Impact of focal segmental glomerulosclerosis over the past decade.

OBJECTIVE: This is a study on the demographics and clinical outcomes including the response to therapy of patients with focal segmental glomerulosclerosis (FSGS) over the past decade. MATERIALS AND METHODS: All histologically proven FSGS cases diagnosed between 2008 and 2018 were analyzed for their clinical, laboratory, and histological characteristics including treatment that could influence the disease progression and renal outcome of these patients. We used the Columbia Classification for FSGS for the renal biopsy. RESULTS: There were two subgroups of FSGS patients; those with nephrotic syndrome and those without nephrotic syndrome. Patients with FSGS with non-nephrotic syndrome had poorer survival rates compared to the nephrotic group. For those without nephrotic syndrome, the indices responsible for progression involved more tubular and blood vessel lesions in addition to glomerular pathology compared to those with nephrotic syndrome. Patients with FSGS with nephrotic syndrome responded to immunosuppressants more favorably compared to the non-nephrotic group, though both groups responded with decreasing proteinuria. The nephrotic group had a better 10-year long-term survival rate of 92 vs. 72% for the non-nephrotic group (log-rank 0.002). The 10-year survival for the whole group of FSGS patients was 64%. CONCLUSION: Our data suggest that in FSGS, one of the significant components of the disease is the vascular and tubular damage, apart from the underlying glomerular pathology, resulting in varying responses to therapy, and the difference is reflected in inherently poorer response to immunosuppressant therapy in those without nephrotic syndrome as opposed to those with nephrotic syndrome, who responded to immunosuppressant therapy (IST) with stabilization of renal function and had less blood vessel and tubular lesions.

Evolution of IgA nephropathy in Singapore over four decades and a comparison of two cohorts from the first and fourth decade.

OBJECTIVE: In this study, we trace the changes in the clinical and histological pattern of IgA nephritis (IgAN) in Singapore as it has evolved over 4 decades and compare the clinical, demographic, histological, and renal outcome of patients with IgAN from the 1st decade and the 4th decade. MATERIALS AND METHODS: This is a retrospective study of all histologically proven IgAN diagnosed between 1976 and 2018. Clinical, laboratory, and histological characteristics between the 1st and the 4th decade, including treatment which could influence the disease progression and renal outcome of these two groups, were compared. We used the Oxford classification to compare the renal biopsy changes for these 2 decades as we were able to retrieve 125 renal biopsy tissues for the 1st cohort of IgAN studied in the 1970s for the comparative study. RESULTS: The commonest clinical presentation throughout the first 3 decades was asymptomatic hematuria and proteinuria (63, 52, and 49%, respectively). In the 4th decade, nephrotic syndrome (31%) was the commonest followed by asymptomatic hematuria and proteinuria (30%), hypertension (21%), and chronic renal failure (11%). The data showed that treatment can modify the Oxford MEST - Crescent scores. Renin-angiotensin system (RAS) blockers modified the S scores, immunosuppressants modified the T and C scores, and combination therapy with RAS blockers and immunosuppressants modified the E, S, and T scores. CONCLUSION: The Oxford MEST classification offers a robust and expressive classification for early and late disease progression with respect to the development of end-stage renal disease (ESRD). E and S seem to be indices of continuing disease activity with progressive glomerulosclerosis, probably still amenable to therapy, but T was a predictive indicator for those destined for ESRD and no longer amenable to therapy.

Population Segmentation Based on Healthcare Needs: Validation of a Brief Clinician-Administered Tool.

