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Comparing fixed and auto adjusting continuous positive airway pressure (CPAP) amongst symptomatic Obstructive Sleep Apnoea patients - A randomised controlled trial

Gan WL, Ban AYL, Mohamed Faisal AH

Med J Malaysia, 2021 09;76(5):611-616.
PMID: 34508364

INTRODUCTION: Continuous Positive Airway Pressure (CPAP) is required for obstructive sleep apnoea (OSA). Thisstudy compares the efficacy between Fixed Pressure CPAP (Fixed CPAP) and Auto-adjusting Pressure (APAP) based on Apnoea Hypopnoea Index (AHI), Epworth Sleepiness Score (ESS) among patients with symptomatic OSA and to ascertain their CPAP preference.
METHODS: This is a prospective, randomised, crossover, single-blinded study conducted from February 2018 to February 2019 among adult subjects attending respiratory clinic Universiti Kebangsaan Malaysia Medical Centre (UKMMC).
RESULTS: Forty-six subjects were recruited with 27 males (58.7%). The mean age was 54 (+11) year old. The baseline median Body Mass Index (BMI) was 34.2 kg/m2 (Interquartile Range IQR: 30.8 kg/m2 -41.7 kg/m2); baseline median AHI 28.8 /hour (IQR 21.2/hour-54.0/hour); andbaseline median ESS 15 (IQR 13-16). After intervention, the median AHI was 5.0 / hour (IQR 4.2/hour-6.0/hour) at fixed CPAP arm; APAP arm was 5.5/ hour (IQR 4.2/hour-6.3/hour); p<0.01. The median ESS at fixed CPAP arm was 2 (IQR 0-3); APAP arm was 2 (IQR 1-3); p < 0.01. Those who preferred APAP were 22 subjects (47.8%) and had median optimal CPAP pressure 13.0 cmH2O (IQR 12.0 cmH2O -13.5 cmH2O); 24 subjects (52.2%) who preferred Fixed CPAP had median optimal CPAP pressure 8.0 cmH2O (IQR 6.3 cmH2O -8.7 cmH2O); p<0.01. Median baseline BMI was 37.6 kg/m2 (IQR 30.8 kg/m2 -43.0 kg/m2) for those who preferred APAP and 32.3 kg/m2 (IQR 30.8 kg/m2 - 38.4 kg/m2) for subjects preferred Fixed CPAP; p=0.03.
DISCUSSION: Fixed CPAP maybe considered as first line therapy for symptomatic moderate and severe OSA with titrated optimal CPAP pressure less than 8 cmH2O and BMI less than 32.3 kg/m2; based on subjects' preference. Baseline AHI and average daily CPAP usage was not statisticallysignificant in affecting patient preference between fixed and auto adjusting CPAP. This is the first study of its kind conducted in Malaysia.
Fulltext Short-course intrapleural alteplase and DNase in complex effusion with bleeding risk

Cheong XK, Yu-Lin Ban A, Abdul Hamid MF

Respirol Case Rep, 2020 Oct;8(7):e00648.
PMID: 32864139 DOI: 10.1002/rcr2.648

Pleural infection is an important clinical problem with significant morbidity. In poorly draining complex pleural effusions, the current management favours a less invasive image-guided placement of smaller bore catheters and adjunctive intrapleural fibrinolysis therapy (IPFT). We describe our experience of using IPFT in three patients with different bleeding risks with complex pleural effusions. The first was a 30-year-old with transfusion-dependent β-thalassemia with haemoglobin of 7.8 g/dL; second was an 87-year-old on dabigatran with haemoglobin of 10 g/dL; and the third was an 80-year-old with diffuse large B-cell lymphoma with haemoglobin of 8.6 g/dL. All three patients received three doses of alteplase and deoxyribonuclease (DNase) without any adverse effects of bleeding and had resolution of the effusion. This case series is an addition to the current literature on the safety of IPFT and we highlight the use of IPFT in patients with low baseline haemoglobin and on anticoagulation therapy.
Fulltext Conjugation of benzylvanillin and benzimidazole structure improves DNA binding with enhanced antileukemic properties

Al-Mudaris ZA, Majid AS, Ji D, Al-Mudarris BA, Chen SH, Liang PH, et al.

