID-19 infection. The ON study by Oliver et al included 13 759 patients with a mean age of 68 years. 61% of the study sample was male. Median follow-up time for patients in the ON study was 102 days. A total of 663 patients developed COVID-19 infection. During the overlapped study periods, BC had 1 pandemic wave compared to 2 in Ontario with substantially higher infection rates. Vaccination timing and roll out among the study population were substantially different. Median time between first and second dose was 77 days (interquartile range [IQR] 66-91) in BC compared to 39 days (IQR = 28-56) in Ontario. Distribution of COVID-19 variants during the study period appeared to be similar. In BC, compared to pre-vaccination person-time, risk of developing COVID-19 infection was 64% (aHR [95% CI] 0.36 [0.21, 0.63]), 80% (0.20 [0.12, 0.35]) and 87% (0.13 [0.06, 0.29]) less when exposed to 1 dose, 2 doses, and 3 doses, respectively. In contrast, risk reduction among Ontario patients was 41% (0.59 [0.46, 0.76]) and 69% (0.31 [0.22, 0.42]) for 1 dose and 2 doses, respectively (patients did not receive the third dose by study end date of June 30, 2021). VE against COVID-19 infection in BC and ON was not statistically significantly different, the P values for exposure to 1 dose and 2 doses comparisons were 0.103 and 0.163, respectively. Similarly, in BC, risk of developing COVID-19-related hospitalization or death were 54% (0.46 [0.24, 0.90]), 75% (0.25 [0.13, 0.48]) and 86% (0.14 [0.06, 0.34]) less for 1 dose, 2 doses, and 3 doses, respectively. Interestingly, exposure to second dose appeared to provide better protection against severe outcomes in Ontario versus BC, risk reduction was 83% (aHR = 0.17, 95% CI [0.10, 0.30]) and 75% (aHR = 0.25, 95% CI [0.13, 0.48]), respectively. However, the adjusted hazard ratios were not statistically significantly different between BC and ON, the P values were 0.676 and 0.369 for exposure to 1 dose and 2 doses, respectively. Limitations: Infection rate, variant distribution, and vaccination strategies were compared using publicly available data. VE estimates were compared from 2 independent cohort studies from 2 provinces without patient-level data sharing. Conclusions: Health Canada approved COVID-19 vaccines were highly effective among patients with maintenance dialysis from BC and ON. Although there appeared to be between province differences in pandemic waves and vaccination strategies, the VE against COVID-19 infection as well as related severe outcome appeared to be not statistically significantly different. A nationally representative VE could be estimated using pooled data from multiple regions.

