Atrial Tachycardias After "Multiple" Previous Ablations for Tachyarrhythmias: Treatment by Anti-arrhythmic Drugs or Additional Ablation?

Pulmonary vein (PV) isolation (PVI) ablation as the first-line therapy for atrial fibrillation (AF) and repeat PVIs for patients who had symptomatic improvement with the index PVI but who develop AF recurrence are directed by practice guidelines. How many catheter ablation (CA) procedures constitute the definition of "multiple" ablations is not known. Whether atrial tachyarrhythmias (AF, atrial tachycardia [AT], atrial flutter [AFL]) that occur post-ablation are due entirely to the proarrhythmic effects of CA or a continuum of the arrhythmia spectrum from the underlying atriopathy is debatable. Herein, we describe a case of a 65-year-old man with a CHA2DS2-VASc score of 5 points who suffered from atrial tachyarrhythmias for which seven CA procedures were performed. Because of symptomatic and drug-refractory AT/AFL that failed cardioversions, he requested another ablation procedure. During the eighth procedure, high-density three-dimensional electroanatomic mapping, including Coherent and Ripple mapping (CARTO® 3; Biosense Webster, Diamond Bar, CA, USA), of AT/AFL was performed. Small discrete areas of relatively viable tissue within an extensively scarred left atrium and a macro-re-entrant circuit with early-meets-late activation between the left atrial anterior wall and the right superior PV were found. Radiofrequency ablation performed at this site resulted in the termination of the tachycardia, and bidirectional conduction block across the line was achieved. On clinical follow-ups and rhythm monitoring by an implantable loop recorder, the patient remained in sinus rhythm with significant clinical improvement. Our case suggests that, in patients with prior multiple CAs, additional clinically indicated ablation should be performed using high-density mapping to accurately identify arrhythmia mechanisms, elucidate the disease substrate, and restore the sinus rhythm successfully.

Heterogeneity in the prevalence of subclinical malaria, other co-infections and anemia among pregnant women in rural areas of Myanmar: a community-based longitudinal study.

BACKGROUND: Due to the low prevalence of clinically suspected malaria among pregnant women in Myanmar, little is known about its impact on mothers and newborns. Helminth and Human Immuno-deficiency Virus (HIV) co-infections cause anemia in pregnant women. This study assessed the prevalence of subclinical malaria and co-infections among pregnant women, and its association with adverse outcomes of pregnancy in the presence of infection. METHODS: A prospective longitudinal study was conducted in 12 villages in two townships in Myanmar between 2013 to 2015. A total of 752 pregnant women, with a mean age of 27 years, were enrolled and followed up once a month until six weeks after childbirth. Prevalence ratio was calculated in the multivariable analysis. RESULTS: The prevalence of subclinical malaria as measured by nested PCR was 5.7% for either P. falciparum or P. vivax, 2.7% prevalence of P. falciparum and 2.8% prevalence of P. vivax. Helminth infections were prevalent in 17% of women, and one woman with an HIV infection was found in our study. The burden of anemia was high, with an overall prevalence of 37% with or without helminth infection, 42% of the women were malaria positive and 43% had dual infections (both malaria and helminth). Only 11 abnormal pregnancy outcomes (7 stillbirths, 2 premature, 2 twins) were identified. Poisson regression showed that women in their first trimester had a 2.9 times higher rate of subclinical malaria compared to women in the third trimester (PR:2.9, 95%CI 1.19, 7.31, p = 0.019), women who were enrolled during the wet season were 2.5 times more likely to be malaria positive than the women enrolled in the dry season (PR: 2.5, 95%CI 1.27, 4.88, p = 0.008), and the malaria positivity rate decreased by 5% when increased in one year of woman's age (PR:0.95, 95%CI 0.91, 0.99, p = 0.02). In the multivariable regression, the age of respondents was the only significant factor associated with subclinical malaria in pregnancy. CONCLUSIONS: A comprehensive approach of integrating interventions for malaria, anemia, and helminths should be delivered during antenatal care services for pregnant women in rural areas of Myanmar.

Dengue in Myanmar: Spatiotemporal epidemiology, association with climate and short-term prediction.

