METHODS: This was a cross-sectional study of COPD patients who attended the outpatient clinic of the Serian Divisional Hospital and Bau District Hospital from 23th January 2018 to 22th January 2019. The HRQoL was assessed using modified Medical Research Council (mMRC), COPD Assessment Test (CAT), and St George's Respiratory Questionnaire for COPD (SGRQ-c).
RESULTS: Of 185 patients, 108 (58.4%) were non-exacerbators (NON-AE), 51 (27.6%) were frequent exacerbators (AE), and the remaining 26 (14.1%) had asthma-COPD overlap (ACO). Of AE patients, 42 (82.4%) had chronic bronchitis and only 9 (17.6%) had emphysema. Of the 185 COPD patients, 65.9% had exposure to biomass fuel and 69.1% were ex- or current smokers. The scores of mMRC, CAT, and SGRQ-c were significantly different between COPD phenotypes (p
Methods: An observational study was conducted among 3935 patients presenting with acute upper respiratory illnesses in the ambulatory settings between 2012 and 2014.
Results: The VP4/VP2 gene was genotyped from all 976 RV-positive specimens, where the predominance of RV-A (49%) was observed, followed by RV-C (38%) and RV-B (13%). A significant regression in median nasopharyngeal viral load (VL) (P < .001) was observed, from 883 viral copies/µL at 1-2 days after symptom onset to 312 viral copies/µL at 3-4 days and 158 viral copies/µL at 5-7 days, before declining to 35 viral copies/µL at ≥8 days. In comparison with RV-A (median VL, 217 copies/µL) and RV-B (median VL, 275 copies/µL), RV-C-infected subjects produced higher VL (505 copies/µL; P < .001). Importantly, higher RV VL (median, 348 copies/µL) was associated with more severe respiratory symptoms (Total Symptom Severity Score ≥17, P = .017). A total of 83 phylogenetic-based transmission clusters were identified in the population. It was observed that the relative humidity was the strongest environmental predictor of RV seasonality in the tropical climate.
Conclusions: Our findings underline the role of VL in increasing disease severity attributed to RV-C infection, and unravel the factors that fuel the population transmission dynamics of RV.
OBJECTIVES: We aimed to investigate the incidence of respiratory viruses in adult patients with suspected COVID-19 in Kuala Lumpur, Malaysia.
STUDY DESIGN: We collected 198 respiratory samples from adult patients hospitalized with suspected COVID-19 in a single teaching hospital in Kuala Lumpur in February-May 2020 and tested combined oro-nasopharyngeal swabs with the NxTAG Respiratory Pathogen Panel (Luminex) and Allplex RV Essential (Seegene) assays. Forty-five negative samples further underwent viral metagenomics analysis.
RESULTS: Of the 198 samples, 74 (37.4%) had respiratory pathogens, including 56 (28.3%) with SARS-CoV-2 and 18 (9.1%) positive for other respiratory pathogens. There were five (2.5%) SARS-CoV-2 co-infections, all with rhinovirus/enterovirus. Three samples (6.7%; 3/45) had viruses identified by metagenomics, including one case of enterovirus D68 and one of Saffold virus genotype 6 in a patient requiring ICU care. Most of the COVID-19 patients (91.1%; 51/56) had mild symptoms but 5.4% (3/56) died.
CONCLUSION: During the early COVID-19 period, common respiratory viruses other than SARS-CoV-2 only accounted for 9.1% of hospitalization cases with ARI and co-infections with SARS-CoV-2 were rare. Continued surveillance is important to understand the impact of COVID-19 and its associated public health control measures on circulation of other respiratory viruses. Metagenomics can identify unexpected or rare pathogens, such as Saffold virus, which is rarely described in adults.
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.
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
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.
METHODS: Adults with asthma were purposively recruited from an urban primary healthcare clinic for in-depth interviews. Audio-recordings were transcribed verbatim and analysed thematically.
RESULTS: We interviewed 24 adults. Four themes emerged: (1) Participants believed in the 'hot and cold' concept of illness either as an inherent hot/cold body constitution or the ambient temperature. Hence, participants tried to 'neutralize' body constitution or to 'warm up' the cold temperature that was believed to trigger acute attacks. (2) Participants managed asthma based on past experiences and personal health beliefs as they lacked formal information about asthma and its treatment. (3) Poor communication and variable advice from healthcare practitioners on how to manage their asthma contributed to poor self-management skills. (4) Embarrassment about using inhalers in public and advice from family and friends resulted in a focus on nonpharmacological approaches to asthma self-management practice.
CONCLUSIONS: Asthma self-management practices were learnt experientially and were strongly influenced by sociocultural beliefs and advice from family and friends. Effective self-management needs to be tailored to cultural norms, personalized to the individuals' preferences and clinical needs, adapted to their level of health literacy and underpinned by patient-practitioner partnerships.
PATIENT AND PUBLIC CONTRIBUTIONS: Patients contributed to data. Members of the public were involved in the discussion of the results.
METHODS: We conducted a multicenter, hospital-based active surveillance study of adults in Malaysia with community-acquired pneumonia (CAP), acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and acute exacerbation of asthma (AEBA), who had influenza-like illness ≤10 days before hospitalization. We estimated the rate of laboratory-confirmed influenza and associated complications over 13 months (July 2018-August 2019) and described the distribution of causative influenza strains. We evaluated predictors of laboratory-confirmed influenza and severe clinical outcomes using multivariate analysis.
