A retrospective study on drug survival of biologic among patients with psoriasis seen in tertiary hospital in Johor Malaysia.

INTRODUCTION: Limited information exists regarding drug survival of biologics among psoriasis patients in Malaysia. This study aimed to determine the drug survival of biologics in Malaysian psoriasis patients, the reasons for drug discontinuation and to identify the predictor of drug survival. MATERIALS AND METHODS: A retrospective review of case notes on adult psoriasis patients treated with biologics in Hospital Sultanah Aminah Johor Bahru Malaysia, between January 2006 and December 2020. Drug survival was analysed using the Kaplan-Meier method. RESULTS: By December 2020, 100 patients with 154 treatment courses of biologics were included in the study. Male to female ratio was 1:1. The mean age at onset was 31.36 ± 11.72 years. Ustekinumab was the most frequently prescribed biologics (39%), followed by adalimumab (29.2%), secukinumab (14.9%), etanercept (13%), and infliximab (3.2%). Overall median drug survival for biologics was 25 months (interquartile range [IQR]= 12.0-.0). The median drug survival for ustekinumab was 35 months (IQR, 12-93); followed by 25 months (IQR, 12.0-), 18 months (IQR, 7-85), 17 months (IQR, 11-43), and 8 months (IQR, 1-10) for secukinumab, adalimumab, etanercept, and infliximab, respectively. The main reason for drug discontinuation was loss of efficacy (26%), inadequate funding (14.3%), loss to follow-up (10.4%), adverse events (4.5%), and patients' request (1.3%). CONCLUSION: Our study shows ustekinumab has the best long-term drug survival among biologics in Malaysian patients with psoriasis in real-life setting. Further study is required to evaluate the long-term drug survival for newer biologics.

Pattern of biopsy-proven renal disease in Sabah: A retrospective cross-sectional study over 3.5 years.

OBJECTIVES: To explore the epidemiological and histopathological patterns of glomerular diseases in Sabah. METHODS: A state-wide cross-sectional study was conducted. There were 336 native renal biopsies in 296 eligible patients from 1st January 2013 to 30th June 2016. All patients aged ≥12 years with sufficient sampling (≥8 glomeruli) for histopathological assessment were included. Graft kidney biopsies, protocol-based biopsies and patients with uncertain demographics were excluded. Demographics of patients, clinical data, laboratory parameters prior to biopsy, and histology findings of renal biopsies were collected from local unit database and recorded into a standardised data collection form. Descriptive statistical analyses were employed and factors associated with Lupus nephritis (LN) were explored using logistic regression. RESULTS: The mean age during biopsy was 34.53 years (Standard Deviation 0.759). Primary glomerulonephritis (PGN) accounted for 42.6% (126) of all native renal biopsies. The commonest cause of PGN was minimal change disease (38.9%, 49) followed by focal segmental glomerulosclerosis (33.3%, 42) and IgA nephropathy (14.3%, 18). LN is the leading cause for secondary glomerulonephritis (SGN) (87.2%, 136). Younger age (Odds Ratio, OR 0.978; 95% Confidence Interval, 95%CI 0.960, 0.996); female gender (OR 17.53; p<0.001); significant proteinuria (OR 132.0; p<0.001); creatinine level at biopsy (OR 11.26; p=0.004); positive antinuclear antibody (ANA) (OR 46.7; p<0.001); and ANA patterns (OR 8.038; p=0.018) were significant in predicting the odds of having LN. CONCLUSION: This is the first epidemiology study of glomerular diseases in Sabah. The predominance of LN suggests lower threshold for renal biopsy in patients with suspected glomerular disorders. We have identified significant predictors for early detection and treatment of LN.

Isoniazid-induced encephalopathy in an end-stage renal disease patient - A case report and literature review.

Patients with end stage renal disease have higher risk of tuberculosis due to lower cell-mediated immunity. Standard regime of anti-tuberculosis contains isoniazid where neurological side effects such as seizure and encephalopathy have been documented. We present a case of isoniazid-induced encephalopathy in a haemodialysis patient. A literature review on isoniazid-induced encephalopathy was done. Recognition of this condition is important as it is reversible with cessation of isoniazid and institution of high dose pyridoxine.

