Long-term trends in incidence and outcomes of rib fractures: A population-based data linkage study from New South Wales, Australia.

OBJECTIVE: Determine long-term trends in population-based incidence and outcomes of rib fracture hospitalisations. METHODS: This was a data linkage study of rib fracture cases identified between 2015 and 2022 in New South Wales, Australia. Routinely collected health data were linked between ED, admitted patient and death registry data collection. The primary outcomes were age-specific incidence of rib fracture hospitalisation cases and risk-adjusted 30 days mortality. Other outcomes of interest were hospital length of stay (LOS), admission rate and ICU admissions. RESULTS: A total of 70 609 cases were analysed. Overall, the number of rib fracture hospitalisations increased by 25% between 2015 and 2022. The highest proportion of cases was in the 45-65 years (28%) and 65-85 years (31%) age groups. On a per population basis, the incidence rate increased by 2% per annum. After adjusting for age, comorbidity and injury severity, there was no significant trend in 30 days mortality observed between 2015 and 2022. The median inpatient LOS was 4 days with 38% of patients staying 1-2 days. Regional and rural areas were associated with more severe chest injuries. CONCLUSION: Rib fracture hospitalisations have increased with older patients driving this trend.

Implementing enhanced extracorporeal membrane oxygenation for CPR (ECPR) in the emergency department.

Refractory out-of-hospital cardiac arrest (OHCA) has a very poor prognosis, with survival rates at around 10%. Extracorporeal membrane oxygenation (ECMO) for patients in refractory arrest, known as ECPR, aims to provide perfusion to the patient whilst the underlying cause of arrest can be addressed. ECPR use has increased substantially, with varying survival rates to hospital discharge. The best outcomes for ECPR occur when the time from cardiac arrest to implementation of ECPR is minimised. To reduce this time, systems must be in place to identify the correct patient, expedite transfer to hospital, facilitate rapid cannulation and ECMO circuit flows. We describe the process of activation of ECPR, patient selection, and the steps that emergency department clinicians can utilise to facilitate timely cannulation to ensure the best outcomes for patients in refractory cardiac arrest. With these processes in place our survival to hospital discharge for OHCA patients is 35%, with most patients having a good neurological function.

Serratus Anterior Plane Blocks for Early Rib Fracture Pain Management: The SABRE Randomized Clinical Trial.

Importance: Rib fractures secondary to blunt thoracic trauma typically result in severe pain that is notoriously difficult to manage. The serratus anterior plane block (SAPB) is a regional anesthesia technique that provides analgesia to most of the hemithorax; however, SAPB has limited evidence for analgesic benefits in rib fractures. Objective: To determine whether the addition of an SAPB to protocolized care bundles increases the likelihood of early favorable analgesic outcomes and reduces opioid requirements in patients with rib fractures. Design, Setting, and Participants: This multicenter, open-label, pragmatic randomized clinical trial was conducted at 8 emergency departments across metropolitan and regional New South Wales, Australia, between April 12, 2021, and January 22, 2022. Patients aged 16 years or older with clinically suspected or radiologically proven rib fractures were included in the study. Participants were excluded if they were intubated, transferred for urgent surgical intervention, or had a major concomitant nonthoracic injury. Data were analyzed from September 2022 to July 2023. Interventions: Patients were randomly assigned (1:1) to receive an SAPB in addition to usual rib fracture management or standard care alone. Main Outcomes and Measures: The primary outcome was a composite pain score measured 4 hours after enrollment. Patients met the primary outcome if they had a pain score reduction of 2 or more points and an absolute pain score of less than 4 out of 10 points. Results: A total of 588 patients were screened, of whom 210 patients (median [IQR] age, 71 [55-84] years; 131 [62%] male) were enrolled, with 105 patients randomized to receive an SAPB plus standard care and 105 patients randomized to standard care alone. In the complete-case intention-to-treat primary outcome analysis, the composite pain score outcome was reached in 38 of 92 patients (41%) in the SAPB group and 18 of 92 patients (19.6%) in the control group (relative risk [RR], 0.73; 95% CI, 0.60-0.89; P = .001). There was a clinically significant reduction in overall opioid consumption in the SAPB group compared with the control group (eg, median [IQR] total opioid requirement at 24 hours: 45 [19-118] vs 91 [34-155] milligram morphine equivalents). Rates of pneumonia (6 patients [10%] vs 7 patients [11%]), length of stay (eg, median [IQR] hospital stay, 4.2 [2.2-7.7] vs 5 [3-7.3] days), and 30-day mortality (1 patient [1%] vs 3 patients [4%]) were similar between the SAPB and control groups. Conclusions and Relevance: This randomized clinical trial found that the addition of an SAPB to standard rib fracture care significantly increased the proportion of patients who experienced a meaningful reduction in their pain score while also reducing in-hospital opioid requirements. Trial Registration: http://anzctr.org.au Identifier: ACTRN12621000040864.

