Adjunctive pascolizumab in rifampicin-susceptible pulmonary tuberculosis: proof-of-concept, partially-randomised, double-blind, placebo-controlled, dose-escalation trial.

BACKGROUND: Interleukin-4 (IL-4), increased in tuberculosis infection, may impair bacterial killing. Blocking IL-4 confers benefit in animal models. We evaluated safety and efficacy of pascolizumab (humanised anti-IL-4 monoclonal antibody) as adjunctive tuberculosis treatment. METHODS: Participants with rifampicin-susceptible pulmonary tuberculosis received a single intravenous infusion of pascolizumab or placebo; and standard 6-month tuberculosis treatment. Pascolizumab dose increased in successive cohorts: [1] non-randomised 0.05 mg/kg (n = 4); [2] non-randomised 0.5 mg/kg (n = 4); [3] randomised 2.5 mg/kg (n = 9) or placebo (n = 3); [4] randomised 10 mg/kg (n = 9) or placebo (n = 3). Co-primary safety outcome was study-drug-related grade 4 or serious adverse event (G4/SAE); in all cohorts (1-4). Co-primary efficacy outcome was week-8 sputum culture time-to-positivity (TTP); in randomised cohorts (3-4) combined. RESULTS: Pascolizumab levels exceeded IL-4 50% neutralising dose for 8 weeks in 78-100% of participants in cohorts 3-4. There were no study-drug-related G4/SAEs. Median week-8 TTP was 42 days in pascolizumab and placebo groups (p = 0.185). Rate of TTP increase was greater with pascolizumab (difference from placebo 0.011 [95% Bayesian credible interval 0.006 to 0.015] log10TTP/day. CONCLUSIONS: There was no evidence to suggest blocking IL-4 was unsafe. Preliminary efficacy findings are consistent with animal models. This supports further investigation of adjunctive anti-IL-4 interventions for tuberculosis in larger phase 2 trials.

Does dose reduction of afatinib affect treatment outcomes of patients with EGFR-mutant metastatic non-small cell lung cancer in real-world clinical practice?

Background: Afatinib can be started at a dose lower than the recommended starting dose of 40 mg/day for the treatment of epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC), however treatment outcomes in real-world clinical practice remains unclear. Methods: This retrospective study of patients with NSCLC from 18 major hospitals (public, private or university teaching hospitals) enrolled in Malaysia's National Cardiovascular and Thoracic Surgical Database (NCTSD) assessed the efficacy of lower doses of afatinib on treatment outcomes in a real-world clinical practice. Data on clinical characteristics, afatinib dosing, and treatment outcomes for patients included in NCTSD from 1st January 2015 to 31st December 2020 were analyzed. Results: Of the 133 patients studied, 94.7% had adenocarcinoma. Majority of the patients (60.9%) had EGFR exon 19 deletion and 23.3% had EGFR exon 21 L858R point mutation. The mean age of patients was 64.1 years and majority (83.5%) had Eastern Cooperative Oncology Group performance status of 2-4 at diagnosis. The most common afatinib starting doses were 40 mg (37.6%), 30 mg (29.3%), and 20 mg (26.3%) once daily (OD), respectively. A quarter of patients had dose reduction (23.3%) due to side effects or cost constraints. Majority of the patients had partial response to afatinib (63.2%) whilst 2.3% had complete response. Interestingly, the objective response rate was significantly higher (72.3%) with afatinib OD doses of less than 40 mg compared to 40 mg (54.0%) (P=0.032). Patients on lower doses of afatinib were two times more likely to achieve an objective response [odds ratio =2.64; 95% confidence interval (CI): 1.20-5.83; P=0.016]. These patients had a numerically but not statistically longer median time to treatment failure (TTF). Median TTF (95% CI) for the overall cohort was 12.4 (10.02-14.78) months. Median overall survival (95% CI) was 21.30 (15.86-26.75) months. Conclusions: Lower afatinib doses (<40 mg OD) could be equally effective as standard dose in patients with EGFR-mutant advanced NSCLC and may be more suited to Asian patients, minimizing side effects that may occur at higher dosages of afatinib leading to dose interruptions and affecting treatment outcomes.

30-Day Readmission Rate of Patients with COPD and Its Associated Factors: A Retrospective Cohort Study from a Tertiary Care Hospital.

