Interleukin-13 genetic polymorphisms in Singapore Chinese children correlate with long-term outcome of minimal-change disease.

BACKGROUND: Minimal-change nephrotic syndrome (MCNS) has been associated with atopy. As interleukin-13 (IL-13) has been implicated in the pathogenesis of MCNS, we postulated that IL-13 genetic polymorphisms could influence either susceptibility or clinical course of the disease. METHODS: Seventy-two Singapore Chinese children with MCNS and 78 normal controls were screened for single nucleotide polymorphisms (SNPs) in the IL-13 gene by direct sequencing. Allele and genotype frequencies of these SNPs were determined and their relationship with different clinical courses was analysed. RESULTS: Six SNPs were identified in the 5' promoter, exon 4 and 3' untranslated region (3'UTR). The three SNPs in the 3'UTR--4738 (G/A), 4793 (C/A) and 4926 (C/T)--were in tight linkage disequilibrium (Delta > or = 0.99). There was no difference in allele or genotype frequencies between MCNS children and normal controls. However, there was a significantly lower frequency of allele 4738G in those MCNS children who were still relapsing after 5 years of follow-up (G = 0.52), compared with those in complete remission (G = 0.72; P<0.05) and normal controls (G = 0.69; P<0.05). Haplotype analysis showed a significantly higher frequency of the GCC haplotype in controls and MCNS patients in complete remission (chi2 = 6.35; P<0.02), while the frequency of AAT haplotype was higher in those MCNS children still relapsing after 5 years of follow-up (chi2 = 5.38; P<0.02). Moreover, peripheral blood mononuclear cell IL-13 mRNA expression in patients with haplotype AAT was significantly higher than in those with haplotype GCC. CONCLUSIONS: These results suggest that genetic polymorphisms in the 3'UTR of the IL-13 gene correlate with long-term outcome of MCNS, rather than disease susceptibility, in Singapore Chinese children.     

Terazosin therapy for chronic prostatitis/chronic pelvic pain syndrome: a randomized,placebo controlled trial

PURPOSE: We evaluate terazosin therapy for chronic prostatitis/chronic pelvic pain syndrome. MATERIALS AND METHODS: The study included 100, 20 to-50-year-old subjects who met the consensus criteria for chronic prostatitis/chronic pelvic pain syndrome and had not received previous alpha-blockers. Subjects were randomized to receive terazosin with dose escalation from 1 to 5 mg. daily or placebo for 14 weeks. The primary criterion for response was scoring 2 or less ("delighted-to-mostly satisfied") on the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) quality of life item. The secondary criterion for response was greater than 50% reduction in NIH-CPSI pain score at 14 weeks. Other outcomes included total and NIH-CPSI domain scores, International Prostate Symptom Score, peak urinary flow rate, post-void residual urine and adverse effects. RESULTS: Using the primary criterion 24 of 43 evaluable subjects (56%) responded in the terazosin group compared to 14 of 43 (36%) in the placebo group (p = 0.03). Using the secondary criterion 26 of 43 subjects (60%) responded in the terazosin group compared to 16 of 43 (37%) in the placebo group (p = 0.03). The terazosin group had greater reductions (p <0.05) in NIH-CPSI total score, individual domain scores and International Prostate Symptom Score than the placebo group. There was no difference in peak urinary flow rate or post-void residual. In the terazosin group 18 patients (42%) had side effects compared to 9 (21%) in the placebo group (p = 0.04). CONCLUSIONS: Terazosin proved superior to placebo for patients with chronic prostatitis/chronic pelvic pain syndrome who had not received alpha-blockers previously.     

Increased HLA-A*11 in Chinese children with steroid-responsive nephrotic syndrome

Human leukocyte antigen (HLA) associations have been frequently reported in childhood steroid-responsive nephrotic syndrome (SRNS) in other populations. The aim of this study was to characterize the immunogenetic background of Singaporean Chinese patients with childhood SRNS. We determined the HLA class I (HLA-A* and HLA-B*) as well as class II (HLA-DRB1*, HLA-DQB1*) gene polymorphisms using the polymerase chain reaction-sequence specific oligonucleotide (PCR-SSO) technique, in patients with SRNS (n=64) and normal controls (n=236 for HLA-A*, n=80 for HLA-B*, HLA-DRB1* and HLA-DQB1*). The frequency of HLA-A*11 allele was significantly higher in the SRNS patients compared to controls (78.1% vs 54.2%, respectively; relative risk, RR=3.01, Pc=0.011). However, there was no significant difference in the allele frequencies of HLA-B*, HLA-DRB1* and HLA-DQB1* between the SRNS patients and controls, unlike that in previous studies. Our data suggest that the immunogenetic background of Singaporean Chinese with childhood SRNS was different from that in other populations. As HLA-A*11 has been strongly associated with other autoimmune diseases, it is conceivable that the HLA-A*11-specific motif may play a role in the development of the abnormal T-cell-mediated immune response that may be responsible for triggering the proteinuria seen in SRNS. Received: 24 April 2001 / Revised: 14 November 2001 / Accepted: 18 November 2001     

The effectiveness of walking as an intervention for low back pain: a systematic review

As current low back pain (LBP) guidelines do not specifically advocate walking as an intervention, this review has explored for the effectiveness of walking in managing acute and chronic LBP. CINAHL, Medline, AMED, EMBASE, PubMed, Cochrane and Scopus databases, as well as a hand search of reference lists of retrieved articles, were searched. The search was restricted to studies in the English language. Studies were included when walking was identified as an intervention. Four studies met inclusion criteria, and were assessed with a quality checklist. Three lower ranked studies reported a reduction in LBP from a walking intervention, while the highest ranked study observed no effect. Heterogeneity of study design made it difficult to draw comparisons between studies. There is only low–moderate evidence for walking as an effective intervention strategy for LBP. Further investigation is required to investigate the strength of effect for walking as a primary intervention in the management of acute and chronic LBP.     