Pathological outcome for Chinese patients with low-risk prostate cancer eligible for active surveillance and undergoing radical prostatectomy: comparison of six different active surveillance protocols.

INTRODUCTION: Active surveillance is one of the therapeutic options for the management of patients with low-risk prostate cancer. This study compared the performance of six different active surveillance protocols for prostate cancer in the Chinese population. METHODS: Patients who underwent radical prostatectomy for prostate cancer from January 1998 to December 2012 at a university teaching hospital in Hong Kong were reviewed. Six active surveillance protocols were applied to the cohort. Statistical analyses were performed to compare the probabilities of missing unfavourable pathological outcome. The sensitivity and specificity of each protocol in identifying low-risk disease were compared. RESULTS: During the study period, 287 patients were included in the cohort. Depending on different active surveillance protocols used, extracapsular extension, seminal vesicle invasion, pathological T3 disease, and upgrading of Gleason score were present on final pathology in 3.3%-17.1%, 0%-3.3%, 3.3%-19.1%, and 20.6%-34.5% of the patients, respectively. The University of Toronto protocol had a higher rate of extracapsular extension at 17.1% and pathological T3 disease at 19.1% on final pathology than the more stringent protocols from John Hopkins (3.3% extracapsular extension, P=0.05 and 3.3% pathological T3 disease, P=0.03) and Prostate Cancer Research International: Active Surveillance (PRIAS; 8.0% pathological T3 disease, P=0.04). The Royal Marsden protocol had a higher rate of upgrading of Gleason score at 34.5% compared with the more stringent protocol of PRIAS at 20.6% (P=0.04). The specificities in identifying localised disease and low-risk histology among different active surveillance protocols were 59%-98% and 58%-94%, respectively. The John Hopkins active surveillance protocol had the highest specificity in both selecting localised disease (98%) and low-risk histology (94%). CONCLUSIONS: Active surveillance protocols based on prostate-specific antigen and Gleason score alone or including Gleason score of 3+4 may miss high-risk disease and should be used cautiously. The John Hopkins and PRIAS protocols are highly specific in identifying localised disease and low-risk histology.

Newly diagnosed end stage kidney disease in a single centre in Sabah.

AIM: To study the epidemiology, clinical characteristics, vascular access, and the short term survival of ESRD patients initiated on dialysis from Hospital Queen Elizabeth (HQE). BACKGROUND: The number of patients with ESRD is increasing in Sabah, Malaysia. Most patients present late and some live in remote areas with difficult access to healthcare services. Many therefore present with potentially fatal complications. METHODS: All the newly confirmed ESRD patients who were initiated on renal replacement therapy (RRT) from 1 January to 31 December 2014 were included. The basic epidemiological and clinical data were collected. They were divided into three groups: Group 1 - those known to the medical service and had been prepared properly for the initiation of RRT; Group 2 - those known to the medical service, but were not prepared for the RRT; Group 3 - those with undiagnosed CKD. Outcome is mainly survival at 3rd, 6th, 9th and 12th month. RESULTS: There were 249 ESRD patients. 153 (61.4%) were male. The average age was 53.3 (range 12 - 83). The main cause of ESRD was diabetic nephropathy (128 patients, 51.4%). Most patients were started on RRT with a catheter (74.3%), 47 patients (18.9%) with a fistula, and 17 patients (6.8%) with a Tenckhoff catheter. 185 (74.3%) patients were not prepared properly (Group 2 - 66.3%, and Group 3 - 8.0%). The survival for 249 patients were 86.3% at 6 months, 77.9% at 12 months. Group 2 has the worst survival (81.9% at 6 months, 71.1% at 12 months). CONCLUSIONS: Our data showed that most patients (74.3%) were started on dialysis in an unplanned manner with poor survival. A comprehensive and well-supported predialysis programme is needed.

Impact of skeletal-related events on survival in patients with metastatic prostate cancer prescribed androgen deprivation therapy.

