INTRODUCTION: Chronic lymphocytic leukaemia (CLL) has a heterogeneous disease course and a variable preva-lence across populations. Appropriate management for achieving optimal outcomes requires consideration of multiple factors, including disease-related factors like genomic alterations, patient characteristics and fitness, availability and access to treatments, and logistics/cost. This review aims to provide comprehen-sive and pragmatic recommendations for the management of treatment-naïve (TN) CLL that are relevant to Singapore's clinical context. METHOD: Clinical consensus statements were developed by an expert panel of haematologists from Singapore through a 2-round modified Delphi process. Statements were drafted using recent evidence-based guidelines and published literature. Panel members reviewed draft statements, provided anonymised feedback and proposed modifications where relevant. A physical meeting was held to facilitate discussion, voting and endorsement of the final consensus statements. RESULTS: The final consensus included 15 statements covering major TN CLL patient subsets. The recommendations highlight the importance of molecular testing for key biomarkers, where available/accessible, to guide initial therapy. Due to the superior efficacy of targeted agents (Bruton's tyrosine kinase inhibitors [BTKis] and B-cell lymphoma 2 inhibitors [BCL2is]) these are favoured over standard chemotherapy or chemotherapy-immunotherapy, especially for patients with del(17p) or TP53 mutation, and less fit patients. CONCLUSION These consensus statements provide practical recommendations for the current manage-ment of TN CLL patients in Singapore and similar healthcare systems based on up-to-date evidence. Regular updates to treatment guidelines are important to ensure responsiveness to emerging evidence and evolving clinical practices and to improve patient outcomes and quality of life.
Humans ; Consensus ; Leukemia, Lymphocytic, Chronic, B-Cell/diagnosis* ; Singapore

BACKGROUND: All Singaporean males undergo medical screening prior to compulsory military service. A history of possible food allergy may require referral to a specialist Allergy clinic to ensure that special dietary needs can be taken into account during field training and deployment. OBJECTIVE: To study the pattern of food allergy among pre-enlistees who were referred to a specialist allergy clinic to work up suspected food allergy. METHODS: Retrospective study of all pre-enlistees registered in the Clinical Immunology/Allergy New Case Registry referred to the Allergy Clinic from 1 August 2015 to 31 May 2016 for suspected food allergy. RESULTS: One hundred twenty pre-enlistees reporting food allergy symptoms other than rash alone were referred to the Allergy Clinic during the study period. Of these, 77 (64.2%) had food allergy. Among those with food allergy, mean age was 19.1 ± 1.5 years. They comprised predominantly Chinese (66.2%) and Malays (20.8%). The most commonly reported foods were shellfish/crustaceans (78%), peanut (15.6%), and egg (6.5%). Self-limiting oral allergy syndrome, OAS (itchy lips and throat with/without lip angioedema) was the most common manifestation (n = 33, 42.9%) followed by anaphylaxis (n = 23, 29.9%). Majority of OAS was from shellfish/crustacean (90.6%); of which shrimp (30.3%), crab (15.2%), and lobster (3.0%) were the most common. Mild childhood asthma (69.7%), allergic rhinitis (6.3%), and eczema (6.1%) were the most common atopic conditions among individuals with shellfish/crustacean OAS. This pattern was similar for shellfish/crustacean anaphylaxis. Skin prick tests were most commonly positive for shrimp (OAS 87.1% vs. anaphylaxis 100%), crab (OAS 95.8% vs. 90.9%), and lobster (OAS 91.7% vs. 63.6%). CONCLUSION: OAS to shellfish/crustaceans was more common than anaphylaxis among this study population of young males referred for food allergy symptoms other than rash alone.
Anaphylaxis ; Arachis ; Asian Continental Ancestry Group ; Asthma ; Eczema ; Exanthema ; Food Hypersensitivity ; Humans ; Hypersensitivity ; Lip ; Male ; Mass Screening ; Military Personnel ; Ovum ; Pharynx ; Referral and Consultation ; Retrospective Studies ; Rhinitis, Allergic ; Shellfish ; Singapore ; Skin ; Specialization

Aged ; Atherosclerosis ; Case-Control Studies ; Coronary Artery Bypass ; methods ; Coronary Artery Disease ; surgery ; Female ; Hemodynamics ; physiology ; Humans ; Male ; Mammary Arteries ; physiology ; transplantation ; Middle Aged ; Pulsatile Flow ; Radial Artery ; physiology ; transplantation ; Rheology ; Saphenous Vein ; physiology ; transplantation ; Shear Strength ; Stress, Mechanical ; Vascular Patency ; physiology

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.

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.

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

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

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

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

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