Vascular Access Considerations in Home Hemodialysis.

There is a global interest in expanding home dialysis utilization amongst patients with end-stage kidney disease. Home hemodialysis (HHD) is an appealing kidney replacement therapy option for this population due to its multiple clinical and quality of life benefits. Central to successful HHD is the establishment and maintenance of a functioning vascular access that serves as a patient's lifeline while on therapy. While the selection of a vascular access type is influenced by individual patient circumstances, the arteriovenous fistula is generally the preferred access method. Training patients to utilize their dialysis access requires attention to safety, risk management, and monitoring for complications to minimize adverse events and technique failure. Policies incorporating systematic frameworks for quality improvement and assurance, in conjunction with the measurement of metrics relating to vascular access, are tools that should be employed by HHD programs to enhance the value of care delivered. In this Perspective, we aim to describe what is currently known about the various vascular access options in HHD and to elucidate what needs to be taken into consideration in the selection and care of this access.

Thoracic epidural blockade after myocardial infarction benefits from anti-arrhythmic pathways mediated in part by parasympathetic modulation.

Background: Thoracic epidural anesthesia (TEA) has been shown to reduce the burden of ventricular tachyarrhythmias (VT) in small case-series of patients with refractory VT and cardiomyopathy. However, its electrophysiological and autonomic effects in diseased hearts remain unclear and its use after myocardial infarction (MI) is limited by concerns for potential RV dysfunction. Methods: MI was created in Yorkshire pigs ( N =22) by LAD occlusion. Six weeks post-MI, an epidural catheter was placed at the C7-T1 vertebral level for injection of 2% lidocaine. RV and LV hemodynamics were recorded using Millar pressure-conductance catheters, and ventricular activation-recovery intervals (ARIs), a surrogate of action potential durations, by a 56-electrode sock and 64-electrode basket catheter. Hemodynamics and ARIs, baroreflex sensitivity (BRS) and intrinsic cardiac neural activity, and ventricular effective refractory periods (ERP) and slope of restitution (S max ) were assessed before and after TEA. VT/VF inducibility was assessed by programmed electrical stimulation. Results: TEA reduced inducibility of VT/VF by 70%. TEA did not affect RV-systolic pressure or contractility, although LV-systolic pressure and contractility decreased modestly. Global and regional ventricular ARIs increased, including in scar and border zone regions post-TEA. TEA reduced ARI dispersion specifically in border zone regions. Ventricular ERPs prolonged significantly at critical sites of arrhythmogenesis, and S max was reduced. Interestingly, TEA significantly improved cardiac vagal function, as measured by both BRS and intrinsic cardiac neural activity. Conclusion: TEA does not compromise RV function in infarcted hearts. Its anti-arrhythmic mechanisms are mediated by increases in ventricular ERP and ARIs, decreases in S max , and reductions in border zone heterogeneity. TEA improves parasympathetic function, which may independently underlie some of its observed anti-arrhythmic mechanisms. This study provides novel insights into the anti-arrhythmic mechanisms of TEA, while highlighting its applicability to the clinical setting. Abstract Illustration: Myocardial infarction is known to cause cardiac autonomic dysfunction characterized by sympathoexcitation coupled with reduced vagal tone. This pathological remodeling collectively predisposes to ventricular arrhythmia. Thoracic epidural anesthesia not only blocks central efferent sympathetic outflow, but by also blocking ascending projections of sympathetic afferents, relieving central inhibition of vagal function. These complementary autonomic effects of thoracic epidural anesthesia may thus restore autonomic balance, thereby improving ventricular electrical stability and suppressing arrhythmogenesis. DRG=dorsal root ganglion, SG=stellate ganglion.

Upregulation of CD8+ regulatory T cells following liver-directed AAV gene therapy.

Liver-directed AAV gene therapy represents a unique treatment modality for a host of diseases. This is due, in part, to the induction of tolerance to transgene products. Despite the plethora of recognized regulatory cells in the body, there is currently a lack of literature supporting the induction of non-CD4+ regulatory cells following hepatic AAV gene transfer. In this work, we show that CD8+ regulatory T cells are up-regulated in PBMCs of mice following capsid only and therapeutic transgene AAV administration. Further, we demonstrate that hepatic AAV gene transfer results in a significant increase in CD8+ regulatory T cells following experimental autoimmune encephalomyelitis induction. Notably, this response occurred only in therapeutic vector treated animals, not capsid only controls. Understanding the role these cells play in treatment efficacy will result in the development of improved AAV vectors that take advantage of the full gamut of regulatory cells within the body.

Virtual Pharmacy: An Integrated Collaborative Redesign Targeting Medication-Related Problems in Patients with Chronic Kidney Disease.