Purpose: Readmission of chronic obstructive pulmonary disease (COPD) has been used as a measure of performance for COPD care. This study aimed to determine the rate of readmission of COPD in tertiary care hospital in Malaysia and its associated factors. Patients and Methods: A retrospective cohort study was conducted at a tertiary care hospital in Malaysia from 1st January to 21st May 2019. Seventy admissions for COPD exacerbation involving 58 patients were analyzed. Results: The majority of the patients were male (89.8%), had a mean age of 71.95 ± 7.24 years and a median smoking history of 40 (IQR = 25) pack-years, 84.5% were in GOLD group D and 91.4% had a mMRC grading of 2 or greater. Approximately 60.3% had upper or lower respiratory tract infection as the cause of exacerbation; one in five patients had uncompensated hypercapnic respiratory failure at presentation, and 27.6% needed mechanical ventilatory support. Approximately 43.1% of patients had a history of exacerbation that required hospitalisation in the past year. The mean blood eosinophil concentration was 0.38 ± 0.46 x109 cells/L. The 30-day readmission rate was 20.3%, revisit rate to the emergency room within 30 days after discharge was 3.4%, and in-hospital mortality rate was 1.7%. Among all characteristics, a higher baseline mMRC grade (p = 0.038) and history of exacerbation in the past 1 year (p < 0.001) were statistically associated with 30-day readmission. Conclusion: The 30-day readmission rate for COPD exacerbation in a Malaysian tertiary hospital is similar to the rates in high-income countries. Exacerbation in the previous year and a higher baseline mMRC grading were significant risk factors for 30-day readmission in patients with COPD. Strategies of COPD management should concentrate on improvement of symptoms control by optimisation of pharmacotherapy, and early initiation of pulmonary rehabilitation, and structured integrated care programs to reduce readmission rates.

Developing a home-based pulmonary rehabilitation programme for patients with chronic respiratory diseases in Malaysia: A mixed-method feasibility study.

Background: The COVID-19 pandemic has underscored the importance of remote healthcare and home-based interventions, including pulmonary rehabilitation, for patients with chronic respiratory diseases (CRDs). It has also heightened the vulnerability of individuals with underlying respiratory conditions to severe illness from COVID-19, necessitating exploration and assessment of the feasibility of delivering home - pulmonary rehabilitation (home-PR) programmes for CRD management in Malaysia and other countries. Home-based programmes offer a safer alternative to in-person rehabilitation during outbreaks like COVID-19 and can serve as a valuable resource for patients who may be hesitant to visit healthcare facilities during such times. We aimed to assess the feasibility of delivering a home-PR programme for patients with CRDs in Malaysia. Methods: We recruited patients with CRDs from two hospitals in Klang Valley, Malaysia to a home-PR programme. Following centre-based assessment, patients performed the exercises at home (five sessions/week for eight weeks (total 40 sessions)). We monitored the patients via weekly telephone calls and asked about adherence to the programme. We measured functional exercise capacity (6-Minutes Walking Test (6MWT) and Health-Related Quality-of-Life (HRQoL) (COPD Assessment Test (CAT)) at baseline and post-PR at nine weeks. We conducted semi-structured interviews with 12 purposively sampled participants to explore views and feedback on the home-PR programme. The interviews were audio recorded, transcribed verbatim, and analysed thematically. Results: We included 30 participants; two withdrew due to hospitalisation. Although 28 (93%) adhered to the full programme, only 11 (37%) attended the post-PR assessment because COVID-19 movement restrictions in Malaysia at that time prevented attendance at the centre. Four themes emerged from the qualitative analysis: involvement of family and caregivers, barriers to home-PR programme, interactions with peers and health care professionals, and programme enhancement. Conclusion: Despite the COVID-19 pandemic, the home-PR programme proved feasible for remote delivery, although centre-based post-PR assessments were not possible. Family involvement played an important role in the home-PR programme. The delivery of this programme can be further improved to maximise the benefit for patients.

Central Nervous System Outcomes of Lazertinib Versus Gefitinib in EGFR-Mutated Advanced NSCLC: A LASER301 Subset Analysis.

