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Background: Previous studies have shown continuous improved overall survival (OS) up to 2015 for young adults with acute lymphoblastic leukaemia (ALL). However, recently several important advances have been made justifying a more contemporary analysis of outcomes in adult with ALL., Methods: In this nationwide population-based cohort study, we included patients above 18 years of age diagnosed with ALL between January 1, 1998, and December 31, 2020. Patients were followed until December 31, 2022. By employing flexible parametric survival models, we quantified progress in OS using the key endpoint of 2-year age standardized OS for all patients and clinical subgroups of interest., Findings: This study includes 657 patients and demonstrates a significant improvement in OS over time with the 2-year age standardized OS increasing from 36·4 % (95 % CI, 27·0-45·8 %) for patients diagnosed in 1998 to 68·6 % (95 % CI, 60·2-76·9)for patients diagnosed in 2020, corresponding to an absolute increase in 2-year OS of 32·2 % points (95 % CI, 19·1-45·2). Stratified analysis revealed improvements for both Philadelphia chromosome positive and negative ALL, across cytogenetic risk groups, and for B- and T-cell ALL, whereas the latter did not reach statistical significance. Improvements were seen across all ages; however, most pronounced for Philadelphia chromosome positive ALL and patients below 60 years of age., Interpretation: These results show a universal and continuous improvement in the treatment of adult ALL. Currently, novel treatment combination and advances in cellular therapy occur rapidly, and we expect even further improvements in the years to come., Funding: Northern Region of Denmark., Competing Interests: Declaration of Competing Interest D.T.K: Consulting/advisory board: AbbVie, Atheneum, Astellas Pharma (non-related, potential); A.S.R: Consulting fees: AbbVie. Travel grant; Jazz Pharmaceuticals (non-related, potential). Other authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Non-Western immigrant patients (NWIPs) may be a vulnerable population when diagnosed and treated for acute myeloid leukaemia (AML). Here we report selected quality parameters related to diagnosis, treatment, and outcome of newly diagnosed AML among NWIPs (n = 119) and Danish-born patients (DBPs) (n = 4689). No adjusted differences were observed for time-to-diagnosis, time-to-treatment, treatment allocation, rates of complete remission, early death, allogeneic stem cell transplantation, and overall survival between NWIPs and DBPs. Among patients allocated for intensive chemotherapy, NWIPs were less likely to participate in clinical trials. The findings highlight equitable AML care but underscore the need to enhance NWIP participation in clinical trials., (© 2024 The Author(s). British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

We evaluated response to VEN/HMA in 46 patients with acute myeloid leukemia (AML) characterized by extramedullary disease (EMD). Median age was 65 (range, 19-81) years. Patients had a median of two EMD sites (range, 1-5) and 35 (76%) patients had concurrent bone marrow involvement. Twenty (43%) patients had highrisk genetic features according to the European Leukemia Net 2022 classification. Twenty-nine (63%) were relapsed or refractory after intensive chemotherapy (CTX) including 13 (28%) with prior allogeneic hematopoietic cell transplantation (allo-HCT). Patients received a median of 2 cycles of VEN/HMA (range, 1-31). Twenty (43%) patients achieved complete remission (CR) or CR with incomplete hematological recovery (CRi) after VEN/HMA and five (11%) achieved a partial remission (PR). Six patients were subsequently consolidated with allo-HCT (CR/CRi, n=4; PR, n=2). Median follow-up was 49.1 months (95%-CI, 26.1 months - not reached) and median overall survival (OS) 6.4 months (95%-CI, 5.1-11 months). One-year and 2-years OS rates were 29.3% (95%-CI, 18.6-46.2%) and 12.3% (95%-CI, 5.5-27.6%), respectively. Age with a cut-off of 60 years had no impact on OS (P=0.90). Relapse occurred in 12 of 20 (60%) patients who achieved CR/CRi after VEN/HMA treatment. Of those, all except one succumbed to their disease. Six (30%) patients were in CR/CRi at last follow-up and 2 (10%) died in CR. In our cohort of patients with AML with EMD with high-risk features, treatment with VEN/HMA resulted in an encouraging ORR of 54% with a CR/CRi rate of 43.5%. However, VEN/HMA alone may not be effective in maintaining disease control.