Perceptions and Information-Seeking Behavior Regarding COVID-19 Vaccination Among Patients With Chronic Kidney Disease in 2023: A Cross-Sectional Survey.

Background: People living with chronic kidney disease (CKD) face an increased risk of severe outcomes such as hospitalization or death from COVID-19. COVID-19 vaccination is a vital approach to mitigate the risk and severity of infection in patients with CKD. Limited information exists regarding the factors that shape COVID-19 vaccine uptake, including health information-seeking behavior and perceptions, within the CKD population. Objective: The objectives were to describe among CKD patients, (1) health information-seeking behavior on COVID-19, (2) their capacity to comprehend and trust COVID-19 information from different sources, and (3) their perceptions concerning COVID-19 infection and vaccination. Design/Setting: Cross-sectional web-based survey administered in British Columbia and Ontario from February 17, 2023, to April 17, 2023. Participants: Chronic kidney disease G3b-5D patients and kidney transplant recipients (CKD G1T-5T) enrolled in a longitudinal COVID-19 vaccine serology study. Methods and Measurements: The survey consisted of a questionnaire that included demographic and clinical data, perceived susceptibility of contracting COVID-19, the ability to collect, understand, and trust information on COVID-19, as well as perceptions regarding COVID-19 vaccination. Descriptive statistics were used to present the data with values expressed as count (%) and chi square tests were performed with a significance level set at P ≤ .05. A content analysis was performed on one open-ended response regarding respondents' questions surrounding COVID-19 infection and vaccination. Results: Among the 902 patients who received the survey via email, 201 completed the survey, resulting in a response rate of 22%. The median age was 64 years old (IQR 53-74), 48% were male, 51% were university educated, 32% were on kidney replacement therapies, and 57% had received ≥5 COVID-19 vaccine doses. 65% of respondents reported that they had sought out COVID-19-related information in the last 12 months, with 91% and 84% expressing having understood and trusted the information they received, respectively. Those with a higher number of COVID-19 vaccine doses were associated with having sought out (P =.017), comprehended (P < .001), and trusted (P =. 005) COVID-19-related information. Female sex was associated with expressing more concern about contracting COVID-19 (P = .011). Most respondents strongly agreed to statements regarding the benefits of COVID-19 vaccination. Respondents' questions about COVID-19 infection and vaccination centered on 4 major themes: COVID-19 vaccination strategy, vaccine effectiveness, vaccine safety, and the impact of COVID-19 infection and vaccination on kidney health. Limitations: This survey was administered within the Canadian health care context to patients with CKD who had at least 1 COVID-19 vaccine dose. Race/ethnicity of participants was not captured. Conclusions: In this survey of individuals with CKD, COVID-19 information-seeking behavior was high and almost all respondents understood and trusted the information they received. Perceptions toward the COVID-19 vaccine and booster were mostly favorable.

Impact of Prior Abdominal Procedures on Peritoneal Dialysis Catheter Outcomes: Findings From the North American Peritoneal Dialysis Catheter Registry.