BACKGROUND: As populations age with increasingly complex chronic conditions, segmenting populations into clinically meaningful categories of healthcare and related service needs can provide healthcare planners with crucial information to optimally meet needs. However, while conventional approaches typically involve electronic medical records (EMRs), such records do not always capture information reliably or accurately. OBJECTIVE: We describe the inter-rater reliability and predictive validity of a clinician-administered tool, the Simple Segmentation Tool (SST) for categorizing older individuals into one of six Global Impression (GI) segments and eight complicating factors (CFs) indicative of healthcare and related social needs. DESIGN: Observational study ( ClinicalTrials.gov , number NCT02663037). PARTICIPANTS: Patients aged 55 years and above. MAIN MEASURES: Emergency department (ED) subjects (between May and June 2016) had baseline SST assessment by two physicians and a nurse concurrently seeing the same individual. General medical (GM) ward subjects (February 2017) had a SST assessment by their principal physician. Adverse events (ED visits, hospitalizations, and mortality over 90 days from baseline) were determined by a blinded reviewer. Inter-rater reliability was measured using Cohen's kappa. Predictive validity was evaluated using Cox hazard ratios based on time to first adverse event. KEY RESULTS: Cohen's kappa between physician-physician, service physician-nurse, and physician-nurse pairs for GI were 0.60, 0.71, and 0.68, respectively. Cox analyses demonstrated significant predictive validity of GI and CFs for adverse outcomes. CONCLUSIONS: With modest training, clinicians can complete a brief instrument to segment their patient into clinically meaningful categories of healthcare and related service needs. This approach can complement and overcome current limitations of EMR-based instruments, particularly with respect to whole-patient care. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02663037.

The Value of Renal Biopsy in Non-Insulin-Dependent Diabetes Mellitus in Singapore over the Past Two Decades.

OBJECTIVE: This study on the prevalence of diabetic nephropathy (DN) and coexistence of non-diabetic renal disease (NDRD) in a cohort of 255 non-insulin-dependent diabetes mellitus (NIDDM) patients aims to determine the value of performing renal biopsies in these patients and elucidate the factors which could affect their progression to end-stage renal disease (ESRD). METHODS: Among 255 NIDDM patients, 93 had DN alone, 69 had NDRD alone, and the remaining 93 had DN plus NDRD (mixed group). The indications for renal biopsy were based on clinical suspicion of superimposed NDRD, including heavy or rapidly increasing proteinuria, renal impairment even though diabetes is of relatively short duration, rapidly declining renal function, and presence of hematuria with dysmorphic red blood cells suggesting presence of glomerulonephritis. RESULTS: The following were predictors of ESRD: high systolic BP at biopsy, longer duration of diabetes, heavy proteinuria, and presence of diabetic retinopathy. Comparing patients in the NDRD group with the DN group and the mixed group, the NDRD group had lower serum creatinine and higher eGFR with lower urinary proteinuria and higher serum albumin at presentation and on follow-up. Kimmelstiel-Wilson nodules were associated with a poorer prognosis leading to a higher occurrence of ESRD among patients with DN. CONCLUSION: Renal biopsy is of value in indicating the prognosis of NIDDM patients with DN based on the diabetic lesions. For NIDDM patients with atypical course and suspicion of associated NDRD, a renal biopsy would enable us to diagnose the underlying NDRD and offer appropriate therapy. Most nephrologists would consider renal biopsy for an NIDDM patient based on clinical indications like atypical clinical course and suspicion of an associated NDRD, but they would not perform a routine renal biopsy like for a CKD patient, unless it is for a research indication.

A Global Evolutionary Trend of the Frequency of Primary Glomerulonephritis over the Past Four Decades.

OBJECTIVE: The pattern of glomerulonephritis (GN) in Singapore is compared with that of 19 other countries to review changing trends in the evolution of GN in Asian, Eastern, and Western countries. METHOD: Three thousand two hundred and eighty-nine renal biopsies in Singapore were reviewed and compared with that of 19 other countries. RESULTS: IgA nephritis is on the decline in many countries, including Singapore, though it still remains the commonest GN in Singapore. Membranous GN that if used to be more frequently present in Western countries has also declined though it continues a rising trend in countries such as Singapore and China. Worldwide, the frequency of focal sclerosing glomerulosclerosis (FSGS) continues to increase in many countries, but in some countries, the frequency is still low with mesangiocapillary GN remaining indigenous. CONCLUSION: Urbanization and socioeconomic changes and less exposure to parasitic and other infestations have transformed Singapore's pattern, which is tending toward that of more developed countries. Antigenic exposure due to lifestyle changes, environmental, and industrial pollution are significant contributory factors that affect the evolutionary trend of GN in many countries. The rising trend in the frequency of FSGS may reflect aging and obesity.

