The Development of Gout Treat-To-Target booklet.

INTRODUCTION: The treat-to-target serum uric acid approach is recommended in local and international guidelines on gout management. Instruction for initiation and dose escalation for urate lowering therapy may cause confusion to the patient. Our aim was to develop and validate Gout Treat-To- Target booklet to aid in patient education. MATERIALS AND METHODS: A content development team which consisted of three consultant rheumatologists developed the booklet. Content validation was performed by a panel of evaluators consisted of eleven physicians (four consultant rheumatologists, two clinical specialists, and five medical officers), who were involved in gout management. Face validation was performed by ten patients with gout. RESULTS: Item-Content Validity Index ranged from 0.9 to 1 with regards to relevancy, clarity, ambiguity and simplicity. Side effects of uricosuric agents were added to the draft based on an evaluator's comment. Item-Face Validity Index was 1, which indicated that all patients were in 100% agreement with all items. CONCLUSION: We developed and validated our Gout Treat-to- Target booklet. There was high agreement in I-FVI and I-CVI among physicians and patients.

Outcome of cardiopulmonary resuscitation in the emergency department of a tertiary hospital in Malaysia.

INTRODUCTION: There are insufficient data available regarding the outcome of cardiac arrest (CA) resuscitated in the emergency department in Malaysia. This study aims to determine the incidence of CA, the return of spontaneous circulation (ROSC), survival to admission (STA), survival to discharge (STD) and factors influencing the overall outcome of CA. MATERIAL AND METHODS: This is a retrospective observational study done in Hospital Sg Buloh (HSB), a tertiary referral centre in an urban area located north of Kuala Lumpur, Malaysia's capital city, from January until December 2018, involving 289 patients. All cases with CPR and a sustained return of spontaneous circulation (ROSC) were included in the study and followed up until discharged or died in the hospital. RESULTS: Out of 236 patients recruited, 25.8% achieved ROSC, 15.7% survived on admission, and 4.2% of patients were discharged alive. Of 74.1% of witnessed OHCA, only 17.5% received bystander CPR. Factors with favourable outcomes include CA in ED (p<0.001), the initial rhythm of ventricular fibrillation (p=0.003), defibrillation (p=0.024), OHCA witnessed by emergency medical services (EMS) (p=0.024) and intravenous adrenaline administration (p=0.001). When using multivariate regression analysis, positive outcomes were associated with the cardiac and respiratory cause of CA (Adjusted Odd Ratio (AOR) 3.66; 95% Confidence Intervals, 95%CI: 2.52 - 12.61 and AOR 8.76; 95%CI: 5.76- 15.46, respectively) as well as OHCA witnessed by EMS (AOR 10.81; 95%CI: 1.84- 19.52). CONCLUSIONS: Despite being an upper-middle-income country and having advancements in the healthcare system, a relatively lower STD rate among survivors of CA in the ED was observed in this study. There was underutilization of the EMS among patients with CA. The bystander CPR rate among patients with CA in Malaysia is also worryingly low. Aggressive community participation in cardiac arrest awareness programmes is much required. Additionally, in achieving better outcomes, implementing standardized post-resuscitation care protocols with existing resources will be a challenge for physicians managing cardiac arrest cases.

Understanding knowledge of hypertension among affected individuals in low-Income (B40) communities in Malaysia: The RESPOND study.