RATIONALE & OBJECTIVE: A history of prior abdominal procedures may influence the likelihood of referral for peritoneal dialysis (PD) catheter insertion. To guide clinical decision making in this population, this study examined the association between prior abdominal procedures and outcomes in patients undergoing PD catheter insertion. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Adults undergoing their first PD catheter insertion between November 1, 2011, and November 1, 2020, at 11 institutions in Canada and the United States participating in the International Society for Peritoneal Dialysis North American Catheter Registry. EXPOSURE: Prior abdominal procedure(s) defined as any procedure that enters the peritoneal cavity. OUTCOMES: The primary outcome was time to the first of (1) abandonment of the PD catheter or (2) interruption/termination of PD. Secondary outcomes were rates of emergency room visits, hospitalizations, and procedures. ANALYTICAL APPROACH: Cumulative incidence curves were used to describe the risk over time, and an adjusted Cox proportional hazards model was used to estimate the association between the exposure and primary outcome. Models for count data were used to estimate the associations between the exposure and secondary outcomes. RESULTS: Of 855 patients who met the inclusion criteria, 31% had a history of a prior abdominal procedure and 20% experienced at least 1 PD catheter-related complication that led to the primary outcome. Prior abdominal procedures were not associated with an increased risk of the primary outcome (adjusted HR, 1.12; 95% CI, 0.68-1.84). Upper-abdominal procedures were associated with a higher adjusted hazard of the primary outcome, but there was no dose-response relationship concerning the number of procedures. There was no association between prior abdominal procedures and other secondary outcomes. LIMITATIONS: Observational study and cohort limited to a sample of patients believed to be potential candidates for PD catheter insertion. CONCLUSION: A history of prior abdominal procedure(s) does not appear to influence catheter outcomes following PD catheter insertion. Such a history should not be a contraindication to PD. PLAIN-LANGUAGE SUMMARY: Peritoneal dialysis (PD) is a life-saving therapy for individuals with kidney failure that can be done at home. PD requires the placement of a tube, or catheter, into the abdomen to allow the exchange of dialysis fluid during treatment. There is concern that individuals who have undergone prior abdominal procedures and are referred for a catheter might have scarring that could affect catheter function. In some institutions, they might not even be offered PD therapy as an option. In this study, we found that a history of prior abdominal procedures did not increase the risk of PD catheter complications and should not dissuade patients from choosing PD or providers from recommending it.

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

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

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.

The Association of Intra-Abdominal Adhesions with Peritoneal Dialysis Catheter-Related Complications.

BACKGROUND: This study investigated the association of intra-abdominal adhesions with the risk of peritoneal dialysis (PD) catheter complications. METHODS: Individuals undergoing laparoscopic PD catheter insertion were prospectively enrolled from eight centers in Canada and the United States. Patients were grouped based on the presence of adhesions observed during catheter insertion. The primary outcome was the composite of PD never starting, termination of PD, or the need for an invasive procedure caused by flow restriction or abdominal pain. RESULTS: Seven hundred and fifty-eight individuals were enrolled, of whom 201 (27%) had adhesions during laparoscopic PD catheter insertion. The risk of the primary outcome occurred in 35 (17%) in the adhesion group compared with 58 (10%) in the no adhesion group (adjusted HR, 1.64; 95% confidence interval [CI], 1.05 to 2.55) within 6 months of insertion. Lower abdominal or pelvic adhesions had an adjusted HR of 1.80 (95% CI, 1.09 to 2.98) compared with the no adhesion group. Invasive procedures were required in 26 (13%) and 47 (8%) of the adhesion and no adhesion groups, respectively (unadjusted HR, 1.60: 95% CI, 1.04 to 2.47) within 6 months of insertion. The adjusted odds ratio for adhesions for women was 1.65 (95% CI, 1.12 to 2.41), for body mass index per 5 kg/m 2 was 1.16 (95% CI, 1.003 to 1.34), and for prior abdominal surgery was 8.34 (95% CI, 5.5 to 12.34). Common abnormalities found during invasive procedures included PD catheter tip migration, occlusion of the lumen with fibrin, omental wrapping, adherence to the bowel, and the development of new adhesions. CONCLUSIONS: People with intra-abdominal adhesions undergoing PD catheter insertion were at higher risk for abdominal pain or flow restriction preventing PD from starting, PD termination, or requiring an invasive procedure. However, most patients, with or without adhesions, did not experience complications, and most complications did not lead to the termination of PD therapy.

Alignment Among Patient, Caregiver, and Health Care Provider Perspectives on Hemodialysis Vascular Access Decision-Making: A Qualitative Study.