Abstract: Previous studies have suggested that metformin has beneficial effects beyond its glucose-lowering properties, particularly in terms of its potential as an antineoplastic and cancer-preventive agent. In this study, we aimed to investigate the association between metformin use and the risk of myeloproliferative neoplasms (MPN). We conducted a population-based case-control study using Danish registers. Cases with MPN diagnosed between 2010 and 2018 were identified, and metformin use before the MPN diagnosis was ascertained. We compared metformin use among cases with MPN and an age- and sex-matched control group from the Danish general population to estimate age- and sex-adjusted odds ratios (ORs) and fully adjusted ORs (aORs) for the association between metformin use and risk of MPN. The study population included 3816 cases and 19 080 controls. Overall, 7.0% of cases and 8.2% of controls were categorized as ever-users of metformin, resulting in an OR for MPN of 0.84 (95% confidence interval [CI], 0.73-0.96) and an aOR of 0.70 (95% CI, 0.61-0.81). Long-term metformin use (≥5 years) was more infrequent and comprised 1.1% of cases and 2.0% of controls, resulting in an OR of 0.57 (95% CI, 0.42-0.79) and an aOR of 0.45 (95% CI, 0.33-0.63). A dose-response relationship was observed when cumulative duration of treatment was analyzed, and this was consistent in stratified analyses of sex, age, and MPN subtypes. In conclusion, metformin use was associated with significantly lower odds of an MPN diagnosis, indicating its potential cancer-preventive effect. Given the retrospective design, causality cannot be inferred., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Importance: In recent years, there has been a focus on reducing the socioeconomic gap in survival for hematological malignant neoplasms. Understanding recent developments is important to develop further intervention to improve care., Objective: To investigate the temporal trend in associations of socioeconomic status (SES) with survival among 3 aggressive hematological malignant neoplasms: multiple myeloma (MM), acute myeloid leukemia (AML), and diffuse large B-cell lymphoma (DLBCL)., Design, Setting, and Participants: This nationwide, population-based cohort study used retrospectively collected data from 3 clinical registries of patients diagnosed in Denmark between January 1, 2005, and December 31, 2020, with follow-up until December 31, 2021. Analyses were stratified by diagnosis year (2005-2009, 2010-2014, and 2015-2020). Participants were patients aged 25 to 65 years with hematological malignant neoplasms. Patients with missing data on education were excluded. Data were analyzed from October 14, 2022, to January 2, 2024., Exposure: Education was used as a proxy for SES and defined low- and high-SES groups based on the completion of tertiary education., Main Outcomes and Measures: The main outcome was overall survival (OS), analyzed using Kaplan-Meier (log rank) method and Cox proportional hazards regression adjusted for age, sex, performance status, comorbidities, and disease-specific prognostic indices. Two-year OS through time and survival difference were estimated using flexible parametric survival models., Results: A total of 5677 patients (median [IQR] age, 58 [51-62] years; 3177 [57.0%] male) were assessed, including 1826 patients with MM, 1236 patients with AML, and 2509 patients with DLBCL. The 2-year OS increased over time for patients with MM (78.8% [95% CI, 75.4%-82.3%] to 91.4% [95% CI, 89.3%-93.5%]), AML (42.2% [95% CI, 37.8%-47.1%] to 52.7% [95% CI, 48.0%-57.9%]), and DLBCL (80.1% [95% CI, 77.4%-82.8%] to 88.1% [95% CI, 86.0%-90.3%]). For MM and DLBCL, no association of SES with survival was observed after adjustment (MM: hazard ratio [HR], 0.99 [95% CI, 0.85-1.15]; DLBCL: HR, 1.08 [95% CI, 0.91-1.29]). For AML, a negative association was observed between low SES and survival (HR, 1.49 [95% CI, 1.25-1.76]), but the association was attenuated in recent years. The difference in hazard for patients with low SES and AML was observed in the first 2 years after diagnosis., Conclusions and Relevance: These findings suggest that survival has improved among patients with these hematological malignant neoplasms. While patients with MM and DLBCL had increased survival in all groups, disparities were observed in AML outcomes, primarily in the first years after diagnosis. These results suggest that differences originate in factors specific to AML.