INTRODUCTION: Achieving optimal control of blood pressure is easier when those affected understand the risks and consequences of hypertension and the principles of management. It is particularly important in disadvantaged groups among whom blood pressure control is often poor. However, effective responses require evidence of the knowledge and beliefs of those affected. This was undertaken as part of a larger study of the therapeutic journeys followed by individuals living in B40 (bottom 40% by income) households in Malaysia, the Responsive and Equitable Health Systems-Partnership on Non- Communicable Diseases (RESPOND).This paper describes their reported knowledge of hypertension, health, and measures that can improve hypertensive control. MATERIALS AND METHODS: The communities were selected from rural and urban populations in four peninsular states (Selangor, Kelantan, Perak, and Johor). Following a multistage sampling approach, communities in each stratum were selected according to probability proportional to the size and identified based on national census data by the community and administrative registers. Households were randomly selected. Eligible individuals were those aged between 35 and 70 years old, self-reported or identified as hypertensive at screening. Informed consent was taken. A survey using validated questionnaires was conducted. RESULTS: The total number of respondents was 579. The mean age was 59.0 (95%: 58.4, 59.7) and more were women (71.5%) than men (28.5%). Regarding respondents selfreported level of hypertension knowledge, 2.9% reported having no knowledge at all, 80.1% had little knowledge, and 17.9% were very familiar. Among all respondents, 56.2% (95% CI: 50.7, 61.6) correctly answered at least four out of five objective knowledge questions.Almost all (91.5%) were aware that hypertension could cause a stroke. However, one-fifth believed it could cause cancer. Almost threequarters said that people with high blood pressure generally felt well (72.1%) and recognized that they should not stop taking their medication (70.7%). Most of the respondents knew that people should take their medication even if they feel well (73.6%). Although more than half (66.0%) of the respondents rated their health as poor. Interestingly, most did not perceive themselves as having a long-term illness (95.0%). CONCLUSION: This study provides reassurance that individuals with hypertension in disadvantaged communities in Malaysia have a relatively good understanding of hypertension. Further research should explore the challenges they face on their therapeutic journeys.

Comparative study on the evaluation of patient's satisfaction on esophagogastroduodenoscopy and colonoscopy between a pre-filled and standard hand-written consent form in Hospital Kuala Lipis.

INTRODUCTION: Informed consent is the patient's selfdetermination authorization of a choice made by themself before any intervention is performed by the health care provider. It should be a structured process that includes the disclosure of relevant procedural information, benefit, risk, and other treatment option. MATERIALS AND METHODS: An open-label static group comparison experimental design was conducted in a singlecentred study starting from April 2021 until January 2022 among patients who were going for OGDS and Colonoscopy at Hospital Kuala Lipis. The patients were stratified by 2-by- 2 randomization to either the standard hand-written prefilled consent forms. The satisfaction was assessed using Gastrointestinal Endoscopy Satisfaction Questionnaire version 2. The difference in the satisfaction was analyzed using multifactorial ANOVA. RESULTS: The percentage score of satisfaction on the endoscopic procedure using pre-filled was significantly higher than standard form consents (mean difference: 18.36 (95%CI: 14.15, 22.58)) and the effect size was large (partial ή = 0.399). The difference in percentage score of satisfaction was associated with gender (p = 0.003) and medical officers' years of working experience (p < 0.001). CONCLUSION: The pre-filled consent form fulfils the ethical and legal aspects of the informed consent process and should be used in endoscopic and other invasive procedures in Malaysia. It is suggested that a formal training, exposure to course in communication skills, breaking bad news on patient consent among junior doctors need to be taken to improve patients' satisfaction of the endoscopic procedure to make them more satisfied.

Validity and reliability of the Patient Activation Measure® (PAM®)-13 Malay version among patients with Metabolic Syndrome in primary care.

INTRODUCTION: The Patient Activation Measure (PAM) is one of the most extensively used, widely translated, and tested instruments worldwide in measuring patient activation levels in self-management. This study aimed to determine the validity and reliability of the PAM-13 Malay version among patients with Metabolic Syndrome (MetS) attending a primary care clinic. METHODS: This work is a cross-sectional validation study among patients with MetS attending a university primary care clinic in Selangor. The PAM-13 Malay version underwent a validation process and field testing. Psychometric properties were examined using principal component analysis (PCA) with varimax rotation, scree plot, Monte Carlo simulation, internal consistency, and test-retest reliability analyses. RESULTS: The content of the PAM-13 Malay version and the original version were conceptually equivalent. The questionnaire was refined after face validation by 10 patients with MetS. The refined version was then field-tested among 130 participants (response rate 89.7%). The Kaiser-Meyer-Olkin test was 0.767, and Bartlett's test of sphericity was ≤0.001, indicating sampling adequacy. Two factors were identified and labeled as (1) Passive and Building Knowledge, and (2) Taking Action and Maintaining Behavior. These labels were chosen as they were conceptually consistent with the items representing the levels of activation in PAM-13. The validated PAM-13 Malay version consisted of 13 items, framed into two domains. The overall Cronbach's α was 0.79, and the intraclass correlation coefficient was 0.45. CONCLUSIONS: The PAM-13 Malay version is valid, reliable, and fairly stable over time. This questionnaire can be used to evaluate the levels of activation among patients with MetS in primary care in Malaysia.