Background: Updates to the Kidney Disease Outcomes Quality Initiative Clinical Practice Guideline for Vascular Access emphasize the "right access, in the right patient, at the right time, for the right reasons." Although this implies a collaborative approach, little is known about how patients, their caregivers, and health care providers engage in vascular access (VA) decision-making. Objective: To explore how the perspectives of patients receiving hemodialysis, their caregivers, and hemodialysis care team align and diverge in relation to VA selection. Design: Qualitative descriptive study. Setting: Five outpatient hemodialysis centers in Calgary, Alberta. Participants: Our purposive sample included 19 patients receiving maintenance hemodialysis, 2 caregivers, and 21 health care providers (7 hemodialysis nurses, 6 VA nurses, and 8 nephrologists). Methods: We conducted semi-structured interviews with consenting participants. Using an inductive thematic analysis approach, we coded transcripts in duplicate and characterized themes addressing our research objective. Results: While participants across roles shared some perspectives related to VA decision-making, we identified areas where views diverged. Areas of alignment included (1) optimizing patient preparedness-acknowledging decisional readiness and timing, and (2) value placed on trusting relationships with the kidney care team-respecting decisional autonomy with guidance. Perspectives diverged in the following aspects: (1) differing VA priorities and preferences-patients' emphasis on minimizing disruptions to normalcy contrasted with providers' preferences for fistulas and optimizing biomedical parameters of dialysis; (2) influence of personal and peer experience-patients preferred pragmatic, experiential knowledge, whereas providers emphasized informational credibility; and (3) endpoints for VA review-reassessment of VA decisions was prompted by access dissatisfaction for patients and a medical imperative to achieve a functioning access for health care providers. Limitations: Participation was limited to individuals comfortable communicating in English and from urban, in-center hemodialysis units. Few informal caregivers of people receiving hemodialysis and younger patients participated in this study. Conclusions: Although patients, caregivers, and healthcare providers share perspectives on important aspects of VA decisions, conflicting priorities and preferences may impact the decisional outcome. Findings highlight opportunities to bridge knowledge and readiness gaps and integrate shared decision-making in the VA selection process.

Contexte: Les mises à jour des lignes directrices de pratiques cliniques en matière d'accès vasculaire de la KDOQI (Kidney Disease Outcomes Quality Initiative) insistent sur la création « du bon accès, à la bonne personne, au bon moment et pour les bonnes raisons ¼. Ces recommandations sous-entendent une approche collaborative, mais la façon dont les patients, leurs soignants et les prestataires de soins de santé participent à la prise de décision sur l'accès vasculaire (AV) demeure mal connue. Objectif: Explorer les accords et les divergences dans les points de vue des patients sous hémodialyse, leurs soignants et leur équipe de soins relativement à la sélection de l'AV. Conception: Étude qualitative et descriptive. Cadre: Cinq centres d'hémodialyse ambulatoire à Calgary (Alberta). Sujets: Notre échantillon choisi à dessein était composé de 19 patients sous hémodialyse d'entretien, 2 soignants et 21 prestataires de soins de santé (7 infirmières en hémodialyse, 6 infirmières en AV et 8 néphrologues). Méthodologie: Nous avons mené des entrevues semi-structurées auprès des participants consentants. Une approche d'analyse thématique inductive a été employée pour coder les transcriptions en double et caractériser les thèmes répondant à l'objectif de recherche. Résultats: Certains points de vue sur la prise de décision en matière d'AV étaient partagés par tous les participants, mais nous avons identifié quelques domaines de divergence. Les participants s'entendaient sur : 1) l'optimisation de la préparation des patients ­ reconnaître l'état de préparation et le moment de prendre la décision; et 2) la valeur accordée aux relations de confiance avec l'équipe de soins rénaux ­ respecter l'autonomie décisionnelle après conseils. Les points de vue divergeaient sur : 1) les priorités et préférences à l'égard de l'AV ­ l'accent mis par les patients sur la minimisation des perturbations de la vie courante contrastait avec les préférences des prestataires de soins pour les fistules et l'optimisation des paramètres biomédicaux de la dialyse; 2) l'influence de l'expérience personnelle et des pairs ­ les patients préféraient des connaissances pragmatiques et expérientielles, tandis que les prestataires de soins mettaient l'accent sur la crédibilité de l'information; et 3) les critères d'évaluation de l'AV ­ la réévaluation du choix de l'AV est motivée par l'insatisfaction des patients à l'égard de l'accès et, du côté des prestataires de soins, par l'impératif médical de parvenir à un accès fonctionnel. Limites: Seules les personnes fréquentant une unité d'hémodialyse en centre urbain et à l'aise de communiquer en anglais ont pu participer. Les participants comptaient peu de patients plus jeunes et de soignants informels de personnes sous hémodialyse. Conclusion: Bien que les patients, les soignants et les prestataires de soins de santé s'entendent sur certains aspects importants de la décision concernant l'AV, celle-ci pourrait être influencée par des priorités et préférences contradictoires. Nos résultats mettent en évidence des occasions d'intégrer la prise de décision partagée dans le processus de sélection d'un AV et de combler les lacunes dans les connaissances et la préparation des patients.

