Management of hypertension will continue to evolve as new studies provide us more evidence on man... more Management of hypertension will continue to evolve as new studies provide us more evidence on many relevant aspects of care for this very common condition. To define hypertension, we need to be able to measure blood pressure (BP) accurately and make it easily reproducible. The mercury sphygmomanometer has been a standard tool to measure BP, but it is evident that it will be phased out soon and replaced by electronic BP devices-both for clinic and home use. There is increasingly more awareness of the benefits of out-of-office (clinic) BP measurement to estimate extent of BP control and also prognosis. The goal for BP treatment has also evolved and, for the first time in decades, there has been a suggestion that a lower-than-140/90 mmHg target is associated with further reduction in adverse cardiovascular outcomes. There is, however, a need for more pills and an increased risk of treatment-related side effects. The choice of which anti-hypertensive to use, as well as the goal of treatment, should be individualised and discussed with the patient.
Objective This study aimed to compare the health-related quality of life (HRQOL) in patients with... more Objective This study aimed to compare the health-related quality of life (HRQOL) in patients with end-stage renal disease (ESRD) treated with continuous ambulatory peritoneal dialysis (CAPD) and automated peritoneal dialysis (APD) in Singapore. Methods T h ed a t au s e di nt h i ss t u d yw e r ef r o mt w oc r o s ssectional surveys of ESRD patients. HRQOL was assessed using the Kidney Disease Quality of Life (KDQOL) instrument. Socio-demographic characteristics and clinical data were collected. The physical component summary (PCS) and mental component summary (MCS) scores, kidney disease component summary (KDCS) score and its three scales (symptoms, effects, burden), and one health utility score [EuroQol 5-dimension (EQ-5D)] were calculated and compared between CAPD and APD using multivariate linear regression. Results In total, 266 patients were included, with 145 on CAPD (mean age 60.8 years) and 121 on APD (mean age 57.4 years). After adjustment for all variables collected, APD patients had significant higher scores in PCS and KDQOL symptoms than CAPD patients, suggesting that APD was associated with better physical health and milder dialysis-related symptoms. Conclusion The HRQOL of CAPD and APD patients was largely equivalent in Singapore, but APD patients seemed to experience better physical health and be less bothered by dialysis-related symptoms.
Fibrillary glomerulonephritis (FGN) is a rare glomerular disease featured by the randomly arrange... more Fibrillary glomerulonephritis (FGN) is a rare glomerular disease featured by the randomly arranged 12- to 24-nm fibrils under electron microscopy (EM). Up to 10% of FGN patients have monoclonal gammopathy. However, distinguishing between FGN as monoclonal gammopathy of renal significance (MGRS) and FGN from other causes with incidental monoclonal gammopathy of undetermined significance (MGUS) can be challenging, as the current way of demonstrating monoclonality is flawed due to (1) the suboptimal sensitivity of kappa staining by immunofluorescence in frozen tissue (IF-F) as compared to pronase-digested paraffin sections (IF-P), causing incorrect labeling of light chain restriction; (2) the unavailability of immunoglobulin G (IgG) subtyping in some centers; and (3) the unavailability of tests demonstrating the monoclonality of highly variable VH or VL domains in immunoglobulin structures in clinical use. The discovery of DnaJ homolog subfamily B member 9 (DNAJB9) allows diagnosis for...
It is a well-established fact that patients with diabetes mellitus are at high risk of cardiovasc... more It is a well-established fact that patients with diabetes mellitus are at high risk of cardiovascular and renal complications in the course of their lifetime. Much effort has been invested in understanding the pathobiology of this as well as in developing an effective strategy to reduce the morbidity and mortality associated with it. Metabolic control together with mitigating other known risk factors for the cardiovascular and renal disease has been the basis of improving the outcomes of all patients with diabetes. Ongoing scientific discoveries continue to provide physicians and patients with better means of treatment over the years. Each is a step forward, and with the addition of new classes of therapeutics, we will need to reconstruct the management pathway that is best for each patient given their risk profiles and characteristics.
