A Double-blind, Randomized Phase 2 Controlled Trial of Intradermal Hepatitis B Vaccination With a Topical Toll-like Receptor 7 Agonist Imiquimod, in Patients on Dialysis.

BACKGROUND: Patients on dialysis are hyporesponsive to the hepatitis B virus vaccines (HBVv). We examined intradermal (ID) HBVv Sci-B-Vac, with topical Toll-like receptor 7 (TLR7) agonist imiquimod pretreatment in dialysis patients. METHODS: We enrolled and prospectively followed adult patients on dialysis between January 2016 and September 2018. Eligible patients were randomly allocated (1:1:1) into 1 treatment group, topical imiquimod cream followed by ID HBVv (IMQ + ID); and 2 control groups: topical aqueous cream (placebo) followed by ID HBVv (AQ + ID) or topical aqueous cream followed by intramuscular HBVv (AQ + IM). The primary endpoint was the seroprotection rate (hepatitis B surface antibody ≥10 mIU/mL) at 52 weeks. RESULTS: Ninety-four patients were enrolled, among which 57.4% were previous nonresponders. Seroprotection rate was significantly better at week 52 for the IMQ + ID group with 96.9% compared to 74.2% and 48.4% for AQ + ID and AQ + IM groups, respectively (P < .0001). The geometric mean concentration was significantly higher at week 52 for the IMQ + ID group: 1135 (95% confidence interval [CI], 579.4-2218.2) mIU/mL, compared to 86.9 (95% CI, 18.5-409.3) mIU/mL and 7.2 (2.0-26.5) mIU/mL for the AQ + ID and AQ + IM groups, respectively (P < .0001). IMQ + ID vaccination (odds ratio, 3.70 [95% CI, 1.16-11.81]; P = .027) was the only factor independently associated with higher 52-week seroprotection rate. Adverse reaction was infrequent. CONCLUSIONS: Pretreatment with topical imiquimod before ID HBVv Sci-B-Vac was safe with favorable seroprotection in dialysis patients. CLINICAL TRIALS REGISTRATION: NCT02621112.

Vaccination in patients with chronic kidney disease-Review of current recommendations and recent advances.

Hepatitis B virus (HBV), influenza, pneumococcus and herpes zoster are important infections which could result in significant morbidity and mortality in patients with chronic kidney disease (CKD). While seroconversion rates after vaccination are often lower in CKD patients compared with healthy adults due to impaired innate and adaptive immunity, vaccinations for HBV, influenza, pneumococcus and herpes zoster are generally effective in reducing the transmission and/or severity of these infections. Practical issues that have an impact on the efficacy of vaccination in the CKD population include the timing, dose, schedule of vaccination, the route of administration, and adjuncts applied at time of vaccination. This review discusses the vaccination regimens and the efficacy of HBV, influenza, pneumococcus and zoster vaccines in CKD patients, and highlights recent advances in enhancing vaccine seroconversion rates.

Exit site infection and peritonitis due to Serratia species in patients receiving peritoneal dialysis: Epidemiology and clinical outcomes.

AIM: To study the epidemiology and clinical outcomes of catheter-related infections of Serratia species in peritoneal dialysis (PD) patients. METHODS: We retrospectively reviewed the patient characteristics, antibiotics susceptibility/resistance patterns and treatment outcomes of exit site infection (ESI) and peritonitis due to Serratia in PD patients during the period of 2004 to 2017. RESULTS: One hundred and sixty-one patients had Serratia ESI, of which 10 (6.2%) progressed to tunnel tract involvement and 11 (6.8%) developed PD peritonitis. Nineteen (11.8%) patients with Serratia ESI failed to respond to medical treatment and required catheter removal. Fifty-six (34.8%) patients had repeat Serratia ESI, which occurred at 12.9 ± 13.6 months after the previous episode. Twenty-two patients had Serratia peritonitis, which accounted for 1% of peritonitis during the study period. Ten (45.5%) patients responded to medical treatment while 12 (54.5%) patients required catheter removal. Nine patients (36.4%) failed to resume PD and were converted to long-term haemodialysis. Two patients had repeat peritonitis at 2 months and 3 years, respectively, after the initial episode. Serratia species in PD patients showed high rates of resistance to ampicillin, and first- and second-generation cephalosporins, but were generally susceptible to aminoglycosides, carboxy-/ureido-penicillins and carbapenems. CONCLUSION: Our results suggest that Serratia ESI show low risk of progression to peritonitis and favourable response to medical therapy, while Serratia peritonitis was associated with high rates of catheter removal and peritoneal failure.