OBJECTIVE: To investigate the impact of skeletal-related events on survival in patients with metastatic prostate cancer prescribed long-term androgen deprivation therapy. METHODS: This historical cohort study was conducted in two hospitals in Hong Kong. Patients who were diagnosed with metastatic prostate cancer and prescribed androgen deprivation therapy between January 2006 and December 2011 were included. Details of skeletal-related events and mortality were examined. RESULTS: The median follow-up was 28 (range, 1-97) months. Of 119 patients, 52 (43.7%) developed skeletal-related events throughout the study, and the majority received bone irradiation for pain control. The median actuarial overall survival and cancer-specific survival for patients with skeletal-related events were significantly shorter than those without skeletal-related events (23 vs 48 months, P=0.003 and 26 vs 97 months, P<0.001, respectively). Multivariate analysis revealed that the adjusted hazard ratio of presence of skeletal-related events on overall and cancer-specific survival was 2.73 (95% confidence interval, 1.46-5.10; P=0.002) and 3.92 (95% confidence interval, 1.87-8.23; P<0.001), respectively. A prostate-specific antigen nadir of >4 ng/mL was an independent poor prognostic factor for overall and cancer-specific survival after development of skeletal-related events (hazard ratio=10.42; 95% confidence interval, 2.10-51.66 and hazard ratio=10.54; 95% confidence interval, 1.94-57.28, respectively). CONCLUSIONS: Skeletal-related events were common in men with metastatic prostate cancer. This is the first reported study to show that a skeletal-related event is an independent prognostic factor in overall and cancer-specific survival in patients with metastatic prostate cancer prescribed androgen deprivation therapy. A prostate-specific antigen nadir of >4 ng/mL is an independent poor prognostic factor for overall and cancer-specific survival following development of skeletal-related events.

Minimally invasive enteroscopically guided small bowel resection.

Localisation of small bowel pathology is often difficult, especially intramural small bowel lesions. Even with the use of laparoscopy, visualisation of small bowel lesion is not always possible. The most accurate method to identify such a lesion is by laparotomy with direct visualisation and palpation of the lesion. However, the recent trend in surgical development aims for minimally invasive procedures while keeping the excision of surgical pathology safe and complete, with less surgical trauma. This report illustrates a case of minimally invasive enteroscopically guided small bowel resection.

How can the R.E.N.A.L. nephrometry scoring system aid management of a solid renal mass?

OBJECTIVES. To investigate use of the R.E.N.A.L. nephrometry score in relation to the choice of treatment and postoperative complications for renal masses. DESIGN. Case series. SETTING. A tertiary referral hospital in Hong Kong. PATIENTS. Data of patients undergoing nephrectomy were collected retrospectively from a clinical database and analysed. A R.E.N.A.L. nephrometry score was allocated to each renal tumour by a blinded qualified radiologist, utilising computerised imaging systems. Patient demographics, choice of surgery (radical vs partial), and approaches (open vs minimally invasive) were analysed with respect to their R.E.N.A.L. score. RESULTS. In all, 74 patients were included during the study period, of which 38 underwent partial nephrectomy and 36 underwent radical nephrectomy. No differences between the groups were found with respect to patient demographics. There were significant differences between the partial and radical nephrectomy groups in terms of their mean nephrometry score (6.9 vs 9.3, P<0.001). The mean nephrometry sum was also significantly different in the open approach versus the minimally invasive approach in patients having partial nephrectomy (7.8 vs 6.0, P=0.001). There was no difference in the postoperative 90-day morbidity and mortality in the partial nephrectomy and radical nephrectomy groups. CONCLUSIONS. The R.E.N.A.L. nephrometry score of a renal mass correlated significantly with our choice of surgery (partial vs radical) and our approach to surgery (open vs minimally invasive surgery), particularly in the partial nephrectomy group. It does not, however, correlate with postoperative complications. The nephrometry score provides a useful tool for objectively describing renal mass characteristics and enhancing better communication for the operative planning directed at renal masses.

Melioidosis and peritoneal dialysis related peritonitis.

We report a case of melioidosis presenting as peritonitis in a patient on continuous ambulatory peritoneal dialysis (CAPD). A 47-year-old man, a lorry driver, with end-stage renal disease due to diabetes mellitus on CAPD presented in PD-related peritonitis. He was started on intraperitoneal cloxacillin and ceftazidime, and changed to intraperitoneal vancomycin and meropenam after day 5 due to nonresponse. Burkholderia pseudomallei was identified from the dialysate culture. He was treated with intraperitoneal meropenam for two weeks, and IV ceftazidime for 4 weeks. He responded, and the Tenckhoff catheter was not removed. He was discharged well and continued on oral sulfamethoxazole/trimethoprim for six months. This patient had done his PD exchanges in a lorry.

