Risk of death in dialysis patients taking cisapride

AbstractBackgroundCisapride is a prokinetic agent that is useful to relieve gastrointestinal symptoms that often occur in dialysis patients. However, sudden death has been reported and alarmed the use of cisapride in dialysis patients. This study was performed to identify whether the use of cisapride increases the risk of death.MethodsWe retrospectively analyzed all records of dialysis patients followed during the period November 1997 to March 2000. Cisapride dosage and risk factors associated with increased risk of sudden death such as cardiovascular disease, hypokalemia, and possible interacting drugs were recorded.ResultsOf 364 dialysis patients, 85 had been prescribed with cisapride (group A) whereas 279 had not (group B). Group A patients were older, with more female patients and longer duration of dialysis. There was no significant difference in mortality or causes of death between the two groups after adjusting for the baseline demographic differences. For group A, eight patients (9.41%) died while still on cisapride and 19 (22.4%) died after cisapride had been stopped. The causes of death were peritonitis (n = 2), infection (n = 2), ischemic heart disease (n = 1), malignancy (n = 1), sudden death (n = 1), and unknown (n = 1). Low serum albumin (p=0.013) and hypokalemia (p=0.066) were potential predictors of death while taking cisapride, but the presence of diabetes mellitus, maximum dosage of cisapride, and underlying cardiovascular disease were not. There was no drug interaction leading to cisapride toxicity.ConclusionsPatients who were given cisapride were older, more often women, and had a longer duration of dialysis. Low serum albumin and hypokalemia were significant predictors of death in patients given cisapride. Although no excessive risk of death was documented, the use of cisapride in dialysis patients should still be cautious and potential drug interactions and electrolyte disturbances should be avoided

Detection of microalbuminuria in non-insulin dependent diabetes mellitus (NIDDM) patients without overt proteinuria by a semiquantitative albumin-creatinine urine strips

AbstractMicroalbuminuria is the hallmark of the reversible stage of incipient diabetic nephropathy. A cost- effective and convenient bedside screening test is essential to detect this phase. We used Clinitek 50® which is a semiquantitative strip test to check spot urine sample from 81 patients with albustix one plus or less. The incidence of Clinitek 50® microalbuminuria was 17%, 18.2% and 75% in 47, 22 and 12 patients with albustix negative, trace or one plus respectively. Nineteen and 13 of the 21 Clinitek 50® positive patients were checked for spot urine DCA 2000® and two 12-hour urine collection for immunoassay respectively. Around 60% of these samples fell into the microalbuminuria range and 40% into the overt albuminuria range by either technique. There was no false positive of Clinitek 50®. The lowest range of microalbuminuria detected by Clinitek 50® was 27 μg/minute (38 mg/day). We concluded that Clinitek 50® is a useful screening test as it is nonexpensive, easily operated and has a sensitivity close to the lower range of microalbuminuria

Mindfulness-based cognitive therapy v. group psychoeducation for people with generalised anxiety disorder: randomised controlled trial

Background: Research suggests that an 8-week mindfulness-based cognitive therapy (MBCT) course may be effective for generalised anxiety disorder (GAD). Aims: To compare changes in anxiety levels among participants with GAD randomly assigned to MBCT, cognitive–behavioural therapy-based psychoeducation and usual care. Method: In total, 182 participants with GAD were recruited (trial registration number: CUHK_CCT00267) and assigned to the three groups and followed for 5 months after baseline assessment with the two intervention groups followed for an additional 6 months. Primary outcomes were anxiety and worry levels. Results: Linear mixed models demonstrated significant group × time interaction (F(4,148) = 5.10, P = 0.001) effects for decreased anxiety for both the intervention groups relative to usual care. Significant group × time interaction effects were observed for worry and depressive symptoms and mental health-related quality of life for the psychoeducation group only. Conclusions: These results suggest that both of the interventions appear to be superior to usual care for the reduction of anxiety symptoms

Frequency of Peripheral CD8+ T Cells Expressing Chemo-Attractant Receptors CCR1, 4 and 5 Increases in NPC Patients with EBV Clearance upon Radiotherapy

Radiotherapy (RT) is the standard-of-care for Epstein–Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC), where the post-RT clearance of plasma EBV DNA is prognostic. Currently, it is not known whether the post-RT clearance of plasma EBV DNA is related to the presence of circulating T-cell subsets. Blood samples from NPC patients were used to assess the frequency of T-cell subsets relating to differentiation, co-signaling and chemotaxis. Patients with undetectable versus detectable plasma EBV DNA levels post-RT were categorized as clearers vs. non-clearers. Clearers had a lower frequency of PD1+CD8+ T cells as well as CXCR3+CD8+ T cells during RT compared to non-clearers. Clearers exclusively showed a temporal increase in chemo-attractant receptors CCR1, 4 and/or 5, expressing CD8+ T cells upon RT. The increase in CCR-expressing CD8+ T cells was accompanied by a drop in naïve CD8+ T cells and an increase in OX40+CD8+ T cells. Upon stratifying these patients based on clinical outcome, the dynamics of CCR-expressing CD8+ T cells were in concordance with the non-recurrence of NPC. In a second cohort, non-recurrence associated with higher quantities of circulating CCL14 and CCL15. Collectively, our findings relate plasma EBV DNA clearance post-RT to T-cell chemotaxis, which requires validation in larger cohorts.</p