Use of the National Early Warning Score (NEWS) to Identify Acutely Deteriorating Patients with Sepsis in Acute Medical Ward.

INTRODUCTION: The National Early Warning Score (NEWS) is well established in acute medical units to identify acutely deteriorating patients and is shown to have good prognostic value. NEWS, however, has only been used in the Emergency Department as a triage tool. We aimed to evaluate the validity of NEWS in Acute Medical Ward (AMW) that treats predominantly acute infection-related conditions to the Internal Medicine service. MATERIALS AND METHODS: We undertook a retrospective cohort study and analysed NEWS records of all patients admitted to AMW at Singapore General Hospital between 1 August 2015 and 30 July 2017. The outcome was defined as deterioration that required transfer to Intermediate Care Area (ICA), Intensive Care Unit (ICU) or death within 24 hours of a vital signs observation set. RESULTS: A total of 298,743 vital signs observation sets were obtained from 11,300 patients. Area under receiver operating characteristic curve for any of the 3 outcomes (transfer to ICA, ICU or death) over a 24-hour period was 0.896 (95% confidence interval, 0.890-0.901). Event rate was noted to be high above 0.250 when the score was >9. In the medium-risk group (score of 5 or 6), event rate was <0.125. CONCLUSION: NEWS accurately triages patients according to the likelihood of adverse outcomes in infection-related acute medical settings.

Changes in primary glomerulonephritis in Singapore over four decades
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This review of 3,289 native kidney biopsies over the past four decades in Singapore documents the changing pattern of biopsy-proven glomerulonephritis (GN)from that of a third world country to that of a developed nation. In the 1st decade, mesangial proliferative GN was the most common form of primary GN, similar to the Asian region. In the 2nd decade, the percentage of mesangial proliferative GN decreased, but membranous GN became more common, as was seen in China and Thailand. In the 3rd decade, focal segmental glomerulosclerosis (FSGS) and membranous nephropathy continued to rise, but it was only recently, in the 4th decade, that FSGS prevalence increased dramatically, although membranous nephropathy continues to increase in some Asian countries. In the last decade in Singapore, Malaysia, and Japan, prevalence of IgA nephritis has decreased but remains the most common GN. The percentage of FSGS continues to increase in many countries like in Italy, United States of America, United Kingdom, China, and Malaysia. We surmise that socioeconomic factors play significant roles in the evolution of the renal biopsy pattern.
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Inpatient glucose management programme in the Asian healthcare setting.

AIM: To implement an inpatient glucose management (IGM) programme in the general medical wards and evaluate its clinical efficacy. METHOD: Consecutive patients admitted to selected medical wards over a 12-month period were included in the IGM programme. All patients with ≥3 capillary blood glucose (CBG) readings (>10.0 mmol/L and/or <4.0 mmol/L) over a 24-hour period were identified electronically. A multidisciplinary team of diabetes care providers would provide specialist input to these patients. The control group comprised of consecutive patients admitted over the preceding 12 months. Outcome glucose measures include mean in-hospital glucose (MHG), mean patient-day glucose (MDG), proportion of CBG readings at predefined cut-offs and length of stay (LOS). RESULTS: Both the MHG and MDG were significantly lower following intervention (10.0±2.4 mmol/L vs 11.2±2.6 mmol/L, P<.001; 10.0±2.3 mmol/L vs 11.2±2.6 mmol/L, P<.001, respectively). Prevalence of hyperglycaemic events, defined by CBG >10.0 mmol/L, was significantly lower at 36.5% versus 51.6% (P<.001). Hypoglycaemic events of CBG <4.0 mmol/L remained infrequent at <1.0% before and after IGM programme. A greater proportion of glucose readings was controlled within the target range of 4.0-10.0 mmol/L (62.6% vs 47.6%, P<.001). With the IGM programme in place, more patients received scheduled CBG monitoring, and a significant shortening of mean LOS by 3.2 days was observed (P=.02). CONCLUSIONS: The IGM programme was effective in improving inpatient glycaemic monitoring and control in the general medical wards, with a significant reduction in LOS observed. These demonstrated the programme's potential to enhance quality and efficiency of patient care.