INTRODUCTION: Collaborative management of kidney disease relies on coordinated and effective partnerships between multiple providers. Siloed traditional health systems often result in delays, barriers to treatment access, and inefficient monitoring. METHODS: We conducted a 1-year observational mixed-methods study. We included all consecutive referrals except for patients without telephone access. We assessed 4 domains of outcomes: (1) patient and caregiver experience, (2) provider experience (e.g., physicians and pharmacists), (3) clinical outcomes specific to medication-related outcomes (e.g., adherence, adverse drug events [ADEs]), and (4) value and efficiency (i.e., medication access, defined as time to treatment and resolution of medication reimbursement issues). RESULTS: Sixty-five patients were referred to the integrated virtual pharmacy (iVRx) model. Most (72%) patients were male. Patients had a median (min, max) age of 60 (27, 85) years and were taking 8 (4, 13) medications. Compared with traditional care delivery models, medication access improved for 56% of participants. Direct home delivery of medication resulted in 91% of patients receiving prescriptions within 2 days of a nephrologist visit. During more than 2,000 pharmacist-patient encounters, 208 ADEs were identified that required clinician intervention to prevent patient harm. When these ADEs were classified by severity, 53% were mild, 45% were moderate (e.g., delaying dose titration in patients initiated on glucagon-like peptide 1 (GLP-1) agonists due to intolerable gastrointestinal side effects), and the remaining 2% of ADEs were severe, meaning clinical intervention was required to prevent a serious outcome (e.g., uncontrolled blood pressure, prevention of acute kidney injury). Nephrologists reported high satisfaction with iVRx, citing efficiency, timely response, and collaboration with pharmacists as key facilitators. Of the 65 patient participants, 98% reported being extremely satisfied. CONCLUSIONS: The iVRx is an acceptable and feasible clinical strategy. Our pilot program was associated with improved kidney care by increasing medication access for patients and avoiding potential harms associated with ADEs.

Pathological personality explains individual differences in global emotion dysregulation within the pathway between child maltreatment and severe depressive symptoms.

OBJECTIVE: Global emotion dysregulation mediates the relationship between child maltreatment and severe depressive symptoms; however, there is a lack of research on maladaptive personality traits and their contribution to individual differences in global emotion dysregulation within this conceptual model. The present study tested a preliminary serial mediation model where maladaptive personality traits and global emotion dysregulation mediate the relationship between child maltreatment and severe depressive symptoms. METHOD: A total of 200 patients with mood disorders (Mage = 36.5 years; 54% females) were assessed for maladaptive personality traits (Personality Inventory for Diagnostic and Statistical Manual of Mental Disorders [5th ed.] Brief Form), global emotion dysregulation (Difficulties in Emotion Regulation Scale-Short), childhood trauma (Childhood Trauma Questionnaire), and depressive symptoms (Patient Health Questionnaire-9). RESULTS: Ordinary least squares regression and partial least squares-structural equation modeling revealed a consistent and significant indirect effect of child maltreatment on severe depressive symptoms through negative affectivity, detachment, psychoticism, and global emotion dysregulation. Among child maltreatment types, only emotional abuse had a significant indirect effect on severe depressive symptoms through maladaptive personality traits and global emotion dysregulation, b = 0.50, SE = 0.09, 95% confidence intervals [0.326, 0.694] after controlling for age, gender, and remaining types of child maltreatment. CONCLUSIONS: Findings support the view that maladaptive personality traits shed important insights on individual differences in global emotion dysregulation, and this information could aid clinical formulation and treatment of childhood adversity-related psychopathology. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Patient-Centered Home Hemodialysis: Approaches and Prescription.

Writing a home hemodialysis (HD) prescription is a complex, multifactorial process that requires the incorporation of patient values, preferences, and lifestyle. Knowledge of the different options available for home HD modality (conventional, nocturnal, short daily, and alternate nightly) is also important when customizing a prescription. Finally, an understanding of the different home HD machines currently approved for use at home and their different attributes and limitations helps guide providers when formulating their prescriptions. In this review article, we set out to address these different aspects to help guide providers in providing a patient-centered home HD approach.

Outcomes of Integrated Home Dialysis Care: Results From the Canadian Organ Replacement Register.