Dengue is a major public health problem in Myanmar. The country aims to reduce morbidity by 50% and mortality by 90% by 2025 based on 2015 data. To support efforts to reach these goals it is important to have a detailed picture of the epidemiology of dengue, its relationship to meteorological factors and ideally to predict ahead of time numbers of cases to plan resource allocations and control efforts. Health facility-level data on numbers of dengue cases from 2012 to 2017 were obtained from the Vector Borne Disease Control Unit, Department of Public Health, Myanmar. A detailed analysis of routine dengue and dengue hemorrhagic fever (DHF) incidence was conducted to examine the spatial and temporal epidemiology. Incidence was compared to climate data over the same period. Dengue was found to be widespread across the country with an increase in spatial extent over time. The temporal pattern of dengue cases and fatalities was episodic with annual outbreaks and no clear longitudinal trend. There were 127,912 reported cases and 632 deaths from 2012 and 2017 with peaks in 2013, 2015 and 2017. The case fatality rate was around 0.5% throughout. The peak season of dengue cases was from May to August in the wet season but in 2014 peak dengue season continued until November. The strength of correlation of dengue incidence with different climate factors (total rainfall, maximum, mean and minimum temperature and absolute humidity) varied between different States and Regions. Monthly incidence was forecasted 1 month ahead using the Auto Regressive Integrated Moving Average (ARIMA) method at country and subnational levels. With further development and validation, this may be a simple way to quickly generate short-term predictions at subnational scales with sufficient certainty to use for intervention planning.

A cross-sectional study of avian influenza A virus in Myanmar live bird markets: Detection of a newly introduced H9N2?

BACKGROUND: Zoonotic influenza surveillance in Myanmar is sparse, despite the risks of introduction of such viruses from neighboring countries that could impact the poultry industry and lead to spillover to humans. METHODS: In July and August 2019, our multi-institutional partnership conducted a One Health-oriented, cross-sectional surveillance (weekly for 3 weeks) for influenza A and influenza D viruses at the three largest live bird markets in Yangon, Myanmar. RESULTS: The 27 bioaerosols, 90 bird cage swabs, 90 bird oropharyngeals, and 90 human nasopharyngeal samples yielded molecular influenza A detections in 8 bioaerosols (30.0%), 16 bird cages (17.8%), 15 bird oropharyngeals (16.7%), and 1 human nasopharyngeal (1.1%) samples. No influenza D was detected. Seven of the influenza A virus detections were found to be subtype A/H9N2, and one human nasopharyngeal sample was found to be subtype A/H1pdm. Among all IAV-positive samples, three of the A/H9N2-positive samples yielded live viruses from egg culture and their whole genome sequences revealing they belonged to the G9/Y280 lineage of A/H9N2 viruses. Phylogenetic analyses showed that these A/H9N2 sequences clustered separately from A/H9N2 viruses that were previously detected in Myanmar, supporting the notion that A/H9N2 viruses similar to those seen in wider Southeast Asia may have been introduced to Myanmar on multiple occasions. CONCLUSIONS: These findings call for increased surveillance efforts in Myanmar to monitor for the introduction of novel influenza viruses in poultry, as well as possible reassortment and zoonotic virus transmission.

Genomic tracking of SARS-COV-2 variants in Myanmar

BackgroundIn December 2019, the COVID-19 disease started in Wuhan, China. WHO declared a pandemic on March 12, 2020, and the disease started in Myanmar on March 23, 2020. December brought variants around the world, threatening the healthcare systems. To counter those threats, Myanmar started the COVID-19 variant surveillance program in late 2020. MethodsWhole genome sequencing was done six times between January 2021 and March 2022. We chose 83 samples with a PCR threshold cycle of less than 25. Then, we used MiSeq FGx for sequencing and Illumina DRAGEN COVIDSeq pipeline, command line interface, GISAID, and MEGA version 7 for data analysis. Result and DiscussionJanuary 2021 results showed no variant. The second run during the rise of cases in June 2021 showed multiple variants like Alpha, Delta, and Kappa. There is only Delta in the third run at the height of mortality in August, and Delta alone continued until the fourth run in December. After the world reported the Omicron variant in November, Myanmar started a surveillance program. The fifth run in January 2022 showed both Omicron and Delta variants. The sixth run in March 2022 showed only Omicron BA.2. Amino acid mutation at receptor binding domain (RBD) of Spike glycoprotein started since the second run coupling with high transmission, recurrence, and vaccine escape. We also found the mutation at the primer targets used in current RT-PCR platforms. ConclusionThe occurrence of multiple variants and mutations claimed vigilance at ports of entry and preparedness for effective control measures. Genomic surveillance with the observation of evolutionary data is required to predict imminent threats of the current disease and diagnose emerging infectious diseases.