Management of hypertension will continue to evolve as new studies provide us more evidence on man... more Management of hypertension will continue to evolve as new studies provide us more evidence on many relevant aspects of care for this very common condition. To define hypertension, we need to be able to measure blood pressure (BP) accurately and make it easily reproducible. The mercury sphygmomanometer has been a standard tool to measure BP, but it is evident that it will be phased out soon and replaced by electronic BP devices-both for clinic and home use. There is increasingly more awareness of the benefits of out-of-office (clinic) BP measurement to estimate extent of BP control and also prognosis. The goal for BP treatment has also evolved and, for the first time in decades, there has been a suggestion that a lower-than-140/90 mmHg target is associated with further reduction in adverse cardiovascular outcomes. There is, however, a need for more pills and an increased risk of treatment-related side effects. The choice of which anti-hypertensive to use, as well as the goal of treatment, should be individualised and discussed with the patient.
Bacterial contamination of surfaces and the associated infection risk is a significant threat to ... more Bacterial contamination of surfaces and the associated infection risk is a significant threat to human health. Some natural antibacterial polymers with low toxicity are promising coating materials for alleviating pathogenic colonization on surfaces. However, widespread application of these polymers as antibacterial coatings is constrained by coating techniques which are not easily scalable due to stringent reaction conditions. Herein, thiol-ol reaction involving oxidative conjugation between thiol and hydroxyl groups is demonstrated as a facile technique to graft two natural polymer derivatives, agarose (AG) and quaternized chitosan (QCS), as antibacterial coatings on polymer and metal substrates. The substrate surfaces are first treated with oxygen plasma followed by UV-induced grafting of the polymers under atmospheric conditions. Dimercaprol, a FDA-approved drug, is used as both surface anchor and cross-linker of the polymer chains during grafting. The AG coating achieves >2 l...
The Patient - Patient-Centered Outcomes Research, 2013
Background To validate a widely used health outcomes instrument for patients with chronic kidney ... more Background To validate a widely used health outcomes instrument for patients with chronic kidney disease and on dialysis, the Kidney Disease Quality of Life questionnaire (KDQOL-36), in English-speaking haemodialysis patients in Singapore. Methods This study is a secondary data analysis using the KDQOL-SF (version 1.3) data collected from a cross-sectional survey of haemodialysis patients in Singapore. Cronbach's a was used to test internal consistency reliability. Multi-item scales were assessed using item-to-scale correlation and factor analysis. Both confirmatory and exploratory factor analyses were performed separately for generic and disease-targeted scales. Construct validity was assessed by correlation between disease-targeted and generic scales. Criterion validity was assessed by correlation of the physical component summary (PCS-12) and mental component summary (MCS-12) from KDQOL-36 with the corresponding PCS-36 and MCS-36 from the KDQOL-SF. Results Three hundred ninety-four patients who completed the interviews in English [male 55.8 %, mean age (SD) 52.4 (11.7) years] were involved. Kidney disease scales exhibited desirable internal consistency (Cronbach's a 0.822-0.906) and item-to-scale correlation (range 0.763-0.903), and a three-factor model fit the data well [comparative fit index (CFI) 0.934, root mean square error of approximation (RMSEA) 0.085]. For the generic Short Form 12 Health Survey (SF-12) items, a two-factor model (physical and mental) showed poor overall fit, but a threefactor structure (role, physical and mental functions) achieved good model fit (CFI 0.999, RMSEA 0.027). Correlation between disease-targeted and generic scales was weak to moderate (range 0.286-0.418). Correlation between SF-12 and SF-36 was 0.750 for PCS and 0.797 for MCS. Conclusion The English version of the KDQOL-36 appears to be reliable and valid to measure quality of life for haemodialysis patients in Singapore. Key Points for Decision Makers • The English version of the Kidney Disease Quality of Life (KDQOL-36) is a valid tool for assessing quality of life for haemodialysis patients in Singapore. • The kidney disease scales of the KDQOL-36 showed desirable psychometric properties. • The generic scales of the KDQOL-36 seem to measure slightly different constructs in Asian patients.