PLoS One, 2013;8(11):e80983.
PMID: 24260527 DOI: 10.1371/journal.pone.0080983

Benzyl-o-vanillin and benzimidazole nucleus serve as important pharmacophore in drug discovery. The benzyl vanillin (2-(benzyloxy)-3-methoxybenzaldehyde) compound shows anti-proliferative activity in HL60 leukemia cancer cells and can effect cell cycle progression at G2/M phase. Its apoptosis activity was due to disruption of mitochondrial functioning. In this study, we have studied a series of compounds consisting of benzyl vanillin and benzimidazole structures. We hypothesize that by fusing these two structures we can produce compounds that have better anticancer activity with improved specificity particularly towards the leukemia cell line. Here we explored the anticancer activity of three compounds namely 2-(2-benzyloxy-3-methoxyphenyl)-1H-benzimidazole, 2MP, N-1-(2-benzyloxy-3-methoxybenzyl)-2-(2-benzyloxy-3-methoxyphenyl)-1H-benzimidazole, 2XP, and (R) and (S)-1-(2-benzyloxy-3-methoxyphenyl)-2, 2, 2-trichloroethyl benzenesulfonate, 3BS and compared their activity to 2-benzyloxy-3-methoxybenzaldehyde, (Bn1), the parent compound. 2XP and 3BS induces cell death of U937 leukemic cell line through DNA fragmentation that lead to the intrinsic caspase 9 activation. DNA binding study primarily by the equilibrium binding titration assay followed by the Viscosity study reveal the DNA binding through groove region with intrinsic binding constant 7.39 µM/bp and 6.86 µM/bp for 3BS and 2XP respectively. 2XP and 3BS showed strong DNA binding activity by the UV titration method with the computational drug modeling showed that both 2XP and 3BS failed to form any electrostatic linkages except via hydrophobic interaction through the minor groove region of the nucleic acid. The benzylvanillin alone (Bn1) has weak anticancer activity even after it was combined with the benzimidazole (2MP), but after addition of another benzylvanillin structure (2XP), stronger activity was observed. Also, the combination of benzylvanillin with benzenesulfonate (3BS) significantly improved the anticancer activity of Bn1. The present study provides a new insight of benzyl vanillin derivatives as potential anti-leukemic agent.
Fulltext Impact of clinical pathway on clinical outcomes in the management of COPD exacerbation

Ban A, Ismail A, Harun R, Abdul Rahman A, Sulung S, Syed Mohamed A

BMC Pulm Med, 2012;12:27.
PMID: 22726610 DOI: 10.1186/1471-2466-12-27

BACKGROUND: Exacerbations, a leading cause of hospitalization in patients with chronic obstructive pulmonary disease (COPD), affect the quality of life and prognosis. Treatment recommendations as provided in the evidence-based guidelines are not consistently followed, partly due to absence of simplified task-oriented approach to care. In this study, we describe the development and implementation of a clinical pathway (CP) and evaluate its effectiveness in the management of COPD exacerbation.
METHODS: We developed a CP and evaluated its effectiveness in a non-randomized prospective study with historical controls on patients admitted for exacerbation of COPD to Universiti Kebangsaan Malaysia Medical Centre (UKMMC). Consecutive patients who were admitted between June 2009 and December 2010 were prospectively recruited into the CP group. Non-CP historical controls were obtained from case records of patients admitted between January 2008 and January 2009. Clinical outcomes were evaluated by comparing the length of stay (LOS), complication rates, readmissions, and mortality rates.
RESULTS: Ninety-five patients were recruited in the CP group and 98 patients were included in the non-CP historical group. Both groups were comparable with no significant differences in age, sex and severity of COPD (p = 0.641). For clinical outcome measures, patients in the CP group had shorter length of stay than the non-CP group (median (IQR): 5 (4-7) days versus 7 (7-9) days, p
Understanding of Coronavirus Disease 2019 (COVID-19) and the practice of preventive measures among doctors and nurses in a university teaching hospital- A cross-sectional study

Ng BH, Low HJ, Nik Nuratiqah NA, Faisal AH, Soo CI, Periyasamy P, et al.