Abstract: Molecular failure in NPM1-mutated acute myeloid leukemia (AML) inevitably progresses to frank relapse if untreated. Recently published small case series show that venetoclax combined with low-dose cytarabine or azacitidine can reduce or eliminate measurable residual disease (MRD). Here, we report on an international multicenter cohort of 79 patients treated for molecular failure with venetoclax combinations and report an overall molecular response (≥1-log reduction in MRD) in 66 patients (84%) and MRD negativity in 56 (71%). Eighteen of 79 patients (23%) required hospitalization, and no deaths were reported during treatment. Forty-one patients were bridged to allogeneic transplant with no further therapy, and 25 of 41 were MRD negative assessed by reverse transcription quantitative polymerase chain reaction before transplant. Overall survival (OS) for the whole cohort at 2 years was 67%, event-free survival (EFS) was 45%, and in responding patients, there was no difference in survival in those who received a transplant using time-dependent analysis. Presence of FLT3-ITD mutation was associated with a lower response rate (64 vs 91%; P < .01), worse OS (hazard ratio [HR], 2.50; 95% confidence interval [CI], 1.06-5.86; P = .036), and EFS (HR, 1.87; 95% CI, 1.06-3.28; P = .03). Eighteen of 35 patients who did not undergo transplant became MRD negative and stopped treatment after a median of 10 months, with 2-year molecular relapse free survival of 62% from the end of treatment. Venetoclax-based low intensive chemotherapy is a potentially effective treatment for molecular relapse in NPM1-mutated AML, either as a bridge to transplant or as definitive therapy., (© 2024 by The American Society of Hematology. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Background: The treatment of relapsed or refractory (R/R) acute myeloid leukaemia (AML) remains challenging and outcomes extremely poor. The introduction of venetoclax has transformed the treatment of AML and emerging data suggest that venetoclax-based therapy may enforce salvage treatment., Materials and Methods: In this nationwide Danish retrospective study, we analysed treatment outcomes of venetoclax-based salvage treatment for R/R AML between 2019 and 2022. Only venetoclax-naive patients who had previously received treatment with intensive chemotherapy therapy were included., Results: The cohort consisted of 43 R/R patients with a median age of 57 years. Nine (20.9%) were primary refractory and 34 (79.1%) patients had relapsed, including 21 after previous allogeneic stem cell transplantation. The overall response rate was 76.2% including 61.9% with composite complete remission (CRc: CR + CRi). Among CRc-responders with information on measurable residual disease (MRD), 8/13 (61.5%) obtained an MRD-negativity response. The overall survival was 9.3 months for all patients with an estimated 1-year overall survival of 34%. For CRc-responders the median overall survival was 13.3 months, and the median relapse-free survival was 12.8 months., Conclusion: Venetoclax-based salvage treatment for R/R AML produced high response rates; however, for most patients the response was of limited duration. This study is limited by an observational design and prone to selection bias., (© 2023 The Authors. European Journal of Haematology published by John Wiley & Sons Ltd.)

Background: A key decision in the treatment of atrial fibrillation is choosing between a rhythm control strategy or a rate control strategy as the main strategy. When choosing rate control, the optimal heart rate target is uncertain. The Danish Atrial Fibrillation trial is a randomized, multicenter, two-group, superiority trial comparing strict rate control versus lenient rate control in patients with either persistent or permanent atrial fibrillation at inclusion. To prevent bias arising from selective reporting and data-driven analyses, we developed a predefined description of the statistical analysis., Methods: The primary outcome of this trial is the physical component score of the SF-36 questionnaire. A total of 350 participants will be enrolled based on a minimal important difference of 3 points on the physical component score of the SF-36 questionnaire, a standard deviation of 10 points, a statistical power of 80% (beta of 20%), and an acceptable risk of type I error of 5%. All secondary, exploratory, and echocardiographic outcomes will be hypothesis-generating. The analyses of all outcomes will be based on the intention-to-treat principle. We will analyze continuous outcomes using linear regression adjusting for "site," type of atrial fibrillation at inclusion (persistent/ permanent), left ventricular ejection fraction (≥ 40% or < 40%), and the baseline value of the outcome (all as fixed effects). We define our threshold for statistical significance as a p-value of 0.05 and assessments of clinical significance will be based on the anticipated intervention effects defined in the sample size and power estimations. Thresholds for both statistical and clinical significance will be assessed according to the 5-step procedure proposed by Jakobsen and colleagues., Discussion: This statistical analysis plan will be published prior to enrolment completion and before any data are available and is sought to increase the validity of the DANish Atrial Fibrillation trial., Trial Registration: Clinicaltrials.gov NCT04542785. Registered on Sept 09, 2020., (© 2023. The Author(s).)

