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Objective: Human regular U-500 (U-500R) insulin (500 units/mL) is increasingly being used clinically, yet its pharmacokinetics (PK) and pharmacodynamics (PD) have not been well studied. Therefore, we compared PK and PD of clinically relevant doses of U-500R with the same doses of human regular U-100 (U-100R) insulin (100 units/mL).Research Design and Methods: This was a single-site, randomized, double-blind, crossover euglycemic clamp study. Single subcutaneous injections of 50- and 100-unit doses of U-500R and U-100R were administered to 24 healthy obese subjects.Results: Both overall insulin exposure (area under the serum insulin concentration versus time curve from zero to return to baseline [AUC(0-)(t)(')]) and overall effect (total glucose infused during a clamp) were similar between formulations at both 50- and 100-unit doses (90% [CI] of ratios contained within [0.80, 1.25]). However, peak concentration and effect were significantly lower for U-500R at both doses (P < 0.05). Both formulations produced relatively long durations of action (18.3 to 21.5 h). Time-to-peak concentration and time to maximum effect were significantly longer for U-500R than U-100R at the 100-unit dose (P < 0.05). Time variables reflective of duration of action (late tR(max50), tR(last)) were prolonged for U-500R versus U-100R at both doses (P < 0.05).Conclusions: Overall exposure to and action of U-500R insulin after subcutaneous injection were no different from those of U-100R insulin. For U-500R, peaks of concentration and action profiles were blunted and the effect after the peak was prolonged. These findings may help guide therapy with U-500R insulin for highly insulin-resistant patients with diabetes. [ABSTRACT FROM AUTHOR]

Background: Typically mobile and vulnerable, migrants face significant barriers to access to routine malaria prevention, diagnostics and treatment, which leads to unchecked malaria transmission, particularly in border regions with a high population displacement. This study aimed to investigate the demographic and socioeconomic obstacles to access to malaria services among Myanmar migrants residing in the Thailand-Myanmar border areas., Methods: A cross-sectional study was conducted in early 2024 across three districts near the Thailand-Myanmar border. Quantitative data were collected from Myanmar migrants using standardized questionnaires through structured surveys. Data analysis included descriptive statistics and simple and multiple logistic regression models., Results: Out of 300 participants, approximately a quarter (27.3%) reported adequate access to comprehensive malaria services, including prevention, diagnostics, treatment and malaria-related health information. In multiple logistic regression models, factors associated with inadequate access included Myanmar migrants aged over 60 years (aOR: 7.63, 95% CI 1.74-20.58), accompanied by one to three family members (aOR: 3.33, 95% CI 1.06-8.45), earning monthly incomes below 3000 THB (aOR: 5.13, 95% CI 1.38-19.09) and 3000 to 6000 THB (aOR: 3.64, 95% CI 1.06-12.51), belonging to the Karen ethnicity (aOR: 2.13, 95% CI 1.02-3.84), with poor perception toward malaria (aOR: 2.03, 95% CI 1.03-4.01) and with poor preventive and health-seeking practices (aOR: 5.83, 95% CI 2.71-9.55)., Conclusions: A significant proportion of Myanmar migrants encounter demographic and socioeconomic barriers to access to routine malaria services in Thailand. Tailored interventions are required to expand such access, including the recruitment of worksite health volunteers, strengthening the role of ethnic health organizations across the border and collaboration with private sector stakeholders (e.g. farm/company owners) to distribute preventive tools and ensure timely referral of suspected malaria cases to health facilities., (© 2024. The Author(s).)

Background: Malaria poses a substantial public health threat in Myanmar, indicating the need for rigorous efforts to achieve elimination of the disease nationwide by 2030. The use of insecticide-treated nets (ITNs) forms part of a pivotal strategy for preventing transmission. This study explored the ownership and use of ITNs in Myanmar and identified factors associated with non-use of ITNs., Methods: Household datasets from the 2015-2016 Myanmar Demographic and Health Survey were utilised, which encompassed all household members except children under the age of five. Descriptive statistics and inferential tests, including simple and multiple logistics regression models and Pearson correlations, were employed for analysis. All analyses, taking the two-stage stratified cluster sampling design into account, used weighting factors and the "svyset" command in STATA. The ownership and use of bed nets were also visualised in QGIS maps., Results: Among the 46,507 participants, 22.3% (95% CI 20.0%, 24.5%) had access to ITNs, with only 15.3% (95% CI 13.7, 17.1%) sleeping under an ITN the night before the survey. Factors associated with the non-use of ITNs included age category (15-34 years-aOR: 1.17, 95% CI 1.01, 1.30; 50+ years-aOR: 1.19, 95% CI 1.06, 1.33), location (delta or lowland-aOR: 5.39, 95% CI 3.94, 7.38; hills-aOR: 1.80, 95% CI 1.20, 2.71; plains-aOR: 3.89, 95% CI 2.51, 6.03), urban residency (aOR: 1.63, 95% CI 1.22, 2.17), and wealth quintile (third-aOR: 1.38, 95% CI 1.08, 1.75; fourth-aOR: 1.65, 95% CI 1.23, 2.23; fifth-aOR: 1.47, 95% CI 1.02, 2.13). A coherent distribution of the ownership and use of ITNs was seen across all states/regions, and a strong correlation existed between the ownership and use of ITNs (r: 0.9795, 95% CI 0.9377, 0.9933, alpha < 0.001)., Conclusions: This study identified relatively low percentages of ITN ownership and use, indicating the need to increase the distribution of ITNs to achieve the target of at least one ITN per every two people. Strengthening the use of ITNs requires targeted health promotion interventions, especially among relatively affluent individuals residing in delta or lowland areas, hills, and plains., (© 2024. The Author(s).)

Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease, with type 2 diabetes mellitus (T2DM) as a major predictor. Insulin resistance and chronic inflammation are key pathways in the pathogenesis of T2DM leading to NAFLD and vice versa, with the synergistic effect of NAFLD and T2DM increasing morbidity and mortality risks. This meta-analysis aims to quantify the prevalence of NAFLD and the prevalence of clinically significant and advanced fibrosis in people with T2DM., Methods: MEDLINE and Embase databases were searched from inception until 13 February 2023. The primary outcomes were the prevalence of NAFLD, non-alcoholic steatohepatitis (NASH) and fibrosis in people with T2DM. A generalised linear mixed model with Clopper-Pearson intervals was used for the analysis of proportions with sensitivity analysis conducted to explore heterogeneity between studies., Results: 156 studies met the inclusion criteria, and a pooled analysis of 1 832 125 patients determined that the prevalence rates of NAFLD and NASH in T2DM were 65.04% (95% CI 61.79% to 68.15%, I 2 =99.90%) and 31.55% (95% CI 17.12% to 50.70%, I 2 =97.70%), respectively. 35.54% (95% CI 19.56% to 55.56%, I 2 =100.00%) of individuals with T2DM with NAFLD had clinically significant fibrosis (F2-F4), while 14.95% (95% CI 11.03% to 19.95%, I 2 =99.00%) had advanced fibrosis (F3-F4)., Conclusion: This study determined a high prevalence of NAFLD, NASH and fibrosis in people with T2DM. Increased efforts are required to prevent T2DM to combat the rising burden of NAFLD., Prospero Registration Number: CRD42022360251., Competing Interests: Competing interests: DQH served as an advisory board member for Gilead and received funding support from the Singapore Ministry of Health’s National Medical Research Council under its NMRC Research Training Fellowship (MOH-000595-01). CHN and MM served as a consultants for Boxer Capital. RL served as a consultant to Aardvark Therapeutics, Altimmune, Anylam/Regeneron, Amgen, Arrowhead Pharmaceuticals, AstraZeneca, Bristol-Myer Squibb, CohBar, Eli Lilly, Galmed, Gilead, Glympse Bio, Hightide, Inipharma, Intercept, Inventiva, Ionis, Janssen Inc., Madrigal, Metacrine, Inc., NGM Biopharmaceuticals, Novartis, Novo Nordisk, Merck, Pfizer, Sagimet, Theratechnologies, 89 Bio, Terns Pharmaceuticals and Viking Therapeutics; in addition, his institutions received research grants from Arrowhead Pharmaceuticals, Astrazeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Eli Lilly, Galectin Therapeutics, Galmed Pharmaceuticals, Gilead, Intercept, Hanmi, Intercept, Inventiva, Ionis, Janssen, Madrigal Pharmaceuticals, Merck, NGM Biopharmaceuticals, Novo Nordisk, Merck, Pfizer, Sonic Incytes and Terns Pharmaceuticals; cofounder of LipoNexus Inc., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Plasmodium vivax malaria is considered a major threat to malaria eradication. The radical cure for P. vivax malaria normally requires a 14-day administration of primaquine (PQ) to clear hypnozoites. However, maintaining adherence to PQ treatment is a significant challenge, particularly in malaria-endemic rural areas. Hence, this study aimed to formulate interventions for promoting patients' commitment to PQ treatment in a highly malaria-endemic township in Myanmar., Methods: A qualitative study was conducted in Waingmaw Township in northern Myanmar, where P. vivax malaria is highly endemic. Key stakeholders including public health officers and community members participated in focus group discussions (FGDs) and in-depth interviews (IDIs) in September 2022. Data were collected using validated guidelines, translated into English, and visualized through thematic analysis., Results: Responsible individuals from different levels of the Myanmar National Malaria Control Programme participated in the IDIs. Most of them reported being aware of the markedly increasing trend of P. vivax and the possibility of relapse cases, especially among migrants who are lost to follow-up. Workload was a key concern surrounding intervention implementation. The respondents discussed possible interventions, such as implementing directly observed treatment (DOT) by family members, piloting a shorter PQ regimen, expanding the community's malaria volunteer network, and strengthening health education activities using local languages to promote reasonable drug adherence. FGDs among community members revealed that although people were knowledgeable about malaria symptoms, places to seek treatment, and the use of bed nets to prevent mosquito bites, most of them still preferred to be treated by quack doctors and rarely used insecticide-treated nets at worksites. Many often stopped taking the prescribed drugs once the symptoms disappeared. Nevertheless, some respondents requested more bed nets to be distributed and health promotion activities to be conducted., Conclusion: In rural areas where human resources are limited, interventions such as implementing family member DOT or shortening PQ regimens should be introduced to enhance the radical cure for the P. vivax infection. Disseminating information about the importance of taking the entire treatment course and emphasizing the burden of relapse is also essential., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Introduction: Myanmar has been identified as one of the tuberculosis (TB) high-burden countries and having an understanding of TB transmission is vital for personal infection prevention as well as preventing transmission to others. This study aimed to identify the determinants of correct knowledge on TB transmission and self-reported TB prevalence among general population in Myanmar., Methods: This is a cross-sectional study using secondary data from Myanmar demographic and health survey 2015-16. The determinants of correct knowledge on TB transmission mode and self-reported prevalence of TB were assessed using multivariable logistic regression models. Weighted estimates were provided in all analyses to account for the multistage sampling design used in the survey., Results: Among the respondents, less than half (44.6%, 95% CI: 43.9, 45.4) had the overall correct knowledge about TB transmission and misconceptions. Older age group, female gender, those with higher education and higher socioeconomic status, and exposed to mass media at least once a week, residents from the delta and lowland region or plain areas were more likely to have correct knowledge about TB transmission. The overall prevalence rate of self-reported TB was 2.6% (95%CI: 2.4, 2.9) and the prevalence was higher among older age group and males., Conclusion: Our study highlights the need for targeted efforts to improve awareness and understanding of TB transmission among general population in Myanmar. The study suggests the implementation of appropriate, innovative, and comprehensive targeted TB education and communication strategies., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Aung et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Targeted mass primaquine treatment (TPT) might be an effective intervention to facilitate elimination of vivax malaria in Myanmar by 2030. In this study, we explored the factors hindering coverage of a TPT campaign conducted in a malarious township of northern Myanmar. From August 2019 to July 2020, a cross-sectional exploratory design including quantitative and qualitative data was conducted in five villages with high P. vivax prevalence following a TPT campaign. Among a targeted population of 2322; 1973 (85.0%) participated in the baseline mass blood survey (MBS) and only 52.0% of the total targeted population (1208, 91.9% of total eligible population) completed the TPT. G6PD deficiency was found among 13.5% of total MBS participants and those were excluded from TPT. Of 1315 eligible samples, farmers and gold miners, males, and those aged 15 to 45 years had higher percentages of non-participation in TPT. Qualitative findings showed that most of the non-participation groups were outside the villages during TPT because of time-sensitive agricultural and other occupational or education-related purposes. In addition to mitigating of some inclusion criteria (i.e. including young children or offering weekly PQ treatment to G6PD deficient individuals), strengthening community awareness and increasing engagement should be pursued to increase community participation., (© 2023. The Author(s).)

Background: Myanmar bears the heaviest malaria burden in the Greater Mekong Subregion (GMS). This study assessed the spatio-temporal dynamics and environmental predictors of Plasmodium falciparum and Plasmodium vivax malaria in Myanmar., Methods: Monthly reports of malaria cases at primary health centers during 2011-2017 were analyzed to describe malaria distribution across Myanmar at the township and state/region levels by spatial autocorrelation (Moran index) and spatio-temporal clustering. Negative binomial generalized additive models identified environmental predictors for falciparum and vivax malaria, respectively., Results: From 2011 to 2017, there was an apparent reduction in malaria incidence in Myanmar. Malaria incidence peaked in June each year. There were significant spatial autocorrelation and clustering with extreme spatial heterogeneity in malaria cases and test positivity across the nation (P < 0.05). Areas with higher malaria incidence were concentrated along international borders. Primary clusters of P. falciparum persisted in western townships, while clusters of P. vivax shifted geographically over the study period. The primary cluster was detected from January 2011 to December 2013 and covered two states (Sagaing and Kachin). Annual malaria incidence was highest in townships with a mean elevation of 500‒600 m and a high variance in elevation (states with both high and low elevation). There was an apparent linear relationship between the mean normalized difference vegetative index and annual P. falciparum incidence (P < 0.05)., Conclusion: The decreasing trends reflect the significant achievement of malaria control efforts in Myanmar. Prioritizing the allocation of resources to high-risk areas identified in this study can achieve effective disease control., (© 2023. The Author(s).)

