Depressive Symptoms in Newly Diagnosed Lung Carcinoma: Prevalence and Associated Risk Factors.

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<0.001) married (η=0.14, p<0.001) with intrinsic religiosity (IR) (η=0.07, p<0.02) are more resistant to depression. CONCLUSION: One in three of lung carcinoma patients, are at increased risk for depression. Clinicians should be aware that risk is highest in those with poor performance status, single, and with poor IR. We suggest routine screening of depression symptoms as it is feasible, to be performed during a regular clinic visit with immediate referral to psychiatrist when indicated.

First-line erlotinib versus gemcitabine/cisplatin in patients with advanced EGFR mutation-positive non-small-cell lung cancer: analyses from the phase III, randomized, open-label, ENSURE study.

BACKGROUND: 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 AND METHODS: 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. RESULTS: 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 P < 0.0001]. 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. CONCLUSION: 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).

Monitoring treatment response in sputum smear positive pulmonary tuberculosis patients: comparison of weight gain, sputum conversion and chest radiograph.

BACKGROUND: Monitoring treatment response to anti-tuberculous therapy remains unsatisfactory in resource-limited countries where sophisticated and expensive tests are not readily available. Sputum culture for mycobacterium is desirable, but not obtainable in many developing countries. Sputum acid-fast bacilli (AFB) smear alone can be misinterpreted in the presence of unviable bacilli or non-tuberculous mycobacteria. Hence the search for a cheaper but reliable monitoring tool, or a combination of several tools, continues. Interesting reports from studies in third world nations have considered weight gain/loss as one such monitoring tool. Since pulmonary tuberculosis is endemic in this country, we take the opportunity to evaluate weight gain and chest radiograph, compared to sputum AFB smear in monitoring patient's response. METHODS: This was a retrospective study of confirmed positive sputum AFB smear patients from January 1999 to December 2004 who attended the Chest Clinic at Hospital Tengku Ampuan Afzan, Kuantan, Malaysia. Data on weight, chest radiograph and sputum AFB smear from initiation of therapy to end of treatment and follow-up were collected and analyzed. RESULTS: 201 patients were included. At week-4 of anti-tuberculous treatment, only 14.7% had positive sputum smear. At completion of therapy 93.1% had improved chest radiographs. 90% had weight gain, 5% had weight loss and the remaining had no change in weight. Amongst patients with weight loss, there were no significant differences in the underlying illnesses (p=0.376), sputum smear at 4 weeks (p=0.697) and chest X-ray changes (p=0.731). Three patients who initially showed sputum smear conversion had reappearance of positive smear results towards the end of treatment. One of them was diagnosed as treatment failure while the other two remained well after discontinuation of therapy. CONCLUSION: Weight gain is very common among smear-positive tuberculosis patients after treatment even though weight gain does not correlate well with underlying disease, sputum conversion and chest X-ray changes. Reappearance of smear-positive sputum must be interpreted with caution and not to be regarded as treatment failure without other evidence.

Outbreak of melioidosis and leptospirosis co-infection following a rescue operation.

We analyzed the epidemiological data of all people who were involved in the search and rescue operation in Lubuk Yu, a natural recreational forest with waterfall and stream. The hospital admission records of the cases who fulfilled the case definition and the environmental samples result taken at Lubuk Yu recreational area were studied. 153 people were exposed to this outbreak, 85 (55.5%) were professional rescuers from various government agencies and 68 (44.5%) were villagers. 21 fulfilled the case definition. Ten cases were confirmed melioidosis, six melioidosis alone and four coinfected with leptospirosis. There were eight deaths in this outbreak, seven were villagers and one professional rescuer. Overall case fatality was 70%. All confirmed melioidosis cases and seven who died had diabetes mellitus. The morbidity rate were higher among the villagers, 23.5% compared to professional rescuers, 5.9%. The case fatality rate were also higher in this group which was 100% compared to 33.3% in professional rescuers. The soil and water samples in Lubuk Yu recreational area were positive for leptospira and Burkholderia pseudomallei. The presence of co-infection and co-morbidities especially diabetes mellitus among the exposed led to the high mortality in this outbreak hence a high index of suspicion is important among the healthcare professionals in the management of melioidosis cases. To avoid similar incident in future, search and rescue operation should be only conducted by professional rescuers with appropriate personal protective equipment. A register of rescuers should be maintained for surveillance and follow up if necessary.

