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Soon Hin How,1,2 Chong Kin Liam,3 Muhammad Adil Zainal Abidin,1 Harissa H Hasbullah,4,5 Lye Mun Tho,6 Gwo Fuang Ho,7 Ibtisam Muhamad Nor,5 Yong Kek Pang,3 Kean Fatt Ho,8 Muthukkumaran Thiagarajan,5 Roziana Ariffin,9 Azlina Samsudin,10 Azza Omar,11 Sin Nee Tan,2 Choo Khoon Ong,12 Sing Yang Soon,13 Mau Ern Poh3 1Kulliyyah of Medicine, International Islamic University Malaysia, Kuantan, Pahang, Malaysia; 2Hospital Tengku Ampuan Afzan, Kuantan, Pahang, Malaysia; 3Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; 4Faculty of Medicine, Universiti Teknologi Mara, Sungai Buloh, Selangor, Malaysia; 5Oncology and Radiotherapy Department, General Hospital Kuala Lumpur, Kuala Lumpur, Malaysia; 6Department of Clinical Oncology, Beacon Hospital, Petaling Jaya, Selangor, Malaysia; 7Clinical Oncology Unit, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; 8Mount Miriam Cancer Hospital, Penang, Malaysia; 9Hospital Tunku Azizah, Kuala Lumpur, Malaysia; 10Hospital Sultanah Nur Zahirah, Kuala Terengganu, Terengganu, Malaysia; 11Respiratory Unit, Medical Department, Hospital Raja Perempuan Zainab II, Kota Bharu, Kelantan, Malaysia; 12Gleneagles Hospital, Penang, Malaysia; 13Sarawak Heart Centre, Kuching, Sarawak, MalaysiaCorrespondence: Mau Ern Poh, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, 50603, Malaysia, Tel +60 3 7949 4422, Email ernestpoh@gmail.comBackground: Although first- and second-generation EGFR TKIs are considered first-line treatment in EGFRm+ NSCLC, most patients develop resistance and progress, commonly, EGFR T790M mutation. The third-generation EGFR-TKI has demonstrated efficacy in patients with progressive disease harboring the T790M mutation and in the first-line setting, bypassing this mode of resistance. The primary objectives of this study are to describe the proportion of EGFRm+ NSCLC patients treated with first-, second- and third-generation EGFR TKIs, and cytotoxic chemotherapy in the first-line setting, and the time on treatment for each category. Secondary objectives are to determine the dropout rate, the rates for T790M mutation testing at disease progression and the type of subsequent treatment.Methods: This multicenter retrospective study utilized data from the Malaysian Lung Cancer Registry that actively registers all lung cancer patients ≥ 18 years, with primary lung cancer confirmed histologically or cytologically. All patients diagnosed with advanced stages (ie stages IIIB, IIIC and IV) EGFRm+ NSCLC from 1st of January 2015 to 31st December 2019 were included.Results: Of 406 patients with EGFRm+ NCSLC, 351 were treated. Types of first-line treatment were as follows: EGFR-TKIs (first generation – 54.1%, second generation – 25.6% and third-generation – 12.5%) and chemotherapy (7.7%). The median time of treatment for each generation of EGFR-TKI was 12 months, 12 months and 24 months, and 2 months for chemotherapy. The dropout rate was 28.7% (n = 101). Nearly half (49.4%) of patients who were on first- or second-generation EGFR-TKI had further genetic testing via liquid or tissue biopsies upon disease progression. About 24.9% of those who developed disease progression after first- or second-generation EGFR TKI were started on a third-generation EGFR TKI.Conclusion: In the real-world, the management of EGFRm+ advanced NSCLC patients in an Asian cost-restrictive setting may adversely affect the choice of first-line therapy, time on each line of treatment and subsequently the overall survival of patients.Keywords: tyrosine kinase inhibitors, lung cancer, time on treatment, overall survival

