Dysregulated immunologic landscape of the early host response in melioidosis.

Melioidosis, a neglected tropical infection caused by Burkholderia pseudomallei, commonly presents as pneumonia or sepsis with mortality rates up to 50% despite appropriate treatment. A better understanding of the early host immune response to melioidosis may lead to new therapeutic interventions and prognostication strategies to reduce disease burden. Whole blood transcriptomic signatures in 164 patients with melioidosis and in 70 patients with other infections hospitalized in northeastern Thailand enrolled within 24 hours following hospital admission were studied. Key findings were validated in an independent melioidosis cohort. Melioidosis was characterized by upregulation of interferon (IFN) signaling responses compared with other infections. Mortality in melioidosis was associated with excessive inflammation, enrichment of type 2 immune responses, and a dramatic decrease in T cell-mediated immunity compared with survivors. We identified and independently confirmed a 5-gene predictive set classifying fatal melioidosis (validation cohort area under the receiver operating characteristic curve 0.83; 95% CI, 0.67-0.99). This study highlights the intricate balance between innate and adaptive immunity during fatal melioidosis and can inform future precision medicine strategies for targeted therapies and prognostication in this severe infection.

Diabetes and risk of hospitalisation due to infection in northeastern Thailand: Retrospective cohort study using population-based healthcare service data.

BACKGROUND: Population-based studies describing the association between diabetes and increased risk of infection have largely been based in high-income countries. There is limited information describing the burden of infectious disease attributable to diabetes in low and middle-income countries. This study aimed to describe the burden and risk of infectious disease hospitalisation in people with diabetes compared to those without diabetes in northeastern Thailand. METHODS: In a retrospective cohort study using electronic health record data for 2012-2018 for 3.8 million people aged ≥20 years in northeastern Thailand, hospitalisation rates for any infectious diseases (ICD-10 codes A00-B99) were estimated and negative binomial regression used to estimate rate ratios (RR) for the association between diabetes and infectious disease hospitalisation adjusted for age, sex and area of residence. RESULTS: In this study, 164,177 people had a diagnosis of diabetes mellitus at any point over the study period. Infectious disease hospitalisation rates per 1000 person-years (95%CI) were 71.8 (70.9, 72.8), 27.7 (27.1, 28.3) and 7.5 (7.5, 7.5) for people with prevalent diabetes, incident diabetes and those without diabetes respectively. Diabetes was associated with a 4.6-fold higher risk of infectious disease hospitalisation (RR (95% CI) 4.59 (4.52, 4.66)). RRs for infectious disease hospitalisation were 3.38 (3.29, 3.47) for people with diabetes managed by lifestyle alone and 5.29 (5.20, 5.39) for people receiving prescriptions for diabetes drugs. CONCLUSIONS: In this Thai population, diabetes was associated with substantially increased risk of hospitalisation due to infectious diseases and people with diabetes who were on pharmacological treatment had a higher risk than those receiving lifestyle modification advice alone.

Factors influencing optimal diabetes care and clinical outcomes in Thai patients with type 2 diabetes mellitus: a multilevel modelling analysis.

BACKGROUND: Increasing levels of poor glycaemic control among Thai patients with type 2 diabetes mellitus (T2DM) motivated us to compare T2DM care between urban and suburban primary care units (PCUs), to identify gaps in care, and to identify significant factors that may influence strategies to enhance the quality of care and clinical outcomes in this population. METHODS: We conducted a cross-sectional study involving 2160 patients with T2DM treated at four Thai PCUs from 2019 to 2021, comprising one urban and three suburban facilities. Using mixed effects logistic regression, we compared care factors between urban and suburban PCUs. RESULTS: Patients attending suburban PCUs were significantly more likely to undergo eye (adjusted OR (AOR): 1.83, 95% CI 1.35 to 1.72), foot (AOR: 1.61, 95% CI 0.65 to 4.59) and HbA1c (AOR: 1.66, 95% CI 1.09 to 2.30) exams and achieved all ABC (HbA1c, blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C)) goals (AOR: 2.23, 95% CI 1.30 to 3.83). Conversely, those at an urban PCU were more likely to undergo albuminuria exams. Variables significantly associated with good glycaemic control included age (AOR: 1.51, 95% CI 1.31 to 1.79), T2DM duration (AOR: 0.59, 95% CI 0.41 to 0.88), FAACE (foot, HbA1c, albuminuria, LDL-C and eye) goals (AOR: 1.23, 95% CI 1.12 to 1.36) and All8Q (AOR: 1.20, 95% CI 1.05 to 1.41). Chronic kidney disease (CKD) was significantly linked with high triglyceride and HbA1c levels (AOR: 5.23, 95% CI 1.21 to 7.61). Elevated HbA1c levels, longer T2DM duration, insulin use, high systolic BP and high lipid profile levels correlated strongly with diabetic retinopathy (DR) and CKD progression. CONCLUSION: This highlights the necessity for targeted interventions to bridge urban-suburban care gaps, optimise drug prescriptions and implement comprehensive care strategies for improved glycaemic control, DR prevention and CKD progression mitigation among in Thai patients with T2DM. The value of the clinical target aggregate (ABC) and the process of care aggregate (FAACE) was also conclusively demonstrated.