Contexte: On ignore si l'efficacité des vaccins contre la COVID-19 varie d'une région à l'autre. Objectif: Examiner les principales différences entre les infections à la COVID-19 en Colombie-Britannique (C.-B.) et en Ontario et déterminer si l'efficacité des vaccins (EV) varie entre ces deux provinces dans la population des personnes sous dialyze d'entretien. Type d'étude: Étude de cohorte rétrospective. Sujets et cadre de l'étude: Cette étude de cohorte rétrospective porte sur des patients issus du registre de la population de Britanno-Colombiens sous dialyze d'entretien entre le 14 décembre 2020 et le 31 décembre 2021. L'EV contre la COVID-19 chez les patients de la C.-B. a été comparée à l'EV précédemment publiée pour une population de patients similaires en Ontario. Un test t à deux échantillons de données non appariées a été utilisé pour déterminer si les estimations de l'EV en C.-B. et en Ontario étaient statistiquement différentes. Exposition: L'exposition aux vaccins contre la COVID-19 (BNT162b2, ChAdOx1nCoV-19, mRNA-1273) a été modélisée en fonction du temps. Résultats: La RT-PCR a confirmé l'infection à la COVID-19 et les résultats graves liés à la maladie ont été définis par une hospitalization ou le décès. Approche analytique: Analyze par régression Cox dépendante du temps. Résultats: L'étude en cours utilisant les données de la C.-B. incluait 4 284 patients. L'âge médian était de 70 ans et 61 % étaient des hommes. Le temps médian de suivi était de 382 jours. De ces patients, 164 avaient contracté la COVID-19. L'étude de l'Ontario (Oliver et coll.) porte sur 13 759 patients (61 % d'hommes) dont la moyenne d'âge était de 68 ans. Le temps médian de suivi pour les patients de l'étude ontarienne était de 102 jours. Un total de 663 patients avait contracté la COVID-19. Au cours des périodes d'étude qui se sont chevauchées, la Colombie-Britannique a connu une vague pandémique, contre deux en Ontario, avec des taux d'infection beaucoup plus élevés. Le calendrier et le déploiement de la vaccination parmi la population étudiée étaient sensiblement différents. Le temps médian entre la première et la deuxième dose de vaccin était de 77 jours en C.-B. (ÉIQ: 66-91) et de 39 jours en Ontario (ÉIQ: 28-56). La répartition des différents variants du virus de la COVID-19 au cours de la période d'étude semble similaire. En C.-B., comparativement au temps-personne avant la vaccination, le risque de contracter la COVID-19 était réduit de 64 % (risque relatif corrigé [IC 95 %]: 0,36 [0,21-0,63]) après une dose, de 80 % (RRc: 0,20 (0,12-0,35)) après deux doses et de 87 % (RRc: 0,13 (0,06-0,29)) après 3 doses. En Ontario, la réduction de ce même risque était de 41 % (RRc: 0,59 (0,46-0,76)) après une dose et de 69 % (RRc: 0,31 (0,22-0,42)) après deux doses (les patients n'avaient pas reçu de troisième dose le 30 juin 2021, la date de fin de l'étude). L'EV contre une infection à la COVID-19 n'était pas statistiquement différente entre les deux provinces, avec des valeurs p pour les comparaisons d'exposition respectivement de 0,103 et de 0,163 pour la 1re et 2e dose. De même, en Colombie-Britannique, le risque d'être hospitalisé ou de décéder en raison d'une infection à la COVID-19 était réduit de 54 % (RRc: 0,46 (0,24-0,90)) après une dose, de 75 % (RRc: 0,25 (0,13-0,48)) après deux doses et de 86 % (RRc: 0,14 [0,06-0,34] après trois doses. Il est intéressant de noter que la deuxième dose semblait offrir une meilleure protection contre les complications graves aux patients de l'Ontario par rapport à ceux de la C.-B., avec une réduction du risque de 83 % [RRc: 0,17 (0,10-0,30)] et de 75 % [RRc: 0,25 (0,13-0,48)], respectivement. Les valeurs du risque relatif corrigé n'étaient cependant pas statistiquement différentes, leurs valeurs p s'établissant à 0,676 après la 1re dose et à 0,369 après la 2e. Limites: Le taux d'infection, la distribution des variants et les stratégies de vaccination ont été comparés à partir des données disponibles au public. Les estimations de l'EV ont été comparées à partir de deux études de cohortes indépendantes dans deux provinces, sans partage de données au niveau des patients. Conclusion: Les vaccins contre la COVID-19 approuvés par Santé Canada ont été très efficaces chez les patients sous dialyze d'entretien en Colombie-Britannique et en Ontario. Bien qu'il y ait des différences entre les provinces en ce qui concerne les vagues de pandémie et les stratégies de vaccination, l'efficacité des vaccins contre une infection à la COVID-19 et ses complications graves ne semble pas significativement différente. Une estimation représentative à l'échelle nationale de l'efficacité des vaccins pourrait être calculée à partir de données regroupées provenant de plusieurs régions.

Long-term effect of COVID-19 infection on kidney function among COVID-19 patients followed in post-COVID-19 recovery clinics in British Columbia, Canada.

BACKGROUND: We investigated the effect of Post-Acute COVID Syndrome or "long-COVID" on kidney function among patients followed in post-COVID recovery clinics (PCRC) in British Columbia, Canada. METHODS: Long-COVID patients referred to PCRC between July 2020 to April 2022, aged ≥18 years who had an estimated glomerular filtration rate (eGFR) value recorded at 3 months from the coronavirus disease 2019 (COVID-19) diagnosis (index) date were included. Those requiring renal replacement therapy prior to index date were excluded. Primary outcome was change in eGFR and urine albumin-creatinine ratio (UACR) after COVID-19 infection. The proportion of patients in each of the six eGFR categories (<30, 30-44, 45-59, 60-89, 90-120 and >120 mL/min/1.73 m2) and three UACR categories (<3, 3-30 and >30 mg/mmol) in all of the study time points were calculated. Linear mixed model was used to investigate change in eGFR over time. RESULTS: The study sample included 2212 long-COVID patients. Median age was 56 years, 51% were male. Half (∼47%-50%) of the study sample had normal eGFR (≥90 mL/min/1.73 m2) from COVID-19 diagnosis to 12 months post-COVID and <5% of patients had an eGFR <30 mL/min/1.73 m2. There was an estimated 2.96 mL/min/1.73 m2 decrease in eGFR within 1 year after COVID-19 infection that was equivalent to 3.39% reduction from the baseline. Decline in eGFR was highest in patients hospitalized for COVID-19 (6.72%) followed by diabetic patients (6.15%). More than 40% of patients were at risk of CKD. CONCLUSIONS: People with long-COVID experienced a substantial decline in eGFR within 1 year from the infection date. The prevalence of proteinuria appeared to be high. Close monitoring of kidney function is prudent among patients with persistent COVID-19 symptoms.