Objective: Nonalcoholic fatty liver disease (NAFLD) affects much of the worldwide population and poses a significant burden to the global healthcare. The rising numbers of individuals with NAFLD and instances of mortality point toward the importance of understanding the association causes of mortality in NAFLD. This meta-analysis aimed to seek the associations of NAFLD with all-cause, cardiovascular disease (CVD)-related, liver-related, and cancer-related mortality., Methods: MEDLINE and Embase were searched for articles relating to causes of mortality between NAFLD and non-NAFLD. The DerSimonian and Laird random-effects model was used to analyze adjusted hazard ratios (HR), and a sensitivity analysis was conducted to reduce heterogeneity through a graphical display of study heterogeneity., Results: Fifteen studies involving 10 286 490 patients were included. Individuals with NAFLD exhibited an increased risk of all-cause mortality (HR, 1.32; 95% CI, 1.09-1.59; P < .01; I 2  = 96.00%), CVD-related mortality (HR, 1.22; 95% CI, 1.06-1.41; P < .01; I 2  = 81.00%), and cancer-related mortality (HR, 1.67; 95% CI, 1.15-2.41; P < .01; I 2  = 95.00%). However, no significant association was found between liver-related mortality and NAFLD (HR, 3.58; 95% CI, 0.69-18.46; P =.13; I 2  = 96.00%). The sensitivity analysis conducted with graphic display of heterogeneity and only population-based studies found similar results., Conclusion: NAFLD was associated with an increased risk of all-cause, CVD-related, and cancer-related mortality but not liver-related mortality. The finding is likely because of low fibrosis prevalence in the community. However, the significant burden in other causes of mortality beyond the liver points to a need for multidisciplinary efforts to reduce the mortality risks., Competing Interests: Disclosure A.J.S. is the President of Sanyal Biotechnology and has stock options in Genfit, Akarna, Tiziana, Indalo, Durect, and Galmed. He has served as a consultant to Astra Zeneca, Nitto Denko, Enyo, Ardelyx, Conatus, Nimbus, Amarin, Salix, Tobira, Takeda, Jannsen, Gilead, Terns, Birdrock, Merck, Valeant, Boehringer Ingelheim, Lilly, Hemoshear, Zafgen, Novartis, Novo Nordisk, Pfizer, Exhalenz, and Genfit. He has been an unpaid consultant to Intercept, Echosens, Immuron, Galectin, Fractyl, Syntlogic, Affimune, Chemomab, Zydus, Nordic Bioscience, Albireo, Prosciento, Surrozen, and Bristol Myers Squibb. His institution has received grant support from Gilead, Salix, Tobira, Bristol Myers, Shire, Intercept, Merck, AstraZeneca, Malinckrodt, Cumberland, and Norvatis. He receives royalties from Elsevier and UptoDate. M.N. has been on the advisory board/consultant for 89BIO, Altimmune, Gilead, cohBar, Cytodyn, Intercept, Pfizer, Novo Nordisk, Blade, EchoSens, Fractyl, Madrgial, NorthSea, Prespecturm, Terns, Siemens, and Roche Diagnostic. He has received research support from Allergan, BMS, Gilead, Galmed, Galectin, Genfit, Conatus, Enanta, Madrigal, Novartis, Pfizer, Shire, Viking, and Zydus. He is a shareholder or has stocks in Anaetos, Chrownwell, Ciema, Rivus Pharma, and Viking. V.W.-S.W. has served as an advisory board member or consultant for 3V-BIO, AbbVie, Allergan, Boehringer Ingelheim, Echosens, Gilead Sciences, Inventiva, Merck, Novartis, Novo Nordisk, Pfizer, ProSciento, Sagimet Biosciences, TARGET PharmaSolutions, and Terns. He is on the speaker's bureau for Abbott, AbbVie, Echosens, Gilead Sciences, and Novo Nordisk. He has received a grant from Gilead Sciences for fatty liver research and is a cofounder of Illuminatio Medical Technology Limited. All authors have made substantial contributions to all of the following: (1) the conception and design of the study, or acquisition of data, or analysis and interpretation of data, (2) drafting the article or revising it critically for important intellectual content, and (3) final approval of the version to be submitted. No writing assistance was obtained in the preparation of the manuscript. The manuscript, including related data, figures, and tables, has not been previously published, and the manuscript is not under consideration elsewhere., (Copyright © 2022 AACE. Published by Elsevier Inc. All rights reserved.)

Background & Aims: As the global prevalence of non-alcoholic fatty liver disease (NAFLD) continues to rise, ubiquity of alcohol use has also prompted discussion regarding the potential interactions between the two. This study aims to examine the effects of modest alcohol consumption on the prevalence and complications of NAFLD in a multi-ethnic population., Methods: This study analyses the 2017-2018 cycles of NHANES that examined liver fibrosis and steatosis with vibration controlled transient elastography. A coarsened exact matching was conducted to reduce confounding. Logistic regression was done with a multivariate model to assess the relationship between alcohol consumption (modest drinkers and non-drinkers) and risk of NAFLD and its complications., Results: 2,067 individuals were found to have NAFLD and 284 NAFLD patients had a total history of alcohol abstinence. After coarsened exact matching, the prevalence of NAFLD was 49% (CI: 0.41 - 0.58) in non-drinkers and 33% (CI: 0.26 - 0.41) in modest drinkers. Non-drinkers had twice the odds of NAFLD compared to modest drinkers (OR: 1.99, CI: 1.22 - 3.22, p <.01) after adjustment for confounders. There were no significant differences in the odds of significant fibrosis, advance fibrosis, cirrhosis, cardiovascular disease and stroke between non-drinkers and modest drinkers. The odds of malignancy in non-drinkers were almost significantly less than modest drinkers (OR: 0.28, CI:0.08 - 1.02, p =.053)., Conclusion: Interestingly, modest alcohol consumption is associated with decreased odds of NAFLD. Further investigations are required to examine the relationship between alcohol consumption and NAFLD and subsequently the potential impact on NAFLD management.

Different villages in a township or an area exhibit different malaria endemicities. This study aimed to investigate malaria preventive practices among people residing in different villages with stratified malaria endemicity in a township in Myanmar. Quantitative data were collected using standardized questionnaires by conducting face-to-face interviews, and qualitative data were obtained through in-depth interviews using a guideline. Quantitative data were analyzed using descriptive statistics and logistic regression models, whereas thematic analysis was used to visualize qualitative data. A total of 360 respondents with similar characteristics participated in the quantitative study. Knowledge regarding malaria and the availability of health information exhibited insignificant differences. Malaria preventive practices were considerably poor among people from moderate- and high-endemic villages (p < 0.05). Adult male farmers or gold miners with low annual family incomes reported poor preventive practices in both moderate- and high-endemic groups. People could not practice some malaria preventive measures because of a lack of resources, e.g., a lack of mosquito repellents. To eliminate the disparities of preventive practices in different malaria-endemic settings, heath-awareness-raising activities should be increased, especially in moderate- and high-endemic villages.