Clinical Presentation of Immune-Related Endocrine Adverse Events during Immune Checkpoint Inhibitor Treatment.

The exact clinical course and factors associated with persistent endocrine immune-related adverse events (irAEs) are not well-established. Elucidation of these information will aid irAEs screening and follow-up planning for patients on immunotherapy. We analysed the clinical course of endocrine irAEs including thyroid and pituitary dysfunction and insulin-dependent diabetes mellitus (IDDM), identified factors associated with persistent thyroid dysfunction, and determined the association between endocrine irAEs and survival parameters. This retrospective observational study enrolled patients with metastatic cancer who underwent anti-PD-1, anti-PD-L1, and/or anti-CTLA-4 treatment and developed endocrine irAE at the National University Cancer Institute, Singapore, between June 2015 and December 2020. Sixty-six patients with endocrine irAE were evaluated, with a median follow-up time of 15.7 months. The median time to onset of thyroid dysfunction, pituitary dysfunction, and IDDM was 1.8 months (range: 0.3-15.8 months), 6.8 months (range: 1.5-27.3 months), and 7.8 months (range: 1.4-9.1 months), respectively. Positive thyroperoxidase antibodies (TPOAb) and/ or thyroglobulin antibodies (TgAb) status at the time of thyroid dysfunction was associated with persistent thyroid dysfunction (OR 11.6, 95% CI 1.3-570.8, p = 0.02; OR 8.8, 95% CI 1.3-106.9, p = 0.01, respectively). All patients with pituitary irAE had central hypocortisolism. All patients with IDDM had grade 4 irAE. Patients with endocrine irAE had longer median survival times. Endocrine irAEs were associated with non-progressive disease. The screening and follow-up approach for endocrine irAEs should be tailored according to each endocrinopathy's clinical course. Early screening is imperative given its wide median time to onset.

Genomic Tracking of SARS-CoV-2 Variants in Myanmar.

In December 2019, the COVID-19 disease started in Wuhan, China. The WHO declared a pandemic on 12 March 2020, and the disease started in Myanmar on 23 March 2020. In December 2020, different variants were brought worldwide, threatening global health. To counter those threats, Myanmar started the COVID-19 variant surveillance program in late 2020. Whole genome sequencing was done six times between January 2021 and March 2022. Among them, 83 samples with a PCR threshold cycle of less than 25 were chosen. Then, we used MiSeq FGx for sequencing and Illumina DRAGEN COVIDSeq pipeline, command line interface, GISAID, and MEGA version 7 for data analysis. In January 2021, no variant was detected. The second run, during the rise of cases in June 2021, showed Alpha, Delta, and Kappa variants. The third and the fourth runs in August and December showed only a Delta variant. Omicron and Delta variants were detected during the fifth run in January 2022. The sixth run in March 2022 showed only Omicron BA.2. Amino acid mutation at the receptor binding domain of Spike glycoprotein started since the second run coupling with high transmission, recurrence, and vaccine escape. We also found the mutation at the primer targets used in current RT-PCR platforms, but there was no mutation at the existing antiviral drug targets. The occurrence of multiple variants and mutations claimed vigilance at ports of entry and preparedness for effective control measures. Genomic surveillance with the observation of evolutionary data is required to predict imminent threats of the current disease and diagnose emerging infectious diseases.

School and community driven dengue vector control and monitoring in Myanmar: Study protocol for a cluster randomized controlled trial.