Effectiveness of Three Doses of mRNA COVID-19 Vaccines in the Hemodialysis Population during the Omicron Period.

BACKGROUND: Coronavirus disease 2019 (COVID-19) vaccine effectiveness studies in the hemodialysis population have demonstrated that two doses of mRNA COVID-19 vaccines are effective against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and severe complications when Alpha and Delta were predominant variants of concern. Vaccine effectiveness after a third dose versus two doses for preventing SARS-CoV-2 infection and severe COVID-19 in the hemodialysis population against Omicron is not known. METHODS: We conducted a retrospective cohort study in Ontario, Canada, between December 1, 2021, and February 28, 2022, in the maintenance hemodialysis population who had received two versus three doses of mRNA COVID-19 vaccines. COVID-19 vaccination, SARS-CoV-2 infection, and related hospitalization and death were determined from provincial databases. The primary outcome was the first RT-PCR confirmed SARS-CoV-2 infection, and the secondary outcome was a SARS-CoV-2-related severe outcome, defined as either hospitalization or death. RESULTS: A total of 8457 individuals receiving in-center hemodialysis were included. At study initiation, 2334 (28%) individuals received three doses, which increased to 7468 (88%) individuals by the end of the study period. The adjusted hazard ratios (aHR) for SARS-CoV-2 infection (aHR, 0.58; 95% confidence interval [CI], 0.50 to 0.67) and severe outcomes (hospitalization or death) (aHR, 0.40; 95% CI, 0.28 to 0.56) were lower after three versus two doses of mRNA vaccine. Prior infection, independent of vaccine status, was associated with a lower risk of reinfection, with an aHR of 0.44 (95% CI, 0.27 to 0.73). CONCLUSIONS: Three-dose mRNA COVID-19 vaccination was associated with lower incidence of SARS-CoV-2 infection and severe SARS-CoV-2-related outcomes during the Omicron period compared with two doses.

Findings of Sodium-Glucose Cotransporter-2 Inhibitor Kidney Outcome Trials Applied to a Canadian Chronic Kidney Disease Population: A Retrospective Cohort Study.

Background: The canagliflozin and renal endpoints in diabetes with established nephropathy clinical evaluation (CREDENCE) and dapagliflozin and prevention of adverse outcomes in chronic kidney disease (DAPA-CKD) trials have demonstrated significant kidney benefits with sodium-glucose cotransporter-2 (SGLT2) inhibitors. SGLT2 inhibitors are now standard of care for patients with diabetic kidney disease and have also been shown to be effective in those with albuminuric CKD with or without diabetes. Objective: We sought to determine how many patients in nephrology care in British Columbia, Canada, would have been eligible for those trials, to compare rates of outcomes, and to estimate cost avoidance arising from widespread use of SGLT2 inhibitors in this cohort. Study design: Retrospective cohort study. Setting: British Columbia, Canada. Participants: CKD patients followed in the Kidney Care Clinics in British Columbia. Measurements: We compared the outcomes of kidney failure, sustained estimated glomerular filtration rate (eGFR) <15 mL/min/1.73 m2, dialysis, transplant, death from any cause, and doubling of serum creatinine. We also compared the composite outcome of kidney failure and doubling of serum creatinine. Methods: The cohort was derived using a provincial database by combining the inclusion criteria of CREDENCE and DAPA-CKD trials. We included adult patients aged ≥18 years, urine albumin to creatinine ratio (UACR) ≥20 mg/mmol, and eGFR between 25 and 90 mL/min/1.73 m2, between April 1, 2014 and March 31, 2017. The primary outcome was compared with the outcomes experienced in the placebo arms of CREDENCE and DAPA-CKD. The composite outcome stratified by eGFR categories were compared in the British Columbia cohort and the CREDENCE trial. Cost avoidance was estimated based on the number needed to treat to prevent one instance of kidney failure. Results: A total of 17.5% (3138/17 963) of patients were eligible, resulting in a cohort with a mean age of 69.7 years and 38% women. The eGFR slope of the British Columbia cohort was -4.21 ± 0.47 mL/min. The mean eGFR was 37.0 mL/min/1.73 m2, median UACR was 55.3 mg/mmol, and use of renin-angiotensin-aldosterone system inhibitors was 56.6%. The British Columbia cohort experienced nearly double the outcomes of kidney failure, death from any cause, and doubling of serum creatinine than the placebo arms of CREDENCE and DAPA-CKD. When stratified by eGFR, the British Columbia cohort and the CREDENCE placebo arm had similar event rates for those with an eGFR <45 mL/min but there were still higher rates of outcome in the greater than 45 mL/min eGFR groups in the British Columbia cohort. Treating the British Columbia cohort with canagliflozin could lead to net cost avoidance of $2.31 million over 2.6 years. Limitations: The database only captures those referred to the Kidney Care Clinics by nephrologists, which may lead to selection bias of higher risk patients in the British Columbia cohort. The cost avoidance analysis was a limited high-level analysis. Conclusions: The British Columbia cohort represents a high-risk group in whom implementation of the use of SGLT2 inhibitors may well improve outcomes and reduce health care system costs.