INTRODUCTION: Lazertinib, a third-generation mutant-selective EGFR tyrosine kinase inhibitor, improved progression-free survival compared with gefitinib in the phase 3 LASER301 study (ClinicalTrials.gov Identifier: NCT04248829). Here, we report the efficacy of lazertinib and gefitinib in patients with baseline central nervous system (CNS) metastases. METHODS: Treatment-naive patients with EGFR-mutated advanced NSCLC were randomized one-to-one to lazertinib (240 mg/d) or gefitinib (250 mg/d). Patients with asymptomatic or stable CNS metastases were included if any planned radiation, surgery, or steroids were completed more than 2 weeks before randomization. For patients with CNS metastases confirmed at screening or subsequently suspected, CNS imaging was performed every 6 weeks for 18 months, then every 12 weeks. End points assessed by blinded independent central review and Response Evaluation Criteria in Solid Tumors version 1.1 included intracranial progression-free survival, intracranial objective response rate, and intracranial duration of response. RESULTS: Of the 393 patients enrolled in LASER301, 86 (lazertinib, n = 45; gefitinib, n = 41) had measurable and or non-measurable baseline CNS metastases. The median intracranial progression-free survival in the lazertinib group was 28.2 months (95% confidence interval [CI]: 14.8-28.2) versus 8.4 months (95% CI: 6.7-not reached [NR]) in the gefitinib group (hazard ratio = 0.42, 95% CI: 0.20-0.89, p = 0.02). Among patients with measurable CNS lesions, the intracranial objective response rate was numerically higher with lazertinib (94%; n = 17) versus gefitinib (73%; n = 11, p = 0.124). The median intracranial duration of response with lazertinib was NR (8.3-NR) versus 6.3 months (2.8-NR) with gefitinib. Tolerability was similar to the overall LASER301 population. CONCLUSIONS: In patients with CNS metastases, lazertinib significantly improved intracranial progression-free survival compared with gefitinib, with more durable responses.

Lazertinib Versus Gefitinib Tyrosine Kinase Inhibitors in Treatment-Naíve Patients With EGFR-Mutated Advanced NSCLC: Analysis of the Asian Subpopulation in LASER301.

INTRODUCTION: Lazertinib is a third-generation central nervous system-penetrant tyrosine kinase inhibitor targeting mutant EGFR in NSCLC. Lazertinib exhibited improved efficacy versus gefitinib in the LASER301 study; this subset analysis compared lazertinib with gefitinib among Asian patients. METHODS: The phase 3 LASER301 study evaluated lazertinib efficacy and safety in treatment-naive patients with EGFR-mutated (exon 19 deletion or L858R) locally advanced or metastatic NSCLC. Patients were randomized one-to-one and received either lazertinib or gefitinib. The primary end point was investigator-assessed progression-free survival using Response Evaluation Criteria in Solid Tumors version 1.1. Secondary end points included overall survival, objective response rate, duration of response, and safety. RESULTS: Between February 13, 2020, and July 29, 2022, among 258 patients of Asian descent, the median progression-free survival was significantly longer with lazertinib than gefitinib (20.6 versus 9.7 mo; hazard ratio: 0.46; 95% confidence interval [CI]: 0.34-0.63, p < 0.001), and the benefit was consistent across predefined subgroups (exon 19 deletion, L858R, baseline central nervous system metastases). Objective response rate and disease control rates were similar between treatment groups. The median duration of response was 19.4 months (95% CI: 16.6-24.9) versus 9.6 months (95% CI: 6.9-12.4) in the lazertinib versus gefitinib group. Adverse event rates in Asian patients were comparable with the overall LASER301 population. Adverse events leading to discontinuation in the lazertinib and gefitinib groups were 13% and 12%, respectively. CONCLUSIONS: In LASER301, efficacy and safety results in Asian patients were consistent with the overall population. Lazertinib exhibited better efficacy than gefitinib in Asian patients with a tolerable safety profile.

Common driver mutations and programmed death-ligand 1 expression in advanced non-small cell lung cancer in smokers and never smokers.