Overweight patients with cancer are frequently reduced in chemotherapy dose due to toxicity concerns, although previous studies have indicated that dose reduction (DR) of overweight patients results in comparable toxicity but may compromise overall survival (OS). Current evidence regarding DR in patients with acute myeloid leukaemia (AML) is limited. To investigate the association between DR and outcome among overweight patients with AML we analysed a Danish nationwide cohort of overweight adult AML patients treated with remission induction chemotherapy. Among 536 patients identified, 10.1% were categorized as DR defined as 95% or less of full body surface area (BSA)-based dose. Risk factors for DR were high body mass index (BMI) and BSA, therapy-related AML and favourable cytogenetics. No significant differences were observed for rates of complete remission (CR), 30- and 90-day mortality between DR and non-DR patients. Furthermore, DR did not affect median relapse-free survival (RFS) [DR, 14.5 (95% confidence interval, 9.0-41.7) months; non-DR, 15.0 (12.3-19.3)] with an adjusted difference in five-year restricted mean survival time (Δ5y-RMST) of 0.2 (-8.4 to 8.8) months nor median OS (DR, 17.0 [11.9 to 45.5] months; non-DR, 17.5 [14.8 to 20.5]) with an adjusted Δ5y-RMST of 0.8 (-5.7 to 7.3) months. In conclusion, we found no statistically significant association between DR and outcomes among overweight patients with AML. However, we acknowledge the limited sample size and encourage further studies in this important subject., (© 2022 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

In this study, a novel nanostructure of fluoride red emitting phosphor is synthesized via soft templates. K 2 SiF 6 :Mn 4+ nanocrystals in the range of 3-5 nm diameter are found inside the porous K 2 SiF 6 :Mn 4+ nanoparticle hosts, forming unique dots-in-nanoparticles (d-NPs) structures with controlled optical properties. The porous K 2 SiF 6 :Mn 4+ d-NPs exhibit a sharp and deep red emission with an excellent quantum yield of ∼95.9%, and ultra-high color purity with the corresponding x and y in the CIE chromaticity coordinates are 0.7102 and 0.2870, respectively. Moreover, this nanophosphor possesses good thermal stability in range of 300 K-500 K, under light excitation of 455 nm. The K 2 SiF 6 :Mn 4+ d-NPs are covered onto a surface of 100×100 µm 2 blue-yellow In x Ga 1-x N nanowire light-emitting diode (LED) to make warm white LEDs (WLEDs). The fabricated WLEDs present an excellent color rendering index of ∼95.4 and a low correlated color temperature of ∼3649 K. Porous K 2 SiF 6 :Mn 4+ d-NPs are suggested as a potential red component for high color quality micro WLED applications.

Objectives: We assessed the impact of MALDITOF-MS on the timeliness of optimal antimicrobial therapy through a parallel-arm randomised controlled trial in two hospitals in Vietnam., Methods: We recruited patients with a pathogen (bacterial or fungal) cultured from a normally sterile sample. Samples were randomly assigned (1:1) to identification by MALDITOF-MS or conventional diagnostics. The primary outcome was the proportion on optimal antimicrobial therapy within 24 h of positive culture, determined by a blinded independent review committee. Trial registered at ClinicalTrials.gov (NCT02306330)., Results: Among 1005 randomised patients, pathogens were isolated from 628 (326 intervention, 302 control), with 377 excluded as likely contaminants or discharged/died before positive culture. Most isolates were cultured from blood (421/628, 67.0%). The proportion receiving optimal antimicrobial therapy within 24 h (the primary outcome) or 48 h of growth was not significantly different between MALDITOF-MS and control arms (135/326, 41.4% vs 120/302, 39.7%; Adjusted Odds ration (AOR) 1.17, p = 0.40 and 151/326, 46.3% vs 141/302, 46.7%; AOR 1.05 p = 0.79, respectively)., Conclusions: MALDITOF-MS, in the absence of an antimicrobial stewardship programme, did not improve the proportion on optimal antimicrobial therapy at 24 or 48 h after first growth in a lower-middle income setting with high rates of antibiotic resistance., (Copyright © 2019. Published by Elsevier Ltd.)

