A 65-year-old lady with End-Stage Renal Failure (ESRF) receiving Continuous Ambulatory Peritoneal Dialysis (CAPD) was admitted acutely for altered mental status and neurological symptoms. She presented to the Emergency Department with bilateral upper limb weakness and clumsiness, bilateral lower limb weakness for 1 day’s duration. In addition, her family members reported altered behaviour for the previous 1 day. On examination, the patient had slurred speech, weakness in all limbs and brisk reflexes throughout. Significantly, she had been diagnosed with herpes zoster 2 days earlier by a family physician, for which she was started on oral acyclovir. Our patient was diagnosed as having acyclovir toxicity and commenced on urgent haemodialysis. Her symptoms resolved completely after 2 days. Our case details the uncommon but potentially fatal complication of acyclovir toxicity in patients with renal impairment, reinforces the importance of dose reduction in these patients and demonstrates haemodialysis as a good form of treatment for acyclovir toxicity. Family physicians should be familiar with dose adjustments for common medications prescribed to ESRF patients in the outpatient setting as the burden of chronic kidney disease increases in Singapore.

INTRODUCTIONIgA nephritis (IgAN) is the most common glomerulonephritis worldwide. We aim to genotype SNPs (single nucleotide polymorphisms) genomewide in patients with IgAN to search for genetic clues to its aetiology.

MATERIALS AND METHODSGenotyping for 10,204 SNPs genomewide was done with the Gene Chip Human Mapping 10K Microarray (Affymetrix). Twenty-eight patients with IgAN and 30 normal subjects were screened and analysed for differences in genotype frequency, allele frequency and heterozygosity reduction.

RESULTSAmong the most significantly associated SNPs, 48 SNPs were found mapping directly to the intron of 42 genes that localised in 13 somatic chromosomes and chromosome X. Genotype distribution of these SNPs did not deviate from the Hardy-Weinberg equilibrium in normal subjects. The most significantly associated gene, glial cells missing homolog 1 (GCM, 2 =13.05, P = 0.000) is a transcription factor mapped to 6p12.2. GCM1 reported decreased in placenta of patients with pre-eclampsia. The second gene, Tenascin-R (TNR, 2 = 9.85, P = 0.002) is a glycoprotein and extra-cellular matrix component mapped to 1q25.1. Tenascin-R was associated with motor coordination impairment and enhanced anxiety profile in deficient mice. Interestingly, Triadin (TRDN, 2 = 9.16, P = 0.01) is an integral membrane protein mapped to 6q22.31 within the IgAN1 locus. Triadin was shown to participate in cardiac myocyte arrhythemia. However, there is no published study of these genes in IgAN.

CONCLUSIONForty-two associated genes (particularly GCM1, TNR and TRDN) are identified as possible susceptibility or marker genes for IgAN. Knowledge of their mesangial expression and binding capacity for IgA-containing complexes may help elucidate the pathogenesis of IgAN.

Animals ; Carrier Proteins ; genetics ; Case-Control Studies ; Chromosome Mapping ; methods ; Disease Susceptibility ; Genetic Markers ; Genetic Testing ; Genotype ; Glomerulonephritis, IGA ; diagnosis ; epidemiology ; genetics ; Humans ; Mice ; Microarray Analysis ; Muscle Proteins ; genetics ; Nuclear Proteins ; genetics ; Odds Ratio ; Pilot Projects ; Polymorphism, Single Nucleotide ; genetics ; Singapore ; epidemiology ; Statistics as Topic ; Tenascin ; genetics ; Transcription Factors ; genetics

INTRODUCTIONThe effectiveness of integrated care pathways for hip fractures in subacute rehabilitation settings is not known. The study objective was to assess if a hip fracture integrated care pathway at a subacute rehabilitation facility would result in better functional outcomes, shorter length of stay and fewer institutionalisations.

MATERIALS AND METHODSA randomised controlled trial on an integrated care pathway for hip fracture patients in a subacute rehabilitation setting. Modified Barthel Index, ambulatory status, SF-12, length of stay, discharge destination, hospital readmission and mortality were measured. Followup assessments were up to 1 year post-hip fracture.

RESULTSThere were no significant differences in Montebello Rehabilitation Factor Scores and proportions achieving premorbid ambulatory status at discharge, 6 months and 12 months respectively. There was a significant reduction in the median length of stay between the control group at 48.0 days and the intervention group at 35.0 days (P = 0.009). The proportion of readmissions to acute hospitals was similar in both groups up to 1 year. There were no significant differences for nursing home stay up to 1 year post-discharge and mortality at 1 year.