BACKGROUND: In non-small cell lung cancer (NSCLC), there may be a relationship between programmed death-ligand 1 (PD-L1) expression, driver mutations and cigarette smoking. METHODS: In this single-center retrospective study, the relationship between common driver mutations (EGFR mutation and ALK rearrangement) and PD-L1 expression in advanced NSCLC according to the patients' smoking history was examined. Light, moderate and heavy smokers had smoked < 20, 20-39, and ≥ 40 pack-years, respectively. The level of PD-L1 expression, assessed using Ventana SP263 monoclonal antibody assay, was defined by the tumor proportion score (TPS) as high expression (TPS ≥ 50%), low expression (TPS 1%-49%) and no expression (TPS < 1%). RESULTS: 101 (52.9%) of 191 advanced NSCLC patients were never smokers. EGFR mutations were more common in never smokers (64.4%) than in smokers (17.8%) with advanced NSCLC (P < 0.0001). A higher proportion of smokers (26.7%) had high PD-L1 expression compared to never smokers (13.9%) (P = 0.042). There was a trend for a higher proportion of male NSCLC patients [28 of 115 (24.3%)] than female patients [10 of 76 (13.2%)] to have high PD-L1 expression (P = 0.087]. High PD-L1 expression was seen in 32 of 110 (29.1%) patients with EGFR wild-type NSCLC but only in 6 of 81 (7.4%) patients with EGFR-mutant tumors (P < 0.0001). Among the 90 smokers with NSCLC, a higher proportion of heavy smokers (35.8%) than non-heavy smokers (13.5%) had high PD-L1 expression (P = 0.034). In patients with adenocarcinoma, high PD-L1 expression was seen in 25 of 77 (32.5%) patients with EGFR wild-type tumors but only in 4 of 70 (5.7%) patients with EGFR-mutant tumors (P < 0.0001). Among patients with adenocarcinoma, a significantly higher proportion of ever smokers (29.3%) than never smokers (13.5%) had high PD-L1 expression (P = 0.032). Among smokers with adenocarcinoma, a significantly higher proportion of heavy smokers (44.1%) than non-heavy smokers (8.3%) had high PD-L1 expression (P = 0.004). On multivariate analysis, after adjusting for gender and smoking status, heavy smoking and EGFR wild-type tumors remained significantly associated with high PD-L1 expression in NSCLCs and also in adenocarcinoma. CONCLUSIONS: Heavy smoking and EGFR wild-type tumors were significantly associated with high PD-L1 expression in NSCLCs and also in adenocarcinoma.

Lazertinib Versus Gefitinib as First-Line Treatment in Patients With EGFR-Mutated Advanced Non-Small-Cell Lung Cancer: Results From LASER301.

PURPOSE: Lazertinib is a potent, CNS-penetrant, third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor. This global, phase III study (LASER301) compared lazertinib versus gefitinib in treatment-naïve patients with EGFR-mutated (exon 19 deletion [ex19del]/L858R) locally advanced or metastatic non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients were 18 years and older with no previous systemic anticancer therapy. Neurologically stable patients with CNS metastases were allowed. Patients were randomly assigned 1:1 to lazertinib 240 mg once daily orally or gefitinib 250 mg once daily orally, stratified by mutation status and race. The primary end point was investigator-assessed progression-free survival (PFS) by RECIST v1.1. RESULTS: Overall, 393 patients received double-blind study treatment across 96 sites in 13 countries. Median PFS was significantly longer with lazertinib than with gefitinib (20.6 v 9.7 months; hazard ratio [HR], 0.45; 95% CI, 0.34 to 0.58; P < .001). The PFS benefit of lazertinib over gefitinib was consistent across all predefined subgroups. The objective response rate was 76% in both groups (odds ratio, 0.99; 95% CI, 0.62 to 1.59). Median duration of response was 19.4 months (95% CI, 16.6 to 24.9) with lazertinib versus 8.3 months (95% CI, 6.9 to 10.9) with gefitinib. Overall survival data were immature at the interim analysis (29% maturity). The 18-month survival rate was 80% with lazertinib and 72% with gefitinib (HR, 0.74; 95% CI, 0.51 to 1.08; P = .116). Observed safety of both treatments was consistent with their previously reported safety profiles. CONCLUSION: Lazertinib demonstrated significant efficacy improvement compared with gefitinib in the first-line treatment of EGFR-mutated advanced NSCLC, with a manageable safety profile.

Pathological complete response in an advance stage IIIB non-small cell lung cancer secondary to neoadjuvant osimertinib targeted therapy: A case report and review of literature.