Contexte: Les essais cliniques CREDENCE et DAPA-CKD ont démontré que les inhibiteurs du cotransporteur sodium-glucose-2 (SGLT2) présentent des avantages significatifs pour les reins. Les inhibiteurs du SGLT2 sont désormais la norme en matière de soins pour les patients atteints de néphropathie diabétique et se sont également avérés efficaces chez les patients atteints d'une insuffisance rénale chronique (IRC) albuminurique avec ou sans diabète. Objectifs: Déterminer le nombre de patients suivis en néphrologie en Colombie-Britannique (Canada) qui auraient été admissibles à ces essais, afin de comparer les résultats et estimer les coûts pouvant être évités par une utilisation généralisée des inhibiteurs du SGLT2 dans cette cohorte. Type d'étude: Étude de cohorte rétrospective. Cadre: Colombie-Britannique (Canada). Sujets: Les patients atteints d'IRC suivis dans les cliniques de prévention rénale (Kidney Care Clinics) en Colombie-Britannique. Mesures: Nous avons comparé les résultats de l'insuffisance rénale terminale (baisse soutenue du taux de filtration glomérulaire estimé [DFGe] à moins de 15 ml/min/1,73 m2, dialyse, transplantation), les décès de toutes causes confondues et le doublement de la concentration de créatinine sérique. Nous avons également comparé le critère composite de l'insuffisance rénale terminale et du doublement de la concentration de créatinine sérique. Méthodologie: La cohorte a été dérivée d'une base de données provinciale en combinant les critères d'inclusion des essais CREDENCE et DAPA-CKD. Ont été inclus les patients adultes répertoriés entre le 1er avril 2014 et le 31 mars 2017 avec un rapport albumine/créatinine urinaire (RACu) ≥ 20 mg/mmol et un DFGe entre 25 et 90 ml/min/1,73 m2. Le critère de jugement principal a été comparé aux résultats observés dans les groupes placebos des essais CREDENCE et DAPA-CKD. Le critère composite, stratifié selon les catégories de DFGe, a été comparé dans la cohorte de la Colombie-Britannique et l'essai CREDENCE. Les coûts évités ont été estimés en fonction du nombre de traitements nécessaires pour prévenir un cas d'insuffisance rénale terminale. Résultats: Des 17 963 patients répertoriés, 3 138 (17,5 %) auraient été admissibles (38 % de femmes; âge moyen: 69,7 ans). La pente du DFGe pour la cohorte de la Colombie-Britannique était de −4,21 ± 0,47 ml/min. Dans cette même cohorte, le DFGe moyen s'établissait à 37,0 ml/min/1,73 m2, le RACu moyen à 55,3 mg/mmol et le taux d'utilisation des inhibiteurs du système rénine-angiotensine-aldostérone à 56,6 %. La cohorte de la Colombie-Britannique a connu près de deux fois plus d'événements liés à l'insuffisance rénale terminale, de décès de toutes causes confondues et de doublement de la concentration de créatinine sérique que les groupes placebos des essais CREDENCE et DAPA-CKD. Après la stratification selon le DFGe, la cohorte de la Colombie-Britannique et le groupe placebo de l'essai CREDENCE ont montré des taux d'événements similaires pour les patients présentant un DFGe < 45 ml/min, mais la cohorte de la Colombie-Britannique a montré des taux plus élevés d'événements dans les groupes avec un DFGe supérieur à 45 ml/min. Le traitement de la cohorte de la Colombie-Britannique par la canagliflozine pourrait permettre d'éviter un coût net de 2,31 M$ canadiens sur 2,6 ans. Limites: La base de données ne contient que les patients orientés par des néphrologues vers les cliniques de prévention rénale (Kidney Care Clinics), ce qui peut entraîner un biais favorisant la sélection des patients à risque élevé dans la cohorte de la Colombie-Britannique. L'analyse des coûts évités était une analyse de haut niveau limitée. Conclusion: La cohorte de la Colombie-Britannique représente un groupe de patients à haut risque chez qui l'utilisation des inhibiteurs du SGLT2 pourrait améliorer les résultats en matière d'insuffisance rénale et permettre de réduire les coûts pour le système de santé.