RATIONALE & OBJECTIVE: The integrated home dialysis model proposes the initiation of kidney replacement therapy (KRT) with peritoneal dialysis (PD) and a timely transition to home hemodialysis (HHD) after PD ends. We compared the outcomes of patients transitioning from PD to HHD with those initiating KRT with HHD. STUDY DESIGN: Observational analysis of the Canadian Organ Replacement Register (CORR). SETTINGS & PARTICIPANTS: All patients who initiated PD or HHD within the first 90 days of KRT between 2005 and 2018. EXPOSURE: Patients transitioning from PD to HHD (PD+HHD group) versus patients initiating KRT with HHD (HHD group). OUTCOME: (1) A composite of all-cause mortality and modality transfer (to in-center hemodialysis or PD for 90 days) and (2) all hospitalizations (considered as recurrent events). ANALYTICAL APPROACH: A propensity score analysis for which PD+HHD patients were matched 1:1 to (1) incident HHD patients ("incident-match" analysis) or (2) HHD patients with a KRT vintage at least equivalent to the vintage of PD+HHD patients at the transition time ("vintage-matched" analysis). Cause-specific hazards models (composite outcome) and shared frailty models (hospitalization) were used to compare groups. RESULTS: Among 63,327 individuals in the CORR, 163 PD+HHD patients (median of 1.9 years in PD) and 711 HHD patients were identified. In the incident-match analysis, compared to the HHD patients, the PD+HHD group had a similar risk of the composite outcome (HR, 0.88 [95% CI, 0.58-1.32]) and hospitalizations (HR, 1.04 [95% CI, 0.76-1.41]). In the vintage-match analysis, PD+HHD patients had a lower hazard for the composite outcome (HR, 0.61 [95% CI, 0.40-0.94]) but a similar hospitalization risk (HR, 0.85 [95% CI, 0.59-1.24]). LIMITATIONS: Risk of survivor bias in the PD+HHD cohort and residual confounding. CONCLUSIONS: Controlling for KRT vintage, the patients transitioning from PD to HHD had better clinical outcomes than the incident HHD patients. These data support the use of integrated home dialysis for patients initiating home-based KRT. PLAIN-LANGUAGE SUMMARY: The integrated home dialysis model proposes the initiation of dialysis with peritoneal dialysis (PD) and subsequent transition to home hemodialysis (HHD) once PD is no longer feasible. It allows patients to benefit from initial lifestyle advantages of PD and to continue home-based treatments after its termination. However, some patients may prefer to initiate dialysis with HHD from the outset. In this study, we compared the long-term clinical outcomes of both approaches using a large Canadian dialysis register. We found that both options led to a similar risk of hospitalization. In contrast, the PD-to-HHD model led to improved survival when controlling for the duration of kidney failure.

Patient Survival With Extended Home Hemodialysis Compared to In-Center Conventional Hemodialysis.

Introduction: More frequent and/or longer hemodialysis (HD) has been associated with improvements in numerous clinical outcomes in patients on dialysis. Home HD (HHD), which allows more frequent and/or longer dialysis with lower cost and flexibility in treatment planning, is not widely used worldwide. Although, retrospective studies have indicated better survival with HHD, this issue remains controversial. In this multicenter study, we compared thrice-weekly extended HHD with in-center conventional HD (ICHD) in a large patient population with a long-term follow-up. Methods: We matched 349 patients starting HHD between 2010 and 2014 with 1047 concurrent patients on ICHD by using propensity scores. Patients were followed-up with from their respective baseline until September 30, 2018. The primary outcome was overall survival. Secondary outcomes were technique survival; hospitalization; and changes in clinical, laboratory, and medication parameters. Results: The mean duration of dialysis session was 418 ± 54 minutes in HHD and 242 ± 10 minutes in patients on ICHD. All-cause mortality rate was 3.76 and 6.27 per 100 patient-years in the HHD and the ICHD groups, respectively. In the intention-to-treat analysis, HHD was associated with a 40% lower risk for all-cause mortality than ICHD (hazard ratio [HR] = 0.60; 95% confidence interval [CI] 0.45 to 0.80; P < 0.001). In HHD, the 5-year technical survival was 86.5%. HHD treatment provided better phosphate and blood pressure (BP) control, improvements in nutrition and inflammation, and reduction in hospitalization days and medication requirement. Conclusion: These results indicate that extended HHD is associated with higher survival and better outcomes compared to ICHD.

Integrated Care: A Person-Centered and Population Health Strategy for the COVID-19 Pandemic Recovery and Beyond.

The COVID-19 pandemic has mandated a re-imagination of how healthcare is administered and delivered, with a view towards focusing on person-centred care and advancing population health while increasing capacity, access and equity in the healthcare system. These goals can be achieved through healthcare integration. In 2019, the University Health Network (UHN), a consortium of four quaternary care hospitals in Ontario, Canada, established the first stage of a pilot program to increase healthcare integration at the institutional level and vertically with other primary, secondary and tertiary institutions in the Ontario healthcare system. Implementation of the program was accelerated during the COVID-19 pandemic and demonstrated how healthcare integration improves person-centred care and population health; therefore serving as the foundation for a health system response for the COVID-19 pandemic recovery and beyond.

Rational Design of AAV-rh74, AAV3B, and AAV8 with Limited Liver Targeting.