Mau Ern Poh,1 Soon Hin How,2,3 Gwo Fuang Ho,4 Yong Kek Pang,1 Harissa H Hasbullah,5,6 Lye Mun Tho,7 Ibtisam Muhamad Nor,6 Bee Chiu Lim,3 Kean Fatt Ho,8 Muthukkumaran Thiagarajan,6 Azlina Samsudin,9 Azza Omar,10 Choo Khoon Ong,11 Sing Yang Soon,12 Justin Yu Kuan Tan,9 Muhammad Adil Zainal Abidin2 1Department of Medicine, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia; 2Kulliyyah of Medicine, International Islamic University Malaysia, Kuantan, Pahang, Malaysia; 3Hospital Tengku Ampuan Afzan, Kuantan, Pahang, Malaysia; 4Clinical Oncology Unit, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia; 5Faculty of Medicine, Universiti Teknologi Mara, Sungai Buloh, Selangor, Malaysia; 6Oncology and Radiotherapy Department, General Hospital Kuala Lumpur, Kuala Lumpur, Malaysia; 7Department of Clinical Oncology, Beacon Hospital, Petaling Jaya, Selangor, Malaysia; 8Mount Miriam Cancer Hospital, Tanjong Bungah, Penang, Malaysia; 9Hospital Sultanah Nur Zahirah, Kuala Terengganu, Terengganu, Malaysia; 10Respiratory Unit, Medical Department, Hospital Raja Perempuan Zainab II, Kota Bharu, Kelantan, Malaysia; 11Gleneagles Penang, George Town, Penang, Malaysia; 12Sarawak Heart Centre, Kuching, Sarawak, MalaysiaCorrespondence: Mau Ern Poh, Department of Medicine, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, 50603, Malaysia, Tel +60-3-7841-4000, Email ernestpoh@gmail.comPurpose: Anaplastic lymphoma kinase (ALK) inhibitors are associated with good overall survival (OS) for ALK-positive metastatic non–small cell lung cancer (NSCLC). However, these treatments can be unavailable or limited by financial constraints in developing countries. Using data from a nationwide lung cancer registry, the present study aimed to identify treatment patterns and clinical outcomes of ALK-positive NSCLC in Malaysia.Methods: This retrospective study examined data of patients with ALK-positive NSCLC from 18 major hospitals (public, private, or university teaching hospitals) throughout Malaysia between January 1, 2015 and December 31, 2020 from the National Cardiovascular and Thoracic Surgical Database (NCTSD). Data on baseline characteristics, treatments, radiological findings, and pathological findings were collected. Overall survival (OS) and time on treatment (TOT) were calculated using the Kaplan–Meier method.Results: There were 1581 NSCLC patients in the NCTSD. Based on ALK gene-rearrangement test results, only 65 patients (4.1%) had ALK-positive advanced NSCLC. Of these 65 patients, 59 received standard-of-care treatment and were included in the analysis. Crizotinib was the most commonly prescribed ALK inhibitor, followed by alectinib and ceritinib. Patients on ALK inhibitors had better median OS (62 months for first-generation inhibitors, not reached at time of analysis for second-generation inhibitors) compared to chemotherapy (27 months), but this was not statistically significant (P=0.835) due to sample-size limitations. Patients who received ALK inhibitors as first-line therapy had significantly longer TOT (median of 11 months for first-generation inhibitors, not reached for second-generation inhibitors at the time of analysis) compared to chemotherapy (median of 2 months; P< 0.01).Conclusion: Patients on ALK inhibitors had longer median OS and significantly longer TOT compared to chemotherapy, suggesting long-term benefit.Keywords: ALK inhibitors, chemotherapy, ALK-positive, NSCLC

Cancer is highly adaptable and is constantly evolving against current targeted therapies such as tyrosine kinase inhibitors. Despite advances in recent decades, the emergence of drug resistance to tyrosine kinase inhibitors constantly hampers therapeutic efficacy of cancer treatment. Continuous therapy versus intermittent clinical regimen has been a debate in drug administration of cancer patients. An ecologically-inspired shift in cancer treatment known as 'adaptive therapy' intends to improve the drug administration of drugs to cancer patients that can delay emergence of drug resistance.We discuss improved understanding of the concept of drug resistance, the basis of continuous therapy, intermittent clinical regimens, and adaptive therapy will be reviewed. In addition, we discuss how adaptive therapy provides guidance for future cancer treatment.The current understanding of drug resistance in cancer leads to poor prognosis and limited treatment options in patients. Fighting drug resistance mutants is constantly followed by new forms of resistance. In most reported cases, continuous therapy leads to drug resistance and an intermittent clinical regimen vaguely delays it. However, adaptive therapy, conceptually, exploits multiple parameters that can suppress the growth of drug resistance and provides safe treatment for cancer patients in the future.

Introduction Immunotherapy has been recognized as the standard of care in addition to chemotherapy in the treatment of advanced non-small cell lung cancer. Most immunotherapy trials, however, exclude patients with autoimmune disease owing to concerns of disease exacerbation. Case report We report a case of a patient with advanced non-small cell lung cancer and underlying active psoriasis who experienced a remarkable response, without developing psoriasis flares, following treatment with a single dose of atezolizumab and first-line chemotherapy. Management and outcome The patient remained asymptomatic 10 months since treatment discontinuation, without disease progression, despite having received only a single dose of atezolizumab and six cycles of chemotherapy. Discussion Little is known about the optimum duration required to achieve a durable response with immunotherapy. Patients with autoimmune disease are commonly excluded from immunotherapy trials owing to a higher risk of autoimmune disease flares or immune-related adverse events. The remarkable outcome observed in this case offers some insights into the possible durable response with limited doses of immunotherapy and a safer approach for administering immunotherapy in patients with autoimmune disease. Initiating chemotherapy to induce remission in active autoimmune disease prior to administering immunotherapy could potentially be an ideal approach that facilitates the use of immunotherapy in this patient population.

Coronavirus disease 2019 (COVID-19) is highly contagious in symptomatic patients as it is thought to be transmitted through respiratory droplets. However, it is debatable whether asymptomatic COVID-19 patients are contagious due to lack of data. From 1st March to 15th April 2020, a total of 247 COVID-19 cases were admitted to Tengku Ampuan Afzan Hospital and 1010 close contacts were identified. We studied the epidemiological and clinical outcomes in asymptomatic subjects, as well as estimated the metrics of disease transmission between asymptomatic, symptomatic, and pneumonia subjects. From a total of 125 asymptomatic subjects, majority (n=116, 92.8%) remained asymptomatic upon discharge. Only 9 (7.2%) subjects developed mild symptoms after admission. Seven subjects had abnormal chest radiograph suggestive of pneumonia, and 22 subjects (17.6%) were found to have mild liver impairment. None of the asymptomatic subjects required oxygen support, inotropic support or ICU care during admission. Fifteen second generation COVID-19 cases were found transmitted from the asymptomatic group, with an attack rate of 3.9%, which was statistically significantly lower compared to the symptomatic (7.6%) or pneumonia groups (25.7%, p