RESULTS: Of 1106 included patients, 114 (10.3%) were influenza-positive; most were influenza A (85.1%), with A/H1N1pdm09 being the predominant circulating strain during the study following a shift from A/H3N2 from January-February 2019 onwards. In multivariate analyses, an absence of comorbidities (none versus any comorbidity [OR (95%CI), 0.565 (0.329-0.970)], p = 0.038) and of dyspnea (0.544 (0.341-0.868)], p = 0.011) were associated with increased risk of influenza positivity. Overall, 184/1106 (16.6%) patients were admitted to intensive care or high-dependency units (ICU/HDU) (13.2% were influenza positive) and 26/1106 (2.4%) died (2.6% were influenza positive). Males were more likely to have a severe outcome (ICU/HDU admission or death).
CONCLUSIONS: Influenza was a significant contributor to hospitalizations associated with CAP, AECOPD and AEBA. However, it was not associated with ICU/HDU admission in this population. Study registration, NMRR ID: NMRR-17-889-35,174.
Methods: We conducted a scoping review to map prevalence surveys conducted in LMICs published between 1995 and 2018. We followed Arksey and O'Malley's six-step framework. The search was conducted in OVID Medline, EMBASE, ISI Web of Science, Global Health, WHO Global Index Medicus and included three domains: CRDs, prevalence and LMICs. After an initial title sift, eight trained reviewers undertook duplicate study selection and data extraction. We charted: country and populations, random sampling strategies, CRD definitions/phenotypes, survey procedure (questionnaires, spirometry, tests), outcomes and assessment of individual, societal and health service burden of disease.
Results: Of 36 872 citations, 281 articles were included: 132 from Asia (41 from China). Study designs were cross-sectional surveys (n = 260), cohort studies (n = 11) and secondary data analysis (n = 10). The number of respondents in these studies ranged from 50 to 512 891. Asthma was studied in 144 studies, chronic obstructive pulmonary disease (COPD) in 112. Most studies (100/144) based identification of asthma on symptom-based questionnaires. In contrast, COPD diagnosis was typically based on spirometry findings (94/112); 65 used fixed-ratio thresholds, 29 reported fixed-ratio and lower-limit-of-normal values. Only five articles used the term 'phenotype'. Most studies used questionnaires derived from validated surveys, most commonly the European Community Respiratory Health Survey (n = 47). The burden/impact of CRD was reported in 33 articles (most commonly activity limitation).
Conclusion: Surveys remain the most practical approach for estimating prevalence of CRD but there is a need to identify the most predictive questions for diagnosing asthma and to standardise diagnostic criteria.
METHODS: Patients aged ≥20 years received once-daily oral olmutinib 800 mg continuously in 21-day cycles. The primary endpoint was the objective response rate (patients who had a confirmed best overall response of a complete or partial response), assessed by central review. Secondary endpoints included the disease control rate, the duration of objective response, progression-free survival, and overall survival. Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.03).
RESULTS: Overall, 162 patients (median age, 63 years; women, >60%) were enrolled from 68 sites in 9 countries. At the time of database cutoff, 23.5% of enrolled patients remained on treatment. The median treatment duration was 6.5 months (range, 0.03-21.68 months). Overall, 46.3% of patients (95% CI, 38.4%-54.3%) had a confirmed objective response (all partial responses). The best overall response (the objective response rate regardless of confirmation) was 51.9% (84 patients; 95% CI, 43.9%-59.8%). The confirmed disease control rate for all patients was 86.4% (95% CI, 80.2%-91.3%). The median duration of objective response was 12.7 months (95% CI, 8.3-15.4 months). Estimated median progression-free survival was 9.4 months (95% CI, 6.9-12.3 months), and estimated median overall survival was 19.7 months (95% CI, 15.1 months to not reached). All patients experienced treatment-emergent adverse events, and 71.6% of patients had grade ≥3 treatment-emergent adverse events.
CONCLUSIONS: Olmutinib has meaningful clinical activity and a manageable safety profile in patients with T790M-positive non-small cell lung cancer who received previous epidermal growth factor receptor-tyrosine kinase inhibitor therapy.
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.
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.
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.
Methods: We administered relevant translations of the BOLD-1 questionnaire with additional questions from ECRHS-II, performed spirometry and arranged specialist clinical review for a sub-group to confirm the diagnosis. Using random sampling, we piloted a community-based survey at five sites in four LMICs and noted any practical barriers to conducting the survey. Three clinicians independently used information from questionnaires, spirometry and specialist reviews, and reached consensus on a clinical diagnosis. We used lasso regression to identify variables that predicted the clinical diagnoses and attempted to develop an algorithm for detecting asthma and COPD.
Results: Of 508 participants, 55.9% reported one or more chronic respiratory symptoms. The prevalence of asthma was 16.3%; COPD 4.5%; and 'other chronic respiratory disease' 3.0%. Based on consensus categorisation (n = 483 complete records), "Wheezing in last 12 months" and "Waking up with a feeling of tightness" were the strongest predictors for asthma. For COPD, age and spirometry results were the strongest predictors. Practical challenges included logistics (participant recruitment; researcher safety); misinterpretation of questions due to local dialects; and assuring quality spirometry in the field.
Conclusion: Detecting asthma in population surveys relies on symptoms and history. In contrast, spirometry and age were the best predictors of COPD. Logistical, language and spirometry-related challenges need to be addressed.