Both encapsulating peritoneal sclerosis (EPS) and calciphylaxis are rare but severe complications involving patients with end-stage renal disease. In this report, we discuss a unique case of a 73-year-old female patient who had undergone 8 years of peritoneal dialysis for IgA nephropathy and concurrently developed these two synchronous complications within 3 months of each other. Diagnosis and management of both conditions were discussed in detail as well as the possible association between the two. With surgical treatment for EPS and measures to minimise bone mineral disorder abnormalities, both complications have been successfully managed to date., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Due to the effectiveness of insecticide-treated nets (ITNs), most malaria-endemic countries resort to free distributions in the population with particular attention to pregnant women, a more vulnerable group. However, the mere issuance of ITNs does not usually translate to proper utilization. This study aimed to examine the utilization of ITNs and its associated factors among pregnant women in Myanmar., Methods: The data analyzed in this cross-sectional study were extracted from available survey datasets of the 2015-16 Myanmar Demographic Health Survey. The secondary data were presented using a chart, descriptive statistics and inferential statistics including simple and multiple logistic regression models. All analyses were performed using STATA, Version 15. A p-value <0.05 was considered statistically significant., Results: Of 466 currently pregnant women, the majority (96%) possessed bed nets for sleeping. Among them, 15.9% slept without a bed net the night before the survey, while 65.7% slept with untreated nets. Only about 1 in 5 (18.4%) slept under ITNs. In the multivariate logistic regression analysis, pregnant women residing in delta and lowland regions [adjusted odds ratio (aOR) = 7.70, 95% confidence interval (CI): 3.62, 16.38], plains (aOR = 7.09, 95%CI: 3.09, 16.25) or hilly areas (aOR = 4.26, 95%CI: 1.91, 9.52) were more likely to report non-utilization of ITNs than those residing in coastal regions., Conclusion: Relatively poor ITN utilization was observed among pregnant women in Myanmar. Health promotion activities for ITN utilization should be implemented especially for pregnant women residing in the delta, lowland, plain and hilly regions. Other social-behavioral factors including perceived susceptibility to malaria, knowledge of ITNs, and attitude towards ITN that might favor the non-utilization of ITNs need to be further explored., Competing Interests: The authors have declared that no competing interests exist.

Background & Aim: Hepatitis B reactivation related to the use of immunosuppressive therapy remains a major cause of liver-related morbidity and mortality in hepatitis B endemic Asia-Pacific region. This clinical practice guidelines aim to assist clinicians in all disciplines involved in the use of immunosuppressive therapy to effectively prevent and manage hepatitis B reactivation., Methods: All publications related to hepatitis B reactivation with the use of immunosuppressive therapy since 1975 were reviewed. Advice from key opinion leaders in member countries/administrative regions of Asian-Pacific Association for the study of the liver was collected and synchronized. Immunosuppressive therapy was risk-stratified according to its reported rate of hepatitis B reactivation., Recommendations: We recommend the necessity to screen all patients for hepatitis B prior to the initiation of immunosuppressive therapy and to administer pre-emptive nucleos(t)ide analogues to those patients with a substantial risk of hepatitis and acute-on-chronic liver failure due to hepatitis B reactivation., (© 2021. Asian Pacific Association for the Study of the Liver.)

Introduction: In the Greater Mekong Subregion, community health workers, known as malaria volunteers, have played a key role in reducing malaria in the control phase, providing essential malaria services in areas with limited formal healthcare. However, the motivation and social role of malaria volunteers, and testing rates, have declined with decreasing malaria burden and reorientation of malaria programmes from control to elimination. Provision of additional interventions for common health concerns could help sustain the effectiveness of volunteers and maintain malaria testing rates required for malaria elimination accreditation by the WHO., Methods and Analysis: The Community-delivered Integrated Malaria Elimination (CIME) volunteer model, integrating interventions for malaria, dengue, tuberculosis, childhood diarrhoea and malaria Rapid Diagnostic Test (RDT)-negative fever, was developed based on global evidence and extensive stakeholder consultations. An open stepped-wedge cluster-randomised controlled trial, randomised at the volunteer level, will be conducted over 6 months to evaluate the effectiveness of the CIME model in Myanmar. One hundred and forty Integrated Community Malaria Volunteers (ICMVs, current model of care) providing malaria services in 140 villages will be retrained as CIME volunteers (intervention). These 140 ICMVs/villages will be grouped into 10 blocks of 14 villages, with blocks transitioned from control (ICMV) to intervention states (CIME), fortnightly, in random order, following a 1-week training and transition period. The primary outcome of the trial is blood examination rate determined by the number of malaria RDTs performed weekly. Difference in rates will be estimated across village intervention and control states using a generalised linear mixed modelling analytical approach with maximum likelihood estimation., Ethics and Dissemination: The study was approved by Institutional Review Board, Myanmar Department of Medical Research (Ethics/DMR/2020/111) and Alfred Hospital Ethics Review Committee, Australia (241/20). Findings will be disseminated in peer-review journals, conferences and regional, national and local stakeholder meetings., Trial Registration Number: NCT04695886., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Abdominal pain is a very common presentation in the accident and emergency department. However, vasculitis is not the usual first differential diagnosis. This paper discusses a case of polyarteritis nodosa presenting with acute abdominal pain alone. Common surgical conditions were obviously considered, but they were not found to cause the patient's problems. We describe how investigations led to this diagnosis discussed in detail in this paper. It is important to remember that prompt recognition of unusual life-threatening conditions can lead to timely intervention., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Malaria volunteers (MVs) play an essential role in resolving malaria problems by delivering greater access to diagnosis and treatment services, mainly for the underserved community residing in hard-to-reach rural areas. The Karen Department of Health and Welfare (KDHW) has implemented community-based malaria control activities among the ethnic minorities in southeastern Myanmar by promoting the roles of MVs. This study aimed to explore the factors influencing the performance of MVs regarding malaria control activities in the area. From July to August 2019, a cross-sectional study was conducted in 12 townships of southeastern Myanmar under the umbrella of the KDHW malaria project. A total of 140 MVs were employed as study participants. Data were collected through face-to-face interviews using a structured questionnaire. For data analyses, descriptive statistics, chi-squared tests, and logistics regression models were applied. More than half of the MVs perceived a good level of performance on malaria control activities. A higher level of performance has been observed among the MVs who had another job (AOR: 1.9, 95% CI: 1.2-3.9), those experienced in health-related fields (AOR: 1.9, 95% CI: 1.4-4.9), who received good community support (AOR: 2.1, 95% CI: 1.3-10.9), who were volunteers beyond three years (AOR: 4.0, 95% CI: 2.8-9.2), and whose family income totaled over 500,000 MMK (AOR: 2.8, 95% CI: 1.6-4.2). The results mentioned the characteristics which should be prioritized in recruiting MVs. MV network and their workforce need to be nurtured by encouraging community support. For performance sustainability, attractive incentive schemes or a salary should be subsidized in support of their livelihoods., Competing Interests: The authors declare they have no conflicts of interest., (Copyright © 2021 Ye Thiha et al.)

Background: Maintaining essential HIV services has being a Global challenge during the COVID-19 crises. Myanmar has 54 million inhabitants. Neighbor of China, Thailand, India and Bangladesh it was impacted by COVID-19, but came up with a comprehensive and effective response, following WHO recommendations. The HIV Prevalence is 0.58% and it is concentrated among key population. A HIV Contingency Plan was developed to face this challenge., Methodology: The programme-based cross-sectional descriptive study with analysis of routinely collected data from MoHS data system, between 2019 and 2020 was conducted, comparing first six months of 2019 and 2020., Results: HIV outreach activities and HIV testing were slightly affected after detection of first COVID-19 case, till mid May 2020. After that, outreach activities resumed. Introduction of HIV self-testing was initiated. 72% of more than 21,000 PWID on MMT were receiving take home dose up to 14 days and 60% of ART patients were receiving 6 months ARV dispensing., Conclusion: Essential HIV services were maintained.