Background: Dengue is the most common and widespread mosquito-borne arboviral disease globally estimated to cause >390 million infections and >20,000 deaths annually. There are no effective preventive drugs and the newly introduced vaccines are not yet available. Control of dengue transmission still relies primarily on mosquito vector control. Although most vector control methods currently used by national dengue control programs may temporarily reduce mosquito populations, there is little evidence that they affect transmission. There is an urgent need for innovative, participatory, effective, and locally adapted approaches for sustainable vector control and monitoring in which students can be particularly relevant contributors and to demonstrate a clear link between vector reduction and dengue transmission reduction, using tools that are inexpensive and easy to use by local communities in a sustainable manner. Methods: Here we describe a cluster randomized controlled trial to be conducted in 46 school catchment areas in two townships in Yangon, Myanmar. The outcome measures are dengue cases confirmed by rapid diagnostic test in the townships, dengue incidence in schools, entomological indices, knowledge, attitudes and practice, behavior, and engagement. Conclusions: The trial involves middle school students that positions them to become actors in dengue knowledge transfer to their communities and take a leadership role in the delivery of vector control interventions and monitoring methods. Following this rationale, we believe that students can become change agents of decentralized vector surveillance and sustainable disease control in line with recent new paradigms in integrated and participatory vector surveillance and control. This provides an opportunity to operationalize transdisciplinary research towards sustainable health development. Due to the COVID-19 pandemic and political instability in Myanmar the project has been terminated by the donor, but the protocol will be helpful for potential future implementation of the project in Myanmar and/or elsewhere.Registration: This trial was registered in the ISRCTN Registry on 31 May 2022 ( https://doi.org/10.1186/ISRCTN78254298).

Dengue is a mosquito-borne disease, causing millions of infections and thousands of deaths annually. Current control efforts focus on reducing mosquito numbers, but there's little evidence of their impact on disease transmission. New innovative and locally adapted approaches are needed to sustain vector control. We describe a trial protocol for Yangon, Myanmar, involving 46 schools, for reducing the number of dengue cases and mosquitoes in schools and communities though various interventions. Middle school students will play a central role, becoming agents in transferring dengue knowledge to their communities, leading vector control efforts. The idea is that students can drive decentralized vector surveillance, aligning with modern disease control approaches. This initiative offers a chance to integrate diverse research disciplines for sustainable health development. Unfortunately, due to the COVID-19 pandemic and political instability in Myanmar, the project could not be realized. Despite this setback, the outlined protocol remains valuable for potential future implementation in Myanmar or elsewhere, emphasizing the importance of student involvement in community-based disease control efforts.

A dilemma of hemorrhage vs thrombosis: a case of watchman device thrombus in a patient with intracranial hemorrhage history.

Recently updated guidelines for Atrial Fibrillation (AF) outline that percutaneous left atrial appendage (LAA) occlusion with the Watchman device may be a reasonable alternative for those who have contraindications to long-term oral anticoagulation. However, optimal periprocedural antithrombotic therapy remains disputable, particularly in patients who are ineligible for oral anticoagulation or those with history of intracranial hemorrhage (ICH). We present the case of a 67-year-old male with a history of ischemic stroke with hemorrhagic conversion and permanent AF, who was treated with the Watchman device and subsequently developed device related thrombus and recurrent ischemic stroke. We discuss the dilemma and review the literature regarding anticoagulation for device related thrombus in this patient with increased bleeding risk, given his history of ICH. His course and antithrombotic strategy are described and despite the use of anticoagulation with warfarin in the setting of recurrent ischemic stroke, he did not develop hemorrhagic transformation. He also did, ultimately, achieve device related thrombus resolution on repeat Transesophageal Echocardiogram (TEE). This case supported the use of warfarin for device related thrombus in the setting of ischemic stroke and history of ICH. However, evidence-based guidelines for periprocedural antithrombotic regimens in patients with high bleeding risk have yet to be released and further research is needed.

Integrative Profiling of T790M-Negative EGFR-Mutated NSCLC Reveals Pervasive Lineage Transition and Therapeutic Opportunities.