Background Studies comparing patient survival of hemodialysis (HD) and peritoneal dialysis (PD) h... more Background Studies comparing patient survival of hemodialysis (HD) and peritoneal dialysis (PD) have yielded conflicting results and no such study was from SouthEast Asia. This study aimed to compare the survival outcomes of patients with end-stage renal disease (ESRD) who started dialysis with HD and PD in Singapore. Methods Survival data for a maximum of 5 years from a single-center cohort of 871 ESRD patients starting dialysis with HD (n = 641) or PD (n = 230) from 2005-2010 was analyzed using the flexible Royston-Parmar (RP) model. The model was also applied to a subsample of 225 propensity-score-matched patient pairs and subgroups defined by age, diabetes mellitus, and cardiovascular disease. Results After adjusting for the effect of socio-demographic and clinical characteristics, the risk of death was higher in patients initiating dialysis with PD than those initiating dialysis with HD (hazard ratio [HR]: 2.08; 95% confidence interval [CI]: 1.67-2.59; p<0.001), although there was no significant difference in mortality between the two modalities in the first 12 months of treatment. Consistently, in the matched subsample, patients starting PD had a higher risk of death than those starting HD (HR: 1.73, 95% CI: 1.30-2.28, p<0.001). Subgroup analysis showed that PD may be similar to or better than HD in survival outcomes among young patients (65 years old) without diabetes or cardiovascular disease.
Abstract Rationale: Hyperammonemia encephalopathy is a rare but severe complication that has been... more Abstract Rationale: Hyperammonemia encephalopathy is a rare but severe complication that has been reported in association with the use of sunitinib, a tyrosine kinase inhibitor. We report here a unique case of a patient with end stage renal disease that was initiated on sunitinib for metastatic renal cell carcinoma. Patient concerns: A 65-year-old man with end stage renal disease on maintenance conventional hemodialysis and had concomitant stable Child-Pugh class B liver cirrhosis consequent of hepatitis C infection was started on sunitinib for metastatic renal cell carcinoma. He developed confusion few weeks after starting therapy with no other indication of worsening liver dysfunction otherwise. Diagnosis: He was later diagnosed with hyperammonemia encephalopathy. Interventions: His treatment was discontinued and reinitiated at a lower dose after recovery and titrated according to tolerance. As ammonia is a very low molecular weight molecule and is cleared well with diffusive clearance, we intensified his dialysis regimen by increasing intensity for each session and frequency per week. Outcomes: With this change in dialysis regimen, patient was able to continue treatment with sunitinib. Lessons: Clinicians prescribing sunitinib should be vigilant to monitor for this complication in patients receiving sunitinib, apart from the more usual presentation of hepatotoxicity. We found that a more intensive hemodialysis regimen consisting of 4× a week conventional high-flux hemodialysis (HD) can permit the continuation of treatment with sunitinib in an end stage renal disease (ESRD) patient with Child-Pugh class B liver cirrhosis.
Polyethyleneimine‐layered membrane with grafted heparin (oXiris) may improve filter life during c... more Polyethyleneimine‐layered membrane with grafted heparin (oXiris) may improve filter life during continuous renal replacement therapy (CRRT) in addition to its immunoadsorptive capability, compared with that of conventional membrane. In this single center, prospective, open‐label pilot study, we randomized critically ill patients with bleeding risk who underwent anticoagulation‐free CRRT, to commence with oXiris or M150 filter with sequential crossover. We examined the filter life with each circuit and its effect on systemic coagulation parameters. We randomized 11 and nine patients to commence CRRT with oXiris and M150 respectively, with 19 oXiris and 20 M150 filter‐circuits in all. Patient profiles in both arms were comparable for illness severity and comorbidities. Median filter lives for oXiris versus M150 circuits were 13 h versus 18 h (p = 0.10). Among 11 patients with paired crossover filters, filter lives for 14 oXiris–M150 circuit pairs were 13 h versus 16 h (p = 0.27), and corresponding transmembrane pressures increased to 111 mmHg versus 75 mmHg by 12 h (p = 0.02). Patients’ coagulation parameters were comparable following both filter‐circuits. CRRT with oXiris (vs. M150) was independently associated with shorter filter life, adjusted for prescribed dose, vascular access, and coagulopathy. Use of oXiris did not prolong filter life over conventional membrane with no evidence of systemic heparin exposure; significant membrane clogging is observed by 12 h with oXiris.