Association of Genetic Variants Related to Combined Exposure to Higher Body Mass Index and Waist-to-Hip Ratio on Lifelong Cardiovascular Risk in UK Biobank

OBJECTIVE: This study examines the individual and combined association of body mass index (BMI) and 7 waist-to-hip ratio (WHR) with cardiovascular diseases (CVD) risk using genetic scores of the 8 obesity measurements as proxies. DESIGN: A 2×2 factorial analysis approach was applied, with participants divided into four groups of lifetime exposure to low BMI and WHR, high BMI, high WHR, and high BMI and WHR based on weighted genetic risk scores. The difference in CVD risk across groups was evaluated using multivariable logistic regression. SETTING: Cohort study. PARTICIPANTS: A total of 408,003 participants were included from the prospective observational UK Biobank study. RESULTS: A total of 58,429 of CVD events were recorded. Compared to the low BMI and WHR genetic scores group, higher BMI or higher WHR genetic scores were associated with an increase in CVD risk (high BMI: odds ratio (OR), 1.07; 95%CI, 1.04-1.10; high WHR: OR, 1.12; 95%CI, 1.09-1.16). A weak additive effect on CVD risk was found between BMI and WHR (high BMI and WHR: OR, 1.16; 95%CI, 1.12-1.19). Subgroup analysis showed similar patterns between different sex, age (<65, ≥65 years old), smoking status, Townsend deprivation index, fasting glucose level and medication uses, but lower systolic blood pressure was associated with higher CVD risk in obese participants. CONCLUSIONS: High BMI or WHR were associated with increased CVD risk, and their effects are weakly additive. Even though there were overlapping of effect, both BMI and WHR are important in assessing the CVD risk in the general population

Age-Specific Associations of Usual Blood Pressure Variability With Cardiovascular Disease and Mortality: 10-Year Diabetes Mellitus Cohort Study.

Background The detrimental effects of increased variability in systolic blood pressure (SBP) on cardiovascular disease (CVD) and mortality risk in patients with diabetes mellitus remains unclear. This study evaluated age-specific association of usual SBP visit-to-visit variability with CVD and mortality in patients with type 2 diabetes mellitus. Methods and Results A retrospective cohort study investigated 155 982 patients with diabetes mellitus aged 45 to 84 years without CVD at baseline (2008-2010). Usual SBP variability was estimated using SBP SD obtained from a mixed-effects model. Age-specific associations (45-54, 55-64, 65-74, 75-84 years) between usual SBP variability, CVD, and mortality risk were assessed by Cox regression adjusted for patient characteristics. After a median follow-up of 9.7 years, 49 816 events (including 34 039 CVD events and 29 211 mortalities) were identified. Elevated SBP variability was independently, positively, and log-linearly associated with higher CVD and mortality risk among all age groups, with no evidence of any threshold effects. The excess CVD and mortality risk per 5 mm Hg increase in SBP variability within the 45 to 54 age group is >3 times higher than the 70 to 79 age group (hazard ratio, 1.66; 95% CI, 1.49-1.85 versus hazard ratio, 1.19; 95% CI, 1.15-1.23). The significant associations remained consistent among all subgroups. Patients with younger age had a higher association of SBP variability with event outcomes. Conclusions The findings suggest that SBP visit-to-visit variability was strongly associated with CVD and mortality with no evidence of a threshold effect in a population with diabetes mellitus. As well as controlling overall blood pressure levels, SBP visit-to-visit variability should be monitored and evaluated in routine practice, in particular for younger patients

The Spill-Over Impact of the Novel Coronavirus-19 Pandemic on Medical Care and Disease Outcomes in Non-communicable Diseases: A Narrative Review

OBJECTIVES: The coronavirus-19 (COVID-19) pandemic has claimed more than 5 million lives worldwide by November 2021. Implementation of lockdown measures, reallocation of medical resources, compounded by the reluctance to seek help, makes it exceptionally challenging for people with non-communicable diseases (NCD) to manage their diseases. This review evaluates the spill-over impact of the COVID-19 pandemic on people with NCDs including cardiovascular diseases, cancer, diabetes mellitus, chronic respiratory disease, chronic kidney disease, dementia, mental health disorders, and musculoskeletal disorders. METHODS: Literature published in English was identified from PubMed and medRxiv from January 1, 2019 to November 30, 2020. A total of 119 articles were selected from 6,546 publications found. RESULTS: The reduction of in-person care, screening procedures, delays in diagnosis, treatment, and social distancing policies have unanimously led to undesirable impacts on both physical and psychological health of NCD patients. This is projected to contribute to more excess deaths in the future. CONCLUSION: The spill-over impact of COVID-19 on patients with NCD is just beginning to unravel, extra efforts must be taken for planning the resumption of NCD healthcare services post-pandemic