CONCLUSIONOur study supports the use of integrated care pathways in subacute rehabilitation settings to reduce length of stay whilst achieving the same functional gains.

Hip Fractures ; Humans ; Prospective Studies

INTRODUCTIONIn this study of 109 patients with IgA nephritis (IgAN), we compared the longterm effects on patients treated with angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor antagonist (ATRA) alone with respect to renal outcome in terms of ESRF from 1995 to 2006. The renal outcome is also correlated with the ACE gene ID polymorphism to study its influence on response to ACEI/ATRA therapy.

MATERIALS AND METHODSSeventy-seven patients were on treatment with ACEI/ATRA (22 on ACEI alone, 47 on ATRA alone and 8 on both). The other 32 patients were on no treatment (control group).

RESULTSCompared to controls, treated patients had lower serum creatinine (P <0.001), lower proteinuria (P <0.001) and fewer number progressing to ESRF (P <0.001). For those with the II and ID genotype there were significantly fewer patients with ESRF in the treatment group. With the DD genotype, treatment did not change the poor renal outcome with regard to ESRF. Patients on ACEI therapy had a higher incidence of ESRF compared to those on ATRA (P <0.001). For the control group, the projected number of years-to-ESRF was 10 years. For those on ACEI therapy it was 11 years, and for those on ATRA therapy it was 24 years. Among patients with the II genotype, those treated with ATRA had significantly less incidence of ESRF compared to those treated with ACEI (P <0.001).

CONCLUSIONATRA therapy was found to be effective in retarding disease progression to ESRF in IgAN compared to ACEI therapy. Genotyping showed better response to ATRA therapy only for those with the II genotype.

Adult ; Angiotensin II Type 1 Receptor Blockers ; therapeutic use ; Angiotensin-Converting Enzyme Inhibitors ; therapeutic use ; Case-Control Studies ; Disease Progression ; Female ; Genetic Predisposition to Disease ; genetics ; Glomerulonephritis, IGA ; complications ; drug therapy ; genetics ; Humans ; Hypertension ; complications ; drug therapy ; Kidney Failure, Chronic ; etiology ; Male ; Peptidyl-Dipeptidase A ; genetics ; Polymorphism, Genetic ; genetics ; Retrospective Studies

INTRODUCTIONIgA nephropathy is a disease where the pathogenesis is still poorly understood. Deoxyribonucleic acid (DNA) microarray technique allows tens of thousands of gene expressions to be examined at the same time. Commercial availability of microarray genechips has made this powerful tool accessible for wider utilisation in the study of diseases.

MATERIALS AND METHODSSeven patients with IgA nephropathy, 6 with minimal change nephrotic syndrome (MCNS) as patient controls and 7 normal healthy subjects were screened for the differential expression of genes, genome-wide. The Human Genome U133 Plus 2.0 Arrays (Affymetrix, USA) were used to quantitate the differential expression of 38,500 well-characterised human genes.

RESULTSA total of 7761 gene expressions were identified that have an IgAN/Normal gene expression ratio of 0.06-fold to 5.58-fold. About 35% of the altered gene expressions have no gene title or just a hypothetical protein label such as FLJ30679. Most of the remaining 65% are identified proteins where their importance to IgAN is not immediately apparent at this time. Among the 30 most upregulated and 30 most downregulated genes are Urotensin 2 (upregulated 3.09-fold, P <0.05) and Fatty-acid binding protein 6 (downregulated to 0.12-fold, P <0.05). Retinoic acid receptor alpha (vitamin A receptor) was also found downregulated to 0.41-fold (P <0.005). Taqman realtime polymerase chain reaction (PCR) for urotensin 2 and retinoic acid receptor alpha (RARA) were performed on 20 patients with IgA nephropathy and 11 with Minimal Change Disease and the data correlated with various clinical indices.

CONCLUSIONSThe findings suggest that there may be a therapeutic role for retinoic acid receptor alpha (RARA) in IgA nephropathy and a clinical monitoring role for Urotensin 2 in Minimal Change Disease.

Adult ; Aged ; Case-Control Studies ; Female ; Gene Expression ; Gene Expression Regulation ; Genome-Wide Association Study ; Glomerulonephritis, IGA ; genetics ; metabolism ; pathology ; Humans ; Immunoglobulin A ; genetics ; metabolism ; Male ; Middle Aged ; Nephrosis, Lipoid ; genetics ; metabolism ; pathology ; Oligonucleotide Array Sequence Analysis ; Polymerase Chain Reaction ; Receptors, G-Protein-Coupled ; genetics ; metabolism ; Receptors, Retinoic Acid ; genetics ; metabolism ; Tretinoin ; metabolism

INTRODUCTIONWhile the readmission rate from community hospitals is known, the factors affecting it are not. Our aim was to determine the factors predicting unplanned readmissions from community hospitals (CHs) to acute hospitals (AHs).