Med J Malaysia, 2021 07;76(4):454-460.
PMID: 34305104

INTRODUCTION: Knowledge and adequate practice of preventive measures among health care workers (HCWs) are important to reduce the risk of COVID-19 transmission.
METHODS: A cross-sectional study was conducted among doctors and nurses in the medical department in Pusat Perubatan Universiti Kebangsaan Malaysia between November 18, 2020 and December 18, 2020 during the third wave of COVID-19 epidemic in Malaysia. We studied the knowledge and practice of preventive measures of COVID-19 among doctors and nurses in the COVID-19 or sudden acute respiratory infection (SARI) wards and general medical wards. Data was collected using a validated self-designed google form online-questionnaire.
RESULTS: A total of 407 subjects completed the study and 80.8% were females; 55.8% were aged between 30-39 years; 46.4% were medical doctors. The main source of COVID-19 knowledge was the Ministry of Health Malaysia (MOH) website (35.1%). Majority (97%) had sufficient knowledge and 82% practiced proper preventive measures. Doctors had a higher mean knowledge score compared to nurses (p < 0.001). HCWs working in COVID-19 or SARI wards scored higher in knowledge questions compared to those in the general medical wards (p = 0.020). Nurses practiced better preventive measures (p < 0.001). Good knowledge could not be predicted based on professions (OR: 0.222, 95% CI: 0.048 - 1.028, p = 0.054). Majority were unable to recall the proper steps of donning (85.8%) and doffing (98.5%).
CONCLUSIONS: Although majority had good knowledge and practiced proper preventive measures, there was a poor recall in donning and doffing steps regardless of place of practice. The MOH website is a useful platform for tailored continuous medical education and regular updates on COVID-19. Regular training and retraining on donning and doffing of PPE is needed to bridge this gap.
Fulltext The crucial role of molecular testing to facilitate the diagnosis of pneumocystis pneumonia during pregnancy

Ding CH, Yusoff H, Muttaqillah NAS, Tang YL, Tan TL, Periyasamy P, et al.

Malays J Pathol, 2018 Apr;40(1):69-72.
PMID: 29704387 MyJurnal

Pneumocystis pneumonia is an important human immunodeficiency virus (HIV)-associated opportunistic infection, and especially so in pregnant HIV-positive patients. We report a case of a 40-year-old woman in her first trimester of pregnancy who initially presented with acute gastroenteritis symptoms but due to a history of high-risk behaviour and the observation of oral thrush, she was worked up for HIV infection. Her retroviral status was positive and her CD4+ T cell count was only 8 cells/µL. She was also worked up for pneumocystis pneumonia due to the presence of mild resting tachypnoea and a notable drop in oxygen saturation (from 100% to 88%) following brief ambulation. Her chest radiograph revealed bilaterally symmetrical lower zone reticular opacities and Giemsa staining of her bronchoalveolar lavage (BAL) was negative for Pneumocystis jirovecii cysts. However, real-time P. jirovecii polymerase chain reaction (PCR) testing on the same BAL specimen revealed the presence of the organism. A course of oral co-trimoxazole plus prednisolone was commenced and her clinical condition improved.
Personalised management of Chronic Obstructive Pulmonary Disease (COPD): Malaysian consensus algorithm for appropriate use of inhaled corticosteroid (ICS) in COPD patients

Marzuki NM, Jaeb MZM, Ban A, Ismail AI, Ali IAH, Razali NM, et al.