Adaption, translation and validation of the Diabetes Mellitus in the Offspring Questionnaire (DMOQ): The Malay version.

BACKGROUND: The Diabetes Mellitus in the Offspring Questionnaire (DMOQ) assesses the perceptions of Type 2 diabetes mellitus (T2DM) patients on the risk of their offspring developing T2DM and the possibility of intervention to reduce this risk. It has 34 items framed within seven domains. This study aimed to adapt, translate and validate the DMOQ from English into the Malay language. METHODS: This was a cross-sectional validation study among 159 T2DM patients attending a public primary care clinic in Selangor. The DMOQ English version underwent adaptation, translation, face validation and field testing to produce the Malay version. Psychometric analysis was performed using Exploratory Factor Analysis, internal consistency and testretest reliability. RESULTS: The DMOQ domains were conceptually equivalent between English and Malay language. A total of 13 items and two domains were removed during the validation process (three items during the content validation, three items due to poor factor loadings, five items as they loaded onto two domains which were not interpretable, one item as it did not fit conceptually into the factor it loaded onto and one openended question as it did not fit into the retained domains). Therefore, the final DMOQ Malay version consisted of 21- items within five domains. The Cronbach alpha was 0.714 and the intraclass-correlation coefficient was 0.868. CONCLUSION: The DMOQ Malay version is a valid and reliable tool which is consistent over time. It can be used to examine the perception of T2DM patients towards the risk of their offspring developing diabetes and possibility of intervention in Malay-speaking patients.

Polyps! Polyps! And More Polyps! - The First Case of Cronkhite-Canada Syndrome in Malaysia.

Cronkhite-Canada Syndrome (CCS) is a syndrome characterised by a constellation of signs including but not limited to onychodystrophy of the finger and toe nails, skin hyperpigmentation and alopecia. Endoscopic features showed hamartomatous polyps involving all segments of the gastrointestinal tract with the characteristic exception of being oesophageal sparring. These polyps show confirmation by the presence of eosinophils and mast cells at the lamina propria upon histological studies.

Risk factors for women attending pre-pregnancy screening in selected clinics in Selangor.

BACKGROUND: The Ministry of Health is committed to achieve Millenium Development Goal (MDG) MDG 4 and 5 by 2015 and include pre-pregnancy care as a strategy. This study evaluates the risk factors detected during the pre-pregnancy screening at selected public primary care clinics in Selangor. OBJECTIVES: The objectives of this study were to determine the proportion of women with risk factors receiving pre-pregnancy care in selected clinics in Selangor, their socio demographic features, the types of risk factors detected and their significance. METHODS: A retrospective review using secondary data was carried out from the month of March until June 2013 in four public primary care clinics in Klang and Petaling districts of Selangor. Data were obtained through non-probability sampling, using the pre-pregnancy screening form utilised in 2012, which is a standard questionnaire to determine the presence of risk factors. Women with at least one defined risk factor were considered as being at risk of an adverse obstetric outcome. Data were analysed using SPSS version 16. RESULTS: A total of 840 pre-pregnancy screening forms were collected. However only 614 (73.1%) were analysed and studied. The proportion of women with at least one risk factor was 68.8% (95% CI: 65.1, 72.5). The majority was Malays who had tertiary education and earned more than RM 1000. Most were in the reproductive age group of 18-35 years old (350, 82.9%). The mean age was 28.68 + 5.78 years. Most of the women were parous (259, 65.1%) and did not practice any form of contraception (308, 80.8%) despite having risks. The percentage of those not receiving any form of immunisation was small i.e. 9.8% but it was of importance and needed to be addressed prior to the conception. This study did not reveal any person with mental disorder or those who endured domestic abuse. Additionally, 3% (12) of them had unhealthy lifestyle habits, which include smoking, alcohol and substance abuse. Approximately one-third (212, 35.2%) of the women screened were overweight and obese, putting them at risk of developing gestational diabetes mellitus, pregnancy induced hypertension or deep vein thrombosis. The mean body mass index (BMI) for those at risk was 25.36 + 5.94 compared to 21.06 ± 1.46 for those with no risk. This study also found a small percentage of women with raised blood pressure (3.9%), abnormal physical examination (1.5%) and anaemia (14.4%), which need to be investigated and treated prior to conception. CONCLUSION: More than half of the women who attended the pre-pregnancy screening were found to have at least one risk factor.