Frequency and mortality rate following antimicrobial-resistant bloodstream infections in tertiary-care hospitals compared with secondary-care hospitals.

There are few studies comparing proportion, frequency, mortality and mortality rate following antimicrobial-resistant (AMR) infections between tertiary-care hospitals (TCHs) and secondary-care hospitals (SCHs) in low and middle-income countries (LMICs) to inform intervention strategies. The aim of this study is to demonstrate the utility of an offline tool to generate AMR reports and data for a secondary data analysis. We conducted a secondary-data analysis on a retrospective, multicentre data of hospitalised patients in Thailand. Routinely collected microbiology and hospital admission data of 2012 to 2015, from 15 TCHs and 34 SCHs were analysed using the AMASS v2.0 (www.amass.website). We then compared the burden of AMR bloodstream infections (BSI) between those TCHs and SCHs. Of 19,665 patients with AMR BSI caused by pathogens under evaluation, 10,858 (55.2%) and 8,807 (44.8%) were classified as community-origin and hospital-origin BSI, respectively. The burden of AMR BSI was considerably different between TCHs and SCHs, particularly of hospital-origin AMR BSI. The frequencies of hospital-origin AMR BSI per 100,000 patient-days at risk in TCHs were about twice that in SCHs for most pathogens under evaluation (for carbapenem-resistant Acinetobacter baumannii [CRAB]: 18.6 vs. 7.0, incidence rate ratio 2.77; 95%CI 1.72-4.43, p<0.001; for carbapenem-resistant Pseudomonas aeruginosa [CRPA]: 3.8 vs. 2.0, p = 0.0073; third-generation cephalosporin resistant Escherichia coli [3GCREC]: 12.1 vs. 7.0, p<0.001; third-generation cephalosporin resistant Klebsiella pneumoniae [3GCRKP]: 12.2 vs. 5.4, p<0.001; carbapenem-resistant K. pneumoniae [CRKP]: 1.6 vs. 0.7, p = 0.045; and methicillin-resistant Staphylococcus aureus [MRSA]: 5.1 vs. 2.5, p = 0.0091). All-cause in-hospital mortality (%) following hospital-origin AMR BSI was not significantly different between TCHs and SCHs (all p>0.20). Due to the higher frequencies, all-cause in-hospital mortality rates following hospital-origin AMR BSI per 100,000 patient-days at risk were considerably higher in TCHs for most pathogens (for CRAB: 10.2 vs. 3.6,mortality rate ratio 2.77; 95%CI 1.71 to 4.48, p<0.001; CRPA: 1.6 vs. 0.8; p = 0.020; 3GCREC: 4.0 vs. 2.4, p = 0.009; 3GCRKP, 4.0 vs. 1.8, p<0.001; CRKP: 0.8 vs. 0.3, p = 0.042; and MRSA: 2.3 vs. 1.1, p = 0.023). In conclusion, the burden of AMR infections in some LMICs might differ by hospital type and size. In those countries, activities and resources for antimicrobial stewardship and infection control programs might need to be tailored based on hospital setting. The frequency and in-hospital mortality rate of hospital-origin AMR BSI are important indicators and should be routinely measured to monitor the burden of AMR in every hospital with microbiology laboratories in LMICs.

Clinical teaching self-efficacy positively predicts professional fulfillment and negatively predicts burnout amongst Thai physicians: a cross-sectional survey.