Prostate cancer detection upon transrectal ultrasound-guided biopsy in relation to digital rectal examination and prostate-specific antigen level: what to expect in the Chinese population?

We investigated the prostate cancer detection rates upon transrectal ultrasound (TRUS)-guided biopsy in relation to digital rectal examination (DRE) and prostate-specific antigen (PSA), and risk factors of prostate cancer detection in the Chinese population. Data from all consecutive Chinese men who underwent first TRUS-guided prostate biopsy from year 2000 to 2013 was retrieved from our database. The prostate cancer detection rates with reference to DRE finding and PSA level of < 4, 4–10, 10.1–20, 20.1–50 and > 50 ng ml⁻¹ were investigated. Multivariate logistic regression analyses were performed to investigate for potential risk factors of prostate cancer detection. A total of 2606 Chinese men were included. In patients with normal DRE, the cancer detection rates were 8.6%, 13.4%, 21.8%, 41.7% and 85.2% in patients with PSA < 4, 4–10, 10.1–20, 20.1–50 and > 50 ng ml⁻¹ respectively. In patients with abnormal DRE, the cancer detection rates were 12.4%, 30.2%, 52.7%, 80.6% and 96.4% in patients with PSA < 4, 4–10, 10.1–20, 20.1–50 and > 50 ng ml⁻¹ respectively. Older age, smaller prostate volume, larger number of biopsy cores, presence of abnormal DRE finding and higher PSA level were associated with increased risk of prostate cancer detection upon multivariate logistic regression analyses (P < 0.001). Chinese men appeared to have lower prostate cancer detection rates when compared to the Western population. Taking the different risk factors into account, an individualized approach to the decision of TRUS-guided biopsy can be adopted.     

Eighteen years experience in pediatric acute dialysis: analysis of predictors of outcome

This study reviewed the 18-year experience of acute dialysis in the pediatric intensive care unit, in order to identify factors that could predict outcome, and to determine whether newer modalities of acute dialysis have influenced this outcome. Sixty-six children (ages 1 day to 19 years) received acute dialysis from May 1980 to April 1998. Factors predicting outcome were analyzed using univariate and Cox regression analysis. Modality of dialysis in the first 15 years was exclusively peritoneal dialysis, with a mortality of 63.9%. However, in the last 3 years, with increasing patient numbers, continuous hemodiafiltration (CHDF) was the modality of choice (56.7%), with a mortality of 73.3%. Univariate analysis showed that age <1 year, coma, acute tubular necrosis, disseminated intravascular coagulopathy, assisted ventilation, and hypotension were associated significantly with poor outcome (P<0.05). Cox regression analysis revealed that mortality was significantly higher in patients on mechanical ventilation (RR 5.96, 95% CI 1.82–19.50), or with age <1 year (RR 2.00, 95% CI 1.08–3.73). In conclusion, despite the increasing use of CHDF over the last 3 years, there was no significant improvement in mortality, probably related to the fact that more critically ill patients were dialyzed. Received: 21 March 2000 / Revised: 12 October 2000 / Accepted: 19 October 2000     

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.     

Self-management in lower urinary tract symptoms: the next major therapeutic revolution

The standard treatments for men with lower urinary tract symptoms (LUTS) range from watchful waiting to medical and finally surgical intervention. However, the role of self-management interventions such as education and reassurance, lifestyle modification and behavioural changes has not been formally investigated, although they are widely advocated and utilised for LUTS. Self-management interventions are well established in other chronic diseases such as diabetes, arthritis and asthma. These interventions, if successfully organised within a structured program for LUTS, could improve patient outcomes as well as reduce the economic burden of LUTS treatment, by replacing or augmenting other treatments. Recent studies showing that long-term urodynamic and symptomatic deterioration of LUTS is minimal suggest that this is a safe and valid treatment option. This is supported by a recent pilot study of a LUTS self-management program which showed significant improvements in I-PSS and frequency–volume parameters. The results of a recently completed randomised controlled trial are awaited.     

Effectiveness of near-peer simulation for managing the acutely deteriorating patient among residents of an internal medicine junior residency programme

INTRODUCTIONNear-peer teaching is gaining popularity as a teaching modality, as it improves the learner’s understanding, is targeted at an appropriate level and promotes familiarisation. This study was initiated to evaluate the effectiveness of incorporating near-peer instruction into simulation-based training within a junior residency programme.METHODS42 first-year residents from an internal medicine junior residency programme were recruited. Participants underwent a simulation-based training programme conducted over five weeks. Each week involved either an emergency or acute clinical scenario. A structured questionnaire was administered prior to and after the course to compare participants’ perceived knowledge, experience and confidence in managing the clinical scenarios.RESULTSIn our study, 83% of participants agreed/strongly agreed that the scenarios were realistic. There were improvements in perceived knowledge, experience and confidence after the course. The greatest improvement was seen for experience (post-simulation: median 7.00 [interquartile range (IQR) 6.00‒8.00] vs. pre-simulation: median 5.00 [IQR 3.00–6.25]). 65% of participants were keen to help with future training.CONCLUSIONNear-peer simulation training was found to be a viable and valuable method of instruction for first-year residents for increasing experience, instilling confidence and improving perceived knowledge. Integration of such programmes within medical education curricula shows good promise of continuity, with many first-year residents inspired to organise subsequent sessions.