Asia has intermediate-to-high prevalence and high morbidity of hepatitis B virus (HBV) infection. The use of guideline-recommended nucleos(t)ide analogs with high barrier to resistance, such as entecavir (ETV), tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide (TAF), is one of the key interventions for curbing HBV infection and associated morbidity in Asia. However, there are some challenges to the use of ETV and TDF; while ETV is associated with high resistance in lamivudine (LAM)-exposed (especially LAM-refractory) patients; bone and renal safety issues are a major concern with TDF. Hence, a panel of twenty-eight expert hepatologists from Asia convened, reviewed the literature, and developed the current expert opinion-based review article for the use of TAF in the resource-constrained settings in Asia. This article provides a comprehensive review of two large, phase 3, double-blind, randomized controlled trials of TAF versus TDF in HBeAg-negative (study 0108) and HBeAg-positive (study 0110) chronic HBV patients (> 70% Asians). These studies revealed as follows: (1) non-inferiority for the proportion of patients who had HBV DNA < 29 IU/mL; (2) significantly high rate of normalization of alanine aminotransferase levels; (3) no incidence of resistance; and (4) significantly better bone and renal safety, with TAF vs. TDF up to 144 weeks. Considering the benefits of TAF, the expert panel proposed recommendations for optimizing the use of TAF in Asia, along with guidance on specific patient groups at risk of renal or bone disease suitable for TAF therapy. The guidance provided in this article may help clinicians optimize the use of TAF in Asia.

The article Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific association for the study of the liver (APASL): an update, written by [Shiv Sarin], was originally published electronically on the publisher's internet portal (currently SpringerLink) on June 06, 2019 without open access.

Exclusive HCV therapy clinical trials with genotype 6 patients in high prevalence areas have been sparse. We analysed the safety and efficacy of two generic, pangenotypic NS5A/NS5B combination oral DAA regimens, primarily in genotypes 3 and 6, in a real-world setting: (a) daclatasvir/sofosbuvir (DCV/SOF) ± ribavirin (RBV) and (b) Velpatasvir/sofosbuvir (VEL/SOF ± RBV). Between December 2015 and November 2017, data from 522 patients were analysed, 311 of whom were treated with DCV/SOF ± RBV for 12/24 weeks (genotype 3: n = 193, genotype 6: n = 89) and 211 were treated with VEL/SOF ± RBV for 12/24 weeks (genotype 3: n = 83, genotype 6: n = 77). Overall SVR rates were high for both DCV/SOF ± RBV (96.1%, n = 299/311) and VEL/SOF ± RBV (95.3%, n = 201/211), and there was a good adverse event profile. Treatment naïve status and inclusion of RBV (in advanced fibrosis/cirrhosis) were significant independent predictors of achieving SVR12, while type of DAA regimen was not predictive. In this large cohort of genotypes 3 (n = 276) and 6 (n = 166; n = 127 unique subtype of 6c-l), high SVR rates of 94.9% (n = 262/276) and 95.2% (n = 158/166), respectively, were noted. In conclusion, generic and pangenotypic DCV/SOF and VEL/SOF ± RBV regimens were highly effective and safe, in genotypes 3 and 6 chronic HCV in Myanmar. These efficacious pangenotypic regimens suggest that baseline genotype testing can be eliminated moving forward. While RBV may still be needed for those with advanced fibrosis/cirrhosis, in a global elimination strategy it would not be practical even if it does compromise SVR in a minority with difficult to treat characteristics., (© 2019 John Wiley & Sons Ltd.)

Background: In resource-constrained areas, generic direct-acting antivirals (DAAs) have considerably reduced the cost of hepatitis C virus (HCV) therapy while there remain significant costs related to the baseline and follow-up virologic assays., Aim: The aim was to assess the efficacy and safety of HCV therapy in Myanmar with pan-genotypic generic DAA sofosbuvir/velpatasvir (SOF/VEL) and with and without the baseline genotype testing, while the duration of treatment and use of ribavirin (RBV) was dictated by cirrhosis and prior treatment failure., Methods: Between September 2016 and June 2017, data from the 359 participants who completed treatment with SOF/VEL (± RBV) for 12-24 weeks were analyzed. Two hundred one patients did not have the baseline HCV genotype tested., Results: Regimens included SOF/VEL for 12 weeks (n = 43), SOF/VEL/RBV for 12 weeks (n = 275), or SOF/VEL/RBV for 24 weeks (n = 41). The mean age was 52 years, 44% were men (n = 159), 41 (11.4%) had a history of previous DAA therapy, 7 (1.9%) had a history of hepatocellular carcinoma, and 55 (15.3%) had cirrhosis. Overall, the sustained viral response (SVR)12 rate was 98.6% (354/359) and with a good adverse event profile. SVR rates were similar to those with and without baseline genotype testing and also across all genotypes in those who had genotype tested., Conclusions: In Myanmar, generic and pan-genotypic SOF/VEL ± RBV is a highly effective and safe treatment for HCV, regardless of the HCV genotype, and therefore, the requirement for the baseline genotype can be eliminated. Future strategies should include elimination of treatment and end of treatment HCV RNA testing to enhance treatment uptake and further reduce cost.

Background: The population of Asia exceeds 4.4 billion people. Chronic hepatitis C virus (HCV) infection in Asia is characterized by specific distribution of genotypes, lack of access to specific therapeutic agents, relatively high cost of treatment, and lack of experienced healthcare providers. Clear consensus on the diagnosis, management, and monitoring of HCV infection specific to the Asian region is a major unmet need. The consensus guidelines documents that have been published to date by major medical societies presume access to an array of direct acting antiviral agents and diagnostic tests that are not broadly applicable to resource limited settings, including Asia., Methods: To address the lack of an Asia-specific set of HCV treatment guidelines, we assembled a panel of 15 HCV experts in the field of hepatology from India, Indonesia, Myanmar, Vietnam, Pakistan, Philippines, and Mongolia convened in April 2017 to review the updated literature and provide recommendations on the diagnosis and management of chronic HCV infection that reflects local conditions., Results: An evidence-based comprehensive compilation of the literature supported by the graded recommendations from the expert panel for the optimization of the diagnosis, pretreatment, on treatment, and posttreatment assessments, and management of chronic HCV infection has been presented in this article., Conclusions: With the evolving treatment landscape and addition of several new direct-acting antiviral agents and combination regimens into the therapeutic armamentarium, the current article may serve as a guide to the clinicians in optimizing the diagnosis and treatment selection for the management of chronic HCV infection in resource-limited settings.