MATERIALS AND METHODSThis was an observational prospective cohort study, involving 842 patients requiring post-acute rehabilitation in 2 CHs admitted from 3 AHs in Singapore. We studied the role of the Cumulative Illness Rating Scale (CIRS) organ impairment scores, the Mini-mental State Examination (MMSE) score, the Shah modified Barthel Index (BI) score, and the triceps skin fold thickness (TSFT) in predicting the rate of unplanned readmissions (UR), early unplanned readmissions (EUPR) and late unplanned readmissions (LUPR). We developed a clinical prediction rule to determine the risk of UR and EUPR.

RESULTSThe rates of EUPR and LUPR were 7.6% and 10.3% respectively. The factors that predicted UR were the CIRS-heart score, the CIRS-haemopoietic score, the CIRS-endocrine / metabolic score and the BI on admission. The MMSE was predictive of EUPR. The TSFT and CIRS-liver score were predictive of LUPR. Upon receiver operator characteristics analysis, the clinical prediction rules for the prediction of EUPR and UR had areas under the curve of 0.745 and 0.733 respectively. The likelihood ratios of the clinical prediction rules for EUPR and UR ranged from 0.42 to 5.69 and 0.34 to 3.16 respectively.

CONCLUSIONSPatients who have UR can be identified by the admission BI, the MMSE, the TSFT and CIRS scores in the cardiac, haemopoietic, liver and endocrine/metabolic systems.

Acute Disease ; therapy ; Aged ; Female ; Follow-Up Studies ; Hospitals, Community ; statistics & numerical data ; Hospitals, Special ; statistics & numerical data ; Humans ; Intensive Care Units ; statistics & numerical data ; Male ; Patient Readmission ; trends ; Prospective Studies ; Risk Factors ; Severity of Illness Index ; Singapore

Caregivers are important in post-stroke rehabilitation, but little work has been done on the caregivers of stroke survivors in Asian cultures. We examined the association between patient profile (age, gender, socioeconomic status, functional level, religion, and ethnicity) and caregiver availability, number of potential caregivers and primary caregiver identity amongst Singaporean community hospitals' stroke patients. Data was obtained from all Singaporean community hospitals from 1996-2005. 3796 patients fulfilled inclusion criteria. Mixed logistic regression identified independent predictors of caregiver availability and primary caregiver identity. Mixed Poisson modelling identified independent predictors of the number of caregiver(s). Among recent stroke survivors, 95.8% (3640/3796) had potential caregivers, of which 94.2% (3429/3640) had identified primary caregivers. Of the latter, 41.2% relied on live-in hired help (foreign domestic workers-FDWs), 27.6% on spouses and 21.6% on first-degree relatives. Independent patient factors associated with caregiver availability and number were older, female, married, higher socioeconomic status, having a religion and lower functional level at admission. Independent patient factors associated with FDW caregivers were older age, female, Chinese compared to Malay, with higher socioeconomic class and lower functional level at admission. Caregiver availability for post-stroke patients in Singapore community hospitals is relatively high, with heavy dependence on FDWs.

Apart from clinical, histological and biochemical indices, genomics are now being employed to unravel the pathogenetic mechanisms in the disease progression of IgA nephritis (IgAN). The results of angiotensin converting enzyme (ACE) gene polymorphism have been controversial. Those patients with the DD genotype seem to have a poorer prognosis. However, with high dose angiotensin receptor blocker (ARB) therapy, the ACE gene polymorphism status of a patient may no longer be a matter for concern as those with the DD genotype would also respond favourably to high dose ARB therapy. Association studies with gene sequencing and haplotypes have suggested that multiple genes are involved in the pathogenesis of IgAN. Some workers have reported a synergistic effect in the combined analysis of AGT-M235T and ACE I/D polymorphism. With the use of deoxyribo nucleic acid (DNA) microarray, tens of thousands of gene expressions genome-wide can be examined together simultaneously. A locus of familial IgAN has been described with strong evidence of linkage to IgAN1 on chromosome 6q22-23. Two other loci were reported at 4q26-31 and 17q12-22. DNA microarray techniques could also help in the identification of specific pathogenic genes that are up- or down-regulated and this may allow genome wide analyses of these genes and their role in the pathogenesis and progression of IgAN. Recently, using genome-wide association studies (GWAS) more loci for disease susceptibility for IgAN have been identified at 17p13, 8p23, 22q12, 1q32 and 6p21.
Angiotensin Receptor Antagonists ; administration & dosage ; Disease Progression ; Dose-Response Relationship, Drug ; Genomics ; methods ; Glomerulonephritis, IGA ; drug therapy ; genetics ; pathology ; Haplotypes ; Humans ; Molecular Sequence Data ; Polymorphism, Single Nucleotide