Acute Medical Ward for better care coordination of patients admitted with infection - evidence from a tertiary hospital in Singapore.

Coordination and consolidation of care provided in acute care hospitals need reconfiguration and reorganization to meet the demand of large number of acute admissions. We report on the effectiveness of an Acute Medical Ward AMW (AMW) receiving cases that were suspected to have infection related diagnosis on admission by Emergency Department (ED), addressing this in a large tertiary hospital in South East Asia. Mean Length of Stay (LOS) was compared using Gamma Generalized Linear Models with Log-link while odds of readmissions and mortality were compared using logistic regression models. The LOS (mean: 5.8 days, SD: 9.1 days) of all patients admitted to AMW was similar to discharge diagnosis-matched general ward (GW) patients admitted before AMW implementation, readmission rates were lower (15-day: 5.3%, 30-day: 8.1%). Bivariate and multivariate models revealed that mean LOS after AMW implementation was not significantly different from before AMW implementation (Ratio: 0.99, p=0.473). Our AMW had reduced readmission rates for patients with infection but has not made an overall impact on the LOS and readmission rates for the department as a whole.

30-year follow-up study of IgA nephritis in a Southeast Asian population: an evaluation of the Oxford histological classification
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BACKGROUND: In 1985 we reported that 11% of a cohort of 151 patients with IgA nephritis (IgAN) had developed end-stage renal disease (ESRD) after a follow-up period of 5 years. 15 years later, 35% had developed ESRD. METHODS: We retrieved 125 stored renal biopsy paraffin blocks of the original cohort. From these, 102 patients were included in the present study and scored according to the Oxford classification as 21 specimens with less than 8 glomeruli were excluded and in 2 others, tissue samples were too tiny for a re-block. ESRD was ascertained by linking the study cohort to the Singapore Renal Registry at the National Registry of Diseases Office. RESULTS: Renal survival curves for each of the Oxford MEST lesions: endocapillary proliferation (E) (p < 0.04), segmental glomerulosclerosis (S) (p < 0.05), tubular atrophy/interstitial fibrosis (p < 0.0001) were significantly associated with ESRD. Mesangial hypercellularity, less commonly associated with progressive chronic kidney disease (CKD) in the study, was independently associated with ESRD at 30 years (p < 0.03). In this cohort, E and S were associated with lower eGFR at presentation and doubling of serum creatinine in the first 5 years. This study's initial 5 years was representative of the "natural history" of IgAN since no renin-angiotensin system (RAS) blockers or immunosuppression were administered. This represents the early phase of disease progression. E and S may be considered "early disease activity predictors". CONCLUSION: Mesangial hypercellularity and tubular atrophy/interstitial fibrosis (M1 and T1/T2 lesion) of the Oxford classification independently predicted long term ESRD.
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Impact of the joint association between sex, age and diabetes on long-term mortality after acute myocardial infarction.