Meaning of empowerment in peritoneal dialysis: focus groups with patients and caregivers.

BACKGROUND: While peritoneal dialysis (PD) can offer patients more independence and flexibility compared with in-center hemodialysis, managing the ongoing and technically demanding regimen can impose a burden on patients and caregivers. Patient empowerment can strengthen capacity for self-management and improve treatment outcomes. We aimed to describe patients' and caregivers' perspectives on the meaning and role of patient empowerment in PD. METHODS: Adult patients receiving PD (n = 81) and their caregivers (n = 45), purposively sampled from nine dialysis units in Australia, Hong Kong and the USA, participated in 14 focus groups. Transcripts were thematically analyzed. RESULTS: We identified six themes: lacking clarity for self-management (limited understanding of rationale behind necessary restrictions, muddled by conflicting information); PD regimen restricting flexibility and freedom (burden in budgeting time, confined to be close to home); strength with supportive relationships (gaining reassurance with practical assistance, comforted by considerate health professionals, supported by family and friends); defying constraints (reclaiming the day, undeterred by treatment, refusing to be defined by illness); regaining lost vitality (enabling physical functioning, restoring energy for life participation); and personal growth through adjustment (building resilience and enabling positive outlook, accepting the dialysis regimen). CONCLUSIONS: Understanding the rationale behind lifestyle restrictions, practical assistance and family support in managing PD promoted patient empowerment, whereas being constrained in time and capacity for life participation outside the home undermined it. Education, counseling and strategies to minimize the disruption and burden of PD may enhance satisfaction and outcomes in patients requiring PD.

Enhanced Psychosocial Support for Caregiver Burden for Patients With Chronic Kidney Failure Choosing Not to Be Treated by Dialysis or Transplantation: A Pilot Randomized Controlled Trial.

BACKGROUND: Family caregivers of patients with chronic kidney failure have increased burden, as reflected by their high frequency of physical and mental disturbances. The impact of enhanced psychosocial support to caregivers of patients with chronic kidney failure remains unclear. STUDY DESIGN: Open-label randomized controlled trial. SETTING & PARTICIPANTS: All new patients referred to the renal palliative clinic were screened. Caregivers of patients who met the following criteria were recruited: (1) chronic kidney failure as defined by creatinine clearance < 15 mL/min, (2) opted for conservative management by nephrology team or patient, (3) never treated with dialysis or transplantation, and (4) able to provide informed consent. INTERVENTIONS: Random assignment to treatment with enhanced psychosocial support or standard renal care (control). Enhanced psychosocial support included counseling and psychosocial interventions by an on-site palliative care nurse and designated social worker. Each caregiver was followed up at 2- to 4-week intervals for up to 6 months. OUTCOMES: Zarit Burden Inventory (ZBI) and Hospital Anxiety and Depression Scale (HADS) in caregivers and McGill Quality of Life scores in patients of both groups were compared. RESULTS: 29 pairs of family caregivers/patients with chronic kidney failure were randomly assigned (intervention, n=14; control, n=15). Mean ages of patients and caregivers were 81.6 ± 5.1 and 59.8 ± 14.2 (SD) years, respectively. The intervention group showed significantly lower ZBI scores than the control group at 1 and 3 months (22.0 ± 5.3 vs 31.6 ± 9.5 and 21.3 ± 6.6 vs 33.4 ± 7.2; P=0.006 and P=0.009, respectively). HADS anxiety scores of caregivers who received the intervention were significantly lower than those of controls at 1 and 3 months (7.1 ± 3.2 vs 10.1 ± 2.2 and 6.5 ± 4.5 vs 11.0 ± 3.1; P=0.01 and P=0.03, respectively). Insignificant reductions in ZBI and HADS scores were found at 6 months. 19 patients died (intervention, n=10; control, n=9) during the study period. LIMITATIONS: The study is limited by a relatively small sample size and short duration. CONCLUSIONS: Enhanced psychosocial support program in patients with chronic kidney failure and caregivers resulted in an early significant reduction in caregiver burden and anxiety.