A short message service (SMS) intervention to prevent diabetes in Chinese professional drivers with pre-diabetes: a pilot single-blinded randomized controlled trial.

AIM: To determine the efficacy of delivering short-message service (SMS) to provide diabetes-related information in reducing the risk of developing diabetes in Chinese professional drivers with pre-diabetes. METHODS: A pilot single-blinded randomized controlled trial was conducted in Hong Kong between 05/2009 and 04/2012. Professional drivers with impaired glucose tolerance (IGT) were randomly allocated to either a SMS group receiving messages comprising knowledge and lifestyle modification on diabetes or to a control group with usual care. Primary outcomes were the incidence rate of diabetes mellitus over 12 and 24 months period. RESULTS: Fifty-four, out of 104 professional drivers recruited, were randomly allocated to intervention group. Fewer subjects developed diabetes at 12 months in intervention group (5.56%) compared to control group (16.00%). Relative risk (RR) of diabetes onset was 0.35 (95%CI: 0.10­1.24) and the number needed to treat (NNT) for preventing one diabetes was 9.57. At 24 months, RR increased to 0.62 (95%CI: 0.24­1.61) with a NNT of 10.58. Logistic regression showed a significant odds ratio of 0.04 (P = 0.021) for intervention group compared to control group at 12-month follow-up for completers and a non-significant odds ratio of 0.34 (P = 0.303) at 24-month follow-up. CONCLUSIONS: The SMS program proved to have potential to reduce the risk of developing diabetes at 12 months but additional measures should be integrated to prevent or delay disease progression.

Effects of microstructure on flow properties of fibrous porous media at moderate Reynolds number.

In this study, effects of microstructure on the viscous permeability and Forchheimer coefficient of monodispersed fibers are investigated. The porous material is represented by a unit cell which is assumed to be repeated throughout the medium. Based on the orientation of the fibers in the space, fibrous media are divided into three categories: one-, two-, and three-directional (1D, 2D, and 3D) structures. Parallel and transverse flow through square arrangements of 1D fibers, simple 2D mats, and 3D simple cubic structures are solved numerically over a wide range of porosity (0.35 < ε < 0.95) and Reynolds number (0.01 < Re < 200). The results are used to calculate the permeability and the inertial coefficient of the considered geometries. An experimental study is performed; the flow coefficients of three different ordered tube banks in the moderate range of Reynolds number (0.001 < Re < 15) are determined. The numerical results are successfully compared with the present and the existing experimental data in the literature. The results suggest that the permeability and Forchheimer coefficient are functions of porosity and fiber orientation. A comparison of the experimental and numerical results with the Ergun equation reveals that this equation is not suitable for highly porous materials. As such, accurate correlations are proposed for determining the Forchheimer coefficient in fibrous porous media.

Prevalence of undiagnosed diabetes mellitus and cardiovascular risk factors in Hong Kong professional drivers.

AIMS: To investigate the prevalence of undiagnosed diabetes mellitus (DM) and cardiovascular risk factors among professional drivers in Hong Kong. METHODS: Chinese professional drivers with no history of DM were invited to complete a questionnaire on their health status, followed by taking their body measurements, fasting blood glucose (FG) and lipids. 75g OGTT were performed when FG≥5.6 to <7.0mmol/L. RESULTS: Of these 3376 drivers (male 92.6%, mean age 50.9±7.6 years), the prevalence of undiagnosed DM, prediabetes, and metabolic syndrome was 8.1% (272/3376, 95% CI 7.1-9.0%), 10.0% (337/3376, 95% CI 9.0-11.0%) and 26.8% (904/3376, 95% CI 25.3-28.3%) respectively, while the corresponding WHO Standard Population age-standardized prevalence was 7.8%, 9.0% and 24.7% respectively. Many of them were obese (51.2%), had hypertension (57.0%) and high cholesterol (58.7%), and a third had hypertriglyceridaemia (34.9%) and low HDL-cholesterol (29.3%). Their median working hours were 60.0 (IQR 14)h. Majority had exercise <1h/week (56.0%) and ate out ≥6times/week (54.9%). CONCLUSIONS: Hong Kong professional drivers have higher prevalence of undiagnosed DM, cardiovascular risk factors and metabolic syndrome than the general population. Therefore, health care measures targeting against them should be taken to prevent and detect DM and cardiovascular diseases.