Defaulters among lung cancer patients in a suburban district in a developing country.

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.

The bug and the big heart --melioidotic pericardial effusion.

Melioidosis is an infection caused by Gram negative bacterium Burkholderia pseudomallei leading to abscesses in lungs, liver, spleen, musculoskeletal system, prostate and sepsis. We present a rare case of purulent pericardial effusion caused by melioidosis with concomitant pneumonia and splenic abscesses. The patient underwent pericardiocentesis and successfully recovered from cardiogenic and septic shock.

The use of multiplex real-time PCR improves the detection of the bacterial etiology of community acquired pneumonia.

Community-acquired pneumonia (CAP) is still a major cause of morbidity and mortality especially to children and compromised hosts, such as the old and those with underlying chronic diseases. Knowledge of pathogens causing CAP constitutes the basis for selection of antimicrobial treatment. Previous data have shown that etiological agents can be identified in only up to 50% of patients, but this figure can be improved by using polymerase chain reaction (PCR). This study was designed to evaluate multiplex real-time PCR as a method for rapid differential detection of five bacterial causes of CAP (Streptococcus pneumoniae, Burkholderia pseudomallei and atypical bacterial pathogens namely Mycoplasma pneumoniae, Chlamydophila pneumoniae and Legionella pneumophila) in CAP patients attending Hospital Tengku Ampuan Afzan (HTAA)/ Kuantan, Pahang, Malaysia. Two previously developed multiplex real-time PCR assays, duplex for the differential detection of S. pneumoniae and B. pseudomallei and triplex for the atypical bacterial pathogens, were used to detect a bacterial cause of CAP in blood and respiratory samples. Thus, 46 blood and 45 respiratory samples collected from 46 adult CAP patients admitted to HTAA were analysed by multiplex real-time PCR assays and conventional methods. The microbial etiology of CAP could be established for 39.1% (18/46) of CAP patients by conventional methods and this was increased to 65.2% (30/46) with the additional use of real-time PCR. The most frequently detected pathogens were S. pneumoniae (21.7% - all by PCR alone), Klebsiella pneumoniae (17.3%), B. pseudomallei (13% - 83% of them positive by PCR alone and 17% by both culture and PCR), Pseudomonas aeruginosa (6.5%), M. pneumoniae (6.5% - all by serology), C. pneumoniae (4.3% - all positive by both PCR and serology), L. pneumophila (2.1% - all by PCR alone), Escherichia coli (4.3%). Haemophilus infuenzae, Acinetobacter lwoffii and Acinetobacter baumannii were detected by conventional methods (2.1% for each).

Development of multiplex real-time PCR for the rapid detection of five bacterial causes of community acquired pneumonia.

Establishing a microbial diagnosis for patients with community-acquired pneumonia (CAP) is still challenging and is often achieved in only 30-50% of cases. Polymerase chain reaction (PCR) has been shown to be more sensitive than conventional microbiological methods and it could help to increase the microbial yield for CAP patients. This study was designed to develop, optimize and evaluate multiplex real-time PCR as a method for rapid differential detection of five bacterial causes of CAP namely Streptococcus pneumoniae, Burkholderia pseudomallei and atypical bacterial pathogens, Mycoplasma pneumoniae, Chlamydophila pneumoniae and Legionella pneumophila. Duplex and triplex real-time PCR assays were developed using five sets of primers and probes that were designed based on an appropriate specific gene for each of the above CAP pathogens. The performance of primers for each organism was tested using SYBR Green melt curve analysis following monoplex realtime PCR amplification. Monoplex real-time PCR assays were also used to optimize each primers-probe set before combining them in multiplex assays. Two multiplex real-time PCR assays were then optimized; duplex assay for the differential detection of S. pneumoniae and B. pseudomallei, and triplex assay for the atypical bacterial pathogens. Both duplex and triplex real-time PCR assays were tested for specificity by using DNA extracted from 26 related microorganisms and sensitivity by running serial dilutions of positive control DNAs. The developed multiplex real-time PCR assays shall be used later for directly identifying CAP causative agents in clinical samples.