Prescription Pattern of Cation Exchange Resins and Their Efficacy in Treating Chronic Hyperkalemia Among Patients With Chronic Kidney Diseases: Findings From a Population-Based Analysis in British Columbia, Canada.

Background: Little was known about how chronic hyperkalemia (cHK) in patients with chronic kidney disease (CKD) is managed in British Columbia, Canada. Objective: To investigate the trend in sodium polystyrene sulfonate (SPS) and calcium polystyrene sulfonate (CPS) utilization and their efficacy in treating cHK in CKD patients from British Columbia, Canada. Study Design: Retrospective cohort. Setting & Patients: CKD patients aged ≥18 years, followed in Kidney Care Clinic (KCC), who had at least 2 potassium values ≥5.0 mmol/L separated by no more than 91 days during the period of June 1, 2015, to July 31, 2021, were included. Index date was the first date of the 2 potassium values ≥5.0 mmol/L. Patients who received SPS or CPS within 90 days before index date were excluded. Patients who were on dialysis or received kidney transplantation on or before index date were also excluded. Exposure: Continuous exposure to SPS and CPS. Outcome: SPS/CPS prescription utilization trend was described by the proportion of patients ever treated with SPS/CPS, median time in days between cHK diagnosis and initiating treatment with SPS/CPS, total and median number of SPS/CPS prescriptions dispensed. Change in mean serum potassium concentration before and after a 90-day continuous treatment with SPS/CPS was estimated. Analytical Approach: Descriptive. Results: This study included 10 495 patients with cHK (median age 74 years, 60% were male). Median follow-up time was 625 days. Only 2864 (27%) patients were dispensed at least 1 prescription of either SPS or CPS. A total 7300 prescriptions were dispensed; median prescriptions dispensed per patients were 2 (interquartile range [IQR]: 1-3). Median time from index date to the first prescription dispensing date was 154 days (IQR: 36-455). Continuous 90-day treatment with SPS/CPS decreased the mean serum potassium concentration by 0.60 mmol/L, from 5.58 to 4.98 mmol/L. Limitations: Descriptive observational study without control group. Conclusions: In British Columbia, only 1 in 4 CKD patients with cHK were dispensed with SPS/CPS, mostly with higher degrees of hyperkalemia. These medications appeared to be moderately effective in reducing the serum potassium concentration. Future research is necessary to evaluate the comparative effectiveness of newer generation medications.

Contexte: On savait peu de choses sur la façon dont l'hyperkaliémie chronique (HKc) est prise en charge chez les patients atteints d'insuffisance rénale chronique (IRC) de la Colombie-Britannique (C.-B.), au Canada. Objectif: Étudier les tendances d'utilisation du sulfonate de polystyrène sodique (SPS) et du sulfonate de polystyrène calcique (SPC), ainsi que l'efficacité de ces agents dans le traitement de l'HKc chez les patients britanno-colombiens atteints d'IRC. Type d'étude: étude de cohorte rétrospective. Sujets et cadre de l'étude: Ont été inclus des adultes atteints d'IRC suivis en clinique de soins rénaux qui avaient au moins 2 valeurs de potassium ≥ 5,0 mmol/L mesurées à moins de 91 jours d'intervalle entre le 1er juin 2015 et le 31 juillet 2021. La date de la première des deux valeurs de potassium ≥ 5,0 mmol/L constitue la date indice. Les patients qui avaient reçu du SPS ou du SPC dans les 90 jours précédant la date indice ont été exclus. Les patients sous dialyse ou ayant reçu une greffe rénale avant ou à la date indice ont également été exclus. Exposition: Exposition continue au SPS et au SPC. Résultats: La tendance d'utilisation de SPS/SPC a été décrite par la proportion de patients ayant déjà été traités par SPS/SPC, par le temps médian en jours entre le diagnostic d'hyperkaliémie chronique et le début du traitement par SPS/SPC, et par le nombre total et médian de prescriptions de SPS/SPC délivrées. La variation de la concentration moyenne de potassium sérique avant et après un traitement continu de 90 jours avec SPS/SPC a été estimée. Approche analytique: Descriptive. Résultats: L'étude porte sur 10 495 patients atteints d'hyperkaliémie chronique (60 % d'hommes; âge médian: 74 ans). Le temps médian de suivi était de 625 jours. Seulement 2 864 (27 %) patients avaient reçu au moins une prescription de SPS ou de SPC. Au total, 7 300 ordonnances ont été délivrées; la moyenne d'ordonnances délivrées par patient était de 2 (IIQ: 1, 3). Le délai médian entre la date indice et la date de la première ordonnance était de 154 jours (IIQ: 36, 455). Un traitement continu de 90 jours avec SPS/SPC a abaissé la concentration moyenne de potassium sérique de 0,60 mmol/L, la faisant passer de 5,58 à 4,98 mmol/L. Limites: Étude observationnelle descriptive sans groupe témoin. Conclusion: En C.-B., seul un patient sur quatre atteint d'IRC avec HKc avait reçu une prescription de SPS/SPC, la plupart présentaient des degrés plus élevés d'hyperkaliémie. Ces médicaments se sont avérés modérément efficaces pour réduire la concentration sérique en potassium. Des recherches supplémentaires sont nécessaires pour évaluer l'efficacité comparative des médicaments de nouvelle génération.