Malaysia is a Southeast Asian country occupying parts of the Malay Peninsula and the island of Borneo. The population of Malaysia (just over 30 million) is multi-ethnic; approximately half the population is ethnically Malay, with large minorities of Chinese, Indians, and indigenous peoples. Approximately 70% of the population is urban (Fig. 1).1 Life expectancy of Malaysians at birth is 74.9 years.2 Health care services in Malaysia are dichotomous between systems of public and private health care. Most patients (w65%) in Malaysia seek health care services in public facilities.3 However, the main drawback of public health care is a shortage of doctors and specialists in public hospitals.3 Public health care in Malaysia is heavily subsidized and offers services at a fraction of the cost of treatment in the private sector. Patients receiving treatment in private facilities, on the other hand, are usually covered by private health care insurance or make out-of-pocket payments.3 There is currently no universal-access national health care scheme in Malaysia.3 The total expenditure on health was 4.24% of the gross domestic product in 2017.4

In the recent years, increased understanding of the molecular profiles of non-small cell lung cancer (NSCLC) has allowed for targeted treatment of actionable genetic mutations. The management of NSCLC now requires multiple molecular tests to guide the treatment strategy. In the light of this, there is a need to establish a molecular testing consensus statement for advanced NSCLC patients in Malaysia. This Malaysian consensus statement was developed by a panel of experts, chaired by a pathologist and composed of three other pathologists, four respiratory physicians and three oncologists. It reflects currently available scientific data and adaptations of recommendations from international guidelines to the local landscape. Expert recommendations on different aspects of molecular testing agreed upon by the panel are provided as structured discussions. These recommendations address the appropriate patients and samples to be tested, as well as when and how these tests should be performed. The algorithms for molecular testing in metastatic NSCLC, in the first line setting and upon disease progression beyond first line therapy, were developed.

INTRODUCTION: In the current climate of urgency in identifying biomarkers for the development of rapid diagnostic kits, the use of urine samples to diagnose acute melioidosis was evaluated, comparing urine samples from Burkholderia pseudomallei culture-positive and culture-negative patients, and comparing pneumonic and septicemic melioidosis. MATERIAL AND METHODS: Eleven urine samples from clinically suspected melioidosis patients from a tertiary referral center, Hospital Tengku Ampuan Afzan, Pahang was used. An in-solution method for the detection of bacterial proteins using liquid chromatography-mass spectrometry quadrupole time-of-flight (LCMS QTOF) was used. RESULTS: Three bacterial proteins were consistently detected among all the culture[1]positive and PCR-positive cases tested, namely SDR family NAD(P)-dependent oxidoreductase protein (32kDa), 3-hydroxyacyl-CoA dehydrogenase Burkholderia sp. (32kDa), and NAD(P)-dependent dehydrogenase (short-subunit alcohol dehydrogenase family) Burkholderia sp. (33kDa). CONCLUSIONS: Short-chain dehydrogenase (SDO) proteins could potentially be a urine biomarker candidate as these have shown to aid in the ability of Burkholderia spp. to invade host cells as this action is important for the initial intracellular survival of the organism.

Background First-line pembrolizumab monotherapy improves overall and progression-free survival in patients with untreated metastatic non-small-cell lung cancer with a programmed death ligand 1 (PD-L1) tumour proportion score (TPS) of 50% or greater. We investigated overall survival after treatment with pembrolizumab monotherapy in patients with a PD-L1 TPS of 1% or greater. Methods This randomised, open-label, phase 3 study was done in 213 medical centres in 32 countries. Eligible patients were adults (≥18 years) with previously untreated locally advanced or metastatic non-small-cell lung cancer without a sensitising EGFR mutation or ALK translocation and with an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1, life expectancy 3 months or longer, and a PD-L1 TPS of 1% or greater. Randomisation was computer generated, accessed via an interactive voice-response and integrated web-response system, and stratified by region of enrolment (east Asia vs rest of world), ECOG performance status score (0 vs 1), histology (squamous vs non-squamous), and PD-L1 TPS (≥50% vs 1-49%). Enrolled patients were randomly assigned 1:1 in blocks of four per stratum to receive pembrolizumab 200 mg every 3 weeks for up to 35 cycles or the investigator's choice of platinum-based chemotherapy for four to six cycles. Primary endpoints were overall survival in patients with a TPS of 50% or greater, 20% or greater, and 1% or greater (one-sided significance thresholds, p=0·0122, p=0·0120, and p=0·0124, respectively) in the intention-to-treat population, assessed sequentially if the previous findings were significant. This study is registered at ClinicalTrials.gov, number NCT02220894. Findings From Dec 19, 2014, to March 6, 2017, 1274 patients (902 men, 372 women, median age 63 years [IQR 57-69]) with a PD-L1 TPS of 1% or greater were allocated to pembrolizumab (n=637) or chemotherapy (n=637) and included in the intention-to-treat population. 599 (47%) had a TPS of 50% or greater and 818 patients (64%) had a TPS of 20% or greater. As of Feb 26, 2018, median follow-up was 12·8 months. Overall survival was significantly longer in the pembrolizumab group than in the chemotherapy group in all three TPS populations (≥50% hazard ratio 0·69, 95% CI 0·56-0·85, p=0·0003; ≥20% 0·77, 0·64-0·92, p=0·0020, and ≥1% 0·81, 0·71-0·93, p=0·0018). The median surival values by TPS population were 20·0 months (95% CI 15·4-24·9) for pembrolizumab versus 12·2 months (10·4-14·2) for chemotherapy, 17·7 months (15·3-22·1) versus 13·0 months (11·6-15·3), and 16·7 months (13·9-19·7) versus 12·1 months (11·3-13·3), respectively. Treatment-related adverse events of grade 3 or worse occurred in 113 (18%) of 636 treated patients in the pembrolizumab group and in 252 (41%) of 615 in the chemotherapy group and led to death in 13 (2%) and 14 (2%) patients, respectively. Interpretation The benefit-to-risk profile suggests that pembrolizumab monotherapy can be extended as first-line therapy to patients with locally advanced or metastatic non-small-cell lung cancer without sensitising EGFR or ALK alterations and with low PD-L1 TPS. Funding Merck Sharp & Dohme.