BACKGROUND: Clinician teachers (physicians who teach in clinical settings) experience considerable psychological challenges in providing both educational training and patient care. This study aimed to determine the prevalence of physician burnout and professional fulfillment, and to identify internal and external factors associated with mental health outcomes among Thai clinician teachers working in non-university teaching hospitals. METHOD: A one-time online questionnaire was completed by physicians at 37 governmental, non-university teaching hospitals in Thailand, with 227 respondents being assessed in the main analyses. Four outcomes were evaluated including burnout, professional fulfillment, quality of life, and intentions to quit. RESULTS: The observed prevalence of professional fulfillment was 20%, and burnout was 30.7%. Hierarchical regression analysis showed a significant internal, psychological predictor (clinical teaching self-efficacy) and external, structural predictors (multiple roles at work, teaching support), controlling for the background variables of gender, years of teaching experience, family roles, and active chronic disease, with clinical teaching self-efficacy positively predicting professional fulfillment (b = 0.29, p ≤.001) and negatively predicting burnout (b = - 0.21, p =.003). CONCLUSIONS: Results highlight the importance of faculty development initiatives to enhance clinical teaching self-efficacy and promote mental health among Thai physicians.

Benchmarking CRISPR-BP34 for point-of-care melioidosis detection in low-income and middle-income countries: a molecular diagnostics study.

BACKGROUND: Melioidosis is a neglected but often fatal tropical disease. The disease has broad clinical manifestations, which makes diagnosis challenging and time consuming. To improve diagnosis, we aimed to evaluate the performance of the CRISPR-Cas12a system (CRISPR-BP34) to detect Burkholderia pseudomallei DNA across clinical specimens from patients suspected to have melioidosis. METHODS: We conducted a prospective, observational cohort study of adult patients (aged ≥18 years) with melioidosis at Sunpasitthiprasong Hospital, a tertiary care hospital in Thailand. Participants were eligible for inclusion if they had culture-confirmed B pseudomallei infection from any clinical samples. Data were collected from patient clinical records and follow-up telephone calls. Routine clinical samples (blood, urine, respiratory secretion, pus, and other body fluids) were collected for culture. We documented time taken for diagnosis, and mortality at day 28 of follow-up. We also performed CRISPR-BP34 detection on clinical specimens collected from 330 patients with suspected melioidosis and compared its performance with the current gold-standard culture-based method. Discordant results were validated by three independent qualitative PCR tests. This study is registered with the Thai Clinical Trial Registry, TCTR20190322003. FINDINGS: Between Oct 1, 2019, and Dec 31, 2022, 876 patients with culture-confirmed melioidosis were admitted or referred to Sunpasitthiprasong Hospital, 433 of whom were alive at diagnosis and were enrolled in this study. Median time from sample collection to diagnosis by culture was 4·0 days (IQR 3·0-5·0) among all patients with known survival status at day 28, which resulted in delayed treatment. 199 (23%) of 876 patients died before diagnosis and 114 (26%) of 433 patients in follow-up were treated, but died within 28 days of admission. To test the CRISPR-BP34 assay, we enrolled and collected clinical samples from 114 patients with melioidosis and 216 patients without melioidosis between May 26 and Dec 31, 2022. Application of CRISPR-BP34 reduced the median sample-to-diagnosis time to 1·1 days (IQR 0·7-1·5) for blood samples, 2·3 h (IQR 2·3-2·4) for urine, and 3·3 h (3·1-3·4) for respiratory secretion, pus, and other body fluids. The overall sensitivity of CRISPR-BP34 was 93·0% (106 of 114 samples [95% CI 86·6-96·9]) compared with 66·7% (76 of 114 samples [57·2-75·2]) for culture. The overall specificity of CRISPR-BP34 was 96·8% (209 of 216 samples [95% CI 93·4-98·7]), compared with 100% (216 of 216 samples [98·3-100·0]) for culture. INTERPRETATION: The sensitivity, specificity, speed, and window of clinical intervention offered by CRISPR-BP34 support its prospective use as a point-of-care diagnostic tool for melioidosis. Future development should be focused on scalability and cost reduction. FUNDING: Chiang Mai University Thailand and Wellcome Trust UK.

