Inflammatory bowel diseases (IBD), encompassing both Crohn Disease (CD) and ulcerative colitis (UC) are globally prevalent diseases, impacting children of all ages. The hallmark of IBD is a perturbed ...immune system that leads to continuous inflammation in the gut and challenges optimal treatment. Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κβ), a nuclear transcription factor, plays a major role in gut homeostasis and contributes significantly toward a balanced, homeostatic immune system. Dysregulation in the NF-κβ pathway and factors that regulate it lead to a state of uncontrolled inflammation and altered immunity, as typically observed in IBD. Levels of proinflammatory cytokines that are regulated through NF-κβ are increased in both CD and UC. Genes known to activate NF-κβ, such as, Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) and Interleukin 23 (IL-23), are associated with IBD. Factors involved in inhibition of NF-κβ, such as A20 and TOLLIP, are also affected in IBD, resulting in failed inflammation suppression/regulation. NOD-2 and A20 have specifically been found to be strongly associated with pediatric IBD. Gut commensals are known to exert anti-inflammatory activities toward NF-κβ and can have a potential role in attenuating inflammation that likely occurs due to microbial dysbiosis in IBD. Failure to terminate/downregulate NF-κβ signaling results in chronic inflammation in IBD. Well-regulated control of inflammation in children with IBD can help better control the disease and suppress immune responses. Better understanding of factors that control NF-κβ can potentially lead toward discovering targeted therapeutic interventions for IBD. Suppression of NF-κβ can be achieved through many modalities including anti-sense oligonucleotides (ASOs), siRNA (small interfering RNA), factors regulating NF-κβ, and microbes. This review focuses on the role of NF-κβ, especially in pediatric IBD, and potential therapeutic venues for attenuating NF-κβ-induced inflammation.
Information on early, guideline discordant referrals in nephrology is limited. Our objective was to investigate trends in referral patterns to nephrology for patients with chronic kidney disease ...(CKD). Retrospective cohort study of adults with greater than or equal to1 visits to a nephrologist from primary care with greater than or equal to1 serum creatinine and/or urine protein measurement <180 days before index nephrology visit, from 2006 and 2019 in Alberta, Canada. Guideline discordant referrals were those that did not meet greater than or equal to1 of: Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73m.sup.2, persistent albuminuria (ACR greater than or equal to 300 mg/g, PCR greater than or equal to 500 mg/g, or Udip greater than or equal to 2+), or progressive and persistent decline in eGFR until index nephrology visit (greater than or equal to 5 mL/min/1.73m.sup.2). Of 69,372 patients with CKD, 28,518 (41%) were referred in a guideline concordant manner. The overall rate of first outpatient visits to nephrology increased from 2006 to 2019, although guideline discordant referrals showed a greater increase (trend 21.9 per million population/year, 95% confidence interval 4.3, 39.4) versus guideline concordant referrals (trend 12.4 per million population/year, 95% confidence interval 5.7, 19.0). The guideline concordant cohort were more likely to be on renin-angiotensin system blockers or beta blockers (hazard ratio 1.14, 95% confidence interval 1.12, 1.16), and had a higher risk of CKD progression (hazard ratio 1.09, 95% confidence interval 1.06, 1.13), kidney failure (hazard ratio 7.65, 95% confidence interval 6.83, 8.56), cardiovascular event (hazard ratio 1.40, 95% confidence interval 1.35,1.45) and mortality (hazard ratio 1.58, 95% confidence interval 1.52, 1.63). A significant proportion nephrology referrals from primary care were not consistent with current guideline-recommended criteria for referral. Further work is needed to identify quality improvement initiatives aimed at enhancing referral patterns of patients with CKD.
Indigenous people represent approximately 5% of the world's population. However, they often have a disproportionately higher burden of cardiovascular disease (CVD) risk and chronic kidney disease ...(CKD) than their equivalent general population. Several non-pharmacological interventions (e.g., educational) have been used to reduce CVD and kidney disease risk factors in Indigenous groups. The aim of this paper is to describe the protocol for a scoping review that will assess the impact of non-pharmacological interventions carried out in Indigenous and remote dwelling populations to reduce CVD risk factors and CKD.
This scoping review will be guided by the methodological framework for conducting scoping studies developed by Arksey and O'Malley. Both empirical (Medline, Embase, Cochrane Library, CINAHL, ISI Web of Science and PsycINFO) and grey literature references will be assessed if they focused on interventions targeted at reducing CVD or CKD among Indigenous groups. Two reviewers will independently screen references in consecutive stages of title/abstract screening and then full-text screening. Impact of interventions used will be assessed using the reach, effectiveness, adoption, implementation, maintenance (RE-AIM) framework. A descriptive overview, tabular summaries, and content analysis will be carried out on the extracted data.
This review will collect and analyse evidence on the impact of interventions of research carried out to reduce CVD and CKD among Indigenous populations. Such evidence will be disseminated using traditional approaches that includes open-access peer-reviewed publication, scientific presentations, and a report. Also, we will disseminate our findings to the government and Indigenous leaders. Ethical approval will not be required for this scoping review as the data used will be extracted from already published studies with publicly accessible data.