Background: Depression is a recognized complication of lung cancer underreported in developing countries such as Malaysia. Treating and identifying depression in cancer patients increases survival and quality of life. Our objectives are to study prevalence of depressive symptoms in newly diagnosed lung carcinoma, and examine the relationship of depressive symptoms with other influencing risk factors. Methods: A 2-year, cross sectional study February 2015–February 2017, was conducted at Hospital Tengku Ampuan Afzan, and Penang General Hospital. One hundred and three patients with newly diagnosed, biopsy confirmed primary lung carcinoma were recruited. Self-rated patient’s identification sheet, validated Center for Epidemiologic Studies Depression (CES-D), and Dukes University Religion Index score from three different main languages were used. Results: Prevalence of current depressive symptoms (CES-D total score ≥16) is 37.9%. The result suggests prevalence of those at high risk of moderate to major depression, may need treatment. Multivariate analysis reveals those with good Eastern Cooperation Oncology Group factor (η2=0.24, p

Introduction: Melioidosis is endemic in Malaysia and an important cause of sepsis. Current gold standard for diagnosis is by culture method,but its long procedure will delay the treatment leading to hospital-related mortality.Thus,a good rapid test is needed to reduce its mortality burden. Recently, Active Melioidosis Detect (AMD) have been shown to be useful. Objectives: (1)To measure the sensitivity and specificity of AMD. (2)To study the sensitivity and specificity of early morning urine AMD compared to spot urine AMD. Materials and method: A prospective crosssectional study of clinically suspected melioidosis patients in HTAA and HSNZ from April until December 2018. Blood and urine samples were tested with AMD. Test results were analysed for sensitivity, specificity,positive predictive value and negative predictive value. Results: A total of 89 patients were included in this study.The mean age is 52 years old, and 56.3% were male gender.64% of patients have diabetes mellitus.11 patients have positive blood culture for Bukholderia pseudomallei, 4 of them were tested positive for AMD.3 of them presented with septic shock (3.4%), however none died.The sensitivity of the AMD was 36.4% ([95% CI 12.4 to 68.4]) and the specificity was 66.7% ( [95% CI 46.0 to 82.8]) in all samples, with positive predictive value of 30.7% and negative predictive value of 72%.Blood samples have lower sensitivity of 9.1% ([95% CI 4.8 to 42.9]) with high specificity of 100% ([95% CI 84.5 to 100]). Urine spot samples have higher sensitivity compared to serum and morning urine, with 36.4% ([95%CI 12.4 to 68.4]) and specificity of 88.9% ([95% CI 69.7 to 97.1]). Conclusion: From this pilot study, this test requires further evaluation before incorporating as point of care assay.

Background This study aimed to evaluate the efficacy, side-effects and resistance mechanisms of first-line afatinib in a real-world setting. Methods This is a multicenter observational study of first-line afatinib in Malaysian patients with epidermal growth factor receptor (EGFR)-mutant advanced non-small cell lung cancer (NSCLC). Patients’ demographic, clinical and treatment data, as well as resistance mechanisms to afatinib were retrospectively captured. The statistical methods included Chi-squared test and independent t-test for variables, Kaplan-Meier curve and log-rank test for survival, and Cox regression model for multivariate analysis. Results Eighty-five patients on first-line afatinib from 1st October 2014 to 30th April 2018 were eligible for the study. EGFR mutations detected in tumors included exon 19 deletion in 80.0%, exon 21 L858R point mutation in 12.9%, and rare or complex EGFR mutations in 7.1% of patients. Among these patients, 18.8% had Eastern Cooperative Oncology Group performance status of 2–4, 29.4% had symptomatic brain metastases and 17.6% had abnormal organ function. Afatinib 40 mg or 30 mg once daily were the most common starting and maintenance doses. Only one-tenth of patients experienced severe side-effects with none having grade 4 toxicities. The objective response rate was 76.5% while the disease control rate was 95.3%. At the time of analysis, 56 (65.9%) patients had progression of disease (PD) with a median progression-free survival (mPFS) of 14.2 months (95% CI, 11.85–16.55 months). Only 12.5% of the progressed patients developed new symptomatic brain metastases. The overall survival (OS) data was not mature. Thirty-three (38.8%) patients had died with a median OS of 28.9 months (95% CI, 19.82–37.99 months). The median follow-up period for the survivors was 20.0 months (95% CI, 17.49–22.51 months). Of patients with PD while on afatinib, 55.3% were investigated for resistance mechanisms with exon 20 T790 M mutation detected in 42.0% of them. Conclusions Afatinib is an effective first-line treatment for patients with EGFR-mutant advanced NSCLC with a good response rate and long survival, even in patients with unfavorable clinical characteristics. The side-effects of afatinib were manageable and T790 M mutation was the most common resistance mechanism causing treatment failure.