PURPOSE: Despite the established role of EGFR tyrosine kinase inhibitors (TKIs) in EGFR-mutated NSCLC, drug resistance inevitably ensues, with a paucity of treatment options especially in EGFR T790M-negative resistance. EXPERIMENTAL DESIGN: We performed whole-exome and transcriptome analysis of 59 patients with first- and second-generation EGFR TKI-resistant metastatic EGFR-mutated NSCLC to characterize and compare molecular alterations mediating resistance in T790M-positive (T790M+) and -negative (T790M-) disease. RESULTS: Transcriptomic analysis revealed ubiquitous loss of adenocarcinoma lineage gene expression in T790M- tumors, orthogonally validated using multiplex IHC. There was enrichment of genomic features such as TP53 alterations, 3q chromosomal amplifications, whole-genome doubling and nonaging mutational signatures in T790M- tumors. Almost half of resistant tumors were further classified as immunehot, with clinical outcomes conditional on immune cell-infiltration state and T790M status. Finally, using a Bayesian statistical approach, we explored how T790M- and T790M+ disease might be predicted using comprehensive genomic and transcriptomic profiles of treatment-naïve patients. CONCLUSIONS: Our results illustrate the interplay between genetic alterations, cell lineage plasticity, and immune microenvironment in shaping divergent TKI resistance and outcome trajectories in EGFR-mutated NSCLC. Genomic and transcriptomic profiling may facilitate the design of bespoke therapeutic approaches tailored to a tumor's adaptive potential.

Smartphone electrocardiogram for detecting atrial fibrillation after a cerebral ischaemic event: a multicentre randomized controlled trial.

AIMS: Atrial fibrillation (AF) is a preventable cause of ischaemic stroke but it is often undiagnosed and undertreated. The utility of smartphone electrocardiogram (ECG) for the detection of AF after ischaemic stroke is unknown. The aim of this study is to determine the diagnostic yield of 30-day smartphone ECG recording compared with 24-h Holter monitoring for detecting AF ≥30 s. METHODS AND RESULTS: In this multicentre, open-label study, we randomly assigned 203 participants to undergo one additional 24-h Holter monitoring (control group, n = 98) vs. 30-day smartphone ECG monitoring (intervention group, n = 105) using KardiaMobile (AliveCor®, Mountain View, CA, USA). Major inclusion criteria included age ≥55 years old, without known AF, and ischaemic stroke or transient ischaemic attack (TIA) within the preceding 12 months. Baseline characteristics were similar between the two groups. The index event was ischaemic stroke in 88.5% in the intervention group and 88.8% in the control group (P = 0.852). AF lasting ≥30 s was detected in 10 of 105 patients in the intervention group and 2 of 98 patients in the control group (9.5% vs. 2.0%; absolute difference 7.5%; P = 0.024). The number needed to screen to detect one AF was 13. After the 30-day smartphone monitoring, there was a significantly higher proportion of patients on oral anticoagulation therapy at 3 months compared with baseline in the intervention group (9.5% vs. 0%, P = 0.002). CONCLUSIONS: Among patients ≥55 years of age with a recent cryptogenic stroke or TIA, 30-day smartphone ECG recording significantly improved the detection of AF when compared with the standard repeat 24-h Holter monitoring.

Human milk banks in the response to COVID-19: a statement of the regional human milk bank network for Southeast Asia and beyond.

BACKGROUND: The World Health Organization (WHO) recommendations on infant feeding in the context of COVID-19 uphold standing recommendations for breastfeeding, non-separation, and skin-to-skin contact, including the use of donor human milk when mother's own milk is not available. INSUFFICIENT GUIDANCE ON THE USE OF DONOR HUMAN MILK AND THE ROLE OF HUMAN MILK BANKS IN THE PANDEMIC RESPONSE: COVID-19 clinical management guidelines in seven countries in Southeast Asia are not aligned with WHO recommendations despite the lack of evidence of transmission through either breastmilk or breastfeeding. The use of safe donor human milk accessed through human milk banks is also insufficiently recommended, even in countries with an existing human milk bank, leading to a gap in evidence-based management of COVID-19. This highlights long-standing challenges as well as opportunities in the safe, equitable, and resilient implementation of human milk banks in the region. CONCLUSIONS: This statement reflects the expert opinion of the Regional Human Milk Bank Network for Southeast Asia and Beyond on the need to revisit national guidelines based on the best evidence for breastfeeding during the COVID-19 pandemic, to incorporate human milk bank services in national obstetric and newborn care guidelines for COVID-19 where possible, and to ensure that operations of human milk banks are adapted to meet the needs of the current pandemic and to sustain donor human milk supply in the long-term. The Network also recommends sustained engagement with the global human milk bank community.

Malaria Exposure in Ann Township, Myanmar, as a Function of Land Cover and Land Use: Combining Satellite Earth Observations and Field Surveys.