Management of hypertension will continue to evolve as new studies provide us more evidence on man... more Management of hypertension will continue to evolve as new studies provide us more evidence on many relevant aspects of care for this very common condition. To define hypertension, we need to be able to measure blood pressure (BP) accurately and make it easily reproducible. The mercury sphygmomanometer has been a standard tool to measure BP, but it is evident that it will be phased out soon and replaced by electronic BP devices-both for clinic and home use. There is increasingly more awareness of the benefits of out-of-office (clinic) BP measurement to estimate extent of BP control and also prognosis. The goal for BP treatment has also evolved and, for the first time in decades, there has been a suggestion that a lower-than-140/90 mmHg target is associated with further reduction in adverse cardiovascular outcomes. There is, however, a need for more pills and an increased risk of treatment-related side effects. The choice of which anti-hypertensive to use, as well as the goal of treatment, should be individualised and discussed with the patient.
Objective This study aimed to compare the health-related quality of life (HRQOL) in patients with... more Objective This study aimed to compare the health-related quality of life (HRQOL) in patients with end-stage renal disease (ESRD) treated with continuous ambulatory peritoneal dialysis (CAPD) and automated peritoneal dialysis (APD) in Singapore. Methods T h ed a t au s e di nt h i ss t u d yw e r ef r o mt w oc r o s ssectional surveys of ESRD patients. HRQOL was assessed using the Kidney Disease Quality of Life (KDQOL) instrument. Socio-demographic characteristics and clinical data were collected. The physical component summary (PCS) and mental component summary (MCS) scores, kidney disease component summary (KDCS) score and its three scales (symptoms, effects, burden), and one health utility score [EuroQol 5-dimension (EQ-5D)] were calculated and compared between CAPD and APD using multivariate linear regression. Results In total, 266 patients were included, with 145 on CAPD (mean age 60.8 years) and 121 on APD (mean age 57.4 years). After adjustment for all variables collected, APD patients had significant higher scores in PCS and KDQOL symptoms than CAPD patients, suggesting that APD was associated with better physical health and milder dialysis-related symptoms. Conclusion The HRQOL of CAPD and APD patients was largely equivalent in Singapore, but APD patients seemed to experience better physical health and be less bothered by dialysis-related symptoms.
Fibrillary glomerulonephritis (FGN) is a rare glomerular disease featured by the randomly arrange... more Fibrillary glomerulonephritis (FGN) is a rare glomerular disease featured by the randomly arranged 12- to 24-nm fibrils under electron microscopy (EM). Up to 10% of FGN patients have monoclonal gammopathy. However, distinguishing between FGN as monoclonal gammopathy of renal significance (MGRS) and FGN from other causes with incidental monoclonal gammopathy of undetermined significance (MGUS) can be challenging, as the current way of demonstrating monoclonality is flawed due to (1) the suboptimal sensitivity of kappa staining by immunofluorescence in frozen tissue (IF-F) as compared to pronase-digested paraffin sections (IF-P), causing incorrect labeling of light chain restriction; (2) the unavailability of immunoglobulin G (IgG) subtyping in some centers; and (3) the unavailability of tests demonstrating the monoclonality of highly variable VH or VL domains in immunoglobulin structures in clinical use. The discovery of DnaJ homolog subfamily B member 9 (DNAJB9) allows diagnosis for...
It is a well-established fact that patients with diabetes mellitus are at high risk of cardiovasc... more It is a well-established fact that patients with diabetes mellitus are at high risk of cardiovascular and renal complications in the course of their lifetime. Much effort has been invested in understanding the pathobiology of this as well as in developing an effective strategy to reduce the morbidity and mortality associated with it. Metabolic control together with mitigating other known risk factors for the cardiovascular and renal disease has been the basis of improving the outcomes of all patients with diabetes. Ongoing scientific discoveries continue to provide physicians and patients with better means of treatment over the years. Each is a step forward, and with the addition of new classes of therapeutics, we will need to reconstruct the management pathway that is best for each patient given their risk profiles and characteristics.