INTRODUCTIONLittle data is available on community hospital admissions. We examined the differences between community hospitals and the annual trends in sociodemographic characteristics of all patient admissions in Singaporean community hospitals over a 10- year period from 1996 to 2005.

MATERIALS AND METHODSData were manually extracted from medical records of 4 community hospitals existent in Singapore from 1996 to 2005. Nineteen thousand and three hundred and sixty patient records were examined. Chisquare test was used for univariate analysis of categorical variables by type of community hospitals. For annual trends, test for linear by linear association was used. ANOVA was used to generate beta coefficients for continuous variables.

RESULTSMean age of all patient admissions has increased from 72.8 years in 1996 to 74.8 years in 2005. The majority was Chinese (88.4%), and female (58.1%) and admissions were mainly for rehabilitation (88.0%). Almost one third had foreign domestic workers as primary caregivers and most (73.5%) were discharged to their own home. There were significant differences in socio-demographic profile of admissions between hospitals with one hospital having more patients with poor social support. Over the 10-year period, the geometric mean length of stay decreased from 29.7 days (95% CI, 6.4 to 138.0) to 26.7 days (95% CI, 7.5 to 94.2), and both mean admission and discharge Barthel Index scores increased from 41.0 (SD = 24.9) and 51.8 (SD = 30.0), respectively in 1996 to 48.4 (SD = 24.5) and 64.2 (SD = 27.3) respectively in 2005.

CONCLUSIONThere are significant differences in socio-demographic characteristics and clinical profile of admissions between various community hospitals and across time. Understanding these differences and trends in admission profiles may help in projecting future healthcare service needs.

Aged ; Aged, 80 and over ; Analysis of Variance ; Confidence Intervals ; Diagnosis ; Female ; Hospitals, Community ; Humans ; Male ; Medical Records ; statistics & numerical data ; Middle Aged ; Odds Ratio ; Patient Admission ; statistics & numerical data ; trends ; Singapore ; Social Class

INTRODUCTIONAwake craniotomy allows accurate localisation of the eloquent brain, which is crucial during brain tumour resection in order to minimise risk of neurologic injury. The role of the anaesthesiologist is to provide adequate analgesia and sedation while maintaining ventilation and haemodynamic stability in an awake patient who needs to be cooperative during neurological testing. We reviewed the anaesthetic management of patients undergoing an awake craniotomy procedure.

MATERIALS AND METHODSThe records of all the patients who had an awake craniotomy at our institution from July 2004 till June 2006 were reviewed. The anaesthesia techniques and management were examined. The perioperative complications and the outcome of the patients were noted.

RESULTSThere were 17 procedures carried out during the study period. Local anaesthesia with moderate to deep sedation was the technique used in all the patients. Respiratory complications occurred in 24% of the patients. Hypertension was observed in 24% of the patients. All the complications were transient and easily treated. During cortical stimulation, motor function was assessed in 16 patients (94%). Three patients (16%) had lesions in the temporal-parietal region and speech was assessed intraoperatively. Postoperative motor weakness was seen in 1 patient despite uneventful intraoperative testing. No patient required intensive care unit stay. The median length of stay in the high dependency unit was 1 day and the median length of hospital stay was 9 days. There was no in-hospital mortality.

CONCLUSIONAwake craniotomy for brain tumour excision can be successfully performed under good anaesthetic conditions with careful titration of sedation. Our series showed it to be a well-tolerated procedure with a low rate of complications. The benefits of maximal tumour excision can be achieved, leading to potentially better patient outcome.

Adult ; Aged ; Anesthesia, Local ; methods ; Anesthetics, Local ; administration & dosage ; Brain Neoplasms ; surgery ; Conscious Sedation ; Craniotomy ; Female ; Humans ; Male ; Medical Audit ; Middle Aged ; Outcome Assessment (Health Care) ; Perioperative Care ; Singapore