BNT162b2 versus mRNA-1273 Third Dose COVID-19 Vaccine in Patients with CKD and Maintenance Dialysis Patients.

BACKGROUND: There is a lack of randomized controlled trial data regarding differences in immunogenicity of varying coronavirus disease 2019 (COVID-19) mRNA vaccine regimens in CKD populations. METHODS: We conducted a randomized controlled trial at three kidney centers in Toronto, Ontario, Canada, evaluating the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody response after third dose vaccination. Participants ( n =273) with CKD not on dialysis or receiving dialysis were randomized 1:1 to third dose 30- µ g BNT162b2 (Pfizer-BioNTech) or 100- µ g mRNA-1273 (Moderna). The primary outcome of this study was SARS-CoV-2 IgG-binding antibodies to the receptor-binding domain (anti-RBD). Spike protein (antispike), nucleocapsid protein, and vaccine reactogenicity were also evaluated. Serology was measured before third dose and 1, 3, and 6 months after third dose. A subset of participants ( n =100) were randomly selected to assess viral pseudovirus neutralization against wild-type D614G, B.1.617.2 (Delta), and B.1.1.529 (Omicron BA.1). RESULTS: Among 273 participants randomized, 94% were receiving maintenance dialysis and 59% received BNT162b2 for initial two dose COVID-19 vaccination. Third dose of mRNA-1273 was associated with higher mean anti-RBD levels (1871 binding antibody units [BAU]/ml; 95% confidence interval [CI], 829 to 2988) over a 6-month period in comparison with third dose BNT162b2 (1332 BAU/ml; 95% CI, 367 to 2402) with a difference of 539 BAU/ml (95% CI, 139 to 910; P = 0.009). Neither antispike levels nor neutralizing antibodies to wild-type, Delta, and Omicron BA.1 pseudoviruses were statistically different. COVID-19 infection occurred in 10% of participants: 15 (11%) receiving mRNA-1273 and 11 (8%) receiving BNT162b2. Third dose BNT162b2 was not associated with a significant different risk for COVID-19 in comparison with mRNA-1273 (hazard ratio, 0.78; 95% CI, 0.27 to 2.2; P = 0.63). CONCLUSIONS: In patients with CKD, third dose COVID-19 mRNA vaccination with mRNA-1273 elicited higher SARS-CoV-2 anti-RBD levels in comparison with BNT162b2 over a 6-month period. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: COVID-19 Vaccine Boosters in Patients With CKD (BOOST KIDNEY), NCT05022329 .

Omicron variant neutralizing antibodies following BNT162b2 BA.4/5 versus mRNA-1273 BA.1 bivalent vaccination in patients with end-stage kidney disease.