Predominance of G to A codon 12 mutation K-ras gene in Dukes' B colorectal cancer.

INTRODUCTION: K-ras gene mutations in codons 12 and 13 are one of the earliest events in colon carcinogenesis. METHODS: DNA was extracted from 25 mg of tumour tissue (n = 70) that were taken from tumour mass and pairs with normal epithelial tissue distant from the tumour of colorectal cancer patients. Exon 1 and exon 2 of the K-ras gene were amplified. Hotspot mutations were detected using polymerase chain reaction-based single-strand conformation polymorphism method and confirmed by direct DNA sequencing analysis. RESULTS: Mutations were identified in 14 out of the 70 (20%) colorectal carcinoma tissues. Single-base transition from GGT to GAT (glycine to aspartate) in codon 12 was detected in nine samples, while three samples presented with GGC to GAC transition in codon 13. Patients with large adenoma had a 12-fold higher likelihood of K-ras mutations (odds ratios [OR] 12.31; 95% confidence intervals [CI] 1.81-83.76). Tumours located at the left colon were more likely to present with K-ras mutations (OR 4.54; 95% CI 0.96-21.54). CONCLUSION: Our study showed a high frequency of G to A transition of codon 12 mutation of the K-ras gene, with significant correlation with tumour size and tumour location.

Brain herniation in a neonate.

Brain herniation is generally thought to be unlikely to occur in newborns due to the presence of the patent fontanelles and cranial sutures. A review of the literature published from 1993 to 2008 via MEDLINE search revealed no reports on neonatal brain herniation from intracranial tumour. We report a preterm Malay male infant born via elective Caesarean section for antenatally diagnosed intracerebral tumour, which subsequently developed herniation. Cerebral magnetic resonance imaging showed features that were compatible with a large complex intracranial tumour causing mass effect and gross hydrocephalus. Tumour excision was scheduled when the infant was two weeks old. Unfortunately, on the morning of the surgery, he developed signs of brain herniation and had profuse tumour haemorrhage during the attempted excision. Histopathological examination revealed an embryonal tumour, possibly an atypical rhabdoid/teratoid tumour. This case illustrates that intracranial tumours in newborns can herniate and should therefore be closely monitored.

Prevalence of diabetes in the Malaysian National Health Morbidity Survey III 2006.

The Malaysian National Health Morbidity Survey III (NHMS III), conducted in 2006, was a cross-sectional household survey of the prevalence of chronic diseases, involving 34,539 respondents of age > or =18 years old, in all states of Malaysia. Data collection was by face-to-face interview. Those who self-professed not to be diabetics underwent finger-prick glucose test following at least 8 hours of fasting. The overall prevalence of diabetes mellitus (known and newly diagnosed) was 11.6%. The Indians had the highest prevalence of 19.9% followed by Malays 11.9% and Chinese 11.4%. The prevalence of people with known diabetes and newly diagnosed diabetes was 7.0% and 4.5% respectively. Impaired Fasting Glycaemia was found to be 4.2%. Majority (73.5%) of the patients used government healthcare facilities for their diabetic care. Usage of insulin alone or in combination was low at 7.2% of patients. Only 45.05% of known diabetics have ever had their eye examined. Amputees formed 4.3% of the patients with known diabetes while 3.4% had suffered a stroke event and 1.6% was on some form of renal replacement therapy.

Differential osteogenic activity of osteoprogenitor cells on HA and TCP/HA scaffold of tissue engineered bone.