Development of multiplex real-time PCR for the rapid detection of five bacterial causes of community acquired pneumonia

Establishing a microbial diagnosis for patients with community-acquired pneumonia (CAP) is still challenging and is often achieved in only 30-50% of cases. Polymerase chain reaction (PCR) has been shown to be more sensitive than conventional microbiological methods and it could help to increase the microbial yield for CAP patients. This study was designed to develop, optimize and evaluate multiplex real-time PCR as a method for rapid differential detection of five bacterial causes of CAP namely Streptococcus pneumoniae, Burkholderia pseudomallei and atypical bacterial pathogens, Mycoplasma pneumoniae, Chlamydophila pneumoniae and Legionella pneumophila. Duplex and triplex real-time PCR assays were developed using five sets of primers and probes that were designed based on an appropriate specific gene for each of the above CAP pathogens. The performance of primers for each organism was tested using SYBR Green melt curve analysis following monoplex realtime PCR amplification. Monoplex real-time PCR assays were also used to optimize each primers-probe set before combining them in multiplex assays. Two multiplex real-time PCR assays were then optimized; duplex assay for the differential detection of S. pneumoniae and B. pseudomallei, and triplex assay for the atypical bacterial pathogens. Both duplex and triplex real-time PCR assays were tested for specificity by using DNA extracted from 26 related microorganisms and sensitivity by running serial dilutions of positive control DNAs. The developed multiplex real-time PCR assays shall be used later for directly identifying CAP causative agents in clinical samples.

The use of multiplex real-time PCR improves the detection of the bacterial etiology of community acquired pneumonia

Community-acquired pneumonia (CAP) is still a major cause of morbidity and mortality especially to children and compromised hosts, such as the old and those with underlying chronic diseases. Knowledge of pathogens causing CAP constitutes the basis for selection of antimicrobial treatment. Previous data have shown that etiological agents can be identified in only up to 50% of patients, but this figure can be improved by using polymerase chain reaction (PCR). This study was designed to evaluate multiplex real-time PCR as a method for rapid differential detection of five bacterial causes of CAP (Streptococcus pneumoniae, Burkholderia pseudomallei and atypical bacterial pathogens namely Mycoplasma pneumoniae, Chlamydophila pneumoniae and Legionella pneumophila) in CAP patients attending Hospital Tengku Ampuan Afzan (HTAA)/ Kuantan, Pahang, Malaysia. Two previously developed multiplex real-time PCR assays, duplex for the differential detection of S. pneumoniae and B. pseudomallei and triplex for the atypical bacterial pathogens, were used to detect a bacterial cause of CAP in blood and respiratory samples. Thus, 46 blood and 45 respiratory samples collected from 46 adult CAP patients admitted to HTAA were analysed by multiplex real-time PCR assays and conventional methods. The microbial etiology of CAP could be established for 39.1% (18/46) of CAP patients by conventional methods and this was increased to 65.2% (30/46) with the additional use of real-time PCR. The most frequently detected pathogens were S. pneumoniae (21.7% - all by PCR alone), Klebsiella pneumoniae (17.3%), B. pseudomallei (13% - 83% of them positive by PCR alone and 17% by both culture and PCR), Pseudomonas aeruginosa (6.5%), M. pneumoniae (6.5% - all by serology), C. pneumoniae (4.3% - all positive by both PCR and serology), L. pneumophila (2.1% - all by PCR alone), Escherichia coli (4.3%). Haemophilus infuenzae, Acinetobacter lwoffii and Acinetobacter baumannii were detected by conventional methods (2.1% for each).

The man with the boggy head: cranial melioidosis.

Melioidosis is known to cause abscesses in various organs, including the cranium, though less commonly. We present a patient with scalp abscess and subdural empyema that was visible on computed tomography of the brain. The neurosurgical drainage grew Burkholderia pseudomallei. Despite our best effort to treat the patient using parenteral antibiotics and surgical drainage, the patient did not survive.

A survey on the initial management of spontaneous pneumothorax.