Neutralization of Omicron subvariants by different bivalent vaccines has not been well evaluated. This study characterizes neutralization against Omicron subvariants in 98 individuals on dialysis or with a kidney transplant receiving the BNT162b2 (BA.4/BA.5) or mRNA-1273 (BA.1) bivalent COVID-19 vaccine. Neutralization against Omicron BA.1, BA.5, BQ.1.1, and XBB.1.5 increased by 8-fold one month following bivalent vaccination. In comparison to wild-type (D614G), neutralizing antibodies against Omicron-specific variants were 7.3-fold lower against BA.1, 8.3-fold lower against BA.5, 45.8-fold lower against BQ.1.1, and 48.2-fold lower against XBB.1.5. Viral neutralization was not significantly different by bivalent vaccine type for wild-type (D614G) (P = 0.48), BA.1 (P = 0.21), BA.5 (P = 0.07), BQ.1.1 (P = 0.10), nor XBB.1.5 (P = 0.10). Hybrid immunity conferred higher neutralizing antibodies against all Omicron subvariants. This study provides evidence that BNT162b2 (BA.4/BA.5) and mRNA-1273 (BA.1) induce similar neutralization against Omicron subvariants, even when antigenically divergent from the circulating variant.

International pharmacy survey of peripheral vasopressor infusions in critical care (INFUSE).

PURPOSE: The primary objective was to determine the proportion of hospitals that administered norepinephrine peripheral vasopressor infusions (PVIs) in critically ill adult patients. Secondary objectives were to describe how norepinephrine is used such as the maximum duration, infusion rate and concentration, and to determine the most common first-line PVI used by country. MATERIALS AND METHODS: An international multi-centre cross-sectional survey study was conducted in adult intensive care units in Australia, US, UK, Canada, and Saudi Arabia. RESULTS: Critical care pharmacists from 132 institutions responded to the survey. Norepinephrine PVIs were utilised in 86% of institutions (n = 113/132). The median maximum duration of norepinephrine PVIs was 24 h (IQR 24-24) (n = 57/113). The most common maximum norepinephrine PVI rate was between 11 and 20 µg/min (n = 16/113). The most common maximum norepinephrine PVI concentration was 16 µg/mL (n = 60/113). Half of the institutions had a preference to administer another PVI over norepinephrine as a first-line agent (n = 66/132). The most common alternative PVI used by country was: US (phenylephrine 41%, n = 37/90), Canada (dopamine 31%, n = 5/16), UK (metaraminol 82%, n = 9/11), and Australia (metaraminol 89%, n = 8/9). CONCLUSIONS: There is variability in clinical practice regarding PVI administration in critically ill adult patients dependent on drug availability and local institutional recommendations.

Short Timeframe Prediction of Kidney Failure among Patients with Advanced Chronic Kidney Disease.

BACKGROUND: Development of a short timeframe (6-12 months) kidney failure risk prediction model may serve to improve transitions from advanced chronic kidney disease (CKD) to kidney failure and reduce rates of unplanned dialysis. The optimal model for short timeframe kidney failure risk prediction remains unknown. METHODS: This retrospective study included 1757 consecutive patients with advanced CKD (mean age 66 years, estimated glomerular filtration rate 18 mL/min/1.73 m2). We compared the performance of Cox regression models using (a) baseline variables alone, (b) time-varying variables and machine learning models, (c) random survival forest, (d) random forest classifier in the prediction of kidney failure over 6/12/24 months. Performance metrics included area under the receiver operating characteristic curve (AUC-ROC) and maximum precision at 70% recall (PrRe70). Top-performing models were applied to 2 independent external cohorts. RESULTS: Compared to the baseline Cox model, the machine learning and time-varying Cox models demonstrated higher 6-month performance [Cox baseline: AUC-ROC 0.85 (95% CI 0.84-0.86), PrRe70 0.53 (95% CI 0.51-0.55); Cox time-varying: AUC-ROC 0.88 (95% CI 0.87-0.89), PrRe70 0.62 (95% CI 0.60-0.64); random survival forest: AUC-ROC 0.87 (95% CI 0.86-0.88), PrRe70 0.61 (95% CI 0.57-0.64); random forest classifier AUC-ROC 0.88 (95% CI 0.87-0.89), PrRe70 0.62 (95% CI 0.59-0.65)]. These trends persisted, but were less pronounced, at 12 months. The random forest classifier was the highest performing model at 6 and 12 months. At 24 months, all models performed similarly. Model performance did not significantly degrade upon external validation. CONCLUSIONS: When predicting kidney failure over short timeframes among patients with advanced CKD, machine learning incorporating time-updated data provides enhanced performance compared with traditional Cox models.