Barriers and enablers to blood culture sampling in Indonesia, Thailand and Viet Nam: a Theoretical Domains Framework-based survey.

OBJECTIVE: Blood culture (BC) sampling is recommended for all suspected sepsis patients prior to antibiotic administration. We examine barriers and enablers to BC sampling in three Southeast Asian countries. DESIGN: A Theoretical Domains Framework (TDF)-based survey, comprising a case scenario of a patient presenting with community-acquired sepsis and all 14 TDF domains of barriers/enablers to BC sampling. SETTING: Hospitals in Indonesia, Thailand and Viet Nam, December 2021 to 30 April 2022. PARTICIPANTS: 1070 medical doctors and 238 final-year medical students were participated in this study. Half of the respondents were women (n=680, 52%) and most worked in governmental hospitals (n=980, 75.4%). OUTCOME MEASURES: Barriers and enablers to BC sampling. RESULTS: The proportion of respondents who answered that they would definitely take BC in the case scenario was highest at 89.8% (273/304) in Thailand, followed by 50.5% (252/499) in Viet Nam and 31.3% (157/501) in Indonesia (p<0.001). Barriers/enablers in nine TDF domains were considered key in influencing BC sampling, including 'priority of BC (TDF-goals)', 'perception about their role to order or initiate an order for BC (TDF-social professional role and identity)', 'perception that BC is helpful (TDF-beliefs about consequences)', 'intention to follow guidelines (TDF-intention)', 'awareness of guidelines (TDF-knowledge)', 'norms of BC sampling (TDF-social influence)', 'consequences that discourage BC sampling (TDF-reinforcement)', 'perceived cost-effectiveness of BC (TDF-environmental context and resources)' and 'regulation on cost reimbursement (TDF-behavioural regulation)'. There was substantial heterogeneity between the countries. In most domains, the lower (higher) proportion of Thai respondents experienced the barriers (enablers) compared with that of Indonesian and Vietnamese respondents. A range of suggested intervention types and policy options was identified. CONCLUSIONS: Barriers and enablers to BC sampling are varied and heterogenous. Cost-related barriers are more common in more resource-limited countries, while many barriers are not directly related to cost. Context-specific multifaceted interventions at both hospital and policy levels are required to improve diagnostic stewardship practices.

BurkHostGEN: a study protocol for evaluating variations in the Burkholderia pseudomallei and host genomes associated with melioidosis infection.

Background: Melioidosis is a frequently fatal disease caused by an environmental bacterium Burkholderia pseudomallei. The disease is prevalent in northeast Thailand, particularly among rice field farmers who are at risk of bacterial exposure through contact with contaminated soil and water. However, not all exposure results in disease, and infection can manifest diverse outcomes. We postulate that genetic factors, whether from the bacterium, the host or the combination of both, may influence disease outcomes. To address this hypothesis, we aim to collect, sequence, and analyse genetic data from melioidosis patients and controls, along with isolates of B. pseudomallei obtained from patients. Additionally, we will study the metagenomics of the household water supply for both patients and controls, including the presence of B. pseudomallei. Methods: BurkHostGEN is an ongoing observational study being conducted at Sunpasitthiprasong Hospital, Ubon Ratchathani, Thailand. We are obtaining consent from 600 melioidosis patients and 700 controls, spanning both sexes, to collect 1 mL of blood for host DNA analysis, 3 mL of blood for RNA analysis, as well as 5 L of household water supply for metagenomic analysis. Additionally, we are isolating B. pseudomallei from the melioidosis patients to obtain bacterial DNA. This comprehensive approach will allow us to identify B. pseudomallei and their paired host genetic factors associated with disease acquisition and severity. Ethical approvals have been obtained for BurkHostGEN. Host and bacterial genetic data will be uploaded to European Genome-Phenome Archive (EGA) and European Nucleotide Archive (ENA), respectively. Conclusions: BurkHostGEN holds the potential to discover bacterial and host genetic factors associated with melioidosis infection and severity of illness. It can also support various study designs, including biomarker validation, disease pathogenesis, and epidemiological analysis not only for melioidosis but also for other infectious diseases.

Melioidosis Vaccines (MeVa): Attitudes to vaccines, melioidosis and clinical trials in key stakeholders in Ubon Ratchathani, Thailand.