Management of hypertension will continue to evolve as new studies provide us more evidence on man... more Management of hypertension will continue to evolve as new studies provide us more evidence on many relevant aspects of care for this very common condition. To define hypertension, we need to be able to measure blood pressure (BP) accurately and make it easily reproducible. The mercury sphygmomanometer has been a standard tool to measure BP, but it is evident that it will be phased out soon and replaced by electronic BP devices-both for clinic and home use. There is increasingly more awareness of the benefits of out-of-office (clinic) BP measurement to estimate extent of BP control and also prognosis. The goal for BP treatment has also evolved and, for the first time in decades, there has been a suggestion that a lower-than-140/90 mmHg target is associated with further reduction in adverse cardiovascular outcomes. There is, however, a need for more pills and an increased risk of treatment-related side effects. The choice of which anti-hypertensive to use, as well as the goal of treatment, should be individualised and discussed with the patient.
Bacterial contamination of surfaces and the associated infection risk is a significant threat to ... more Bacterial contamination of surfaces and the associated infection risk is a significant threat to human health. Some natural antibacterial polymers with low toxicity are promising coating materials for alleviating pathogenic colonization on surfaces. However, widespread application of these polymers as antibacterial coatings is constrained by coating techniques which are not easily scalable due to stringent reaction conditions. Herein, thiol-ol reaction involving oxidative conjugation between thiol and hydroxyl groups is demonstrated as a facile technique to graft two natural polymer derivatives, agarose (AG) and quaternized chitosan (QCS), as antibacterial coatings on polymer and metal substrates. The substrate surfaces are first treated with oxygen plasma followed by UV-induced grafting of the polymers under atmospheric conditions. Dimercaprol, a FDA-approved drug, is used as both surface anchor and cross-linker of the polymer chains during grafting. The AG coating achieves >2 l...
The Patient - Patient-Centered Outcomes Research, 2013
Background To validate a widely used health outcomes instrument for patients with chronic kidney ... more Background To validate a widely used health outcomes instrument for patients with chronic kidney disease and on dialysis, the Kidney Disease Quality of Life questionnaire (KDQOL-36), in English-speaking haemodialysis patients in Singapore. Methods This study is a secondary data analysis using the KDQOL-SF (version 1.3) data collected from a cross-sectional survey of haemodialysis patients in Singapore. Cronbach's a was used to test internal consistency reliability. Multi-item scales were assessed using item-to-scale correlation and factor analysis. Both confirmatory and exploratory factor analyses were performed separately for generic and disease-targeted scales. Construct validity was assessed by correlation between disease-targeted and generic scales. Criterion validity was assessed by correlation of the physical component summary (PCS-12) and mental component summary (MCS-12) from KDQOL-36 with the corresponding PCS-36 and MCS-36 from the KDQOL-SF. Results Three hundred ninety-four patients who completed the interviews in English [male 55.8 %, mean age (SD) 52.4 (11.7) years] were involved. Kidney disease scales exhibited desirable internal consistency (Cronbach's a 0.822-0.906) and item-to-scale correlation (range 0.763-0.903), and a three-factor model fit the data well [comparative fit index (CFI) 0.934, root mean square error of approximation (RMSEA) 0.085]. For the generic Short Form 12 Health Survey (SF-12) items, a two-factor model (physical and mental) showed poor overall fit, but a threefactor structure (role, physical and mental functions) achieved good model fit (CFI 0.999, RMSEA 0.027). Correlation between disease-targeted and generic scales was weak to moderate (range 0.286-0.418). Correlation between SF-12 and SF-36 was 0.750 for PCS and 0.797 for MCS. Conclusion The English version of the KDQOL-36 appears to be reliable and valid to measure quality of life for haemodialysis patients in Singapore. Key Points for Decision Makers • The English version of the Kidney Disease Quality of Life (KDQOL-36) is a valid tool for assessing quality of life for haemodialysis patients in Singapore. • The kidney disease scales of the KDQOL-36 showed desirable psychometric properties. • The generic scales of the KDQOL-36 seem to measure slightly different constructs in Asian patients.