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.

Determining the Longitudinal Serologic Response to COVID-19 Vaccination in the Chronic Kidney Disease Population: A Clinical Research Protocol.

Background: People living with chronic kidney disease (CKD) have been disproportionately affected by the coronavirus disease 2019 (COVID-19) pandemic, including higher rates of infection, hospitalization, and death. Data on responsiveness to COVID-19 vaccination strategies and immunogenicity are limited, yet required to inform vaccination strategies in this at-risk population. Objective: The objective of this study is to characterize the longitudinal serologic response to COVID-19 vaccination. Design: This is a prospective observational cohort study. Setting: Participating outpatient kidney programs within Ontario and British Columbia. Patients: Up to 2500 participants with CKD G3b-5D receiving COVID-19 vaccination, including participants receiving dialysis and kidney transplant recipients (CKD G1T-5T). Measurements: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG antibodies (anti-spike, anti-receptor binding domain, anti-nucleocapsid) will be detected by ELISA (enzyme-linked immunosorbent assay) from serum or dried blood spot testing. In a subset of participants, neutralizing antibodies against novel variants of concern will be evaluated. Peripheral blood mononuclear cells will be collected for exploratory immune profiling of SARS-CoV-2 specific cellular immunity. Methods: Participants will be recruited prior to or following any COVID-19 vaccine dose and have blood sampled for serological testing at multiple timepoints: 1, 3, 6, 9, and 12 months post vaccination. When possible, samples will be collected prior to a dose or booster. Participants will remain in the study for at least 1 year following their last COVID-19 vaccine dose. Strengths and limitations: The adaptive design of this study allows for planned modification based on emerging evidence or rapid changes in public health policy surrounding vaccination. Limitations include incomplete earlier timepoints for blood collection due to rapid vaccination of the population. Conclusions: This large multicenter serologic study of participants living with kidney disease will generate data on the kinetics of SARS-CoV-2 immune response to vaccination across the spectrum of CKD, providing insights into the amplitude and duration of immunity conferred by COVID-19 vaccination and allowing for characterization of factors associated with immune response. The results of this study may be used to inform immunization guidelines and public health recommendations for the 4 million Canadians living with CKD.

Contexte: Les personnes atteintes d'insuffisance rénale chronique (IRC) ont été touchées de façon disproportionnée par la pandémie de COVID-19 ayant notamment présenté des taux plus élevés d'infection, d'hospitalisation et de décès. Les données sur la réactivité aux stratégies de vaccination de la COVID-19 et à l'immunogénicité sont limitées, mais elles sont nécessaires pour développer des stratégies de vaccination dans cette population à risque. Objectif: Caractériser la réponse sérologique longitudinale à la vaccination contre la COVID-19. Conception: Étude de cohorte observationnelle prospective. Cadre: Les programmes ambulatoires de santé rénale participants en Ontario et en Colombie-Britannique. Sujets: Jusqu'à 2 500 personnes atteintes d'IRC G3B-5D recevant un vaccin contre la COVID-19, y compris des patients suivant des traitements de dialyse et des receveurs d'une greffe rénale (IRC G1T-5T). Mesures: Les anticorps IgG anti-SARS-CoV-2 (anti-spike, anti-domaine de liaison au récepteur, anti-nucléocapside) seront détectés par ELISA à partir du sérum ou de taches de sang séché. Un sous-groupe de sujets participera également à l'évaluation d'anticorps neutralisants dirigés contre les nouveaux variants préoccupants. Des cellules mononuclées de sang périphérique seront prélevées pour établir un profil immunitaire exploratoire de l'immunité cellulaire spécifique au SARS-CoV-2. Méthodologie: Les sujets seront recrutés avant ou après toute dose du vaccin contre la COVID-19 et se soumettront à des prélèvements sanguins pour les tests sérologiques à 1, 3, 6, 9 et 12 mois post-vaccination. Lorsque possible, des échantillons seront prélevés avant l'administration d'une dose ou d'un rappel. Les sujets demeureront dans l'étude pendant au moins un an après leur dernière dose de vaccin contre la COVID-19. Points forts et limites: La conception adaptative de l'étude permet d'apporter des modifications planifiées fondées sur de nouvelles données ou des changements rapides dans les politiques de santé publique entourant la vaccination. Les résultats sont limités par l'absence de certains prélèvements sanguins antérieurs (point temporels) en raison de la vaccination rapide de la population. Conclusion: Cette vaste étude sérologique multicentrique menée auprès de personnes atteintes de néphropathie fournira des données sur la cinétique de la réponse immunitaire à la vaccination contre le SARS-CoV-2 dans l'ensemble du spectre de l'IRC. Elle fournira des informations sur l'amplitude et la durée de l'immunité conférée par la vaccination contre la COVID-19 et permettra de caractériser les facteurs associés à la réponse immunitaire. Ces résultats serviront à orienter les recommandations de santé publique et les lignes directrices en matière d'immunisation pour les quatre millions de Canadiens et Canadiennes qui vivent avec l'IRC.