Background : Afatinib is an irreversible, second-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) that has been shown to be more potent than platinum doublet chemotherapy as well as the firstgeneration EGFR-TKI in patients with EGFR-mutant advanced non-small cell lung cancer (NSCLC). This study aimed to evaluate the efficacy, side-effects and resistance mechanisms of first-line afatinib in a real-world setting. Method : This is a multicentre observational study of Malaysian patients with EGFR-mutant advanced NSCLC started on first-line afatinib from 1st October 2014 to 30th April 2018. Results : The demographic and clinical characteristics of 85 patients who met the study criteria are shown in Table 1. EGFR mutations harboured by the tumours included exon 19 deletion in 80.0%, exon 21 L858R point mutation in 12.9%, and rare or complex EGFR mutations in 7.1%. Of the patients. 18.8% of the patients had an ECOG performance status of 2-4, 29.4% had baseline symptomatic brain metastases and 17.6% had abnormal organ function. Table 2 shows the starting dose, dose adjustment and optimal dose of afatinib. Afatinib 40 mg or 30 mg once daily were the most common starting and maintenance doses. Treatment outcome (Tables 3, 4 and 5; Figures 1 and 2) Response to afatinib The objective response rate (ORR) was 76.5% while the disease control rate (DCR) was 95.3% on first-line afatinib (Table 3). Two (2.4%) patients had complete response. Patients without baseline brain metastases had a significantly higher ORR than those with baseline brain metastases (Table 4). There was a trend for patients in whom the dose of afatinib was reduced to experience higher ORR than those without dose adjustment. On multivariate subgroup analyses involving covariates shown in Table 4, patients without symptomatic brain metastases had significantly higher ORR than that of those with symptomatic brain metastases (81.7% versus 56.0%; OR, 4.51; 95% CI, 1.45–14.00; p = 0.009); while patients with afatinib dose reduction had significantly higher ORR than that of those without dose adjustment (88.5% versus 65.3%; OR, 5.53; 95% CI, 1.32–23.24; p = 0.019). Progression-free survival 56 (65.9%) patients had PD at the time of analysis with a mPFS of 14.2 (95% CI, 11.85 – 16.55) months (Figure 1) Conclusion : Afatinib is an effective first-line treatment for patients with EGFR-mutant advanced NSCLC with good response and disease control rates as well as long PFS even in patients with unfavourable clinical characteristics. The side-effects of afatinib were manageable and acquired T790M mutation was the acquired resistance mechanism in 42% of patients with PD who underwent rebiopsy

In past decades, we have seen several epidemics of respiratory infections from newly emerging viruses, most of which originated in animals. These emerging infections, including severe acute respiratory syndrome coronavirus (SARS‐CoV), Middle East respiratory syndrome coronavirus (MERS‐CoV) and the pandemic influenza A(H1N1) and avian influenza (AI) viruses, have seriously threatened global health and the economy. In particular, MERS‐CoV and AI A(H7N9) are still causing infections in several areas, and some clustering of cases of A(H5N1) and A(H7N9) may imply future possible pandemics. Additionally, given the inappropriate use of antibiotics and international travel, the spread of carbapenem‐resistant Gram‐negative bacteria is also a significant concern. These infections with epidemic or pandemic potential present a persistent threat to public health and a huge burden on healthcare services in the Asia‐Pacific region. Therefore, to enable efficient infection prevention and control, more effective international surveillance and collaboration systems, in the context of the ‘One Health’ approach, are necessary.

Malaysia is an endemic hot spot for melioidosis; however, a comprehensive picture of the burden of disease, clinical presentations, and challenges faced in diagnosis and treatment of melioidosis is not available. This review provides a nonexhaustive overview of epidemiological data, clinical studies, risk factors, and mortality rates from available literature and case reports. Clinical patterns of melioidosis are generally consistent with those from South and Southeast Asia in terms of common primary presentations with diabetes as a major risk factor. Early diagnosis and appropriate management of Malaysian patients is a key limiting factor, which needs to be addressed to reduce serious complications and high mortality and recurrence rates. Promoting awareness among the local healthcare personnel is crucial to improving diagnostics and early treatment, as well as educating the Malaysian public on disease symptoms and risk factors. A further matter of urgency is the need to make this a notifiable disease and the establishment of a national melioidosis registry. We also highlight local studies on the causative agent, Burkholderia pseudomallei, with regards to bacteriology and identification of virulence factors as well as findings from host–pathogen interaction studies. Collectively, these studies have uncovered new correlations and insights for further understanding of the disease.

Aim Data on lung cancer survival are lacking in developing countries. Our objectives were to describe the survival of our lung cancer patients and to determine independent prognostic factors affecting survival. Method All patients diagnosed with lung cancer from August 2007 to August 2010 were recruited from a single referral hospital of the state of Pahang, Malaysia. Detailed demographic data, ECOG (Eastern Cooperation Oncology Group) performance status, stage of disease and treatment were recorded. The date of histology or cytology confirmation was used as the date of entry. Survival time was calculated from the date of entry to the date of death. Results One hundred forty-nine patients were included for survival analysis. The median age was 62 years and patients were predominantly males (78%) and smokers (78%). The majority had non-small cell lung cancer (NSCLC) (94%); only six patients (4%) had small cell lung cancer. All patients presented with stage 3 or stage 4 disease. Overall median survival was 18 weeks. “No definitive treatment” and “ECOG 3–4” were the significant independent predictors of death, with the hazard ratios of 2.1 (95% confidence interval [CI] 1.4, 3.0) and 1.6 (95% CI 1.1, 2.3) times, respectively. Among NSCLC patients on treatment, 1- and 2-year survival rates were 27% and 15%, respectively. Conclusion The majority of lung cancer patients in Pahang presented with advanced disease. No definitive treatment and ECOG 3–4 were independent poor prognostic factors.