Neoadjuvant chemotherapy is a therapeutic option for potentially resectable non-small cell lung cancer (NSCLC). The role of neoadjuvant targeted therapy (NTT) remains less explored. This case highlights the use of neoadjuvant osimertinib in a case of advanced NSCLC. A 67-year-old woman had a left lower lobe lung mass measuring 5.0 × 5.1 × 7.0 cm with an enlarged subcarinal lymph node (LN) on her positron emission tomography scan. Following biopsy, a diagnosis of stage IIIB N2 (cT3N2M0) EGFR exon 19 deletion mutation-positive lung adenocarcinoma was established. NTT using osimertinib 80 mg once daily was commenced. Subsequent re-imaging at 3 months (ycT2bN2M0), 6 months (ycT1cN2M0) and 9 months showed tumour downstaging and resolution of the subcarinal LN (ycT1cN0M0). She underwent left lower lobectomy with systematic nodal dissection. All surgical specimens demonstrated no evidence of malignant cells (ypT0N0). Osimertinib could be the preferred NTT for potentially resectable NSCLC.

Asthma control and care among six public health clinic attenders in Malaysia: A cross-sectional study.

Background and Aims: Asthma is common in Malaysia but neglected. Achieving optimal asthma control and care is a challenge in the primary care setting. In this study, we aimed to identify the risk factors for poor asthma control and pattern of care among adults and children (5-17 years old) with asthma attending six public health clinics in Klang District, Malaysia. Methods: We conducted a cross-sectional study collecting patients' sociodemographic characteristics, asthma control, trigger factors, healthcare use, asthma treatment, and monitoring and use of asthma action plan. Descriptive statistics and stepwise logistic regression were used in data analysis. Results: A total of 1280 patients were recruited; 85.3% adults and 14.7% children aged 5-17 years old. Only 34.1% of adults had well-controlled asthma, 36.5% had partly controlled asthma, and 29.4% had uncontrolled asthma. In children, 54.3% had well-controlled asthma, 31.9% had partly controlled, and 13.8% had uncontrolled asthma. More than half had experienced one or more exacerbations in the last 1 year, with a mean of six exacerbations in adults and three in children. Main triggers for poor control in adults were haze (odds ratio [OR] 1.51; 95% confidence interval [CI] 1.13-2.01); cold food (OR 1.54; 95% CI 1.15-2.07), extreme emotion (OR 1.90; 95% CI 1.26-2.89); air-conditioning (OR 1.63; 95% CI 1.20-2.22); and physical activity (OR 2.85; 95% CI 2.13-3.82). In children, hot weather (OR 3.14; 95% CI 1.22-8.11), and allergic rhinitis (OR 2.57; 95% CI 1.13-5.82) contributed to poor control. The majority (81.7% of adults and 64.4% of children) were prescribed controller medications, but only 42.4% and 29.8% of the respective groups were compliant with the treatment. The importance of an asthma action plan was reported less emphasized in asthma education. Conclusion: Asthma control remains suboptimal. Several triggers, compliance to controller medications, and asthma action plan use require attention during asthma reviews for better asthma outcomes.

COPD exacerbations and patient-reported outcomes according to post-bronchodilator FEV1 - a post-hoc analysis of pooled data.

BACKGROUND: Management strategies of chronic obstructive pulmonary disease (COPD) need to be tailored to the forced expiratory volume in one second (FEV1), exacerbations, and patient-reported outcomes (PROs) of individual patients. In this study, we analyzed the association and correlation between the FEV1, exacerbations, and PROs of patients with stable COPD. METHODS: This was a post-hoc analysis of pooled data from two cross-sectional studies that were previously conducted in Malaysia from 2017 to 2019, the results of which had been published separately. The parameters measured included post-bronchodilator FEV1 (PB-FEV1), exacerbations, and scores of modified Medical Research Council (mMRC), COPD Assessment Test (CAT), and St George's Respiratory Questionnaire for COPD (SGRQ-c). Descriptive, association, and correlation statistics were used. RESULTS: Three hundred seventy-four patients were included in the analysis. The PB-FEV1 predicted was < 30% in 85 (22.7%), 30-49% in 142 (38.0%), 50-79% in 111 (29.7%), and ≥ 80% in 36 (9.6%) patients. Patients with PB-FEV1 < 30% predicted had significantly more COPD exacerbations than those with PB-FEV1 30-49% predicted (p < 0.001), 50-79% predicted (p < 0.001), and ≥ 80% predicted (p = 0.002). The scores of mMRC, CAT, and SGRQ-c were not significantly higher in patients with more severe airflow limitation based on PB-FEV1 (p = 0.121-0.271). The PB-FEV1 predicted had significant weak negative correlations with exacerbations (r = - 0.182, p < 0.001), mMRC (r = - 0.121, p = 0.020), and SGRQ-c scores (r = - 0.114, p = 0.028). There was a moderate positive correlation between COPD exacerbations and scores of mMRC, CAT, and SGRQ-c (r = 0.407-0.482, all p < 0.001). There were significant strong positive correlations between mMRC score with CAT (r = 0.727) and SGRQ-c scores (r = 0.847), and CAT score with SGRQ-c score (r = 0.851) (all p < 0.001). CONCLUSIONS: In COPD patients, different severity of airflow limitation was not associated with significant differences in the mMRC, CAT, and SGRQ-c scores. Exacerbations were significantly more frequent in patients with very severe airflow limitation only. The correlation between airflow limitation with exacerbations, mMRC, and SGRQ-c was weak.