Magnesium and Fracture Risk in the General Population and Patients Receiving Dialysis: A Narrative Review.

Purpose of Review: Magnesium is an essential mineral for bone metabolism, but little is known about how magnesium intake alters fracture risk. We conducted a narrative review to better understand how magnesium intake, through supplementation, diet, or altering the concentration of dialysate magnesium, affects mineral bone disease and the risk of fracture in individuals across the spectrum of kidney disease. Sources of Information: Peer-reviewed clinical trials and observational studies. Methods: We searched for relevant articles in MEDLINE and EMBASE databases. The methodologic quality of clinical trials was assessed using a modified version of the Downs and Black criteria checklist. Key Findings: The role of magnesium intake in fracture prevention is unclear in both the general population and in patients receiving maintenance dialysis. In those with normal kidney function, 2 meta-analyses showed higher bone mineral density in those with higher dietary magnesium, whereas 1 systematic review showed no effect on fracture risk. In patients receiving maintenance hemodialysis or peritoneal dialysis, a higher concentration of dialysate magnesium is associated with a lower concentration of parathyroid hormone, but little is known about other bone-related outcomes. In 2 observational studies of patients receiving hemodialysis, a higher concentration of serum magnesium was associated with a lower risk of hip fracture. Limitations: This narrative review included only articles written in English. Observed effects of magnesium intake in the general population may not be applicable to those with chronic kidney disease particularly in those receiving dialysis.

Justification: Le magnésium est un minéral essentiel pour le métabolisme osseux, mais on en sait peu sur la façon dont un apport en magnésium modifie le risque de fracture. Nous avons procédé à un examen narratif afin de mieux comprendre comment les maladies liées à la densité minérale osseuse et le risque de fracture sont affectés par un apport en magnésium (supplémentation, régime alimentaire ou modification de la concentration de dialysat de magnésium) chez les personnes atteintes d'insuffisance rénale. Sources: Essais cliniques et études observationnelles examinés par des pairs. Méthodologie: Nous avons répertorié les articles pertinents dans les bases de données MEDLINE et EMBASE. Une version modifiée des critères de contrôle de la qualité des études de Downs et Black a servi à évaluer la qualité méthodologique des essais cliniques retenus. Principaux résultats: Le rôle d'un apport en magnésium dans la prévention des fractures n'est pas clair, tant dans la population générale que chez les patients sous dialyse d'entretien. Chez les personnes ayant une fonction rénale normale, deux méta-analyses ont montré que les personnes dont le régime alimentaire est riche en magnésium présentent une densité minérale osseuse plus élevée; alors qu'une revue systématique n'a montré aucun effet sur le risque de fracture. Chez les patients sous hémodialyse d'entretien ou dialyse péritonéale, une concentration plus élevée de dialysat de magnésium est associée à une plus faible concentration d'hormone parathyroïdienne, mais on en sait peu sur les autres effets liés aux os. Dans deux études observationnelles portant sur des patients sous hémodialyse, une concentration plus élevée de magnésium sérique a été associée à un risque plus faible de fracture de la hanche. Limites: Cet examen narratif ne comprend que des articles rédigés en anglais. Il est possible que les effets d'un apport en magnésium observés dans la population générale ne puissent s'appliquer aux personnes atteintes d'une néphropathie chronique, en particulier aux personnes sous dialyse.