Introduction: This study was carried out to determine the prevalence, patient′s characteristic and reasons for defaulting follow-up and treatment among patients with lung cancer. Methods: Patients with histologically confirmed lung cancer were recruited. Patient′s detailed demographic data, occupation, socioeconomic status, and educational level of both the patients and their children were recorded. Defaulters were classified as either intermittent or persistent defaulters. By using Chi-square test, defaulter status was compared with various demographic and disease characteristic factors. The reasons for default were determined. Results: Ninety five patients were recruited. Among them, 81.1% patients were males; 66.3% were Malays. The mean age (SD) was 60 ± 10.5 years. About 46.3% of the patients had Eastern Cooperation Oncology Group (ECOG) functional status 0/1 and 96.8% of the patients presented with advanced stage (Stage 3b or 4). Overall, 20 patients (21.1%) were defaulters (35.0% intermittent defaulters; 65.0% persistent defaulters). Among the intermittent defaulters, 8 patients defaulted once and one patient defaulted 3 times. Among the 20 defaulters, only 2 (10%) patients turned up for the second follow-up appointment after telephone reminder. Two main reasons for default were ′too ill to come′ (38.5.5%) and logistic difficulties (23.1%). No correlation was found between patient education, children education, income, ECOG status, stage of the disease, race, and gender with the defaulter rate. Conclusion: Defaulter rate among lung cancer patients was 21.1%. Children education level is the only significant factor associated with the defaulter rate.

Introduction: Various initiatives and medications have been introduced to achieve better control of bronchial asthma. However total control according to Global Initiative for Asthma (GINA) remains elusive even at tertiary referral hospitals. Our study is to determine the level of asthma control (according to GINA 2009), Asthma Control Test (ACT) scores and the types of medications used among patients with bronchial asthma in a large tertiary hospital. Methods: A cross-sectional study of all patients with bronchial asthma who attended the Chest Clinic at Hospital Tengku Ampuan Afzan (HTAA) from 2009 to 2011. Patient demographics, self-administered ACT scores, GINA-defined level of asthma control and medications were documented. Results: 208 patients were recruited. There were 23.2%, 46.3% and 30.5% of patients with controlled, partly controlled and uncontrolled asthma respectively. The median ACT scores was 19 [inter quartile range (IQR) 6]. The most frequently used preventer therapy was inhaled long-acting β-agonist/corticosteroids (LABA/ICS) fixed-dose combination (61.7%), and 9.6% were not on preventer therapy. 75% of patients with controlled asthma were on LABA/ICS compared to 58.5% of the partly controlled and uncontrolled groups (p=0.039). Conclusion: The majority of the asthmatic patients attending the Chest Clinic at HTAA did not have GINA-defined controlled asthma. Patients with higher ACT scores had better control of asthma. There were more patients with controlled asthma who were on LABA/ ICS combination.

Massive haemoptysis can occur in lung abscess. Massive haemoptysis itself may be life threatening due to asphyxiation or respiratory failure secondary to acute large airway obstruction by blood clots. Prompt removal of the obstructing blood clots save life. We describe a case of lung abscess causing massive haemoptysis resulting in acute airway obstruction which required rigid bronchoscopy to remove the huge blood clot.

The phase III, randomized, open-label ENSURE study (NCT01342965) evaluated first-line erlotinib versus gemcitabine/cisplatin (GP) in patients from China, Malaysia and the Philippines with epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC).Patients ≥18 years old with histologically/cytologically confirmed stage IIIB/IV EGFR mutation-positive NSCLC and Eastern Cooperative Oncology Group performance status 0-2 were randomized 1:1 to receive erlotinib (oral; 150 mg once daily until progression/unacceptable toxicity) or GP [G 1250 mg/m(2) i.v. days 1 and 8 (3-weekly cycle); P 75 mg/m(2) i.v. day 1, (3-weekly cycle) for up to four cycles]. Primary end point: investigator-assessed progression-free survival (PFS). Other end points include objective response rate (ORR), overall survival (OS), and safety.A total of 217 patients were randomized: 110 to erlotinib and 107 to GP. Investigator-assessed median PFS was 11.0 months versus 5.5 months, erlotinib versus GP, respectively [hazard ratio (HR), 0.34, 95% confidence interval (CI) 0.22-0.51; log-rank P0.0001]. Independent Review Committee-assessed median PFS was consistent (HR, 0.42). Median OS was 26.3 versus 25.5 months, erlotinib versus GP, respectively (HR, 0.91, 95% CI 0.63-1.31; log-rank P = .607). ORR was 62.7% for erlotinib and 33.6% for GP. Treatment-related serious adverse events (AEs) occurred in 2.7% versus 10.6% of erlotinib and GP patients, respectively. The most common grade ≥3 AEs were rash (6.4%) with erlotinib, and neutropenia (25.0%), leukopenia (14.4%), and anemia (12.5%) with GP.These analyses demonstrate that first-line erlotinib provides a statistically significant improvement in PFS versus GP in Asian patients with EGFR mutation-positive NSCLC (NCT01342965).