Prevalence of CMMSE defined cognitive impairment among peritoneal dialysis patients and its impact on peritonitis.

BACKGROUND: Peritoneal dialysis (PD) exchange procedure is complex. Patients with cognitive impairment (CI) may require assistance. We studied the prevalence of CI among PD patients, its impact on PD-related peritonitis and the outcome of assisted PD. METHODS: Cantonese version of Mini-Mental State examination (CMMSE) was performed in 151 patients newly started on PD. Data on patient characteristics including demographics, co-morbidities, blood parameters, medications, and number of PD-related peritonitis in the first 6 months were collected. RESULTS: 151 subjects were recruited. The age of studied patients was 60 ± 15.0 years, and 45% were female. The prevalence of CI was 13.9% using education-adjusted cut-off of CMMSE. Patients older than 65-year-old, female, and lower education level were independent risk factors for CI (OR 9.27 p = 0.001, OR 14.84 p = 0.005, and OR 6.10 p = 0.009, respectively). Age greater than 65-year old is an independent risk factor for PD-related peritonitis but CI was not. Patients requiring assisted PD were of older age (p < 0.001), lower CMMSE (p < 0.001), and scored higher for age-adjusted Charlson Co-morbidity index (p < 0.001). Compared with self-care PD patients, assisted PD patients did not have higher rates exit site infection (p = 0.30) but had a trend of higher PD peritonitis (p = 0.07). CONCLUSION: CI is common among local PD patients. Overall, CI could not be identified as an independent risk factor for PD peritonitis. There is a higher prevalence of CI among assisted PD patients but helpers may not completely eliminate the risk of PD-related peritonitis.

Prevalence of and associations with reduced exercise capacity in peritoneal dialysis patients.

BACKGROUND: Exercise capacity is reduced in patients with end-stage renal disease on maintenance home peritoneal dialysis therapy, although the potential mechanisms and clinical implications remain unclear. STUDY DESIGN: Cross-sectional study. SETTING & PARTICIPANTS: 95 ambulatory prevalent and incident peritoneal dialysis patients in a well-established renal dialysis center (mean age, 58.26 ± 12.6 [SD] years; 63% men; mean duration of peritoneal dialysis therapy, 3.2 ± 4.1 years). PREDICTOR: Estimated volume status using spectral bioelectrical impedance, echocardiography-derived hemodynamic parameters. OUTCOME: Exercise capacity measured as peak oxygen consumption using symptom-limiting treadmill exercise testing. RESULTS: Exercise capacity was reduced in 96% of patients and severely reduced in 65%. Extracellular to intracellular fluid volume ratio showed the strongest correlation with reduced exercise capacity (R = -0.63; P < 0.001) and was superior to age, pulmonary capillary wedge pressure (E:E' ratio), lean tissue mass index, and hemoglobin and albumin levels in predicting exercise intolerance. LIMITATIONS: Relatively small sample size and echocardiogram that was performed only at rest. CONCLUSIONS: There was a strong relationship between body extracellular to intracellular fluid volume ratio and exercise capacity in peritoneal dialysis patients. These findings provide new evidence for a connection between fluid distribution, muscle mass, and exercise capacity. Therapeutic strategies targeting fluid status and muscle mass may improve the exercise capacity of patients on peritoneal dialysis therapy.

Dosing regimen and tolerability of methoxy polyethylene glycol-epoetin beta in Chinese dialysis patients.