Background: Ventilator-associated respiratory infection (VARI) comprises ventilator-associated pneumonia (VAP) and ventilator-associated tracheobronchitis (VAT). Although their diagnostic criteria vary, together these are the most common hospital-acquired infections in intensive care units (ICUs) worldwide, responsible for a large proportion of antibiotic use within ICUs. Evidence-based strategies for the prevention of VARI in resource-limited settings are lacking. Preventing the leakage of oropharyngeal secretions into the lung using continuous endotracheal cuff pressure control is a promising strategy. The aim of this study is to investigate the efficacy of automated, continuous endotracheal cuff pressure control in preventing the development of VARI and reducing antibiotic use in ICUs in Vietnam., Methods/design: This is an open-label randomised controlled multicentre trial. We will enrol 600 adult patients intubated for ≤ 24 h at the time of enrolment. Eligible patients will be stratified according to admission diagnosis (180 tetanus, 420 non-tetanus) and site and will be randomised in a 1:1 ratio to receive either (1) automated, continuous control of endotracheal cuff pressure or (2) intermittent measurement and control of endotracheal cuff pressure using a manual cuff pressure meter. The primary outcome is the occurrence of VARI, defined as either VAP or VAT during the ICU admission up to a maximum of 90 days after randomisation. Patients in both groups who are at risk for VARI will receive a standardised battery of investigations if their treating physician feels a new infection has occurred, the results of which will be used by an endpoint review committee, blinded to the allocated arm and independent of patient care, to determine the primary outcome. All enrolled patients will be followed for mortality and endotracheal tube cuff-related complications at 28 days and 90 days after randomisation. Other secondary outcomes include antibiotic use; days ventilated, in ICU and in hospital; inpatient mortality; costs of antibiotics in ICU; duration of ICU stay; and duration of hospital stay., Discussion: This study will provide high-quality evidence concerning the use of continuous endotracheal cuff pressure control as a method to reduce VARI, antibiotic use and hospitalisation costs and to shorten stay., Trial Registration: ClinicalTrials.gov, NCT02966392 . Registered on November 9, 2016. Protocol version: 2.0; issue date March 3, 2017.