A Population-Based Analysis of the Risk of Glomerular Disease Relapse after COVID-19 Vaccination.

BACKGROUND: Although case reports have described relapses of glomerular disease after COVID-19 vaccination, evidence of a true association is lacking. In this population-level analysis, we sought to determine relative and absolute risks of glomerular disease relapse after COVID-19 vaccination. METHODS: In this retrospective population-level cohort study, we used a centralized clinical and pathology registry (2000-2020) to identify 1105 adult patients in British Columbia, Canada, with biopsy-proven glomerular disease that was stable on December 14, 2020 (when COVID-19 vaccines first became available). The primary outcome was disease relapse, on the basis of changes in kidney function, proteinuria, or both. Vaccination was modeled as a 30-day time-varying exposure in extended Cox regression models, stratified on disease type. RESULTS: During 281 days of follow-up, 134 (12.1%) patients experienced a relapse. Although a first vaccine dose was not associated with relapse risk (hazard ratio [HR]=0.67; 95% confidence interval [95% CI], 0.33 to 1.36), exposure to a second or third dose was associated with a two-fold risk of relapse (HR=2.23; 95% CI, 1.06 to 4.71). The pattern of relative risk was similar across glomerular diseases. The absolute increase in 30-day relapse risk associated with a second or third vaccine dose varied from 1%-2% in ANCA-related glomerulonephritis, minimal change disease, membranous nephropathy, or FSGS to 3%-5% in IgA nephropathy or lupus nephritis. Among 24 patients experiencing a vaccine-associated relapse, 4 (17%) had a change in immunosuppression, and none required a biopsy. CONCLUSIONS: In a population-level cohort of patients with glomerular disease, a second or third dose of COVID-19 vaccine was associated with higher relative risk but low absolute increased risk of relapse.

The association between rheumatoid arthritis and cardiovascular disease among adults in the United States during 1999-2018, and age-related effect modification in relative and absolute scales.

PURPOSE: To explore the rheumatoid arthritis (RA)-cardiovascular diseases (CVD) association in relative and absolute risk scales among US adults aged ≥20 years over time and the effect modification of the association by age. METHODS: We analyzed aggregated data from all ten continuous National Health and Nutrition Examination Survey cycles. A sample of 35,062 complete-case subjects was considered. The design-based regressions were used to investigate the associations in relative and absolute scales. RESULTS: In relative scale, the CVD odds ratio was 2.32, 2.19, and 1.97 among adults with RA than no arthritis in 1999-2006, 2007-2012, and 2013-2018 cycles, respectively. This time trend was not statistically significant. The absolute risk estimates were 11, 10, and 9 per 100 CVD events. We also observed a significant effect modification by age; the higher relative risk among younger adults (<50 years) with RA and higher absolute risk in older adults (≥80 years) with RA were consistent across survey cycles. CONCLUSIONS: There is a significant association between RA and CVD among US adults in both relative and absolute risks. Moreover, age is a significant effect modifier for this association; but with opposing age-related trends in relative and absolute scales.

Vaccine Effectiveness Against SARS-CoV-2 Infection and Severe Outcomes in the Maintenance Dialysis Population in Ontario, Canada.