AIM: To investigate methoxy polyethylene glycol-epoetin beta dosing regimen in treatment naïve subjects and dose conversion in darbepoetin alpha treated subjects, in Chinese dialysis patients. METHODS: Adult Chinese patients on peritoneal dialysis (PD) or haemodialysis (HD), with no prior treatment with erythropoiesis-stimulating agents and haemoglobin below 8 g/dL (Group I) or receiving darbepoetin alpha and had stable haemoglobin at 10-12 g/dL (Group II) were included in this prospective open-label study. In Group I methoxy polyethylene glycol-epoetin beta was started at 0.6 µg/kg subcutaneously fortnightly till haemoglobin reached 10 g/dL, after which it was given monthly. A dose conversion table was devised for Group II. Follow-up was 36 weeks. RESULTS: Forty-five patients were included. Haemoglobin in Group I (n=23, PD/HD:19/4) increased from 7.5 ± 0.9 g/dL at baseline to 10.7 ± 1.0 g/dL after 16 weeks, while it remained stable at 10.4 ± 1.0 g/dL after conversion in Group II (n=22, PD/HD:15/7). Actual dose required after stabilization was 1.7 µg/kg per month in Group I and 2.3 µg/kg per month in Group II. Median number of dose adjustment was three in Group I and one in Group II, while haemoglobin overshoot to 13 g/dL or above occurred in 4.4% and 9.1%, respectively. No significant side-effect was observed. CONCLUSIONS: Our dosing regimen for methoxy polyethylene glycol-epoetin beta, for treatment naïve subjects or for conversion from darbepoetin alpha, is safe and effective. The dose required to achieve a haemoglobin concentration of 10-11 g/dL in Chinese dialysis patients is approximately 2 µg/kg monthly.

Charlson co-morbidity index and albumin significantly associated with fracture risk in peritoneal dialysis patients.

Published literature on fracture in dialysis patients seldom addressed the effect of co-morbidity and malnutrition. In this study, we reported the incidence and risk factors for fracture in peritoneal dialysis patients. Peritoneal dialysis patients who had fractures between 2006 and 2011 were recruited. Demographic data, details of fracture, Charlson Co-morbidity Index (CCI) and biochemical parameters were also collected. Non-fracture controls, matched for age, gender and duration of dialysis, were also recruited at ratio 1:1 for fracture risk analysis. The incidence of fracture was 1 in 37 patient-years. The commonest site of fracture was neck of femur (n = 16, 55.2%). Twenty-four patients (82.8%) developed fracture after slip and fall injury. Eight out of 17 self-ambulatory patients (47.1%) became non-ambulatory after fracture. Infection was the commonest complication during hospitalization. Univariant analysis demonstrated high CCI (P = 0.001), hypoalbuminaemia (P < 0.001), loss of self autonomy (P = 0.006) and non-ambulatory state (P = 0.011) significantly associated with increased fracture risk. However, only CCI (odds ratio (OR) 1.373, P = 0.028) and albumin (OR 0.893, P = 0.025) increased fracture risk significantly on multivariant analysis. Bone profile and parathyroid hormone were not significant risk factors. To conclude, fracture associated with adverse outcome in peritoneal dialysis patients. High CCI score and hypoalbuminaemia significantly increase risk of fracture.

Brimonidine Eye Drops Causing Encephalopathy in a Patient With Advanced Chronic Kidney Disease.

Brimonidine eye drops are frequently prescribed for the treatment of glaucoma and ocular hypertension in adults. Systemic toxicities including neurological side effects have been reported with its use, especially in the paediatric population. In this report, we present a case of encephalopathy secondary to the use of brimonidine eye drops in a patient with underlying advanced chronic kidney disease, who recovered promptly after drug cessation. Herein, we also review the pharmacokinetics of eye drops leading to their systemic side effects, especially in the context of renal impairment. We also explore the possibility of extracorporeal treatment, such as by haemodialysis, for the treatment of these manifestations. This case demonstrates the need to clarify a patient's drug history and stop offending medications early on in a patient with delirium, while treatments such as antidotes or extracorporeal treatment are being considered.