BACKGROUND: The role of sex, and its joint effect with age and diabetes mellitus, on mortality subsequent to surviving an acute myocardial infarction (AMI) beyond 30 days are unclear. The high prevalence of diabetes mellitus in an ethnically diverse Asian population motivates this study. METHODS: The study population comprised of a nationwide cohort of Asian patients with AMI, hospitalized between 2000 to 2005, who survived the first 30 days post-admission and were followed prospectively until death or 12 years. RESULTS: Among the 13,389 survivors, there were fewer women (25.5%) who were older than men (median 70 vs. 58 years) and a larger proportion had diabetes mellitus at admission (51.4% vs. 31.4%). During follow-up 4,707 deaths (women 13.2%; men 22.0%) occurred, with women experiencing higher mortality than men with an averaged hazard ratio (HR): 2.08; 95% confidence interval : 1.96-2.20. However the actual adverse outcome, although always greater, reduced over time with an estimated HR: 2.23 (2.04-2.45) at 30 days to HR: 1.75; (1.47-2.09) 12 years later. The difference in mortality also declined with increasing age: HR 1.80 (1.52-2.13) for those aged 22-59, 1.26 (1.11-1.42) for 60-69, 1.06 (0.96-1.17) and 0.96 (0.85-1.09) for those 70-79 and 80-101 years. Significant two-factor interactions were observed between sex, age and diabetes (P < 0.001). Diabetic women <60 years of age had greater mortality than diabetic men of the same age (adjusted HR: 1.44; 1.14-1.84; P = 0.003), while diabetic women and men ≥60 years of age had a less pronounced mortality difference (adjusted HR: 1.12; 0.99-1.26). CONCLUSIONS: One in two women hospitalized for AMI in this Asian cohort had diabetes and the sex disparity in post-MI mortality was most pronounced among these who were <60 years of age. This underscores the need for better secondary prevention in this high-risk group.

Preserving differential privacy for similarity measurement in smart environments.

Advances in both sensor technologies and network infrastructures have encouraged the development of smart environments to enhance people's life and living styles. However, collecting and storing user's data in the smart environments pose severe privacy concerns because these data may contain sensitive information about the subject. Hence, privacy protection is now an emerging issue that we need to consider especially when data sharing is essential for analysis purpose. In this paper, we consider the case where two agents in the smart environment want to measure the similarity of their collected or stored data. We use similarity coefficient function (F SC) as the measurement metric for the comparison with differential privacy model. Unlike the existing solutions, our protocol can facilitate more than one request to compute F SC without modifying the protocol. Our solution ensures privacy protection for both the inputs and the computed F SC results.

Aliskiren and losartan trial in non-diabetic chronic kidney disease.

INTRODUCTION: This is a report of a clinical trial on the therapeutic efficacy and safety of combined aliskiren and losartan (an angiotensin II receptor blocker (ARB)) versus aliskiren alone and ARB alone in non-diabetic chronic kidney disease (CKD) over a 3-year period. MATERIALS AND METHODS: This was a randomised trial in 155 patients with non-diabetic CKD comparing aliskiren (150 mg/day) (n=52) versus losartan (100 mg/day) (n=52) and the third group aliskiren (150 mg/day) combined with losartan (100 mg/day) (n=51). The trial utilised primary renal end points of eGFR <15 ml/min or end-stage renal failure. RESULTS: All three groups had significant reduction of proteinuria (p<0.001 for all). The changes in eGFR, total urinary protein from baseline to each year were not significantly different between the three therapeutic groups. CONCLUSION: This study in non-diabetic CKD patients showed that combination therapy with aliskiren and ARB was as efficacious as aliskiren alone and ARB alone. There was one patient who developed a non-fatal stroke in the combined aliskiren and ARB group while the other two groups had none.

Percutaneous transluminal angioplasty of transplant renal artery stenosis.

INTRODUCTION: This study aimed to assess the outcome of percutaneous transluminal angioplasty (PTA) as the primary treatment for transplant renal artery stenosis (TxRAS). MATERIALS AND METHODS: A retrospective review of PTA of TxRAS from April 1999 to December 2008 was performed. Twenty-seven patients (17 males (M):10 females (F)) with the mean age of 49.5 years underwent PTA of TxRAS in the review period. Indications for PTA were suboptimal control of hypertension (n=12), impaired renal function (n=6) and both suboptimal control of hypertension and impaired renal function (n=9). All patients had doppler ultrasound scans prior to their PTA. In addition, 5 of these patients had computed tomography angiography (CTA) and another 7 had magnetic resonance angiography (MRA) evaluation. Mean follow-up period was 57.0 months (range, 7 to 108 months). RESULTS: The stenotic lesions were located proximal to the anastomosis (n=2), at the anastomosis (n=15), and distal to the anastomosis (n=14). Technical success rate was 96.3%. One case was complicated by extensive dissection during PTA, resulting in subsequent graft failure. The overall clinical success rate was 76.9%. Seven out of 26 patients had restenoses (26.9% of cases). These were detected at a mean of 14.3 months post angioplasty (range, 5 to 38 months). All 7 patients underwent a second PTA successfully. Three of these patients required more than 1 repeat PTA. CONCLUSION: PTA is safe and effective in the management of symptomatic TxRAS and should be the primary treatment of choice. Close surveillance for restenosis is required and when diagnosed, re-angioplasty can be performed.