Biomaterial, an essential component of tissue engineering, serves as a scaffold for cell attachment, proliferation, and differentiation; provides the three dimensional (3D) structure and, in some applications, the mechanical strength required for the engineered tissue. Both synthetic and naturally occurring calcium phosphate based biomaterial have been used as bone fillers or bone extenders in orthopedic and reconstructive surgeries. This study aims to evaluate two popular calcium phosphate based biomaterial i.e., hydroxyapatite (HA) and tricalcium phosphate/hydroxyapatite (TCP/HA) granules as scaffold materials in bone tissue engineering. In our strategy for constructing tissue engineered bone, human osteoprogenitor cells derived from periosteum were incorporated with human plasma-derived fibrin and seeded onto HA or TCP/HA forming 3D tissue constructs and further maintained in osteogenic medium for 4 weeks to induce osteogenic differentiation. Constructs were subsequently implanted intramuscularly in nude mice for 8 weeks after which mice were euthanized and constructs harvested for evaluation. The differential cell response to the biomaterial (HA or TCP/HA) adopted as scaffold was illustrated by the histology of undecalcified constructs and evaluation using SEM and TEM. Both HA and TCP/HA constructs showed evidence of cell proliferation, calcium deposition, and collagen bundle formation albeit lesser in the former. Our findings demonstrated that TCP/HA is superior between the two in early bone formation and hence is the scaffold material of choice in bone tissue engineering.

Pediatric auricular chondrocytes gene expression analysis in monolayer culture and engineered elastic cartilage.

OBJECTIVES: This study was aimed at regenerating autologous elastic cartilage for future use in pediatric ear reconstruction surgery. Specific attentions were to characterize pediatric auricular chondrocyte growth in a combination culture medium and to assess the possibility of elastic cartilage regeneration using human fibrin. STUDY DESIGN: Laboratory experiment using human pediatric auricular chondrocytes. METHODS: Pediatric auricular chondrocytes growth kinetics and quantitative gene expression profile in three different types of media were compared in primary culture and subsequent three passages. Large-scale culture-expanded chondrocytes from the combination medium were then mixed with human fibrin for the formation of elastic cartilage via tissue engineering technique. RESULTS: The equal mixture of Ham's F12 and Dulbecco's Modified Eagle Medium (FD) promoted the best chondrocyte growth at every passage compared to the individual media. Chondrocytes differentiation index; ratio of type II to type I collagen gene expression level, aggrecan and elastin expression gradually decreased while passaging but they were then restored in engineered tissues after implantation. The engineered cartilage was glistening white in color and firm in consistency. Histological evaluation, immunohistochemistry analysis and quantitative gene expression assessment demonstrated that the engineered cartilage resemble the features of native elastic cartilage. CONCLUSION: Pediatric auricular chondrocytes proliferate better in the combination medium (FD) and the utilization of human fibrin as a biomaterial hold promises for the regeneration of an autologous elastic cartilage for future application in ear reconstructive surgery.

Reconstruction of living bilayer human skin equivalent utilizing human fibrin as a scaffold.

Our aim of this study was to develop a new methodology for constructing a bilayer human skin equivalent to create a more clinical compliance skin graft composite for the treatment of various skin defects. We utilized human plasma derived fibrin as the scaffold for the development of a living bilayer human skin equivalent: fibrin-fibroblast and fibrin-keratinocyte (B-FF/FK SE). Skin cells from six consented patients were culture-expanded to passage 1. For B-FF/FK SE formation, human fibroblasts were embedded in human fibrin matrix and subsequently another layer of human keratinocytes in human fibrin matrix was stacked on top. The B-FF/FK SE was then transplanted to athymic mice model for 4 weeks to evaluate its regeneration and clinical performance. The in vivo B-FF/FK SE has similar properties as native human skin by histological analysis and expression of basal Keratin 14 gene in the epidermal layer and Collagen type I gene in the dermal layer. Electron microscopy analysis of in vivo B-FF/FK SE showed well-formed and continuous epidermal-dermal junction. We have successfully developed a technique to engineer living bilayer human skin equivalent using human fibrin matrix. The utilization of culture-expanded human skin cells and fibrin matrix from human blood will allow a fully autologous human skin equivalent construction.