Med J Malaysia, 2020 11;75(6):717-721.
PMID: 33219183

BACKGROUND: Regarding the long-term safety issues with the use of inhaled corticosteroids (ICS) and the clinical predominance of dual bronchodilators in enhancing treatment outcomes in chronic obstructive pulmonary disease (COPD), ICS is no longer a "preferred therapy" according to the Global Initiative for Chronic Obstructive Lung Disease except on top of a dual bronchodilator. This has necessitated a change in the current therapy for many COPD patients.
OBJECTIVE: To determine a standardised algorithm to reassess and personalise the treatment COPD patients based on the available evidence.
METHODS: A consensus statement was agreed upon by a panel of pulmonologists in from 11 institutes in Malaysia whose members formed this consensus group.
RESULTS: According to the consensus, which was unanimously adopted, all COPD patients who are currently receiving an ICS-based treatment should be reassessed based on the presence of co-existence of asthma or high eosinophil counts and frequency of moderate or severe exacerbations in the previous 12 months. When that the patients meet any of the aforementioned criteria, then the patient can continue taking ICS-based therapy. However, if the patients do not meet the criteria, then the treatment of patients need to be personalised based on whether the patient is currently receiving long-acting beta-agonists (LABA)/ICS or triple therapy.
CONCLUSION: A flowchart of the consensus providing a guidance to Malaysian clinicians was elucidated based on evidences and international guidelines that identifies the right patients who should receive inhaled corticosteroids and enable to switch non ICS based therapies in patients less likely to benefit from such treatments.
Fulltext Management of asthma in adults in primary care

Ban A, Omar A, Chong LY, Lockman H, Ida Zaliza ZA, Ali I, et al.

Malays Fam Physician, 2018;13(3):20-26.
PMID: 30800229 MyJurnal

Asthma is a chronic inflammatory disease of the airway which is often misdiagnosed and undertreated. Early diagnosis and vigilant asthma control are crucial to preventing permanent airway damage, improving quality of life and reducing healthcare burdens. The key approaches to asthma management should include patient empowerment through health education and self-management and, an effective patient-healthcare provider partnership.
Fulltext A partially randomised trial of pretomanid, moxifloxacin and pyrazinamide for pulmonary TB

Tweed CD, Wills GH, Crook AM, Amukoye E, Balanag V, Ban AYL, et al.

Int J Tuberc Lung Dis, 2021 Apr 01;25(4):305-314.
PMID: 33762075 DOI: 10.5588/ijtld.20.0513

BACKGROUND: Treatment for TB is lengthy and toxic, and new regimens are needed.METHODS: Participants with pulmonary drug-susceptible TB (DS-TB) were randomised to receive: 200 mg pretomanid (Pa, PMD) daily, 400 mg moxifloxacin (M) and 1500 mg pyrazinamide (Z) for 6 months (6Pa200MZ) or 4 months (4Pa200MZ); 100 mg pretomanid daily for 4 months in the same combination (4Pa100MZ); or standard DS-TB treatment for 6 months. The primary outcome was treatment failure or relapse at 12 months post-randomisation. The non-inferiority margin for between-group differences was 12.0%. Recruitment was paused following three deaths and not resumed.RESULTS: Respectively 4/47 (8.5%), 11/57 (19.3%), 14/52 (26.9%) and 1/53 (1.9%) DS-TB outcomes were unfavourable in patients on 6Pa200MZ, 4Pa200MZ, 4Pa100MZ and controls. There was a 6.6% (95% CI -2.2% to 15.4%) difference per protocol and 9.9% (95%CI -4.1% to 23.9%) modified intention-to-treat difference in unfavourable responses between the control and 6Pa200MZ arms. Grade 3+ adverse events affected 68/203 (33.5%) receiving experimental regimens, and 19/68 (27.9%) on control. Ten of 203 (4.9%) participants on experimental arms and 2/68 (2.9%) controls died.CONCLUSION: PaMZ regimens did not achieve non-inferiority in this under-powered trial. An ongoing evaluation of PMD remains a priority.