Background: Melioidosis is a bacterial infection which kills an estimated 89,000 people per year in tropical and sub-tropical regions, chiefly affecting the poorest. Diabetes is the primary risk factor, conferring a 12-fold increase in risk. Despite limited funding compared to other neglected tropical diseases, melioidosis vaccine development has generated several candidates for clinical development. CPS-CRM 197/Hcp1 is a promising vaccine candidate developed at the University of Nevada, Reno which is due to enter a Phase I clinical trial in Oxford, UK in 2024. As we move closer to the possibility of field trials of a melioidosis vaccine, it is critical to work in parallel to understand perceptions toward a vaccine among those living where melioidosis rates are high. Reasons for vaccine acceptance versus hesitancy are complex, and include perceived risk of the target disease, concern about side effects, and above all trust in government, scientists, the pharmaceutical industry and other authorities. Methods: We will carry out a qualitative study in Ubon Ratchathani, Thailand, an endemic region for melioidosis, as groundwork for a potential future melioidosis vaccine efficacy study, and in the longer-term vaccine introduction. This study seeks to explore knowledge and attitudes in three main areas; 1) melioidosis disease, 2) vaccines, and 3) participation in clinical vaccine trials. In-depth interviews and focus group discussions will take place in five participant groups of different risks and exposure to melioidosis. Purposive, convenience sampling will be used, also snowball sampling to reach some participant groups. Sample size will be based on participant's experience, to inform the line of enquiries of study, or until data saturation, expecting 66-90 participants across all groups. Discussion: The findings of this study will be written up and published in an open access journal, and will be valuable to inform future design of clinical trials as well as engagement and communications associated with future vaccine rollout.

Prevalence and DALYs of skin diseases in Ubonratchathani based on real-world national healthcare service data.

There is little evidence to describe the burden of skin diseases in developing countries and its accuracy remained uncertain. We aimed to examine prevalence and disability adjusted life years (DALYs) of skin diseases in a Thai general population in Ubonratchathani. Based on real-world healthcare service data (diagnoses, prevalence, and cause-specific mortality) retrieved from the National Health Security Office reimbursement database, we used a simplified prevalence-based approach adopted in the Global Burden of Diseases to compute disease burden, measured as DALYs, of skin diseases. DALYs was calculated as the sum of years lost due to disability and years of life lost due to skin diseases, with adoption of previously published averaged disability weights and a 95% uncertainty interval (UI) estimated using a Bayesian bootstrap technique. From a total population of 1,503,945, 110,205 people were affected by skin disease in 2018-an overall prevalence of 7%. The prevalence varied across sex, age group and geographic areas. The most common skin diseases treated in Ubonratchathani's healthcare services were dermatitis, bacterial skin diseases and urticaria (prevalence of 2.35%, 2.21% and 0.89% respectively). Overall DALYs of skin diseases in Ubonratchathani population was 26,125 (95%UI 24,783-27,467), and this was relatively higher in men than women. (DALYs 13,717 (12,846-14,588) and 12,408 (11,417-13,399) for men and women respectively). The greatest contributors of DALYs were cellulitis, decubitus ulcer and contact dermatitis (11,680, 4,806 and 1,598 years respectively). In conclusion, skin disease caused substantial disease burden in this Thai population, with cellulitis being the largest contributor.

Effects of a Technology-Assisted Integrated Diabetes Care Program on Cardiometabolic Risk Factors Among Patients With Type 2 Diabetes in the Asia-Pacific Region: The JADE Program Randomized Clinical Trial.