Lymphangioleiomyomatosis (LAM) is a rare disease. The reported prevalence is around one per million in the West but the exact prevalence in Asia is unknown. It affects primarily young women of reproductive age, with a mean age of onset at 34 years. The disease is characterised by an abnormal proliferation of smooth muscle-like cells that grow over a course of time to obstruct airways, lymphatic andblood vessels. We report a case of LAM in a young woman who presented with a spontaneous pneumothorax. Computed tomography scan of the thorax and abdomen showed homogenous thin-walled cystic lesions with normal intervening lung parenchyma and multiple lesions in her kidneys with Hounsfield units similar to that of fat.

Background: Mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) in nonsmall cell lung cancer (NSCLC) are predictive of response to EGFR-targeted therapy in advanced stages of disease. This study aimed to determine the frequency of EGFR mutations in NSCLCs and to correlate their presence with clinical characteristics in multiethnic Malaysian patients. Materials and Methods: In this prospective study, EGFR mutations in exons 18, 19, 20 and 21 in formalin-fixed paraffin-embedded biopsy specimens of consecutive NSCLC patients were asessed by real-time polymerase chain reaction. Results: EGFR mutations were detected in NSCLCs from 55 (36.4%) of a total of 151 patients, being significantly more common in females (62.5%) than in males (17.2%) [odds ratio (OR), 8.00; 95% confidence interval (CI), 3.77-16.98; p

Data on lung cancer survival are lacking in developing countries. Our objectives were to describe the survival of our lung cancer patients and to determine independent prognostic factors affecting survival.All patients diagnosed with lung cancer from August 2007 to August 2010 were recruited from a single referral hospital of the state of Pahang, Malaysia. Detailed demographic data, ECOG (Eastern Cooperation Oncology Group) performance status, stage of disease and treatment were recorded. The date of histology or cytology confirmation was used as the date of entry. Survival time was calculated from the date of entry to the date of death.One hundred forty-nine patients were included for survival analysis. The median age was 62 years and patients were predominantly males (78%) and smokers (78%). The majority had non-small cell lung cancer (NSCLC) (94%); only six patients (4%) had small cell lung cancer. All patients presented with stage 3 or stage 4 disease. Overall median survival was 18 weeks. "No definitive treatment" and "ECOG 3-4" were the significant independent predictors of death, with the hazard ratios of 2.1 (95% confidence interval [CI] 1.4, 3.0) and 1.6 (95% CI 1.1, 2.3) times, respectively. Among NSCLC patients on treatment, 1- and 2-year survival rates were 27% and 15%, respectively.The majority of lung cancer patients in Pahang presented with advanced disease. No definitive treatment and ECOG 3-4 were independent poor prognostic factors.

Intrapulmonary bronchogenic cyst is a rare congenital lesion originating from abnormal budding of the embryonic foregut. It is less common than mediastinal bronchogenic cyst. We describe a case of intrapulmonary bronchogenic cyst and discuss the treatment of this condition.

This case report describes a rigid bronchoscopy-assisted placement of a silicone airway Y-stent in a patient who developed tracheobronchomalacia following repeated dilatations for post-tuberculous airway stenosis. This is the first report of an airway Y-stent insertion in Malaysia.

Chylothorax is suspected when milky white turbid fluid is obtained from thoracocentesis. Conservative management usually involves intercostal tube drainage, dietary restriction, and total parenteral nutrition. Surgery is indicated when conservative management fails. We describe a young woman with idiopathic chylothorax who failed conservative therapy but refused surgery. We instilled intrapleural streptokinase, which improved her condition.

We describe a patient with empyema thoracis that had eroded through the apical chest wall to the supraclavicular fossa and lung parenchyma, ultimately leading to a bronchopleural fistula manifesting as lobulated, localized subcutaneous emphysematous swellings over the chest wall and supraclavicular fossa. This is a rarely reported phenomenon and the reason why the lobulated subcutaneous emphysematous swellings remained localized is unknown.

A 22-year-old Indonesian oil palm plantation worker presented with a 1-week history of fever associated with severe headache, pain in the right upper abdomen and seizure a day earlier. He had a cough with expectoration but no bowel symptom. There was no history of injury reported before the present illness. The patient was febrile, dehydrated and drowsy on admission, with Glasgow coma score of 14/15. His blood pressure and pulse rate were 100/60 mmHg and 96/min respectively. Lung examination showed right-sided crackle, with no neck stiffness or any signs suggestive of immunocompromized state. Abdominal examination revealed tender hepatomegaly of 10 cm in length. The initial chest radiograph showed opacity in the right middle lobe. Total white cells count was 11.1 × 109/litre. Platelet count was 100 × 109/litre with normal haemoglobin. Random blood glucose and renal profile were normal. Coagulation profiles were deranged with international normalization ratio of 4.5 and activated partial thromboplastin time ratio of 3.4. Liver function tests revealed alanine aminotransferase of 446 U/litre, aspartate aminotrasferase of 253 U/litre and albumin of 30.5 g/litre. The patient was given empherical intravenous ceftriaxone, metronidazole and acyclovir for possibility of meningo-encephalitis. Despite fluid resuscitation, he remained hypotensive and required inotropic support. On the second day, multiple pustular skin lesions (Figure 1) were noted on the patient's trunk, upper and lower limbs. Aspiration of the pustules revealed pus that contained gram-negative bacilli. Lumbar puncture was done and cerebrospinal fluid was normal. He required multiple platelet concentrates and plasma transfusions for disseminated intravascular coagulation. Abdomen ultrasound revealed multiple liver abscesses (Figure 2). He was intubated and ventilated for worsening respiratory failure. Samples of pus and blood cultures were positive for Chromobacterium violaceum. Intravenous imipenem 500 mg four times daily and ciprofloxacin 400 mg twice daily were administered. However, he died the same evening.