There is a paucity of information on chronic hepatitis C (CHC) patients treated with direct antiviral agents (DAAs) in Asia. We invited Asia-Pacific physicians to collate databases of patients enrolled for CHC treatment, recording baseline clinical, virologic and biochemical characteristics, sustained virologic response at week 12 (SVR12) and virologic failure. SVR12 outcome was based on intention to treat (ITT). Multivariate analysis was used to assess independent risk factors for SVR12 using SPSS version 20. A total of 2171 patients from India (n = 977), Myanmar (n = 552), Pakistan (n = 406), Thailand (n = 139), Singapore (n = 72) and Malaysia (n = 25) were collected. At baseline, mean age was 49 years, 50.2% were males, and 41.8% had cirrhosis. Overall, SVR12 was 89.5% and by genotype (GT) based on ITT and treatment completion, respectively, was 91% and 92% for GT1, 100% and 100% for GT2, 91% and 97% for GT3, 64% and 95% for GT4, 87% and 87% for GT6 and 79% and 91% for GT untested. Patients with cirrhosis had SVR12 of 85% vs 93% for noncirrhosis (P < 0.001) (RR 2.1, 95% CI 1.4-3.1, P = 0.0002). Patients with GT1 and GT3 treated with sofosbuvir/ribavirin (SR) had 88% and 89% SVR12, respectively, but those GT6 treated with sofosbuvir/ledipasvir (SL) had only 77.6% SVR12. Multivariate analysis showed absence of cirrhosis was associated with higher SVR12 (OR 2.0, 95% CI 1.3-3.1, P = 0.002). In conclusion, patients with GT1 and GT3 with/without cirrhosis had surprisingly high efficacy using SR, suggesting that Asians may respond better to some DAAs. However, poor GT6 response to SL suggests this regimen is suboptimal for this genotype., (© 2018 John Wiley & Sons Ltd.)

Background: As Myanmar progresses towards lymphatic filariasis (LF) elimination, it is important to know how well the anti-filarial activities have performed. The present study was conducted to study the implementation of the key anti-filarial activities and their impact on key indicators of LF transmission., Methods: A secondary analysis of aggregate program data on the anti-filarial activities was conducted in four endemic state/regions of Myanmar receiving at least six mass drug administration (MDA) rounds during 2001-2016., Results: MDA coverage has been expanded to cover all the endemic implementation units (IUs), i.e., 45 by 2015 and 6 IUs out of them have already stopped MDA. The reported coverage of MDA ranges from 87 to 100% whereas surveyed coverage ranges from 78 to 100% among the eligible population. The prevalence of microfilaria has significantly declined especially in Magway from 4.7 to 0.2% and Sagaing region from 7.9 to 1.3% during 2001-2016. Around 2.5% of estimated cases of hydrocele were reported to the program during 2009-2014., Conclusion: Myanmar has achieved significant success in interrupting LF transmission through several MDA rounds with high coverage. However, morbidity reporting and management, being in its initial phase requires an active surveillance system for identifying and managing people with LF-associated morbidities under the program., Competing Interests: Ethics approval for this study was obtained from The Union Ethics Advisory Group (International Union against Tuberculosis and Lung Disease, Paris, France) (EAG Number: 79/16) and the Institutional Ethics Review Committee, Department of Medical Research, Myanmar (Ethics/DMR/20117/018).Not applicableThe authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Background: Microtia reconstruction is a challenging procedure, especially in developing nations. The most complex part is learning how to fabricate a framework from costal cartilage. We herein propose a training regimen for ear reconstruction with the use of a plastic eraser., Materials and Methods: The texture of a plastic eraser made from polyvinyl chloride is similar to that of human costal cartilage. The first step of the training is carving out the sixth through eighth rib cartilages from a block of plastic eraser. The second step is a fabrication of the framework from plastic rib cartilages, referring to a template from the intact auricle., Results: As plastic erasers are inexpensive and universally available, inexperienced surgeons can repeatedly perform this framework training. Following several of these training sessions in developing nations, the co-authors and local surgeons successfully performed their microtia reconstructions in a reasonable operative time., Conclusions: This realistic carving model allows surgeons to gain experience before performing an actual ear reconstruction, even in resource-constrained circumstances., Competing Interests: There are no conflicts of interest.

This open-label, clinical experience investigated the safety and efficacy of direct-acting antiviral (DAA) hepatitis C virus (HCV) therapy in Myanmar; 344 patients completed treatment between June 2015 and May 2016. Patients with HCV genotypes 1-4 and 6 received one of four treatments: (i) Peg-interferon (PEG-IFN)+sofosbuvir (SOF)+ribavirin (RBV) for 12 weeks, (ii) SOF+RBV for 24 weeks, (iii) ledipasvir (LDV)+SOF for 12 weeks or (iv) daclatasvir (DCV)+SOF+RBV for 12 or 24 weeks. Genotype 3 was most common (n=133, 38.7%), followed by genotype 6 (n=122, 35.5%) and genotype 1 (n=86, 25%). Overall, 91% of patients achieved sustained virologic response (SVR); 99% in group 1, (n=148/149), 90% in group 2 (n=95/106), 78% in group 3 (n=65/83) and 100% in group 4 (n=6/6). In group 3, SVR rates were 96.8% in genotype 1 (n=30/31) and 64.1% in genotype 6 (n=25/39). Multivariable regression analysis identified advanced fibrosis (F3-4) (OR=.16 CI: 0.05-0.57, P=.005), genotype 6 (OR=.35, CI: 0.16-0.79, P=.012) and diabetes (OR=.29, CI: 0.12-0.71, P=.007) as negative independent predictors of response. Adverse events were mild with all-oral therapy., Conclusion: DAA therapy ±PEG-IFN achieved high SVR rates. Genotype 6 patients had a low SVR to 12 weeks of LDV and SOF raising the need for other regimens, RBV or longer treatment duration in this population., (© 2017 John Wiley & Sons Ltd.)

Singapore is a high-income country in a region with a high prevalence of tuberculosis. The Singapore Tuberculosis (TB) Elimination Program (STEP) was set up in 1997, and the better surveillance and clinical management practices initiated under STEP led to a decade-long decline in the incidence levels. However, incidence rates started to rise again since 2008. The reasons for this rise are unclear. This study involved a spatial analysis of the epidemiology of TB among Singapore residents. More than 30 000 cases reported during 1995-2011 and their residential addresses were analysed for spatial risk and spatial clustering, using spatial point pattern methodology. The principal factor responsible for the increasing resident TB incidence in Singapore is the changing age profile of the population. In particular the burgeoning population aged above 65 years accounts for the increase in reported cases. Singapore's population has one of the world's lowest fertility and mortality rates, and the elderly population is projected to grow substantially over the next few decades. Tuberculosis rates may therefore continue to rise even with static or improving case management and surveillance.