Real-World Treatment and Outcomes of ALK-Positive Metastatic Non-Small Cell Lung Cancer in a Southeast Asian Country.

Purpose: 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.

Severe COVID-19 with persistent respiratory failure-A retrospective cohort study in a tertiary centre in Malaysia.

INTRODUCTION: Management of severe COVID-19 patients with persistent respiratory failure after acute phase treatment is not only challenging, but evidence for treatment is scarce, despite some authors reporting favourable clinical responses to corticosteroid therapy in histologically proven secondary organising pneumonia (OP). This study aimed to report the course of the disease, radiological pattern and clinical outcomes of severe COVID-19 patients with persistent respiratory failure. METHODS: This was a retrospective cohort study of severe COVID-19 patients who were admitted to a single tertiary centre from 1 January 2021 to 30 June 2021. The clinical data of the patients during admission and clinic follow-up, including radiological images, were traced using electronic medical records. RESULTS: In our cohort, the mortality rate for those with severe COVID-19 was 23.1% (173/749). Among the survivors, 46.2% (266/576) had persistent respiratory failure (PRF) after 14 days of illness. Of them, 70.3% (187/266) were followed up, and 68% (128/187) received oral corticosteroid (prednisolone) maintenance treatment. OP pattern made up the majority (81%) of the radiological pattern with a mean severity CT score of 10 (SD±3). The mean prednisolone dose was 0.68mg/kg/day with a mean treatment duration of 47 days (SD±18). About one-third of patients (67/187) had respiratory symptoms at 4 weeks (SD±3). Among 78.1% (146/187) who had a repeated CXR during follow-up, only 12 patients (8.2%, SD±3) had radiological improvement of less than 50% at 6 weeks (SD±3), with 2 of them later diagnosed as pulmonary tuberculosis. Functional assessments, such as the 6-minute walk test and the spirometry, were only performed in 52.4% and 15.5% of the patients, respectively. CONCLUSION: Almost half of the patients with severe COVID-19 had PRF, with a predominant radiological OP pattern. More than two-thirds of the PRF patients required prolonged oral corticosteroid treatment. Familiarising clinicians with the disease course, radiological patterns, and potential outcomes of this group of patients may better equip them to manage their patients.

Dearth of influenza among older adults admitted with respiratory symptoms in Malaysia during the coronavirus disease 2019 pandemic in 2021.

Introduction: Influenza is a common respiratory virus which leads to over 400,000 annual deaths globally. Mortality from influenza is highest among those aged 75 years and over living in Africa and Southeast Asia. Objective: To determine the burden of influenza among older adults presenting to public hospitals with severe acute respiratory infection (SARI) during the coronavirus disease 2019 (COVID-19) pandemic. Methods: This multi-center, prospective, observational study recruited individuals aged 65 years and over who presented to four Malaysian hospitals with SARI from 1 January to 31 December 2021. Those with prior confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection were excluded. SARS-CoV-2 was detected through real-time polymerase chain reaction (PCR) with routine diagnostic kits. Influenza A, influenza B and respiratory syncytial virus (RSV) viruses were detected with Xpress Flu/RSV kits using the GeneXpert rapid real-time PCR system (Cepheid, USA). Results: Samples were obtained from 512 participants, comprising 296 (57.8%) men and 216 (42.2%) women, with a mean age (SD) of 74.0 (7.1) years. Inpatient death occurred in 48 (9.6%) individuals. Significant differences existed in age, ethnicity, and comorbidities across study sites. One (0.2%) case of influenza A, two (0.4%) cases of RSV and 63 (12.5%) cases of SARS-CoV-2 infection were detected over the 1-year period. Cases of COVID-19 mirrored national trends derived from open source data, while the dearth of influenza cases mirrored national and global Flunet figures. Conclusion: Our observational study conducted during the COVID-19 pandemic detected only one case of influenza, alongside a high SARS-CoV-2 positivity rate. The poor uptake of influenza vaccination nationally, worsened by the recent pandemic restrictions, could lead to waning immunity from the absence of seasonal exposure. Potentially deadly outbreaks may then occur when lockdown and infection control measures are eventually removed.