Background: Ventilator-associated respiratory infection (VARI) is a significant problem in resource-restricted intensive care units (ICUs), but differences in casemix and etiology means VARI in resource-restricted ICUs may be different from that found in resource-rich units. Data from these settings are vital to plan preventative interventions and assess their cost-effectiveness, but few are available., Methods: We conducted a prospective observational study in four Vietnamese ICUs to assess the incidence and impact of VARI. Patients ≥ 16 years old and expected to be mechanically ventilated > 48 h were enrolled in the study and followed daily for 28 days following ICU admission., Results: Four hundred fifty eligible patients were enrolled over 24 months, and after exclusions, 374 patients' data were analyzed. A total of 92/374 cases of VARI (21.7/1000 ventilator days) were diagnosed; 37 (9.9%) of these met ventilator-associated pneumonia (VAP) criteria (8.7/1000 ventilator days). Patients with any VARI, VAP, or VARI without VAP experienced increased hospital and ICU stay, ICU cost, and antibiotic use ( p  < 0.01 for all). This was also true for all VARI ( p  < 0.01 for all) with/without tetanus. There was no increased risk of in-hospital death in patients with VARI compared to those without (VAP HR 1.58, 95% CI 0.75-3.33, p  = 0.23; VARI without VAP HR 0.40, 95% CI 0.14-1.17, p  = 0.09). In patients with positive endotracheal aspirate cultures, most VARI was caused by Gram-negative organisms; the most frequent were Acinetobacter baumannii (32/73, 43.8%) Klebsiella pneumoniae (26/73, 35.6%), and Pseudomonas aeruginosa (24/73, 32.9%). 40/68 (58.8%) patients with positive cultures for these had carbapenem-resistant isolates. Patients with carbapenem-resistant VARI had significantly greater ICU costs than patients with carbapenem-susceptible isolates (6053 USD (IQR 3806-7824) vs 3131 USD (IQR 2108-7551), p  = 0.04) and after correction for adequacy of initial antibiotics and APACHE II score, showed a trend towards increased risk of in-hospital death (HR 2.82, 95% CI 0.75-6.75, p  = 0.15)., Conclusions: VARI in a resource-restricted setting has limited impact on mortality, but shows significant association with increased patient costs, length of stay, and antibiotic use, particularly when caused by carbapenem-resistant bacteria. Evidence-based interventions to reduce VARI in these settings are urgently needed., Competing Interests: The study was approved by the Oxford Tropical Research Ethics Committee and local Ethics Committees of participating hospitals (Scientific and Ethics Committees of Bach Mai Hospital Hanoi, National Hospital for Tropical Diseases Hanoi, and Hospital for Tropical Diseases, Ho Chi Minh City). The study was carried out according to the principals of the Declaration of Helsinki and all participants gave written informed consent to take part in the study.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Background: Bloodstream infections (BSIs) are associated with high morbidity and mortality worldwide. However their aetiology, antimicrobial susceptibilities and associated outcomes differ between developed and developing countries. Systematic data from Vietnam are scarce. Here we present aetiologic data on BSI in adults admitted to a large tertiary referral hospital for infectious diseases in Hanoi, Vietnam., Methods: A retrospective study was conducted at the National Hospital for Tropical Diseases between January 2011 and December 2013. Cases of BSI were determined from records in the microbiology department. Case records were obtained where possible and clinical findings, treatment and outcome were recorded. BSI were classified as community acquired if the blood sample was drawn ≤48 h after hospitalization or hospital acquired if >48 h., Results: A total of 738 patients with BSI were included for microbiological analysis. The predominant pathogens were: Klebsiella pneumoniae (17.5%), Escherichia coli (17.3%), Staphylococcus aureus (14.9%), Stenotrophomonas maltophilia (9.6%) and Streptococcus suis (7.6%). The overall proportion of extended spectrum beta-lactamase (ESBL) production among Enterobacteriaceae was 25.1% (67/267 isolates) and of methicillin-resistance in S. aureus (MRSA) 37% (40/108). Clinical data was retrieved for 477 (64.6%) patients; median age was 48 years (IQR 36-60) with 27.7% female. The overall case fatality rate was 28.9% and the highest case fatality was associated with Enterobacteriaceae BSI (34.7%) which accounted for 61.6% of all BSI fatalities., Conclusions: Enterobacteriaceae (predominantly K. pneumoniae and E. coli) are the most common cause of both community and hospital acquired bloodstream infections in a tertiary referral clinic in northern Vietnam.

We performed a systematic investigation on silicon-doped boron clusters BnSi (n = 8-14) in both neutral and anionic states using quantum chemical methods. Thermochemical properties of the lowest-lying isomers of BnSi(0/-) clusters such as total atomization energies, heats of formation at 0 and 298 K, average binding energies, dissociation energies, etc. were evaluated by using the composite G4 method. The growth pattern for BnSi(0/-) with n = 8-14 is established as follows: (i) BnSi(0/-) clusters tend to be constructed by substituting B atom by Si-atom or adding one Si-impurity into the parent Bn clusters with n to be even number, and (ii) Si favors an external position of the Bn frameworks. Our theoretical results reveal that B8Si, B9Si(-), B10Si and B13Si(-) are systems with enhanced stability due to having high average binding energies, second-order difference in energies and dissociation energies. Especially, by analyzing the MOs, ELF, and ring current maps, the enhanced stability of B8Si can be rationalized in terms of a triple aromaticity.

Rhodococcus equi infection is increasing in regions with high HIV prevalence worldwide. The microbiological features and clinical mimicry of tuberculosis infection pose diagnostic challenges in high-tuberculosis-incidence settings. We present two HIV-associated cases of R. equi infection from Vietnam and discuss the unique diagnostic challenges in such settings., (Copyright © 2015, Le et al.)