Importance: Many health care systems lack the efficiency, preparedness, or resources needed to address the increasing number of patients with type 2 diabetes, especially in low- and middle-income countries. Objective: To examine the effects of a quality improvement intervention comprising information and communications technology and contact with nonphysician personnel on the care and cardiometabolic risk factors of patients with type 2 diabetes in 8 Asia-Pacific countries. Design, Setting, and Participants: This 12-month multinational open-label randomized clinical trial was conducted from June 28, 2012, to April 28, 2016, at 50 primary care or hospital-based diabetes centers in 8 Asia-Pacific countries (India, Indonesia, Malaysia, the Philippines, Singapore, Taiwan, Thailand, and Vietnam). Six countries were low and middle income, and 2 countries were high income. The study was conducted in 2 phases; phase 1 enrolled 7537 participants, and phase 2 enrolled 13 297 participants. Participants in both phases were randomized on a 1:1 ratio to intervention or control groups. Data were analyzed by intention to treat and per protocol from July 3, 2019, to July 21, 2020. Interventions: In both phases, the intervention group received 3 care components: a nurse-led Joint Asia Diabetes Evaluation (JADE) technology-guided structured evaluation, automated personalized reports to encourage patient empowerment, and 2 or more telephone or face-to-face contacts by nurses to increase patient engagement. In phase 1, the control group received the JADE technology-guided structured evaluation and automated personalized reports. In phase 2, the control group received the JADE technology-guided structured evaluation only. Main Outcomes and Measures: The primary outcome was the incidence of a composite of diabetes-associated end points, including cardiovascular disease, chronic kidney disease, visual impairment or eye surgery, lower extremity amputation or foot ulcers requiring hospitalization, all-site cancers, and death. The secondary outcomes were the attainment of 2 or more primary diabetes-associated targets (glycated hemoglobin A1c <7.0%, blood pressure <130/80 mm Hg, and low-density lipoprotein cholesterol <100 mg/dL) and/or 2 or more key performance indices (reduction in glycated hemoglobin A1c≥0.5%, reduction in systolic blood pressure ≥5 mm Hg, reduction in low-density lipoprotein cholesterol ≥19 mg/dL, and reduction in body weight ≥3.0%). Results: A total of 20 834 patients with type 2 diabetes were randomized in phases 1 and 2. In phase 1, 7537 participants (mean [SD] age, 60.0 [11.3] years; 3914 men [51.9%]; 4855 patients [64.4%] from low- and middle-income countries) were randomized, with 3732 patients allocated to the intervention group and 3805 patients allocated to the control group. In phase 2, 13 297 participants (mean [SD] age, 54.0 [11.1] years; 7754 men [58.3%]; 13 297 patients [100%] from low- and middle-income countries) were randomized, with 6645 patients allocated to the intervention group and 6652 patients allocated to the control group. In phase 1, compared with the control group, the intervention group had a similar risk of experiencing any of the primary outcomes (odds ratio [OR], 0.94; 95% CI, 0.74-1.21) but had an increased likelihood of attaining 2 or more primary targets (OR, 1.34; 95% CI, 1.21-1.49) and 2 or more key performance indices (OR, 1.18; 95% CI, 1.04-1.34). In phase 2, the intervention group also had a similar risk of experiencing any of the primary outcomes (OR, 1.02; 95% CI, 0.83-1.25) and had a greater likelihood of attaining 2 or more primary targets (OR, 1.25; 95% CI, 1.14-1.37) and 2 or more key performance indices (OR, 1.50; 95% CI, 1.33-1.68) compared with the control group. For attainment of 2 or more primary targets, larger effects were observed among patients in low- and middle-income countries (OR, 1.50; 95% CI, 1.29-1.74) compared with high-income countries (OR, 1.20; 95% CI, 1.03-1.39) (P = .04). Conclusions and Relevance: In this 12-month clinical trial, the use of information and communications technology and nurses to empower and engage patients did not change the number of clinical events but did reduce cardiometabolic risk factors among patients with type 2 diabetes, especially those in low- and middle-income countries in the Asia-Pacific region. Trial Registration: ClinicalTrials.gov Identifier: NCT01631084.

Effectiveness of a sepsis programme in a resource-limited setting: a retrospective analysis of data of a prospective observational study (Ubon-sepsis).