A retrospective Aliskiren and Losartan study in non-diabetic chronic kidney disease.

AIM: To assess the efficacy of combined Aliskiren and Losartan vs high dose Losartan and Aliskiren alone in chronic kidney disease (CKD). METHODS: This is a retrospective study of 143 patients with non-diabetic CKD comparing combined Aliskiren (150 mg/d) with Losartan (100 mg/d) therapy vs High dose Angiotensin receptor blockers (ARB) (Losartan 200 mg/d) and the third group Aliskiren (150 mg/d) alone. This study involved only patient medical records. Entry criteria included those patients who had been treated with the above drugs for at least 36 mo within the 5 years period; other criteria included proteinuria of 1 g or more and or CKD Stage 3 at the start of the 36 mo period. The study utilised primary renal end points of estimated Glomerular Filtration Rate (eGFR) < 15 mL/min or end stage renal failure. RESULTS: Patients treated with high dose ARB compared to the other two treatment groups had significantly less proteinuria at the end of 36 mo (P < 0.007). All 3 groups had significant reduction of proteinuria (P < 0.043, P < 0.001). Total urinary protein was significantly different between the 3 groups over the 3-year study period (P = 0.008), but not eGFR. The changes in eGFR from baseline to each year were not significantly different between the 3 therapeutic groups (P < 0.119). There were no significant differences in the systolic and diastolic blood pressure between the 3 drug groups throughout the 3 years. The incidence of hyperkalemia (> 5.5 mmol/L) was 14.2% (7/49) in the Combined Aliskiren and ARB group, 8.7% (4/46) in the Aliskiren alone group and 6.3% (3/48) in the High dose ARB group (P < 0.001). CONCLUSION: This study in non-diabetic CKD patients showed that Combination therapy with Aliskiren and ARB was effective but was not safe as it was associated with a high prevalence of hyperkalaemia.

Epstein-Barr virus-associated smooth muscle tumors after kidney transplantation: treatment and outcomes in a single center.

BACKGROUND: Epstein-Barr virus-associated smooth muscle tumors (EBV SMT) in adult kidney transplant recipients (KTR) are rare. The aims of this study are to document the clinical features, types of treatment given, and outcomes of KTR with EBV SMT in our institution. METHODS: Sixteen patients were identified from our institution's databases. Patients' survival, tumor outcome, and graft survival were compared between patients who remained on cyclosporine-based immunosuppressant and those who converted to sirolimus-based therapy. RESULTS: The median time of diagnosis was 9.4 yr after kidney transplantation, and majority of the patients had multifocal disease at the time of diagnosis. Overall, the patient survival rate was 75% over a mean follow-up period of five yr. Two patients with non-functioning allograft at the time of diagnosis of EBV SMT were excluded from the treatment outcome analysis. Comparing the sirolimus (n = 7) vs. cyclosporine groups (n = 7), patient survival rate was 100% vs. 42.9% (p = 0.08), graft survival 71.4% vs. 28.7% (p = 0.53), and disease-free status 42.9% vs. 14.3% (p = 0.73), respectively. CONCLUSION: Surgical resection in combination with decreasing immunosuppression or conversion to sirolimus appears to be effective in the treatment of EBV SMT in KTR.