Quality of diabetes care in public primary care clinics in Hong Kong.

BACKGROUND: Little is known about the quality of care for patients with Type 2 diabetes in primary care setting in Hong Kong. OBJECTIVES: To investigate the quality of care for patients with Type 2 diabetes in Hong Kong primary care setting and potential disparities by patient characteristics and clinics. METHODS: Cross-sectional study in three general outpatient clinics (GOPCs; public primary care clinics) in Hong Kong involving 1970 patients. Main outcome measures were achievement rates of seven process measures and three intermediate outcome targets and adjusted odds ratios of age, sex, socio-economic status and clinic on the quality measures. RESULTS: The achievement rates for the recording of HbA1c, blood pressure (BP), cholesterol, body mass index, smoking status, nephropathy screening and retinopathy screening in the previous 12 months were 92.8%, 99.9%, 91.0%, 47.9%, 91.3%, 69.0% and 38.0%, respectively. A total of 58.0%, 38.2% and 36.4% of patients achieved the glycaemic, BP and cholesterol targets, respectively. Older patients were less likely to have records of process measures and more likely to achieve the HbA1c target. Women were less likely to have smoking status recorded and to achieve the HbA1c target. Patients of lower socio-economic status were less likely to have records of process measures and to achieve the BP target. Family medicine training practices had better achievements of the quality measures. CONCLUSIONS: There is scope for improvement in the quality of diabetes care in the GOPCs. Variations in the quality of care were observed. Family medicine training may enhance the health care quality.

Allelic imbalance at 13q31 is associated with reduced GPC6 in Chinese with sporadic retinoblastoma.

BACKGROUND/AIMS: Loss of heterozygosity (LOH) has been discovered in retinoblastoma (RB) in previous studies. In this study, we aimed to discover potential tumour suppressor genes through investigation of the incidence of allelic loss in chromosome 1, 6, 9, 13, 19, 20, 21, 22 and X in Chinese sporadic retinoblastoma patients and to study the expression of genes flanking LOH region 13q31. METHODS: Twenty-five microdissected RB samples were analysed to investigate the LOH in 140 microsatellite markers. Expression of genes flanking D13S265 was investigated by real-time quantitative-PCR on available frozen samples. The promoter and entire coding region of GPC6 were examined for sequence changes in an extended batch of 29 RB samples. RESULTS: Allele losses were found in 92% (23/25) of the tumours. We identified a new LOH locus at 13q31 (D13S265) with a high occurrence rate (67%, 14/21) apart from the RB1 locus (68%, 17/25). Expression study detected the reduced expression of Glypican 6 (GPC6) transcript significantly associated with the LOH at 13q31 (p=0.024). Furthermore, mutation screening revealed no remarkable sequence alteration in GPC6 that could affect its expression. CONCLUSION: Results suggest that a reduction in GPC6 mRNA in retinoblastoma is associated with the non-random allelic loss at 13q31 that could contribute to RB development.

Is ultrasonography-guided modified coaxial core biopsy of the breast a better technique?