OBJECTIVE: To evaluate the effectiveness of a Sepsis Fast Track (SFT) programme initiated at a regional referral hospital in Thailand in January 2015. DESIGN: A retrospective analysis using the data of a prospective observational study (Ubon-sepsis) from March 2013 to January 2017. SETTING: General medical wards and medical intensive care units (ICUs) of a study hospital. PARTICIPANTS: Patients with community-acquired sepsis observed under the Ubon-sepsis cohort. Sepsis was defined as modified Sequential Organ Failure Assessment (SOFA) Score ≥2. MAIN EXPOSURE: The SFT programme was a protocol to identify and initiate sepsis care on hospital admission, implemented at the study hospital in 2015. Patients in the SFT programme were admitted directly to the ICUs when available. The non-exposed group comprised of patients who received standard of care. MAIN OUTCOME: The primary outcome was 28-day mortality. The secondary outcomes were measured sepsis management interventions. RESULTS: Of 3806 sepsis patients, 903 (24%) were detected and enrolled in the SFT programme of the study hospital (SFT group) and 2903 received standard of care (non-exposed group). Patients in the SFT group had more organ dysfunction, were more likely to receive measured sepsis management and to be admitted directly to the ICU (19% vs 4%). Patients in the SFT group were more likely to survive (adjusted HR 0.72, 95% CI 0.58 to 0.88, p=0.001) adjusted for admission year, gender, age, comorbidities, modified SOFA Score and direct admission to the ICUs. CONCLUSIONS: The SFT programme is associated with improved sepsis care and lower risk of death in sepsis patients in rural Thailand, where some critical care resources are limited. The survival benefit is observed even when all patients enrolled in the programme could not be admitted directly into the ICUs. TRIAL REGISTRATION NUMBER: NCT02217592.

Survival of Patients with Cholangiocarcinoma Receiving Surgical Treatment in an O. viverrini Endemic Area in Thailand: A Retrospective Cohort Study.

OBJECTIVE: To investigate risk factors associated with mortality in cholangiocarcinoma patients receiving surgical treatment in Thailand's endemic area and their survival rate. MATERIALS AND METHODS: Medical records of patients with histologically confirmed cholangiocarcinoma, who underwent surgical treatment at Sanpasitthiprasong Regional Hospital from  October 1, 2013 to  October, 31 2015, were retrospectively included. Patients' vital status (death/alive) and date of death were obtained from the Interior Ministry's death certificate. Cox proportional hazard regression was used to examine factors associated with mortality. RESULTS: Out of 295 patients with cholangiocarcinoma (CCA), 180(58%) were intrahepatic CCA, 86(28%) were perihilar CCA, and 29 (9%) were distal CCA. Three groups were homogenous in terms of age and gender. Most of our patients referred with abdominal pain (63%), especially those who were intrahepatic CCA (77%). However, almost 80% of the perihilar CCA and distal CCA patients came with jaundice. Tumor markers (CEA and CA19-9) were not different between groups p=0.74 and p=0.43 respectively. Median survival of patients with intrahepatic CCA, perihilar CCA, and distal CCA patients was 14.6, 14.2, and 14.0 months, respectively. Factors independently associated with mortality in intrahepatic CCA patients were number and size of tumors and presence of perineural invasion (Hazard ratio (HR) 1.09[1.03 - 1.15], 1.07[1.02 - 1.13], and 2.09 [1.28 - 3.39], respectively). In perihilar CCA patients, having positive lymph nodes and resection status were independently associated with mortality. Compared to R0 resection, R1, R2, and no resection of perihilar CCA were associated with a 2-, 8- and 4-fold increase in the risk of mortality (HR 2.17 (0.99 - 4.78), 7.97 (3.22 - 19.71), and 4.21 (0.51 - 34.82), respectively). CONCLUSION: CCA patients in this endemic area had fairly poor survival. Factors associated with mortality in intrahepatic CCA were number and size of tumors and perineural invasion. However, risk factors for perihilar CCA included positive lymph nodes and resection status.

Efficacy and safety of gemigliptin as add-on therapy to insulin, with or without metformin, in patients with type 2 diabetes mellitus (ZEUS II study).

The objective of this study was to evaluate the efficacy and safety of gemigliptin added to a stable dose of insulin alone or of insulin in combination with metformin in patients with type 2 diabetes mellitus. After a two-week run-in period, patients were randomized 2:1 to receive gemigliptin 50 mg or placebo once daily as add-on to background therapy with insulin or insulin plus metformin for 24 weeks. The primary endpoint was change in haemoglobin A1c (HbA1c) from baseline at Week 24. Baseline characteristics were similar between the gemigliptin (n = 188) and placebo (n = 95) groups in terms of HbA1c (8.1%). At Week 24, the gemigliptin group showed a statistically significant reduction in mean HbA1c from baseline as compared with placebo (between-group mean difference, -0.7% [95% CI, -0.9% to -0.4%]; P-value < 0.0001). The incidence of overall adverse events and the number of hypoglycaemic adverse events were similar between the study groups. Gemigliptin added to insulin alone or to insulin in combination with metformin resulted in superior glycaemic control compared to that in the placebo group and was well tolerated for 24 weeks in patients with type 2 diabetes mellitus, without causing weight gain or increasing the incidence of hypoglycaemia.