Recombinant adeno-associated viruses (rAAVs) have become one of the leading gene therapies for treating a variety of diseases. One factor contributing to rAAVs' success is the fact that a wide variety of tissue types can be transduced by different serotypes. However, one commonality amongst most serotypes is the high propensity for liver transduction when rAAVs are administered peripherally. One of the few exceptions is the naturally occurring clade F AAV hematopoietic stem cell 16 (AAVHSC16). AAVHSC16 represents an interesting capsid in that it shows minimal liver transduction when injected peripherally. For capsids other than AAVHSC16, targeting non-liver tissues via peripheral AAV injection represents a challenge due to the high liver transduction. Thus, there is a demand for liver-de-targeted rAAV vectors. The rational design of rAAV capsids relies on current knowledge to design improved capsids and represents one means of developing capsids with reduced liver transduction. Here, we utilized data from the AAVHSC16 capsid to rationally design four non-clade F rAAV capsids that result in reduced liver transduction following peripheral injection.

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 .

"We're trained to trust our patients": a qualitative study on the general practitioners' trust in patients for colorectal cancer shared care.

BACKGROUND: In a therapeutic partnership, physicians rely on patients to describe their health conditions, join in shared decision-making, and engage with supported self-management activities. In shared care, the patient, primary care, and specialist services partner together using agreed processes and outputs for the patient to be placed at the centre of their care. However, few empirical studies have explored physicians' trust in patients and its implications for shared care models. AIM: To explore trust in patients amongst general practitioners (GPs), and the impacts of trust on GPs' willingness to engage in new models of care, such as colorectal cancer shared care. METHODS: GP participants were recruited through professional networks for semi-structured interviews. Transcripts were integrity checked, coded inductively, and themes developed iteratively. RESULTS: Twenty-five interviews were analysed. Some GPs view trust as a responsibility of the physician and have a high propensity for trusting patients. For other GPs, trust in patients is developed over successive consultations based on patient characteristics such as honesty, reliability, and proactivity in self-care. GPs were more willing to engage in colorectal cancer shared care with patients with whom they have a developed, trusting relationship. CONCLUSIONS: Trust plays a significant role in the patient's access to shared care. The implementation of shared care should consider the relational dynamics between the patient and health care providers.

In a therapeutic partnership, physicians rely on patients to describe their health conditions, join in shared decision-making and engage with supported self-management activities. In shared care, the patient, primary care, and specialist services partner together using agreed processes and outputs for the patient to be placed at the centre of their care. Trust is key to this partnership. However, few studies have explored the physicians' trust in patients and its implications for shared care models. This study aims to explore trust in patients amongst general practitioners (GPs), and the impacts of trust on GPs' willingness to engage in new models of care, such as colorectal cancer shared care. After analysing 25 interview transcripts with GPs, we found some GPs view trust as a responsibility of the physicians, while in others, trust in patients developed over successive consultations based on patient characteristics such as honesty, reliability, and proactivity in self-care. GPs were more willing to engage in colorectal cancer shared care with patients whom they have a developed, trusting relationship. Trust plays a significant role in the patient's access to shared care. The rollout of shared care should consider the relational dynamics between the patient and health care providers.

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.

Honest, Open, Proud (HOP) for people with mental illness in Hong Kong: a randomized controlled trial.

BACKGROUND: Self-stigma among people with mental illness is negatively associated with personal and clinical recovery. Due to the concealable nature of mental illness, people with mental illness experience constant struggles between concealment and disclosure. Disclosure of mental health challenges can potentially minimize negative impacts of self-stigma and enhance self-esteem and sense of empowerment. Honest, Open, Proud (HOP) is a peer-led intervention that promotes autonomous and dignified decisions about disclosure. PURPOSE: This study examined the effectiveness of HOP on concealment motivation, empowerment, self-stigma, stigma stress, and recovery among people with lived experience of mental illness in Hong Kong. METHODOLOGY: A total of 162 participants with a mean age of 45.38 were recruited and randomized into intervention group and waitlist control group. Participants in the intervention group were invited to attend a 6-session HOP group intervention. RESULTS: Significant improvement in optimism score from the empowerment scale was found in the intervention group compared to the waitlist control group and the effect was sustained at 1-month follow-up. However, significant changes were not found in other outcome variables. CONCLUSION: Only improvement in optimism was observed in the current study. Future study needs to examine the effects of HOP with further modification to maximize the benefit for people with lived experience of mental illness in the local context.

Andreas Pierratos Tribute: Personal Reflections.

Since the passing of Andreas Pierratos on November 15, 2022, we have had many occasions to reflect on what our relationship with a friend and colleague has meant. We have done this in solitude, with colleagues while at work and more recently, in a tribute organized at Humber River Hospital on March 26, 2023. We also had the opportunity to expand, in the February 2023 issue of the Nephrology News & Issues, on his many contributions to nephrology and to the betterment of patients' lives. For this collaboration, we thought we would share our personal reflections of this unique individual, with the hope that this effort would provide a deeper appreciation of his unique humanity.