The B30 boron cluster has a bowl rather than a double-ring or a triple-ring tubular structure. This bowl isomer exhibits disk-aromaticity similar to that found for B20(2-) and B19(-) clusters. We confirmed that the concept of disk-aromaticity can be applied to both planar and non-planar systems.

Problem: Streptococcus suis is a common cause of adult bacterial meningitis in Viet Nam, and possibly other parts of Asia, yet this disabling infection has been largely neglected. Prevention, diagnosis and treatment are relatively straightforward and affordable but, in early 2007, no national diagnostic, case management or prevention guidelines existed in Viet Nam., Approach: Enhanced detection of S. suis infections was established in 2007 as part of a collaborative research programme between the National Hospital for Tropical Diseases, a key national hospital with very close links to the Ministry of Health, and a research group affiliated with Oxford University based in Viet Nam. The results were reported directly to policy-makers at the Ministry of Health., Local Setting: Viet Nam is a low-income country with a health-care system that has seen considerable improvements and increased autonomy. However, parts of the system remain fairly centralized the Ministry of Health., Relevant Changes: Following the improved detection and reporting of S. suis cases, the Ministry of Health issued guidance to all hospitals in Viet Nam on the clinical and laboratory diagnosis, treatment and prevention of S. suis. A public health laboratory diagnostic service was established at the National Institute of Hygiene and Epidemiology and training courses were conducted for clinicians and microbiologists. Ministry of Health guidance on surveillance and control of communicable diseases was updated to include a section on S. suis., Lessons Learnt: Research collaborations can efficiently inform and influence national responses if they are well positioned to reach policy-makers.

A set of packed micro paddy lysimeters, placed in a greenhouse, was used to simulate the dissipation of two herbicides, simetryn and thiobencarb, in a controlled environment. Data from a field monitoring study in 2003, including the soil condition and water balances, were used in the simulation. The herbicides were applied and monitored over a period of 21 d. The water balances under two water management scenarios, intermittent irrigation management (AI) and continuous irrigation management (CI), were simulated. In the AI scenario, the pattern of herbicide dissipation in the surface water of the field were simulated, following the first-order kinetics. In the CI scenario, similarity was observed in most lysimeter and field concentrations, but there were differences in some data points. Dissipation curves of both herbicides in the surface water of the two simulated scenarios were not significantly different (P>0.05) from the field data except for intercept of the thiobencarb curve in the CI scenario. The distribution of simetryn and thiobencarb in the soil profile after simulation were also similar to the field data. The highest concentrations of both herbicides were found on the topsoil layer at 0-2.5 cm depth. Only a small amount of herbicides moved down to the deeper soil layers. Micro paddy lysimeters are thus a good alternative for the dissipation study of pesticides in the paddy environment.

The behavior of sprayed tricyclazole in rice paddy lysimeters was studied. Tricyclazole residues were measured from rice leaves and paddy water after tricyclazole spraying in paddy lysimeters. The rate of photolysis and hydrolysis of tricyclazole on the surface of rice leaves was also determined in a laboratory experiment. Tricyclazole was extracted from leaf and water samples and determined by liquid chromatography with UV or mass spectrometry. The hydrolysis half-lives of tricyclazole on rice leaves were 11.9 and 5.1 d for the formulated product and standard, respectively. The photolysis half-lives were longer, 16.4d for the formulated product and 20.9 d for the standard. In the paddy lysimeter, tricyclazole dissipation on leaves involved either biphasic first-order kinetics or single-phase first-order kinetics, depending on the rainfall pattern. Half-lives of tricyclazole on lysimeter rice leaves were from 3.0 to 5.7 d. The dissipation of tricyclazole in paddy water followed single-phase first-order kinetics with half-lives ranging from 2.1 to 5.0 d.

Two rainfall simulations of 30 mm h(-1), with 48-h interval between two simulations, were performed on rice lysimeters at 24, 48, and 72 h after being sprayed with tricyclazole. In the first simulated rainfall, wash-off concentration of tricyclazole was significant irrespective of the interval between the spray time and the rainfall simulation. And from 20.5% to 24.2% of tricyclazole deposited on leaves was removed from the rice foliage. In the second simulated rainfall, concentration of tricyclazole in wash-off water was significantly lower and less than 3.6% of the deposited tricyclazole was lost.