BACKGROUND: Vaccination studies in the hemodialysis population have demonstrated decreased antibody response compared with healthy controls, but vaccine effectiveness for preventing SARS-CoV-2 infection and severe disease is undetermined. METHODS: We conducted a retrospective cohort study in the province of Ontario, Canada, between December 21, 2020, and June 30, 2021. Receipt of vaccine, SARS-CoV-2 infection, and related severe outcomes (hospitalization or death) were determined from provincial health administrative data. Receipt of one and two doses of vaccine were modeled in a time-varying cause-specific Cox proportional hazards model, adjusting for baseline characteristics, background community infection rates, and censoring for non-COVID death, recovered kidney function, transfer out of province, solid organ transplant, and withdrawal from dialysis. RESULTS: Among 13,759 individuals receiving maintenance dialysis, 2403 (17%) were unvaccinated and 11,356 (83%) had received at least one dose by June 30, 2021. Vaccine types were BNT162b2 (n=8455, 74%) and mRNA-1273 (n=2901, 26%); median time between the first and second dose was 36 days (IQR 28-51). The adjusted hazard ratio (HR) for SARS-CoV-2 infection and severe outcomes for one dose compared with unvaccinated was 0.59 (95% CI, 0.46 to 0.76) and 0.54 (95% CI, 0.37 to 0.77), respectively, and for two doses compared with unvaccinated was 0.31 (95% CI, 0.22 to 0.42) and 0.17 (95% CI, 0.1 to 0.3), respectively. There were no significant differences in vaccine effectiveness among age groups, dialysis modality, or vaccine type. CONCLUSIONS: COVID-19 vaccination is effective in the dialysis population to prevent SARS-CoV-2 infection and severe outcomes, despite concerns about suboptimal antibody responses.

Differences in mRNA-1273 (Moderna) and BNT162b2 (Pfizer-BioNTech) SARS-CoV-2 vaccine immunogenicity among patients undergoing dialysis.

BACKGROUND: Differences in immunogenicity between mRNA SARS-CoV-2 vaccines have not been well characterized in patients undergoing dialysis. We compared the serologic response in patients undergoing maintenance hemodialysis after vaccination against SARS-CoV-2 with BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna). METHODS: We conducted a prospective observational cohort study at 2 academic centres in Toronto, Canada, from Feb. 2, 2021, to July 20, 2021, which included 129 and 95 patients who received the BNT162b2 and mRNA-1273 SARS-CoV-2 vaccines, respectively. We measured SARS-CoV-2 immunoglobulin G antibodies to the spike protein (anti-spike), receptor binding domain (anti-RBD) and nucleocapsid protein (anti-NP) at 6-7 and 12 weeks after the second dose of vaccine and compared those levels with the median convalescent serum antibody levels from 211 controls who were previously infected with SARS-CoV-2. RESULTS: At 6-7 weeks after 2-dose vaccination, we found that 51 of 70 patients (73%) who received BNT162b2 and 83 of 87 (95%) who received mRNA-1273 attained convalescent levels of anti-spike antibody (p < 0.001). In those who received BNT162b2, 35 of 70 (50%) reached the convalescent level for anti-RBD compared with 69 of 87 (79%) who received mRNA-1273 (p < 0.001). At 12 weeks after the second dose, anti-spike and anti-RBD levels were significantly lower in patients who received BNT162b2 than in those who received mRNA-1273. For anti-spike, 70 of 122 patients (57.4%) who received BNT162b2 maintained the convalescent level versus 68 of 71 (96%) of those who received mRNA-1273 (p < 0.001). For anti-RBD, 47 of 122 patients (38.5%) who received BNT162b2 maintained the anti-RBD convalescent level versus 45 of 71 (63%) of those who received mRNA-1273 (p = 0.002). INTERPRETATION: In patients undergoing hemodialysis, mRNA-1273 elicited a stronger humoral response than BNT162b2. Given the rapid decline in immunogenicity at 12 weeks in patients who received BNT162b2, a third dose is recommended in patients undergoing dialysis as a primary series, similar to recommendations for other vulnerable populations.

Anti-Epileptic Medication Exposure Influences Functional Status in New Zealand Stroke Patients: A Retrospective Population-Level Study.