Impact of structured advance care planning program on patients' wish items and healthcare utilization.

BACKGROUND: Structured advance care planning (ACP) program is an important service in the end-of-life care for patients with advanced medical illness. We pioneered a structured and coordinated ACP program for patients with advanced malignancies and end-stage organ failure in Hong Kong. This study investigated the impact of a structured ACP program on the concordance rate for patients' final wishes, patient/family satisfaction, and the number of acute admissions (AA) and length of stay (LOS) in hospital. METHODS: Patients with advanced malignancy or end-stage organ failure who were able to complete ACP forms during the current admission to medical units were recruited. Patients who could not complete ACP forms or <18 years of age were excluded. The ACP program comprised the following components: (I) baseline education (workshop/role play) in ACP sessions for linked nurses of different medical units; (II) structured ACP discussions with recruited patients and their proxies during admission, after any change in clinical status, and also at monthly intervals; (III) formal structured review of patients' goals at regular team meetings; (IV) "flagging" of advance directive (AD) in hospital computer system and (V) feedback to linked nurse on the congruence of care. Mentally competent patients who did not receive ACP and matched for disease and demographics were selected as controls in a 1:2.5 ratio. RESULTS: Two hundred forty-three patients were included for analysis between August 2016 and July 2017, of which 69 patients joined the ACP program and 174 of them did not. Two hundred and one patients (83%) had advanced cancer. All had done do-not-attempt-cardiopulmonary-resuscitation (DNACPR) order in the ACP group. The concordance rates for patients' wishes on quality of life, end-of-life and funeral arrangements were 95%, 100% and 100% respectively. Over 70% of patients and their families (N=10) showed satisfaction with the program. The ACP group also had lower mean AA and shorter LOS (0.78±0.23 vs. 1.2±0.8 episode/patient, 4.6±1.7 vs. 7.5±2.5 days, P=0.037 and P=0.023 respectively) in the last 3 months of life compared with the non-ACP group. CONCLUSIONS: This ACP program achieved high concordance rate for patients' wish items and reduced healthcare utilization.

Patient and caregiver perspectives on burnout in peritoneal dialysis.

BACKGROUND: Peritoneal dialysis (PD) can offer patients more autonomy and flexibility compared with in-center hemodialysis (HD). However, burnout - defined as mental, emotional, or physical exhaustion that leads to thoughts of discontinuing PD - is associated with an increased risk of transfer to HD. We aimed to describe the perspectives of burnout among patients on PD and their caregivers. METHODS: In this focus group study, 81 patients and 45 caregivers participated in 14 focus groups from 9 dialysis units in Australia, Hong Kong, and the United States. Transcripts were analyzed thematically. RESULTS: We identified two themes. Suffering an unrelenting responsibility contributed to burnout, as patients and caregivers felt overwhelmed by the daily regimen, perceived their life to be coming to a halt, tolerated the PD regimen for survival, and had to bear the burden and uncertainty of what to expect from PD alone. Adapting and building resilience against burnout encompassed establishing a new normal, drawing inspiration and support from family, relying on faith and hope for motivation, and finding meaning in other activities. CONCLUSIONS: For patients on PD and their caregivers, burnout was intensified by perceiving PD as an unrelenting, isolating responsibility that they had no choice but to endure, even if it held them back from doing other activities in life. More emphasis on developing strategies to adapt and build resilience could prevent or minimize burnout.

Roles of neutrophil gelatinase-associated lipocalin in continuous ambulatory peritoneal dialysis-related peritonitis.