The Asia-Pacific region has disparate hepatitis C virus (HCV) epidemiology, with prevalence ranging from 0·1% to 4·7%, and a unique genotype distribution. Genotype 1b dominates in east Asia, whereas in south Asia and southeast Asia genotype 3 dominates, and in Indochina (Vietnam, Cambodia, and Laos), genotype 6 is most common. Often, availability of all-oral direct-acting antivirals (DAAs) is delayed because of differing regulatory requirements. Ideally, for genotype 1 infections, sofosbuvir plus ledipasvir, sofosbuvir plus daclatasvir, or ombitasvir, paritaprevir, and ritonavir plus dasabuvir are suitable. Asunaprevir plus daclatasvir is appropriate for compensated genotype 1b HCV if baseline NS5A mutations are absent. For genotype 3 infections, sofosbuvir plus daclatasvir for 24 weeks or sofosbuvir, daclatasvir, and ribavirin for 12 weeks are the optimal oral therapies, particularly for patients with cirrhosis and those who are treatment experienced, whereas sofosbuvir, pegylated interferon, and ribavirin for 12 weeks is an alternative regimen. For genotype 6, sofosbuvir plus pegylated interferon and ribavirin, sofosbuvir plus ledipasvir, or sofosbuvir plus ribavirin for 12 weeks are all suitable. Pegylated interferon plus ribavirin has been replaced by sofosbuvir plus pegylated interferon and ribavirin, and all-oral therapies where available, but cost and affordability remain a major issue because of the absence of universal health coverage. Few patients have been treated because of multiple barriers to accessing care. HCV in the Asia-Pacific region is challenging because of the disparate epidemiology, poor access to all-oral therapy because of availability, cost, or regulatory licensing. Until these problems are addressed, the burden of disease is likely to remain high., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Aim: To investigate peg-interferon (peg-IFN) and ribavirin (RBV) therapy in Myanmar and to predict sustained virologic response (SVR)., Methods: This single-center, open-label, study was conducted in Myanmar between 2009 and 2014. A total of 288 patients infected with HCV genotypes 1, 2, 3 and 6 were treated with peg-IFN alpha-2a (180 μg/wk) or alpha-2b (50 to 100 μg as a weight-based dose) and RBV as a weight-based dose (15 mg/kg/d). Treatment duration was 48 wk for genotypes 1 and 6, 24 wk for genotype 2, and 24 or 48 wk for genotype 3 based on rapid virologic response (RVR). Those co-infected with hepatitis B received 48 wk of therapy., Results: Overall, SVR was achieved for 82% of patients and the therapy was well tolerated. All patients achieved SVR at equivalent rates regardless of HCV genotype ( P = 0.314). Low fibrosis scores ( P < 0.001), high baseline albumin levels ( P = 0.028) and low baseline viral loads ( P = 0.029) all independently predicted SVR. On the other hand, IL-28B TT and CC genotypes were not found to significantly predict SVR ( P = 0.634; P = 0.618). Among those who completed treatment, the occurrence of RVR showed a > 96% positive predictive value for achieving SVR. Treatment duration did not significantly impact the likelihood of achieving SVR for patients infected with genotype 3 HCV ( P = 0.371). The most common adverse events were fatigue (71%) and poor appetite (60%). Among patients with genotype 3 HCV, more patients in the 48-wk treatment group required erythropoietin than in the 24-wk treatment group (61.1% vs 49.2%)., Conclusion: SVR rates were high with peg-IFN and RBV therapy in Myanmar. Fibrosis scores, baseline albumin, HCV RNA levels and RVR independently predicted SVR., Competing Interests: Conflict-of-interest statement: Reddy KR serves on the advisory boards for BMS, Gilead, Abbvie, Merck and Jansen. Research support from BMS, Gilead, Abbie, Merck and Janssen is paid to the University of Pennsylvania. All other authors do not have any conflicts-of-interest.

An expert panel met to review the evidence for selective internal radiation therapy (SIRT) using yttrium-90 microspheres in hepatocellular carcinoma and metastases from colorectal cancer and neuroendocrine tumors. There is now convincing evidence for the safety and efficacy of SIRT in these situations albeit mostly from retrospective cohort studies. There are a number of ongoing prospective randomized controlled clinical trials investigating the role of SIRT in liver tumors; however, data from these trials are still several years away (although the SIRFLOX study has been recently published). In this evolving environment, published evidence and the authors' experience were used to summarize the current and potential role of SIRT in the management of hepatocellular carcinoma of intermediate or advanced stage and in liver-dominant metastatic colorectal cancer and metastatic neuroendocrine tumors.

Objectives: To examine the performance of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) global health status/quality of life (QoL) scale and two summary scores to detect changes in the QoL profile over time, according to changes in the individual scales., Study Design and Setting: Data came from 167 clinical trial patients with unresectable (advanced) hepatocellular carcinoma. The global health status/QoL scale of the questionnaire contained two items: overall health and overall QoL. Nordin and Hinz proposed summary scores for the questionnaire. A mixed-effect model was fitted to estimate trends in scores over time., Results: Predominantly the individual scale scores declined over time; however, the global health status/QoL score was stable [rate of change = -0.3 per month; 95% confidence interval (CI): -1.2, 0.6]. Nordin's summary score, which gave equal weight to the 15 questionnaire scales, and Hinz's summary score, which gave equal weight to the 30 questionnaire items, showed a statistically significant decline over time, 3.4 (95% CI: -4.5, -2.4) and 4.2 (95% CI: -5.3, -3.0) points per month, respectively., Conclusion: In contrast to the global health status/QoL scale, the summary scores proposed by Nordin and Hinz detected changes in subjects' QoL profile described by the EORTC QLQ-C30 individual scales., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Singapore is an intermediate tuberculosis (TB) incidence country, with a recent rise in TB incidence from 2008, after a fall in incidence since 1998. This study identified population characteristics that were associated with the recent increase in TB cases, and built a predictive model of TB risk in Singapore., Methods: Retrospective time series analysis was used to study TB notification data collected from 1995 to 2011 from the Singapore Tuberculosis Elimination Program (STEP) registry. A predictive model was developed based on the data collected from 1995 to 2010 and validated using the data collected in 2011., Results: There was a significant difference in demographic characteristics between resident and non-resident TB cases. TB risk was higher in non-residents than in residents throughout the period. We found no significant association between demographic and macro-economic factors and annual incidence of TB with or without adjusting for the population-at-risk. Despite growing non-resident population, there was a significant decrease in the non-resident TB risk (p < 0.0001). However, there was no evidence of trend in the resident TB risk over this time period, though differences between different demographic groups were apparent with ethnic minorities experiencing higher incidence rates., Conclusion: The study found that despite an increasing size of non-resident population, TB risk among non-residents was decreasing at a rate of about 3% per year. There was an apparent seasonality in the TB reporting.

Setting: The National Tuberculosis Programme in Singapore where, among resident cases, higher tuberculosis (TB) rates have been reported in ethnic Malays., Objective: To describe the socio-demographic and clinical characteristics of resident TB cases by ethnicity, and to assess whether Malays differ from other groups in terms of the above parameters., Design: Cross-sectional review of records from the tuberculosis registry's electronic database., Results: Among 15 622 resident cases notified, 72.2% were Chinese, 18.7% Malay, 5.8% Indian and 2.9% were from other minorities. Compared to other ethnicities, Malays were more likely to be incarcerated at the time of notification (odds ratio [OR] 3.70, 95%CI 3.03-4.52) and clustered at the same residential address (OR 1.65, 95%CI 1.44-1.89), but were less likely to be aged ≥65 years (OR 0.61, 95%CI 0.54-0.70) or to reside in high-cost housing (OR 0.11, 95%CI 0.07-0.17). In terms of disease characteristics, more Malays had diabetes mellitus (OR 1.54, 1.37-1.73), a highly-positive acid-fast bacilli smear (OR 1.64, 95%CI 1.47-1.83) and cavitary disease on chest X-ray (OR 1.41, 95%CI 1.28-1.55)., Conclusion: Compared to other ethnicities, reported TB cases among Malays were more severe and were likely to be more infectious. Increased vigilance in case management and contact investigations, as well as an improvement in the socio-economic conditions of this community, are required to reduce TB rates in this ethnic group.