Despite progress toward malaria elimination in the Greater Mekong Subregion, challenges remain owing to the emergence of drug resistance and the persistence of focal transmission reservoirs. Malaria transmission foci in Myanmar are heterogeneous and complex, and many remaining infections are clinically silent, rendering them invisible to routine monitoring. The goal of this research is to define criteria for easy-to-implement methodologies, not reliant on routine monitoring, that can increase the efficiency of targeted malaria elimination strategies. Studies have shown relationships between malaria risk and land cover and land use (LCLU), which can be mapped using remote sensing methodologies. Here we aim to explain malaria risk as a function of LCLU for five rural villages in Myanmar's Rakhine State. Malaria prevalence and incidence data were analyzed through logistic regression with a land use survey of ~1,000 participants and a 30-m land cover map. Malaria prevalence per village ranged from 5% to 20% with the overwhelming majority of cases being subclinical. Villages with high forest cover were associated with increased risk of malaria, even for villagers who did not report visits to forests. Villagers living near croplands experienced decreased malaria risk unless they were directly engaged in farm work. Finally, land cover change (specifically, natural forest loss) appeared to be a substantial contributor to malaria risk in the region, although this was not confirmed through sensitivity analyses. Overall, this study demonstrates that remotely sensed data contextualized with field survey data can be used to inform critical targeting strategies in support of malaria elimination.

Acute Bacterial Suppurative Thyroiditis following Fine Needle Aspiration: A Case Report and Review of the Literature.

BACKGROUND: Fine needle aspiration (FNA) of thyroid nodules is a simple, reliable, and inexpensive procedure performed on suspicious thyroid nodules found in thyroid ultrasound (US). Acute bacterial suppurative thyroiditis is an uncommon complication of FNA which, however, can be life threatening. Case Presentation. A 49-year-old lady presented with fever and neck pain 1 month after FNA with biochemical evidence of thyrotoxicosis. Repeat US of the thyroid showed interval enlargement of the thyroid nodule, and the culture of the cystic fluid of repeat FNA grew Propionibacterium acnes. She responded well to bedside aspiration and 2 weeks of antibiotic therapy without requiring surgical intervention. Discussion. Acute bacterial suppurative thyroiditis following FNA has been increasingly reported in immunocompetent hosts. There are 2 peculiar features in our case: a smoldering course caused by an indolent organism and a significant time lag between initial FNA and clinical presentation. On literature review, it was found that the onset of acute bacterial suppurative thyroiditis after FNA can range from a few days to up to 3 months. Clinicians should be aware of this complication even if FNA has been performed a few months ago. Thyroid US and US-guided FNA are useful initial investigations. Conventional management of acute bacterial suppurative thyroiditis has been surgery combined with antimicrobial therapy. However, recently, a more conservative approach has been reported to be effective in the treatment of acute bacterial suppurative thyroiditis as well. CONCLUSION: Proper infection control practices are necessary in performing the FNA. Initial management (conservative versus surgical) of acute bacterial thyroiditis should be based on the patient's clinical status and the extent of infective focus.

A hospital-based study on ischaemic stroke characteristics, management, and outcomes in Sarawak: Where do we stand?