Small solute clearance target as an index of adequacy of dialysis in peritoneal dialysis

Peritoneal dialysis (PD) is an important renal replacement therapy for survival of patients with end-stage renal failure. In the 1980s and early 1990s, the standard PD regime was four 2-liter daily exchanges in the western world but was only three 2-liter exchanges in Hong Kong. One important dimension of dialysis is small solute clearance. The formula Kt/V (K = urea clearance, t = time = 1 week, V = volume of distribution of urea = total body water) is a popular index used to represent adequacy of dialysis in terms of small solute clearance. The finding of better patient survival with higher Kt/V in an observational study in North America had led to the recommendation of a target Kt/V of 2.0 for PD by the National Kidney Foundation of the USA in 1997.In this thesis, a series of studies were conducted to better define the adequacy of dialysis in terms of small solute clearance in a stepwise manner. We started with analyzing and comparing the survival of 507 patients received PD in Tung Wah Hospital from 1983-1994 and the Kt/V of the existing 201 PD patients to the western world. The mean Kt/V (1.76+0.36) was substantially lower than the western world, and yet patient survival was not inferior. This casted doubt on the Kt/V target recommended. We then analyzed the Kt/V, nutritional status and subsequent survival of 937 prevalent PD patients in nine hospitals in Hong Kong and found no correlation between Kt/V and nutritional status. Nutritional status predicted patient survival but Kt/V did not. Peritoneal Kt/V in the anuric patients was also not predictive of survival. A randomized control study was conducted in six hospitals from 1996 to 2000. 320 incident PD patients with renal Kt/V less than 1.0 were randomized into three different Kt/V targets: 1.5-2.0. There was no difference in the 2-year patient survival and outcome between groups except that more patients in the lowest Kt/V group were withdrawn for clinical problems and required erythropoietin treatment, suggesting that they had inadequate dialysis. We concluded that the total Kt/V(renal + peritoneal)target should be at least 1.7. To define the peritoneal Kt/V target for anuric patients whose survival is dependent on peritoneal clearance, we retrospectively analyzed the relationship between peritoneal Kt/V and anuric patients’ survival counting from the time of documentation of anuria. We found that baseline peritoneal Kt/V less than 1.67 was associated with worse survival, and patients with peritoneal Kt/V above 1.7 throughout had better survival than those with Kt/V less than 1.7, whether it was corrected to above 1.7 subsequently or not. This suggested that anuric patients should have peritoneal Kt/V maintained above 1.7 at all times. These findings led to the revision or formation of several international guidelines on adequacy of peritoneal dialysis in 2005-6. All recommended Kt/V 1.7 or above being the treatment target, and the peritoneal Kt/V target should also be above 1.7 for anuric patients. These recommendations were subsequently adopted into different national guidelines and quality assurance programs.published_or_final_versionMedicineMasterDoctor of Medicin

Renal transplantation in patients with primary immunoglobulin A nephropathy

Background. Opinions on the clinical course and outcome of renal transplantation in patients with primary immunoglobulin A nephropathy (IgAN) have been controversial. Methods. We conducted a retrospective single-centre study on 542 kidney transplant recipients over the period 1984&ndash;2001. Long-term outcome and factors affecting recurrence in recipients with primary IgAN were analysed. Results. Seventy-five patients (13.8%) had biopsy-proven IgAN as the cause of renal failure, and their mean duration of follow-up after transplantation was 100 &plusmn; 5.8 months. Fourteen (18.7%) of the 75 patients had biopsy-proven recurrent IgAN, diagnosed at 67.7 &plusmn; 11 months after transplantation. The risk of recurrence was not associated with HLA DR4 or B35. Graft failure occurred in five (35.7%) of the 14 patients: three due to IgAN and two due to chronic rejection. Three (4.9%) of the 61 patients without recurrent IgAN had graft failure, all due to chronic rejection. Graft survival was similar between living-related and cadaveric/living-unrelated patients (12-year graft survival, 88 and 72%, respectively, P = 0.616). Renal allograft survival within the first 12 years was better in patients with primary IgAN compared with those with other primary diseases (80 vs 51%, P = 0.001). Thereafter, IgAN patients showed an inferior graft survival (74 vs 97% in non-IgAN patients, P = 0.001). Conclusions. Our data suggested that around one-fifth of patients with primary IgAN developed recurrence by 5 years after transplantation. Recurrent IgA nephropathy in allografts runs an indolent course with favourable outcome in the first 12 years. However, the contribution of recurrent disease to graft loss becomes more significant on long-term follow up.<br /