Spontaneous pneumothorax (SP) is a common medical condition but continues to be a frequent management problem among doctors. Despite the availability of guidelines on management of SP, studies have shown that the compliance with the guidelines is low. The various treatment options available in treating this condition further confuse doctors on the right approach in managing SP. The objective of this study is to investigate the awareness of the availability of these existing guidelines and to investigate how the doctors involved in the initial management of SP would manage this condition. A self completed questionnaire which included three case scenarios were distributed among doctors in two teaching university hospitals and two large Ministry of Health hospitals. This study showed that there is a lack of awareness of the existing guidelines even among the senior doctors and there is a variation in the initial management of SP. Therefore a locally produced guideline may be beneficial to standardise and improve the management of SP.

Pahang melioidosis registry.

Melioidosis has a high annual incidence and mortality rate in Pahang, Malaysia. We initiated the first melioidosis registry in the country on 1st July 2005 to improve the management of melioidosis in the state. Continuous medical education on melioidosis was carried out in all hospitals in the state to highlight the magnitude of the disease and to educate the doctors on the treatment of the disease. All culture confirmed cases were registered and analysed. During the one-year study period from 1st July 2005 till 30th June 2006, a total of 63 patients had positive culture for Burkholderia pseudomallei. The calculated annual incidence of melioidosis in Pahang state was 4.3 per 100,000 population per year (Adult, 6.0 per 100, 000 population per year and paediatric, 1.6 per 100,000 population per year). There were 55 Malays (87.3%), three Chinese (4.8%), four aborigines (6.3%) and one Indonesian. Nine (14.3%) were less than 18 years old. The median age was 49 years (range: 1-68 years). Only one patient (1.6%) had a previous history of confirmed melioidosis. With this programme, we had observed a decline in adult mortality from 54% to 44%, although this was not statistically significant. However, culture-confirmed relapses had dropped from 19% to nil. Several measures need to be taken to decrease mortality from melioidosis in endemic countries.

Hospitalised patients' awareness of their rights: a cross-sectional survey from a tertiary care hospital on the east coast of Peninsular Malaysia.

INTRODUCTION: Optimal patient care varies considerably from place to place and is influenced by scientific as well as social developments. The purpose of this study was to investigate awareness and pertinent issues regarding informed consent among hospitalised patients and to determine lapses, in order to improve the standard of care. METHODS: A questionnaire-based cross-sectional survey was conducted among inpatients at a tertiary care level hospital. RESULTS: 90 percent of patients were aware of their rights, and 85 percent had enough information regarding their illness and modality of treatment. However, treatment options were discussed with 45 percent of cases only, and 65 percent of patients were informed of their duration of treatment. Most of the patients from the surgical group, haemodialysis unit and those with minor ailments were very satisfied with the doctors (92 percent, 86 percent and 96 percent, respectively), as opposed to only 36 percent of cancer patients and 70 percent of acquired immunodeficiency syndrome (AIDS) patients (p-value is less than 0.0001). Almost all patients (99 percent) said that their religious beliefs were respected by the staff and they had no problems in accessing them in times of need. Informed consent was obtained by the doctor in 98 percent of cases and by the nurse in two percent. 98 percent of the patients mentioned that their treatments/examinations were conducted in an atmosphere of privacy and that their personal information was kept confidential by their doctors. CONCLUSION: Patients were reasonably informed about their illness. Their privacy and religious beliefs were duly respected. Treatment options and the duration of treatment were not discussed with all patients. Cancer and AIDS patients were less satisfied with the attending staff. The results suggest that there is a need for periodic surveys of patient satisfaction with the quality of care.

Melioidotic prostatic abscess in Pahang.

Melioidosis is caused by Burkholderia pseudomallei, a Gram-negative bacillus. Melioidosis can affect many organs, including the prostate. However, prostatic abscess due to melioidosis is uncommon. We describe five cases of melioidosis with prostatic abscess. Four of five patients had diabetes mellitus and had more than one organ involvement. The diagnosis of prostatic abscess in our patients was only made with computed tomography of the abdomen and pelvis. None of our patients underwent surgical drainage and all remained well after treatment with antibiotics, except for one mortality secondary to severe septicaemia.

Risk factors associated with development of dengue haemorrhagic fever or dengue shock syndrome in adults in Hospital Tengku Ampuan Afzan Kuantan.