BACKGROUND: Located on the Borneo Island, Sarawak is the largest state of Malaysia and has a population distinctive from Peninsular Malaysia. The ischaemic stroke data in Sarawak had not been reported despite the growing number of patients annually. We aimed to investigate patient characteristics, management, and outcomes of ischaemic stroke in Sarawak and benchmark the results with national and international published data. METHODS: We included ischaemic stroke cases admitted to Sarawak General Hospital between June 2013 and August 2018 from Malaysia National Stroke Registry. We performed descriptive analyses on patient demographics, cardiovascular risk factors, prior medications, smoking status, arrival time, thrombolysis rate, Get With The Guidelines (GWTG)-Stroke measures, and outcomes at discharge. We also numerically compared the results from Sarawak with the published data from selected national and international cohorts. RESULTS: We analysed 1435 ischaemic stroke cases. The mean age was 60.1±13.2 years old; 64.9% were male; median baseline National Institute of Health Stroke Scale was seven points. Hypertension was the most prevalent risk factor of ischaemic stroke; 12.7% had recurrent stroke; 13.7% were active smokers. The intravenous thrombolysis rate was 18.8%. We achieved 80-90% in three GWTG-Stroke performance measures and 90-98% in four additional quality measures in our ischaemic stroke management. At discharge, 57% had modified Rankin Scale of 0-2; 6.7% died during hospitalisation. When compared with selected national and international data, patients in Sarawak were the youngest; Sarawak had more male and more first-ever stroke. Thrombolysis rate in Sarawak was higher compared with most studies in the comparison. Functional outcome at discharge in Sarawak was better than national cohort but still lagging behind when compared with the developed countries. In-hospital mortality rate in Sarawak was slightly lower than the national data but higher when compared with other countries. CONCLUSION: Our study described characteristics, management, and outcomes of ischaemic stroke in Sarawak. We achieved high compliance with most of GTWG-Stroke performance and quality indicators. Sarawak had better outcomes than the national results on ischaemic stroke. However, there is still room for improvement when compared with other countries. Actions are needed to reduce the cardiovascular burdens for stroke prevention, enhance healthcare resources for stroke care, and improve intravenous thrombolysis treatment in Sarawak.

Genomic landscape of lung adenocarcinoma in East Asians.

Lung cancer is the world's leading cause of cancer death and shows strong ancestry disparities. By sequencing and assembling a large genomic and transcriptomic dataset of lung adenocarcinoma (LUAD) in individuals of East Asian ancestry (EAS; n = 305), we found that East Asian LUADs had more stable genomes characterized by fewer mutations and fewer copy number alterations than LUADs from individuals of European ancestry. This difference is much stronger in smokers as compared to nonsmokers. Transcriptomic clustering identified a new EAS-specific LUAD subgroup with a less complex genomic profile and upregulated immune-related genes, allowing the possibility of immunotherapy-based approaches. Integrative analysis across clinical and molecular features showed the importance of molecular phenotypes in patient prognostic stratification. EAS LUADs had better prediction accuracy than those of European ancestry, potentially due to their less complex genomic architecture. This study elucidated a comprehensive genomic landscape of EAS LUADs and highlighted important ancestry differences between the two cohorts.

Challenges in early phase of implementing the 1-3-7 surveillance and response approach in malaria elimination setting: A field study from Myanmar.

BACKGROUND: The National Plan for Malaria Elimination (NPME) in Myanmar (2016-2030) aims to eliminate indigenous Plasmodium falciparum malaria in six states/regions of low endemicity by 2020 and countrywide by 2030. To achieve this goal, in 2016 the National Malaria Control Program (NMCP) implemented the "1-3-7" surveillance and response strategy. This study aims to identify the barriers to successful implementation of the NPME which emerged during the early phase of the "1-3-7" approach deployment. METHODS: A mixed-methods study was conducted with basic health staff (BHS) and Vector Born Disease Control Program (VBDC) staff between 2017 and 2018 in six townships of six states/regions targeted for sub-national elimination by 2020. A self-administered questionnaire, designed to assess the knowledge required to implement the "1-3-7" approach, was completed by 544 respondents. Bivariate analysis was performed for quantitative findings and thematic analysis was conducted for qualitative findings using Atals.ti software. RESULTS: Although 83% of participants reported performing the key activities in the "1-3-7" surveillance and response approach, less than half could report performing those activities within 3 days and 7 days (40 and 43%, respectively). Low proportion of BHS correctly identified six categories of malaria cases and three types of foci (22 and 26%, respectively). In contrast, nearly 80% of respondents correctly named three types of case detection methods. Most cited challenges included 'low community knowledge on health' (43%), 'inadequate supplies' (22%), and 'transportation difficulty' (21%). Qualitative data identified poor knowledge of key surveillance activities, delays in reporting, and differences in reporting systems as the primary challenges. The dominant perceived barrier to success was inability to control the influx of migrant workers into target jurisdictions especially in hard-to-reach areas. Interviews with township medical officers and the NMCP team leaders further highlighted the necessity of refresher training for every step in the "1-3-7" surveillance and response approach. CONCLUSIONS: The performance of the "1-3-7" surveillance and response approach in Myanmar delivers promising results. However, numerous challenges are likely to slow down malaria elimination progress in accordance with the NPME. Multi-stakeholder engagement and health system readiness is critical for malaria elimination at the sub-national level.