Rhinovirus/enterovirus was the most common respiratory virus detected in adults with severe acute respiratory infections pre-COVID-19 in Kuala Lumpur, Malaysia.

BACKGROUND: Severe acute respiratory infections (SARI) pose a great global burden. The contribution of respiratory viruses to adult SARI is relatively understudied in Asia. We aimed to determine viral aetiology of adult SARI patients in Kuala Lumpur, Malaysia. METHODS: The prevalence of 20 common (mainly viral) respiratory pathogens, and MERS-CoV, SARS-CoV and 5 bacterial select agents was investigated from May 2017 to October 2019 in 489 SARI adult patients in Kuala Lumpur, Malaysia, using molecular assays (Luminex NxTAG-RPP kit and qPCR assays). Viral metagenomics analysis was performed on 105 negative samples. RESULTS: Viral respiratory pathogens were detected by PCR in 279 cases (57.1%), including 10 (2.0%) additional detections by metagenomics analysis. The most detected viruses were rhinovirus/enterovirus (RV/EV) (49.1%) and influenza virus (7.4%). Three melioidosis cases were detected but no SARS-CoV, MERS-CoV or other bacterial select agents. Bacterial/viral co-detections and viral co-detections were found in 44 (9.0%) and 27 (5.5%) cases respectively, mostly involving RV/EV. Independent predictors of critical disease were male gender, chronic lung disease, lack of runny nose and positive blood culture with a significant bacterial pathogen. Asthma and sore throat were associated with increased risk of RV/EV detection, while among RV/EV cases, males and those with neurological disease were at increased risk of critical disease. CONCLUSIONS: Prior to the COVID-19 pandemic, the high prevalence of respiratory viruses in adults with SARI was mainly attributed to RV/EV. Continued surveillance of respiratory virus trends contributes to effective diagnostic, prevention, and treatment strategies.

Feasibility of supported self-management with a pictorial action plan to improve asthma control.

Supported self-management reduces asthma-related morbidity and mortality. This paper is on a feasibility study, and observing the change in clinical and cost outcomes of pictorial action plan use is part of assessing feasibility as it will help us decide on outcome measures for a fully powered RCT. We conducted a pre-post feasibility study among adults with physician-diagnosed asthma on inhaled corticosteroids at a public primary-care clinic in Malaysia. We adapted an existing pictorial asthma action plan. The primary outcome was asthma control, assessed at 1, 3 and 6 months. Secondary outcomes included reliever use, controller medication adherence, asthma exacerbations, emergency visits, hospitalisations, days lost from work/daily activities and action plan use. We estimated potential cost savings on asthma-related care following plan use. About 84% (n = 59/70) completed the 6-months follow-up. The proportion achieving good asthma control increased from 18 (30.4%) at baseline to 38 (64.4%) at 6-month follow-up. The proportion of at least one acute exacerbation (3 months: % difference -19.7; 95% CI -34.7 to -3.1; 6 months: % difference -20.3; 95% CI -5.8 to -3.2), one or more emergency visit (1 month: % difference -28.6; 95% CI -41.2 to -15.5; 3 months: % difference -18.0; 95% CI -32.2 to -3.0; 6 months: % difference -20.3; 95% CI -34.9 to -4.6), and one or more asthma admission (1 month: % difference -14.3; 95% CI -25.2 to -5.3; 6 months: % difference -11.9; 95% CI -23.2 to -1.8) improved over time. Estimated savings for the 59 patients at 6-months follow-up and for each patient over the 6 months were RM 15,866.22 (USD3755.36) and RM268.92 (USD63.65), respectively. Supported self-management with a pictorial asthma action plan was associated with an improvement in asthma control and potential cost savings in Malaysian primary-care patients.Trial registration number: ISRCTN87128530; prospectively registered: September 5, 2019, http://www.isrctn.com/ISRCTN87128530 .