Background: Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths worldwide. We tested megestrol acetate (MA) against placebo in the treatment of advanced HCC., Methods: From 2002 through 2007, this randomised double-blind trial enrolled 204 patients with treatment-naive advanced HCC (Eastern Cooperative Oncology Group (ECOG) performance rating of 0-3) from specialist care centres in six Asia-Pacific nations. Patients received placebo or MA (320 mg day(-1)). End points were overall survival (OS) and quality of life., Results: An adverse but not statistically significant difference in OS was found for MA vs placebo: median values 1.88 and 2.14 months, respectively (hazard ratio (HR)=1.25, 95% CI=0.92-1.71, P=0.16). However, OS was similar among patients of good functional status (Child-Pugh A and ECOG 0, 1 or 2) (44.3%) in both treatment groups, with the adverse effect of MA confined to those of poor status. Megestrol acetate patients had a worse global health status (not statistically significant) but reduced levels of appetite loss and nausea/vomiting., Conclusion: Megestrol acetate has no role in prolonging OS in advanced treatment-naive HCC. Overall survival with placebo differed markedly from that in similar trials conducted elsewhere, suggesting therapeutic outcomes may be strongly dependent on ECOG status and Child-Pugh score.

We determined the proportion of foreign-born persons with tuberculosis (TB) in Singapore. This proportion increased from 25.5% in 2004 to 37.6% in 2009. Unskilled workers from countries with high incidences of TB accounted for the highest number of and greatest increase in foreign-born TB case-patients.

Differential expression, activity, phosphorylation, and oligomerization of tau play a critical role during neuronal development and in a number of age-related neurodegenerative diseases. An experimental system that accurately models the molecular changes involved in tauopathies, particularly changes in tau isoform activity, requires the expression at physiological levels of the full complement of tau isoforms present in the adult human brain. To this end, we analyzed tau expression in human cortical neurons (HCNs) in culture. Here, we show that the isoform profile of tau in HCNs is similar to that in the adult human brain and that isoform expression is regulated during neuronal development and by cellular substrates. Interestingly, 4R tau exhibited a distinct pattern of expression and subcellular localization, suggesting the presence of specific functional roles for tau isoforms in HCNs. Tau phosphorylation, microtubule binding, and subcellular localization were markedly altered by pharmacological manipulation of tau-directed phosphatase activities, which also induced the appearance of tau oligomeric forms associated with memory loss in animal models of tauopathy. Thus, experimentally induced changes in tau activity and function in HCNs recapitulate critical features of tauopathies that may lead to neuronal dysfunction and degeneration in the human brain.

Induction of curative immune responses by therapeutic vaccination in chronic viral infections such as chronic hepatitis B (CHB) is expected to be facilitated by reduction of viral load by antiviral treatment. In this open label, controlled, randomized study, 195 patients with HBeAg positive CHB were randomized to receive 12 doses of HBsAg with AS02B adjuvant candidate vaccine plus lamivudine daily for 52 weeks or lamivudine daily alone. The combined administration of vaccine and lamivudine was safe and well tolerated, but did not improve the HBe seroconversion rate (18.8%) when compared to treatment with lamivudine alone (16.1%) (p=0.6824). Despite induction of a vigorous HBsAg-specific lymphoproliferative response, cytokine production and anti-HBs antibodies, therapeutic vaccination with an adjuvanted HBsAg vaccine administered concomitantly with lamivudine did not demonstrate superior clinical efficacy in HBeAg positive CHB patients as compared to lamivudine therapy alone.

Background: The aim of this study was to survey the effect of deposited iron on the cell kinetics of hepatitis C virus (HCV)-positive hepatocellular carcinoma (HCC) in Myanmar (Burmese) patients., Methods: Formalin-fixed and paraffin-embedded liver tissues from 34 Myanmar patients with HCC were used. To detect iron deposition, Prussian blue staining was performed. Cell proliferation and apoptosis were assessed by Ki-67 staining and by the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL) assay, respectively. HCV RNA was detected by in situ hybridization, and HCV protein, Fas and Fas ligand (FasL) were localized by immunohistochemistry. To identify the subtype of lymphocytes, CD8 was used as a surface marker., Results: Iron deposition was found in 43% of the HCC cases, and was heavier in moderately differentiated HCC than in well-differentiated HCC. The Ki-67 labeling index (LI) in cancer cells was higher in Prussian blue-positive-HCC than in -negative HCC (3.8 +/- 2.2 vs 1.5 +/- 1.7, mean +/- SD; P=0.0067), whereas there was no significant difference between these groups in TUNEL LI. HCV protein was localized in cancer cells, and was found in 89% of the patients. In addition, Fas was expressed in HCC cells, and FasL was localized in HCC cells as well as in infiltrating CD8+ T lymphocytes. The frequency of apoptosis of HCC cells was correlated significantly with the population density of infiltrating CD8+ T lymphocytes., Conclusions: Our results indicated that, in Myanmar patients with HCC, iron deposition might accelerate hepatocarcinogenesis, by promoting cancer cell proliferation, without affecting the Fas/FasL apoptotic system.

We conducted seroepidemiological studies on antibody prevalence to hepatitis E virus (HEV) in 5,233 sera from 11 countries to ascertain the present state of HEV infection on a global basis. The prevalence of anti-HEV IgG increased with age in these tested countries, but the rate of antibody positivity was over 20% in the 16-30 year-old group in most of the participating countries, except for Japan, the USA, and Spain. Of patients with acute hepatitis of unknown etiology from Nepal, 56% (14/25) were positive for the IgM class of anti-HEV antibody. In addition, HEV RNAs in the serum from 3 Nepali patients who had the IgM antibody were detected by nested PCR and all of the HEV genes isolated belonged to genotype 1. Our results indicate that HEV is spreading worldwide, not only in developing countries, but also in more industrialized countries than previously thought.

We examined the histochemical characteristics of soleus muscle in the angiotensin-converting enzyme (ACE) gene (Ace in mice, ACE in humans) knockout mice. Serial sections of soleus muscle of wild-type (Ace+/+, n=20) and heterozygous mutant (Ace+/-, n=24) mice were stained for myosin adenosine triphosphatase activity to identify different muscle fiber types. Capillaries were visualized by amylase-periodic acid-Schiff staining. ACE activity in the serum and gastrocnemius muscle was higher in male mice than in female mice. Female and male Ace+/- mice had markedly lower ACE activity in the serum and the gastrocnemius muscle than did female and male Ace+/+ mice, respectively. In both male and female mice, the composition of fiber types (type I and IIa) did not differ significantly between Ace+/+ and Ace+/- mice. There was no significant gender difference in capillary density. Ace+/- mice had significantly more capillaries around type IIa fibers (5.44 +/- 0.18 vs. 5.01 +/- 0.13, p<0.05) than Ace+/+ mice. The differences in the number of capillaries around type I fibers and in the number of capillaries around per fiber (capillary:fiber ratio) between Ace+/- and Ace+/+ mice were not significant (p<0.1). There was no significant difference in the mean cross-sectional area occupied by one capillary and the number of capillaries per fiber area between Ace+/+ and Ace+/- mice. In conclusion, knockout of the Ace gene in mice increased capillary density, as expressed by the mean number of capillaries around type IIa fibers. This finding suggests a possible mechanism for the cardioprotective effects of ACE inhibitors.