In the present study, an original chlorhexidine-loaded nanocapsule-based gel (Nanochlorex) was tested as hand rub gel against the resident skin flora in comparison with 2-propanol 60% (v/v) and 62% (v/v) ethanol-based gel (Purell). After 30-s hand rub, the immediate bactericidal effect of Nanochlorex was found comparable to 2-propanol 60% (v/v) (reduction factor, RF: 0.30+/-0.35 versus 0.38+/-0.55, P>0.05) against aerobic bacteria, whereas the post-values of surviving anaerobes were shown significantly lower from Nanochlorex (P<0.001) and insignificant from 2-propanol 60% (v/v) (P>0.05). Sustained antibacterial effect of Nanochlorex was confirmed against the resident and transient hand flora in two sets of experiment. In the first, the results obtained with the glove-juice technique showed that the bactericidal effect induced by Nanochlorex hand rub persisted throughout 3-h period, while Purell failed to reduce significantly the post-values of surviving bacteria. In the second, repeated artificial contaminations with Staphylococcus epidermidis was carried out onto ex vivo human skin pre-treated by either Nanochlorex or Purell for 5min, then maintained in cell diffusion apparatus for 4h. The log(10) reduction of surviving bacteria was significantly higher with Nanochlorex than that determined with Purell after three successive contaminations (from approximately 5.5 to 1.5 log(10) reduction for Nanochlorex between the first and the third contamination; approximately 1log(10) reduction for Purell throughout the experiment), confirming the sustained antibacterial effect of chlorhexidine-loaded nanocapsule-based gel. The immediate and sustained antibacterial effect of Nanochlorex was explained by chlorhexidine carrier system which improved the drug targeting to bacteria and reduced from osmotic gel further bacterial growth on the skin. Nanochlorex) might constitute a promising approach for hygienic hand disinfection in care practice performing multiple procedures.

Escherichia coli O157:H7 producing Shiga like toxins is a food-borne pathogen frequently isolated in Bangui from patients with hemorrhagic colitis (HC). This survey provides comprehensive data on the high prevalence of E. coli O157:H7 infection in Bangui: carriage of E. coli O157:H7 by zebu (Bos indicus) and fish, contamination of the fields at N'Goila where the butchers kill the zebus, and contamination of the field surface water along the M'Poko River upstream of the Oubangui River where fish are caught, appear to be important contributory factors. We also describe novel strains of serogroup O157:NM isolated from zebu and from fish; a variety of assays indicate that these strains belong to the enteropathogenic pathotype, though they lack certain genetic elements thought to be diagnostic for this pathotype.

We characterized 523 Vibrio parahaemolyticus strains isolated during a survey of diarrhea patients in Khanh Hoa province, Vietnam between 1997 and 1999. Forty-nine percent of the strains were judged to belong to the pandemic strains that emerged around 1996 and spread to many countries. These strains were positive in the GS-PCR assay and carried the tdh gene. The ORF8 of the f237 phage genome, a possible marker of the pandemic clone, was absent in 10% of these strains. Eleven O: K serovars were detected among the pandemic strains and the strains representing all 11 serovars of pandemic strains were shown to be closely related regardless of the ORF8 genotype using arbitrarily primed PCR and pulsed field gel electrophoresis analyses. It was clear that a transition of major serovars occurred among the pandemic strains represented by the emergence of O3: K6 in 1997, O4: K68 in 1998, and O1: K25 in 1998 and 1999.

From 1996 onward, a pandemic spread of Vibrio parahaemolyticus infections due to one clone has been reported in several Asian countries. During a population-based study that relied on passive surveillance, 548 cases of V. parahaemolyticus infection were detected between 1997 and 1999 in the Khanh Hoa province of Vietnam. Detection of cases of V. parahaemolyticus infection abruptly stopped in November 1999, although Vibrio species other than V. parahaemolyticus continued to be isolated throughout 2000. Of the infections, 90% occurred in individuals >5 years old; 53% of the patients presented with watery stools, and 6% reported blood in their stools. All patients had recovered by the time of discharge. A surprising risk factor for V. parahaemolyticus infections was high socioeconomic status. Like the interruption of the transmission of V. cholerae infections that had been observed earlier, the transmission of V. parahaemolyticus came to a halt without meteorological changes or changes in water supply and sanitation.