Metastatic pulmonary calcification mimicking pulmonary tuberculosis: A case report.

Metastatic pulmonary calcification (MPC) is characterized by deposition of calcium in the normal lung parenchyma secondary to elevation of serum calcium. Most patients are asymptomatic and routine chest radiograph is not sensitive to make the diagnosis. Further imaging is needed such as computed tomography (CT) which typically shows small centrilobular nodules in the upper lobes. We report a case of a 30-year-old woman with end stage kidney disease who was diagnosed with pulmonary tuberculosis which was then revised to metastatic pulmonary calcification. The CT thorax feature for this patient was atypical for metastatic pulmonary calcification where it demonstrated tree-in-bud nodules suggestive of infection. The final diagnosis was made based on bronchoalveolar lavage which was culture-negative for Mycobacterium and transbronchial lung biopsy demonstrating calcium deposition in the interstitium.

Outcomes of Patients with EGFR-Mutant Advanced NSCLC in a Developing Country in Southeast Asia.

Background: 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.

Programmed death-ligand 1 expression and use of immune checkpoint inhibitors among patients with advanced non-small-cell lung cancer in a resource-limited country.

INTRODUCTION: Immune checkpoint inhibitor (ICI) therapy is an established treatment for advanced non-small-cell lung cancer (NSCLC) and programmed death ligand-1 (PD-L1) expression is a recognized biomarker to determine response to therapy. We retrospectively analyzed NSCLC patients in the Malaysia Lung Cancer Registry (MLCR) and report on the clinical characteristics associated with PD-L1 expression and ICI use in Malaysia, a low- to middle-income country. METHODS: All 901 NSCLC patients in the MLCR who were diagnosed from January 1, 2017 to December 31, 2020 from 14 hospitals across the country were analyzed. RESULTS: Out of 901 patients, 505 had PDL-1 testing done with complete data available only in 489 patients. The most common histology was adenocarcinoma (84.7%) followed by squamous cell carcinoma (10.2%). The majority (95%) presented with stage 3 or 4. The number and percentage of patients with PDL-1 tumor proportion scores of ≥50%, 1-49%, and <1% were 138 (28.2%), 158 (32.3%), and 193 (39.5%), respectively. In multivariate analysis, the presence of genomic mutation is the only independent characteristic associated with negative PD-L1 expression (crude odds ratio 0.579, 95% confidence interval 0.399-0.840, p = 0.004). Of 292 patients eligible for ICI therapy, only 100 patients (34.2%) received ICIs. Seventy-eight patients received ICI therapy as first-line treatment, 15 patients as second-line treatment, and 7 patients as third-line treatment. CONCLUSIONS: This is the first analysis on PD-L1 expression and ICI use in Malaysia. Despite the proven efficacy of ICI therapy, only 56% of our patients had PD-L1 tests performed and only 34.2% of eligible patients received ICIs.

Changing predominant SARS-CoV-2 lineages drives successive COVID-19 waves in Malaysia, February 2020 to March 2021.

Malaysia has experienced three waves of coronavirus disease 2019 (COVID-19) as of March 31, 2021. We studied the associated molecular epidemiology and SARS-CoV-2 seroprevalence during the third wave. We obtained 60 whole-genome SARS-CoV-2 sequences between October 2020 and January 2021 in Kuala Lumpur/Selangor and analyzed 989 available Malaysian sequences. We tested 653 residual serum samples collected between December 2020 to April 2021 for anti-SARS-CoV-2 total antibodies, as a proxy for population immunity. The first wave (January 2020) comprised sporadic imported cases from China of early Pango lineages A and B. The second wave (March-June 2020) was associated with lineage B.6. The ongoing third wave (from September 2020) was propagated by a state election in Sabah. It is due to lineage B.1.524 viruses containing spike mutations D614G and A701V. Lineages B.1.459, B.1.470, and B.1.466.2 were likely imported from the region and confined to Sarawak state. Direct age-standardized seroprevalence in Kuala Lumpur/Selangor was 3.0%. The second and third waves were driven by super-spreading events and different circulating lineages. Malaysia is highly susceptible to further waves, especially as alpha (B.1.1.7) and beta (B.1.351) variants of concern were first detected in December 2020/January 2021. Increased genomic surveillance is critical.