Adverse Drug Reactions in Selected Wards of the Yangon General Hospital and Yangon Specialty Hospital During the First Quarter of 2019: An Active Pharmacovigilance Study in Myanmar.

BACKGROUND: Previous studies in Europe and the USA have reported a high prevalence of adverse drug reactions (ADRs), but data on local ADRs in Myanmar are sparse. OBJECTIVE: Our objective was to study ADRs in patients admitted to selected wards of Yangon General Hospital (YGH) and Yangon Specialty Hospital (YSH), Myanmar. METHODS: This was a prospective observational study in three hospital wards during the first quarter of 2019. Suspected ADRs were carefully investigated in a face-to-face interview with each patient and via review of clinical records. Patients transferred to other wards or discharged were followed-up by the researchers until day 28 after admission. ADRs were divided into those that (1) led to the admission and (2) occurred during the hospital stay or after discharge (up to day 28 after admission). RESULTS: A total of 65 ADRs were identified, with 47 (29.4%) of 160 patients experiencing at least one ADR. Among these, 16 (24.6%) had led to hospital admission and 49 (75.4%) occurred in 31 patients during their hospital stay. Of 160 patients, 21 had taken at least one herbal remedy and six of these developed an ADR. Five ADR-drug associations (hypokalaemia with methylprednisolone, increased transaminase levels with standard antituberculosis drugs, upper gastrointestinal bleeding with nonsteroidal anti-inflammatory drugs, constipation with tramadol, and increased transaminase levels with herbal remedies) represented 18 (27.7%) of the 65 ADRs in this study. According to the Schumock and Thornton preventability scale, more than half of these ADRs (35 [53.9%]) were preventable. CONCLUSION: The present study highlights the existence of ADRs among patients attending these hospitals. The implementation of active pharmacovigilance in hospitals could be a helpful first step to improving the awareness of unwanted effects of medicines and patient safety, as well as a way to strengthen the national pharmacovigilance system in countries such as Myanmar.

Utility of incorporating next-generation sequencing (NGS) in an Asian non-small cell lung cancer (NSCLC) population: Incremental yield of actionable alterations and cost-effectiveness analysis.

OBJECTIVES: There is an expanding list of therapeutically relevant biomarkers for non-small cell lung cancer (NSCLC), and molecular profiling at diagnosis is paramount. Tissue attrition in scaling traditional single biomarker assays from small biopsies is an increasingly encountered problem. We sought to compare the performance of targeted next-generation sequencing (NGS) panels with traditional assays and correlate the mutational landscape with PD-L1 status in Singaporean patients. MATERIALS AND METHODS: We identified consecutive patients diagnosed between Jan 2016 to Sep 2017 with residual tissue after standard molecular testing. Tissue samples were tested using a targeted NGS panel for DNA alterations (29 selected genes including BRAF, EGFR, ERBB2 and TP53) and an RNA fusion panel (ALK, ROS1 and RET). PD-L1 immunohistochemistry was also performed. A cost-effectiveness analysis of NGS compared to standard molecular testing was conducted. RESULTS: A total of 174 samples were evaluated: PD-L1 (n = 169), NGS DNA panel (n = 173) and RNA fusion (n = 119) testing. Median age was 68 years, 53 % were male, 58 % were never smokers, 85 % were Chinese, 66 % had stage IV disease and 95 % had adenocarcinoma histology. In patients profiled with NGS on DNA, EGFR (56 %), KRAS (14 %), BRAF (2 %) and ERBB2 (1 %) mutations were found. RNA fusion testing revealed fusions in ALK (6 %), RET (3 %) and ROS1 (1 %). Cost-effectiveness analysis demonstrated that compared to sequential testing in EGFR negative patients, upfront NGS testing would result in an additional 1 % of patients with actionable alterations for targeted therapy being identified without significant increases in testing cost or turnaround time. CONCLUSIONS: This study demonstrates that even in an EGFR mutant predominant population, upfront NGS represents a feasible, cost-effective method of diagnostic molecular profiling compared with sequential testing strategies. Our results support the implementation of diagnostic NGS in non-squamous NSCLC in Asia to allow patients access to the most appropriate personalized therapy.