A 51-year-old Chinese woman without any significant past medical history was admitted in October 2003 for cough of 18 months' duration. There was minimal clear expectoration and no haemoptysis. She denied any shortness of breath, anorexia and weight loss. There were no symptoms of rhinitis, gastrooesophageal reflux or choking. She was afebrile with good dental hygiene. There were fine crepitations and localized rhonchi over the right lung base. Despite short courses of antibiotics from her general practitioner there was no improvement in her symptoms. The initial chest radiograph showed opacity in the right middle lobe with a subtle air-bronchogram. Blood investigations revealed an erythrocyte sedimentation rate of 113 mm/hr, and fasting and random blood glucose levels of 10.4 mmol/litre and 13.4 mmol/litre respectively. The full blood count, renal and liver function tests were within normal limits. Contrast enhanced chest computed tomogram (Figure 1) revealed a right middle lobe consolidation with air-bronchogram. A few pre-tracheal and subcarinal lymph nodes of less than 1 cm in diameter were present. Bronchoscopy showed nodular lesions causing subtotal occlusion of the middle lobe bronchus. Biopsy of these lesions revealed filamentous-like bacterial colonies which were Gram stain positive and modified Ziehl–Neelson stain negative with a background of acute and chronic inflammation consistent with actinomycosis. Bronchoalveolar lavage specimens were culture-negative. She was treated with intravenous benzylpenicillin 5 mega units 6-hourly for 1 month followed by oral penicillin V 1 g 6-hourly for 6 months. She returned to the clinic with complete resolution of symptoms 7 months after the treatment and a follow-up chest radiograph showed near complete resolution the right middle lobe opacity. Repeat bronchoscopy still showed nodular lesions in the right main bronchus which appeared much smaller now. The bronchoscope could now be passed beyond the lesion and a piece of ‘tissue’ was seen at the bifurcation of the middle bronchus. The ‘tissue’ was grasped with a biopsy forceps. However, it dropped above the vocal cords and most likely was swallowed by the patient. A repeat biopsy of the nodule showed persistence of actinomycosis. In addition, necrotic vegetative matter was present. Oral penicillin at the same dose was continued. Three months later, a third bronchoscopy showed complete resolution.

Introduction: Prolonged use of oral corticosteroids is a risk factor for osteoporosis. However, the effect of inhaled corticosteroids (ICS) on bone mineral density (BMD) of asthmatic patients remains controversial. Objectives: We aimed to determine the prevalence of osteopenia and osteoporosis in our patients with asthma receiving ICSs for more than one year compared with patients who did not have asthma and to determine the risk factors for osteopenia and osteoporosis among the asthmatic patients. Methods: This was a cross-sectional study conducted from August 2007 to July 2009. Asthmatic patients aged 18 years and older who had been on ICS for at least one year and a control group of subjects not on ICS were included. BMD was measured using DEXA (dual energy X-ray absorptiometry) scan. The WHO classification of T-scores for osteopenia and osteoporosis were used. Results: A total of 143 subjects were recruited (69 asthmatics and 74 control subjects). T-scores of the spine, femur, and hip of the asthmatics vs the control subjects were mean, −0.72 vs −0.57 (P=0.98); median, −0.60 vs −0.80 (P=0.474); and mean, 0.19 vs 0.06 (P=0.275); respectively. T-scores of the spine, femur, and hip showed significant negative correlation with age and significant positive correlation with body mass index (BMI). Conclusion: The risk factors for osteoporosis and osteopenia among asthmatic patients were older age and lower BMI, but not the cumulative dose of ICS. Asthmatic patients on ICS have no added risk of osteoporosis or osteopenia as compared with non-asthmatic subjects.

AIM: To determine the learning curves for antegrade double-balloon enteroscopy (aDBE) and retrograde DBE (rDBE) by analyzing the technical success rates. METHODS: A retrospective analysis in a tertiary referral center. This study reviewed all cases from June 2006 to April 2011 with a target lesion in the small-bowel identified by either capsule endoscopy or computed tomography scan posted for DBE examinations. Main outcome measurements were: (1) Technical success of aDBE defined by finding or excluding a target lesion after achieving sufficient length of small bowel intubation; and (2) Technical success for rDBE was defined by either finding the target lesion or achieving stable overtube placement in the ileum. RESULTS: Two hundred and eighty two procedures fulfilled the inclusion criteria and were analyzed. These procedures were analyzed by blocks of 30 cases. There was no distinct learning curve for aDBE. Technical success rates for rDBE continued to rise over time, although on logistic regression analysis testing for trend, there was no significance (P = 0.09). The odds of success increased by a factor of 1.73 (95% CI: 0.93-3.22) for rDBE. For these data, it was estimated that at least 30-35 cases of rDBE under supervision were needed to achieve a good technical success of more than 75%. CONCLUSION: There was no learning curve for aDBE. Technical success continued to increase over time for rDBE, although a learning curve could not be proven statistically. Approximately 30-35 cases of rDBE will be required for stable overtube intubation in ileum.