Inflammatory bowel diseases (IBD) are a group of complex and multifactorial disorders with unknown etiology. Chronic intestinal inflammation develops against resident intestinal bacteria in ...genetically susceptible hosts. We hypothesized that host intestinal immunoglobulin (Ig) G can be used to identify bacteria involved in IBD pathogenesis.
IgG-bound and -unbound microorganisms were collected from 32 pediatric terminal ileum aspirate washes during colonoscopy non-IBD (n = 10), Crohn disease (n = 15), and ulcerative colitis (n = 7), and composition was assessed using the Illumina MiSeq platform. In vitro analysis of invasive capacity was evaluated by fluorescence in situ hybridization and gentamicin invasion assay; immune activation was measured by qPCR. Despite considerable inter-individual variations, IgG binding favored specific and unique mucosa-associated species in pediatric IBD patients. Burkholderia cepacia, Flavonifractor plautii, and Rumminococcus sp. demonstrated increased IgG binding, while Pseudomonas ST29 demonstrated reduced IgG binding, in IBD. In vitro validation confirmed that B. cepacia, F. plautii, and Rumminococcus display invasive potential while Pseudomonas protogens did not.
Using IgG as a marker of pathobionts in larger patient cohorts to identify microbes and elucidate their role in IBD pathogenesis will potentially underpin new strategies to facilitate development of novel, targeted diagnostic, and therapeutic approaches. Interestingly, this method can be used beyond the scope of this manuscript to evaluate altered gut pathobionts in a number of diseases associated with altered microbiota including arthritis, obesity, diabetes mellitus, alcoholic liver disease, cirrhosis, metabolic syndrome, and carcinomas.
BackgroundGaps in identification, medical management and appropriate referral for patients with chronic kidney disease (CKD) are evident.ObjectiveWe designed and implemented an interactive ...educational intervention (accredited workshop) to improve primary care providers’ awareness of tools to support guideline-concordant CKD management.DesignWe used the Kern method to design the educational intervention and targeted the accredited workshops to primary care team members (physicians, nurses and allied health) in Alberta, Canada. We conducted anonymous pre-workshop and post-workshop surveys to identify practice-specific barriers to care, identify potential solutions, and evaluate provider confidence pre-intervention and post-intervention. We used non-parametric statistics to analyse Likert-type survey data and descriptive content analysis to categorise responses to open-ended survey questions.ResultsWe delivered 12 workshops to 114 providers from September 2017 through March 2019. Significant improvements (p<0.001) in confidence to appropriately identify, manage and refer patients with CKD were observed. Participants identified several patient-level, provider-level, and system-level barriers and potential solutions to care for patients with CKD; the majority of these barriers were addressed in the interactive workshop.ConclusionsThe Kern model was an effective methodology to design and implement an educational intervention to improve providers’ confidence in managing patients with CKD in primary care. Future research is needed to determine if these perceived knowledge and confidence improvements affect patient outcomes and whether improvements are sustained long term.
IntroductionElectronic consultation (eConsult)—provider-to-provider electronic asynchronous exchanges of patient health information at a distance—is emerging as a potential tool to improve the ...interface between primary care providers and specialists. Despite growing evidence that eConsult has clinical benefits, it is not widely adopted. We investigated factors influencing the adoption and implementation of eConsult services.MethodsWe applied established methods to guide the review, and the recently published Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews to report our findings. We searched five electronic databases and the grey literature for relevant studies. Two reviewers independently screened titles and full texts to identify studies that reported barriers to and/or facilitators of eConsult (asynchronous (store-and-forward) use of telemedicine to exchange patient health information between two providers (primary and secondary) at a distance using secure infrastructure). We extracted data on study characteristics and key barriers and facilitators were analysed thematically and classified using the Quadruple Aim framework taxonomy. No date or language restrictions were applied.ResultsAmong the 2579 publications retrieved, 130 studies met eligibility for the review. We identified and summarised key barriers to and facilitators of eConsult adoption and implementation across four domains: provider, patient, healthcare system and cost. Key barriers were increased workload for providers, privacy concerns and insufficient reimbursement for providers. Main facilitators were remote residence location, timely responses from specialists, utilisation of referral coordinators, addressing medicolegal concerns and incentives for providers to use eConsult.ConclusionThere are multiple barriers to and facilitators of eConsult adoption across the domains of Quadruple Aim framework. Our findings will inform the development of practice tools to support the wider adoption and scalability of eConsult implementation.
Background:
Hypertension is a major cause of cardiovascular disease, chronic kidney disease (CKD), and death. Several studies have demonstrated the efficacy of home blood pressure telemonitoring ...(HBPT) for blood pressure (BP) control and outcomes, but the effects of this intervention remain unclear in patients with CKD.
Objective:
To determine the impact of HBPT on cardiovascular–related and kidney disease–related outcomes in patients with CKD.