OBJECTIVE: To compare the diagnostic rate, patient comfort, and complications of ultrasonography-guided breast biopsy using a modified coaxial technique with ultrasonography-guided fine needle aspiration and traditional core biopsy. A secondary objective was to describe the use of the coaxial technique for the biopsy of breast lesions and our initial experience. DESIGN: Retrospective study. SETTING: A regional hospital in Hong Kong. PATIENTS: Patients, who were referred for ultrasonography-guided fine needle aspiration or biopsy from 23 November 2007 to 19 March 2008, were divided into three groups. For breast lesions of 8 mm or smaller, fine needle aspirations were performed. For breast lesions larger than 8 mm, the patients were randomly divided into groups receiving traditional core biopsies and coaxial biopsies. The pathological reports were reviewed. MAIN OUTCOME MEASURES: Diagnostic rate, patient comfort assessed in terms of pain, and any procedural complications. RESULTS: A total of 45 ultrasonography-guided fine needle aspirations or biopsies of breast lesions were performed. All core biopsies using the traditional core technique (n=15) and coaxial technique (n=16) were diagnostic. While for fine needle aspirations, three (21%) of 14 were not diagnostic and repeat biopsies were undertaken for the corresponding patients. Except for one breast lesion biopsied with the coaxial technique that revealed invasive ductal carcinoma, all others yielded benign lesions. The average pain score for coaxial biopsies was 2.2, while for traditional core biopsies and fine needle aspirations, average scores were 3.7 and 3.8, respectively (P=0.022). No procedure-related complication was documented with either of the three techniques. CONCLUSION: Modified coaxial core biopsy of the breast has an optimal diagnostic rate and hence avoids the need for repeat biopsies. It is associated with better patient comfort and no increase in the risk of complications.

Simple co-electrodeposition of functionalized multi-walled carbon nanotubes/chitosan composite coating on mainspring for enhanced modulus of elasticity.

Co-electrodeposition of functionalized multi-walled carbon nanotubes (f-MWCNTs) with chitosan was performed on pieces of a stainless steel mainspring. Under moderate conditions, composite coatings with controllable thickness from a few hundred nanometers to tens of micrometers can be achieved. After coating an 8 microm composite layer on a piece of mainspring 120 microm thick (i.e. 6.7% increase in thickness), the Young's modulus of the mainspring was found to have increased by more than approximately 25%. Moreover, the coated mainsprings possess much stronger mechanical strength as demonstrated by fatigue tests. The significant enhancement of Young's modulus and intrinsic strength are mostly attributed to the effect exerted by the subtle combination of chitosan and MWCNT. In the current study, the intensive cross-linkages formed between the -COOH groups in f-MWCNTs and the hydroxyl (-OH) and amino (-NH2) groups in chitosan were exploited. The chitosan molecular chains and f-MWCNTs both chemically react and physically knot with each other, leading to a three-dimensional interlaced f-MWCNT/chitosan composite coating. The reported co-electrodeposition provides a simple approach to form a stable, reproducible and rigid f-MWCNTs composite coating, which leads to the realization of a high-performance mainspring with reinforced mechanical strength.

Identification of molecular markers and signaling pathway in endometrial cancer in Hong Kong Chinese women by genome-wide gene expression profiling.

Endometrial cancer is the third most common gynecologic malignancy and the ninth most common malignancy for females overall in Hong Kong. Approximately 80% or more of these cancers are endometrioid endometrial adenocarcinomas. The aim of this study was to reveal genes contributing to the development of endometrioid endometrial cancer, which may impact diagnosis, prognosis and treatment of the disease. Whole-genome gene expression analysis was completed for a set of 55 microdissected sporadic endometrioid endometrial adenocarcinomas and 29 microdissected normal endometrium specimens using the Affymetrix Human U133 Plus 2.0 oligonucleotide microarray. Selected genes of interest were validated by quantitative real-time-polymerase chain reaction (qRT-PCR). Pathway analysis was performed to reveal gene interactions involved in endometrial tumorigenesis. Unsupervised hierarchical clustering displayed a distinct separation between the endometrioid adenocarcinomas and normal endometrium samples. Supervised analysis identified 117 highly differentially regulated genes (>or=4.0-fold change), which distinguished the endometrial cancer specimens from normal endometrium. Twelve novel genes including DKK4, ZIC1, KIF1A, SAA2, LOC16378, ALPP2, CCL20, CXCL5, BST2, OLFM1, KLRC1 and MBC45780 were deregulated in the endometrial cancer, and further validated in an independent set of 56 cancer and 29 normal samples using qRT-PCR. In addition, 10 genes were differentially regulated in late-stage cancer, as compared to early-stage disease, and may be involved in tumor progression. Pathway analysis of the expression data from this tumor revealed an interconnected network consisting of 21 aberrantly regulated genes involved in angiogenesis, cell proliferation and chromosomal instability. The results of this study highlight the molecular features of endometrioid endometrial cancer and provide insight into the events underlying the development and progression of endometrioid endometrial cancer.