Changes in risk behaviors among Thai men who have sex with men and transgender women enrolled in the test and treat cohort.

The test-and-treat approach has the potential to reduce high-risk sexual behaviors by linking high-risk individuals to health education, although this has not been proven yet. We used longitudinal data from the Test and Treat Demonstration Project among Thai men who have sex with men (MSM) and transgender women (TGW) who were not known to be HIV-positive to analyze changes in risk behaviors during the 24-month study period categorized by three groups: HIV-negative without seroconversion, seroconverters, and HIV-positive at enrollment. Five binary risk behavior outcomes - laboratory-diagnosed sexually transmitted infections (STIs); multiple sexual partners, unprotected anal intercourse, self-perceived HIV risk, and amphetamine-type stimulants use in the past month - were assessed. Among 689 participants, with a mean (SD) age of 23.1 (6.2) years, 165 participants were diagnosed with HIV: 115 at enrollment and 50 with seroconversions. HIV-positive participants at enrollment showed significant reductions in all five behavioral risk outcomes. Seroconverters demonstrated higher risks at enrollment than HIV-negative participants, and continued to practice high-risk behaviors even after seroconversion despite a significant reduction in self-perceived moderate-to-high HIV risk. Continuation of risk behaviors among seroconverters could negatively affect the ending AIDS goal, thus the integration of other effective preventive measures into HIV/STIs management programs are needed.

High subsequent and recurrent sexually transmitted infection prevalence among newly diagnosed HIV-positive Thai men who have sex with men and transgender women in the Test and Treat cohort.

We determined subsequent and recurrent sexually transmitted infections (STIs) among men who have sex with men (MSM) and transgender women (TGW) in the Test and Treat cohort. Thai MSM and TGW adults with previously unknown HIV status were enrolled and tested for HIV. Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and syphilis were tested at baseline, month 12, and month 24 to identify subsequent STIs (any STIs diagnosed after baseline) and recurrent STIs (any subsequent STIs diagnosed among those with positive baseline STIs). Among 448 participants, 17.8% were HIV-positive, the prevalence of subsequent STIs and recurrent STIs was 42% (HIV-positive versus HIV-negative: 66.3% versus 36.7%, p < 0.001) and 62.3% (81% versus 52.5%, p < 0.001), respectively. Common subsequent STIs by anatomical site were rectal CT infection (21.7%), rectal NG infection (13.8%), pharyngeal NG infection (13.1%), and syphilis (11.9%). HIV-positive status was associated with both subsequent STIs (adjusted hazard ratio [aHR] 2.38; 95%CI 1.64-3.45, p < 0.001) and recurrent STIs (aHR 1.83; 95%CI 1.16-2.87, p = 0.01). The results show that newly diagnosed HIV-positive MSM and TGW were at increased risk of STIs despite being in the healthcare system. STI educational counseling is necessary to improve STI outcomes among MSM and TGW in both HIV prevention and treatment programs.

The double burden of diabetes and global infection in low and middle-income countries.

Four out of five people in the world with diabetes now live in low- and middle-income countries (LMIC), and the incidence of diabetes is accelerating in poorer communities. Diabetes increases susceptibility to infection and worsens outcomes for some of the world's major infectious diseases such as tuberculosis, melioidosis and dengue, but the relationship between diabetes and many neglected tropical diseases is yet to be accurately characterised. There is some evidence that chronic viral infections such as hepatitis B and HIV may predispose to the development of type 2 diabetes by chronic inflammatory and immunometabolic mechanisms. Helminth infections such as schistosomiasis may be protective against the development of diabetes, and this finding opens up new territory for discovery of novel therapeutics for the prevention and treatment of diabetes. A greater understanding of the impact of diabetes on risks and outcomes for infections causing significant diseases in LMIC is essential in order to develop vaccines and therapies for the growing number of people with diabetes at risk of infection, and to prioritise research agendas, public health interventions and policy. This review seeks to give an overview of the current international diabetes burden, the evidence for interactions between diabetes and infection, immune mechanisms for the interaction, and potential interventions to tackle the dual burden of diabetes and infection.