Background Studies comparing patient survival of hemodialysis (HD) and peritoneal dialysis (PD) h... more Background Studies comparing patient survival of hemodialysis (HD) and peritoneal dialysis (PD) have yielded conflicting results and no such study was from SouthEast Asia. This study aimed to compare the survival outcomes of patients with end-stage renal disease (ESRD) who started dialysis with HD and PD in Singapore. Methods Survival data for a maximum of 5 years from a single-center cohort of 871 ESRD patients starting dialysis with HD (n = 641) or PD (n = 230) from 2005-2010 was analyzed using the flexible Royston-Parmar (RP) model. The model was also applied to a subsample of 225 propensity-score-matched patient pairs and subgroups defined by age, diabetes mellitus, and cardiovascular disease. Results After adjusting for the effect of socio-demographic and clinical characteristics, the risk of death was higher in patients initiating dialysis with PD than those initiating dialysis with HD (hazard ratio [HR]: 2.08; 95% confidence interval [CI]: 1.67-2.59; p<0.001), although there was no significant difference in mortality between the two modalities in the first 12 months of treatment. Consistently, in the matched subsample, patients starting PD had a higher risk of death than those starting HD (HR: 1.73, 95% CI: 1.30-2.28, p<0.001). Subgroup analysis showed that PD may be similar to or better than HD in survival outcomes among young patients (65 years old) without diabetes or cardiovascular disease.
Abstract Rationale: Hyperammonemia encephalopathy is a rare but severe complication that has been... more Abstract Rationale: Hyperammonemia encephalopathy is a rare but severe complication that has been reported in association with the use of sunitinib, a tyrosine kinase inhibitor. We report here a unique case of a patient with end stage renal disease that was initiated on sunitinib for metastatic renal cell carcinoma. Patient concerns: A 65-year-old man with end stage renal disease on maintenance conventional hemodialysis and had concomitant stable Child-Pugh class B liver cirrhosis consequent of hepatitis C infection was started on sunitinib for metastatic renal cell carcinoma. He developed confusion few weeks after starting therapy with no other indication of worsening liver dysfunction otherwise. Diagnosis: He was later diagnosed with hyperammonemia encephalopathy. Interventions: His treatment was discontinued and reinitiated at a lower dose after recovery and titrated according to tolerance. As ammonia is a very low molecular weight molecule and is cleared well with diffusive clearance, we intensified his dialysis regimen by increasing intensity for each session and frequency per week. Outcomes: With this change in dialysis regimen, patient was able to continue treatment with sunitinib. Lessons: Clinicians prescribing sunitinib should be vigilant to monitor for this complication in patients receiving sunitinib, apart from the more usual presentation of hepatotoxicity. We found that a more intensive hemodialysis regimen consisting of 4× a week conventional high-flux hemodialysis (HD) can permit the continuation of treatment with sunitinib in an end stage renal disease (ESRD) patient with Child-Pugh class B liver cirrhosis.
Polyethyleneimine‐layered membrane with grafted heparin (oXiris) may improve filter life during c... more Polyethyleneimine‐layered membrane with grafted heparin (oXiris) may improve filter life during continuous renal replacement therapy (CRRT) in addition to its immunoadsorptive capability, compared with that of conventional membrane. In this single center, prospective, open‐label pilot study, we randomized critically ill patients with bleeding risk who underwent anticoagulation‐free CRRT, to commence with oXiris or M150 filter with sequential crossover. We examined the filter life with each circuit and its effect on systemic coagulation parameters. We randomized 11 and nine patients to commence CRRT with oXiris and M150 respectively, with 19 oXiris and 20 M150 filter‐circuits in all. Patient profiles in both arms were comparable for illness severity and comorbidities. Median filter lives for oXiris versus M150 circuits were 13 h versus 18 h (p = 0.10). Among 11 patients with paired crossover filters, filter lives for 14 oXiris–M150 circuit pairs were 13 h versus 16 h (p = 0.27), and corresponding transmembrane pressures increased to 111 mmHg versus 75 mmHg by 12 h (p = 0.02). Patients’ coagulation parameters were comparable following both filter‐circuits. CRRT with oXiris (vs. M150) was independently associated with shorter filter life, adjusted for prescribed dose, vascular access, and coagulopathy. Use of oXiris did not prolong filter life over conventional membrane with no evidence of systemic heparin exposure; significant membrane clogging is observed by 12 h with oXiris.
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