INTRODUCTION: We measured the neutrophil gelatinase-associated lipocalin (NGAL) concentration in peritoneal dialysate effluent (PDE) collected following an acute episode of continuous ambulatory peritoneal dialysis (CAPD)-related peritonitis. RESULTS: NGAL concentration in PDE increased in the first 3 days after developing peritonitis and correlated well with the neutrophil count. In patients with culture-negative peritonitis, the NGAL in PDE was lower than that in patients with gram-positive or gram-negative peritonitis. Apart from providing additional diagnostic support to bacterial-induced peritonitis, measurement of NGAL in PDE may be useful to differentiate the neutrophil-dependent culture-negative peritonitis from that associated with non-bacterial or non-cellular etiologies. CONCLUSION: Human peritoneal mesothelial cell (HPMC) is another source of NGAL during peritonitis. NGAL was specifically induced in HPMC by IL-1beta. Incubation of HPMC with recombinant NGAL reversed the transforming growth factor-beta-induced up-regulation of Snail and vimentin but rescued the down-regulation of E-cadherin. Our data suggest that NGAL may exert a protective effect in modulating the epithelial-to-mesenchymal transition activated following peritonitis.

Management of hepatitis B reactivation in patients with lupus nephritis.

Hepatitis B is endemic in many Asian countries and immunosuppression may precipitate hepatitic flare. There is little data on the treatment of hepatitis B in patients with systemic lupus erythematosus. We monitored serial transaminase and HBV DNA levels in our HBsAg-positive patients with a history of lupus nephritis and instituted anti-viral treatment in patients who showed virological reactivation. This retrospective pilot study reports the data with this pre-emptive management strategy. Amongst 228 patients with lupus nephritis, eight (3.51%) were HBsAg-positive and five had received Lamivudine treatment for hepatitis B. In two patients the virological flares were preceded by lupus flares that necessitated an increase in immunosuppressive treatment. Median HBV DNA level was 1.9 x 10(7) copies/mL (range 1.2 x 10(4)-1.0 x 10(9) copies/mL) at baseline, and it decreased by 2-5 logs after treatment. Four patients had abnormal transaminase levels at baseline, with mean alanine aminotransferase at 125.0 +/- 67.4 U/L, and all achieved normalisation after 3-24 months (median 13 months) of treatment. Discontinuation of Lamivudine treatment was attempted in three patients after 9-15 months. In one patient treatment was recommenced because of virological flare. For the remaining two patients in whom treatment was not interrupted, one showed sustained viral suppression and one developed drug resistance. All antiviral treatments were well-tolerated. These results indicate the importance of serial monitoring of HBV DNA and transaminase levels, and prompt anti-viral therapy, in the management of HBsAg-positive lupus patients. Also, it may be feasible to discontinue treatment in stable patients to avoid the selection of drug-resistant variants.

Patient and Caregiver Priorities for Outcomes in Peritoneal Dialysis: Multinational Nominal Group Technique Study.

BACKGROUND AND OBJECTIVES: The absence of accepted patient-centered outcomes in research can limit shared decision-making in peritoneal dialysis (PD), particularly because PD-related treatments can be associated with mortality, technique failure, and complications that can impair quality of life. We aimed to identify patient and caregiver priorities for outcomes in PD, and to describe the reasons for their choices. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Patients on PD and their caregivers were purposively sampled from nine dialysis units across Australia, the United States, and Hong Kong. Using nominal group technique, participants identified and ranked outcomes, and discussed the reasons for their choices. An importance score (scale 0-1) was calculated for each outcome. Qualitative data were analyzed thematically. RESULTS: Across 14 groups, 126 participants (81 patients, 45 caregivers), aged 18-84 (mean 54, SD 15) years, identified 56 outcomes. The ten highest ranked outcomes were PD infection (importance score, 0.27), mortality (0.25), fatigue (0.25), flexibility with time (0.18), BP (0.17), PD failure (0.16), ability to travel (0.15), sleep (0.14), ability to work (0.14), and effect on family (0.12). Mortality was ranked first in Australia, second in Hong Kong, and 15th in the United States. The five themes were serious and cascading consequences on health, current and impending relevance, maintaining role and social functioning, requiring constant vigilance, and beyond control and responsibility. CONCLUSIONS: For patients on PD and their caregivers, PD-related infection, mortality, and fatigue were of highest priority, and were focused on health, maintaining lifestyle, and self-management. Reporting these patient-centered outcomes may enhance the relevance of research to inform shared decision-making.