The utility of hepatocyte paraffin 1 antibody in the immunohistological distinction of hepatocellular carcinoma from cholangiocarcinoma and metastatic carcinoma.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and its diagnosis on routine stains is usually straightforward, except in some cases where there may be difficulty in distinguishing HCCs from metastatic carcinomas (MC) and cholangiocarcinomas (CC). Hepatocyte Paraffin 1 antibody (Hep Par 1) is a new monoclonal antibody which reacts with normal and neoplastic hepatocytes, and this study aims to determine its specificity and sensitivity in distinguishing hepatocellular carcinoma (HCC) from cholangiocarcinoma (CC) and metastatic carcinomas (MC). Hep Par 1 antibody was applied to 28 cases of HCC, 22 cases of MC from varying sites and 8 CCs, and produced a strong, diffuse, granular, cytoplasmic staining of all benign hepatocytes. 23 out of 28 cases of HCC showed heterogeneously positive staining for Hep Par 1 irrespective of their degree of differentiation, while 2 out of 8 cases of cholangiocarcinoma were positive for Hep Par 1, and all 22 cases of metastatic carcinoma were negative. The sensitivity and specificity of Hep Par 1 for HCC was 82.1% and 93.3% respectively; whereby the antibody was noted to show occasional false positivity in cases of cholangiocarcinoma and non-neoplastic bowel mucosa, while its variable staining in HCC produced false negative results in some small biopsies. Thus, Hep Par 1 should be used in a panel with other antibodies to obtain useful information in distinguishing HCC from CC and MC.

Tissue engineered human articular neocartilage using serial expanded chondrocytes.

Autologous cells are usually preferred in treating damaged tissue to avoid risks of immunological rejection and transmitting infectious diseases. Since only limited amount of tissue can be obtained without causing morbidity at the donor site, in vitro expansion of isolated cell is essential in order to acquire sufficient number of cells to reconstruct neocartilage. The aim of this study was to examine whether serial expanded chondrocytes can be use to generate neocartilage in vivo.

In vitro development of autologous tissue engineered human articular neocartilage for orthopaedic surgery.

Treatment of articular cartilage lesions remains a clinical challenge. The uses of prosthetic joint replace allograft and/or autograft transplant carry a risk of complications due to infection, loosening of its component, immunological rejection and morbidity at the donor site. There has been an increasing interest in the management of cartilage damages, owing to the introduction of new therapeutic options. Tissue engineering as a method for tissue restoration begins to provide a potential alternative therapy for autologous grafts transplantations. We aimed to evaluate how well a tissue engineered neocartilage implant, consist of human articular chondrocytes cultured with the presence of autologous serum and mixed in a fresh fibrin derived from patient, would perform in subcutaneous implantation in athymic mice.

Quality evaluation analysis of bioengineered human skin.

Our objective is to determine the quality of tissue engineered human skin via immunostaining, RT-PCR and electron microscopy (SEM and TEM). Culture-expanded human keratinocytes and fibroblasts were used to construct bilayer tissue-engineered skin. The in vitro skin construct was cultured for 5 days and implanted on the dorsum of athymic mice for 30 days. Immunostaining of the in vivo skin construct appeared positive for monoclonal mouse anti-human cytokeratin, anti-human involucrin and anti-human collagen type I. RT-PCR analysis revealed loss of the expression for keratin type 1, 10 and 5 and re-expression of keratin type 14, the marker for basal keratinocytes cells in normal skin. SEM showed fibroblasts proliferating in the 5 days in vitro skin. TEM of the in vivo skin construct showed an active fibrocyte cell secreting dense collagen fibrils. We have successfully constructed bilayer tissue engineered human skin that has similar features to normal human skin.

Gene expression characteristic in human auricular cartilage tissue engineering.

This study was to assess collagen type II and collagen type I gene expression in tissue-engineered human auricular: cartilage formed via tissue engineering technique. Large-scale culture expansions were transformed into 3D in vitro construct and were implanted subcutaneously on the dorsal of athymic mice. After 8 weeks, explanted construct was processed in the same manner of native cartilage to facilitate cells for gene expression analysis. Isolated cells from in vivo construct demonstrated expression of type II collagen gene comparable to native cartilage. This study verified that tissue-engineered auricular cartilage expressed cartilage specific gene, collagen type II after in vivo maturation.

Formation of tissue-engineered human auricular cartilage via tissue engineering technique for future use in ear surgery.

To date there is no optimal approach to reconstruct an external ear. However, advances in tissue engineering technologies have indicated that in vitro autologous elastic cartilage might be of great importance in the future treatment of these patients. The aim of this study was to observe monolayer expansion of auricular cartilage and to evaluate engineered cartilage using standard histochemical study.