A retrospective study was conducted to investigate 183 serologically-confirmed cases of dengue fever (DF) admitted from October 2004 to March 2005 in a large hospital in Pahang. Clinical and laboratory features, progress and outcome of these patients were analysed in order to identify risk factors associated with development of dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS). Individually, we found that older patients, secondary dengue infection, high baseline haematocrit levels, low platelet levels and prolonged activated partial thromboplastin time (APTT) ratio were significant associations with bleeding tendencies. Of these risk factors, haematocrit and APTT ratio were two independent significant risk factors on multivariate analysis. Older patients with primary infection and younger patients with secondary infection had significant bleeding tendencies. We also verified the validity of the haematocrit levels suggested as cut-off levels for plasma leakage for the Malaysian population by Malaysian Clinical Practice Guidelines for Dengue Infection in Adults (2003).

A mimicry of melioidosis by Klebsiella ozaenae infection.

Klebsiella ozaenae is a Gram negative bacillus. It has been described as a colonizer of oral and nasopharyngeal mucosa and is a cause of atrophic rhinitis. Klebsiella ozaenae has seldom been isolated from serious infections. However, several reports have stated that Klebsiella ozaenae may cause invasive infections and even mortality. We report a 55-year-old man with Klebsiella ozaenae infection causing abscesses involving the right eye and left kidney and possibly also in the brain, lungs and prostate. The isolates were sensitive to ceftazidime, ciprofloxacin, chloramphenicol, gentamicin and sulfamethoxazole-trimethoprim but resistant to ampicillin. He responded well to 4 weeks of i.v. ceftazidime and i.v. amoxycillin-clavulanic acid. To our knowledge, such a multiorgan infection has not been reported previously for this organism.

Transbronchial needle aspiration of mediastinal lymph node.

In Malaysia, transbronchial needle aspiration (TBNA) is a relatively new procedure performed only in a handful of respiratory centres. We reviewed TBNA of mediastinal lymph node performed in Hospital Tengku Ampuan Afzan (HTAA) to determine the yield and its complications. Data was retrieved from endoscopy databases and patients' records, CT thorax images and all cytological and histological slides were reviewed. Twenty-five patients had TBNA performed. TBNA was positive in 15 patients (60%). Overall, 80% had confirmed malignancy after bronchoscopy. Only four patients had documented bleeding after TBNA and in two of them, bleeding stopped spontaneously and another two patients required diluted adrenaline to stop the bleed. No mortality was reported from this procedure. Hence, TBNA is a safe procedure.

The urine bag used in pneumothorax.

Pneumothorax is the presence of air in the pleural cavity. It can be classified into spontaneous, traumatic or iatrogenic. The majority of pneumothorax cases are spontaneous, which can be further classified into primary spontaneous pneumothorax (PSP) or secondary spontaneous pneumothorax (SSP), defined by the absence or presence of obvious underlying lung disease respectively. The treatment of spontaneous pneumothorax includes simple aspiration, intercostal tube drainage or surgical intervention. When intercostal tube drainage is used, it is usually attached to an underwater-seal system. Mobile chest drains, such as the Heimlich valve, replace the underwater-seal and allow outpatient management of spontaneous pneumothoraces. The Heimlich valve however, is costly and not readily available in many local hospitals. Cheaper and easily obtainable alternatives which are also safe are being sought. This is a case report describing the use of the urine bag in the management of a patient with spontaneous pneumothrax.

Transbronchial needle aspiration of mediastinal lymph node.

In Malaysia, transbronchial needle aspiration (TBNA) is a relatively new procedure performed only in a handful of respiratory centres. We reviewed TBNA of mediastinal lymph node performed in Hospital Tengku Ampuan Afzan (HTAA) to determine the yield and its complications. Data was retrieved from endoscopy databases and patients' records, CT thorax images and all cytological and histological slides were reviewed. Twenty-five patients had TBNA performed. TBNA was positive in 15 patients (60%). Overall, 80% had confirmed malignancy after bronchoscopy. Only four patients had documented bleeding after TBNA and in two of them, bleeding stopped spontaneously and another two patients required diluted adrenaline to stop the bleed. No mortality was reported from this procedure. Hence, TBNA is a safe procedure.