BACKGROUND: Patients who develop seizures after stroke have disproportionately poorer outcomes and increased mortality. OBJECTIVE: Our objective was to investigate whether exposure to anti-epileptic medications influenced long-term functional status after stroke. METHODS: We used linked health administrative data from a cohort of adult stroke patients in New Zealand. Demographics and prescription information were obtained from the National Minimum Dataset and Pharmaceutical Collection, respectively. Activities of daily living (ADL) scores for the same patients were obtained using the International Resident Assessment Instrument. Beta regression was used to investigate the relationship between anti-epileptic drug (AED) exposure and functional status. RESULTS: The study included 3606 patients with a single ischaemic stroke between 2012 and 2017. In total, 15% were dispensed an AED in the 3 months before or after stroke. The adjusted odds ratio (OR) for AED exposure was 1.29 (95% confidence interval [CI] 1.15-1.45). Overall AED exposure, categorical body mass index (BMI), ethnicity, length of hospital stay, and exposure to paracetamol, opioids, anti-psychotics, and anti-nausea medications were significantly associated with changes in the mean ADL score percentages. Considering the exposure timeframe, the ORs for AED exposure only after stroke and for exposure both before and after stroke were 1.52 (95% CI 1.31-1.78) and 1.09 (95% CI 0.93-1.27), respectively. CONCLUSION: Stroke patients with AED exposure had greater odds of a higher ADL score, indicating a poorer long-term functional status than those unexposed to AEDs. The timeframe of exposure impacted on functional status, with patients exposed only after stroke having increased odds of higher ADL scores than those exposed both before and after stroke.

Role of Nonsteroidal Antiinflammatory Drugs in the Association Between Osteoarthritis and Cardiovascular Diseases: A Longitudinal Study.

OBJECTIVE: To elucidate the role of nonsteroidal antiinflammatory drugs (NSAIDs) in the increased risk of cardiovascular disease (CVD) among osteoarthritis (OA) patients. METHODS: This longitudinal study was based on linked health administrative data from British Columbia, Canada. From a population-based cohort of 720,055 British Columbians, we selected 7,743 OA patients and 23,229 age- and sex-matched non-OA controls. We used multivariable Cox proportional hazards models to estimate the risk of developing incident CVD (primary outcome) as well as ischemic heart disease, congestive heart failure, and stroke (secondary outcomes). To estimate the mediating effect of NSAIDs, defined as current use of an NSAID according to linked PharmaNet data, in the OA-CVD relationship, we implemented a marginal structural model. RESULTS: OA patients had a higher risk of developing CVD than controls without OA. After adjusting for socioeconomic status, body mass index, hypertension, diabetes, hyperlipidemia, chronic obstructive pulmonary disease, and Romano comorbidity score, the adjusted hazard ratio (HR) was 1.23 (95% confidence interval [95% CI] 1.17-1.28). The adjusted HRs for congestive heart failure, ischemic heart disease, and stroke were 1.42 (95% CI 1.33-1.51), 1.17 (95% CI 1.10-1.26), and 1.14 (95% CI 1.07-1.22), respectively. Approximately 41% of the total effect of OA on increased CVD risk was mediated through NSAIDs. For the secondary outcomes, the proportion mediated through NSAIDs was 23%, 56%, and 64% for congestive heart failure, ischemic heart disease, and stroke, respectively. CONCLUSION: The findings of this first study to evaluate the mediating role of NSAIDs in the relationship between OA and CVD suggest that NSAID use contributes substantially to the OA-CVD association.

Influenza vaccination for HIV-positive people: Systematic review and network meta-analysis.

BACKGROUND: People with Human Immunodeficiency Virus (HIV) are highly susceptible to influenza-related morbidity and mortality. In order to assess comparative efficacy of influenza vaccine strategies among HIV-positive people, we performed a systematic review and Bayesian network meta-analysis (NMA). METHODS: In this systematic review, we searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and CINAHL between 1946 and July 2015 for randomized controlled trials (RCTs) on influenza vaccines for HIV-positive adults reporting seroconversion or seroprotection outcomes. The NMAs were conducted within a Bayesian framework and logistic models were used for comparing the effect of the vaccine strategies on the two outcomes. RESULTS: A total of 1957 publications were identified, 143 were selected for full review, and 13 RCTs were included in our final analysis. Fourteen separate NMAs were conducted by outcomes, vaccine strain, and different outcome measurement timepoints. For example, compared with the 15 µg single vaccine strategy, the odds ratio was the highest for the adjuvant 7.5 µg booster strategy (2.99 [95% credible interval 1.18-7.66]) when comparing seroconversion for H1N1 at 14-41 days after the last dose of vaccination and for the 60 µg single strategy (2.33 [1.31-4.18]) when comparing seroconversion for strain B. CONCLUSIONS: The adjuvant 7.5 µg booster and 60 µg single vaccine strategies provided better seroconversion and seroprotection outcomes. These findings have important implications for national and international guidelines for influenza vaccination for HIV-positive people and future research.