Design:
Systematic review and meta-analysis.
Setting:
All studies that met our criteria regardless of country of origin.
Participants:
Patients with chronic kidney disease included in studies using HBPT for BP assessment and control.
Measurements:
Descriptive and quantitative analysis of our primary and secondary outcomes.
Methods:
We searched MEDLINE, Embase, CINAHL Plus, PsycINFO, Cochrane CENTRAL, Web of Science, and gray literature from inception for observational and randomized controlled studies in nondialysis (ND) CKD using HBPT for BP control. We selected studies that used HBPT as intervention (with or without a control arm) for BP control in ND-CKD populations. The primary outcome was change in mean systolic BP (SBP) and mean diastolic BP (DBP).
Results:
We selected 7 studies from 1669 articles that were initially identified. Overall, pooled estimates in the mean difference (MD) for SBP and DBP were −8.8 mm Hg; 95% confidence interval (CI): −16.2 to −1.4; P = .02 and −2.4 mm Hg; 95% CI: −3.8 to −1.0; P < .001, respectively. For studies comparing intervention with usual care (UC), pooled estimate in MD for SBP was −8.0 mm Hg (P = .02) with no significant reduction for DBP (−2.6 mm Hg; P = .18). In studies without a UC arm, both SBP and DBP were not significantly reduced (P > .05). The pooled estimate in MD for estimated glomerular filtration rate showed a significant improvement (5.4 mL/min/1.73 m2; P < .001).
Limitations:
Heterogeneity and few available studies for inclusion limited our ability to identify a robust link between HBPT use and BP and kidney function improvement.
Conclusion:
Home blood pressure telemonitoring is associated with mild lowering of BP and moderately improved kidney function in patients with CKD. However, larger studies with improved designs and prolonged interventions are still needed to assess the effects of HBPT on patients’ outcomes.
PROSPERO registration ID
CRD42020190705
Patients with advanced chronic kidney disease (CKD) or kidney failure receiving replacement therapy (KFRT) are highly vulnerable to COVID-19 infection, morbidity and mortality. Vaccination is ...effective, but access differs around the world. We aimed to ascertain the availability, readiness and prioritisation of COVID-19 vaccines for this group of patients globally.
Collaborators from the International Society of Nephrology (ISN), Dialysis Outcomes and Practice Patterns Study and ISN-Global Kidney Health Atlas developed an online survey that was administered electronically to key nephrology leaders in 174 countries between 2 July and 4 August 2021.
Survey responses were received from 99 of 174 countries from all 10 ISN regions, among which 88/174 (50%) were complete. At least one vaccine was available in 96/99 (97%) countries. In 71% of the countries surveyed, patients on dialysis were prioritised for vaccination, followed by patients living with a kidney transplant (KT) (62%) and stage 4/5 CKD (51%). Healthcare workers were the most common high priority group for vaccination. At least 50% of patients receiving in-centre haemodialysis, peritoneal dialysis or KT were estimated to have completed vaccination at the time of the survey in 55%, 64% and 51% of countries, respectively. At least 50% of patients in all three patient groups had been vaccinated in >70% of high-income countries and in 100% of respondent countries in Western Europe.The most common barriers to vaccination of patients were vaccine hesitancy (74%), vaccine shortages (61%) and mass vaccine distribution challenges (48%). These were reported more in low-income and lower middle-income countries compared with high-income countries.
Patients with advanced CKD or KFRT were prioritised in COVID-19 vaccination in most countries. Multiple barriers led to substantial variability in the successful achievement of COVID-19 vaccination across the world, with high-income countries achieving the most access and success.
IntroductionHypertension is a common public health problem and a key modifiable risk factor for cardiovascular (CV) and chronic kidney disease (CKD). Home blood pressure (BP) telemonitoring (HBPT) ...and management is associated with improved BP control, accelerated delivery of care and decision-making strategies that can reduce adverse outcomes associated with hypertension. The aim of this paper is to describe the protocol for a systematic review to assess the impact of HBPT interventions used for improving BP control and reducing CV and kidney outcomes in non-dialysis CKD patients.MethodsWe developed this protocol using the Preferred Reporting Items for Systematic reviews and Meta-Analyses for Protocols 2015. We will search empirical databases such as MEDLINE, Embase, Cochrane Library, CINAHL, Web of Science and PsycINFO and grey literature for studies conducted in non-dialysis CKD patients on interventions using HBPT and reporting outcomes related to BP control and other outcomes such as CV events and kidney disease progression. All studies meeting these criteria, in adults and published from inception until 2020 with no language barrier will be included.Ethics and disseminationEthical approval will not be required for this review as the data used will be extracted from already published studies with publicly accessible data. As this study will assess the impact of HBPT on BP control in non-dialysis CKD patients, evidence gathered through it will be disseminated using traditional approaches that includes open-access peer-reviewed publication, scientific presentations and a report. We will also disseminate our findings to appropriate government agencies.PROSPERO registration numberCRD42020190705).
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