Oseltamivir Is Adequately Absorbed Following Nasogastric Administration to Adult Patients with Severe H5N1 Influenza

In the absence of a parenteral drug, oral oseltamivir is currently recommended by the WHO for treating H5N1 influenza. Whether oseltamivir absorption is adequate in severe influenza is unknown. We measured the steady state, plasma concentrations of nasogastrically administered oseltamivir 150 mg bid and its active metabolite, oseltamivir carboxylate (OC), in three, mechanically ventilated patients with severe H5N1 (male, 30 yrs; pregnant female, 22 yrs) and severe H3N2 (female, 76 yrs). Treatments were started 6, 7 and 8 days after illness onset, respectively. Both females were sampled while on continuous venovenous haemofiltration. Admission and follow up specimens (trachea, nose, throat, rectum, blood) were tested for RNA viral load by reverse transcriptase PCR. In vitro virus susceptibility to OC was measured by a neuraminidase inhibition assay. Admission creatinine clearances were 66 (male, H5N1), 82 (female, H5N1) and 6 (H3N2) ml/min. Corresponding AUC0–12 values (5932, 10,951 and 34,670 ng.h/ml) and trough OC concentrations (376, 575 and 2730 ng/ml) were higher than previously reported in healthy volunteers; the latter exceeded 545 to 3956 fold the H5N1 IC50 (0.69 ng/ml) isolated from the H5N1 infected female. Two patients with follow-up respiratory specimens cleared their viruses after 5 (H5N1 male) and 5 (H3N2 female) days of oseltamivir. Both female patients died of respiratory failure; the male survived. 150 mg bid of oseltamivir was well absorbed and converted extensively to OC. Virus was cleared in two patients but two patients died, suggesting viral efficacy but poor clinical efficacy

Safety and efficacy of fluoxetine on functional outcome after acute stroke (AFFINITY): a randomised, double-blind, placebo-controlled trial

Background Trials of fluoxetine for recovery after stroke report conflicting results. The Assessment oF FluoxetINe In sTroke recoverY (AFFINITY) trial aimed to show if daily oral fluoxetine for 6 months after stroke improves functional outcome in an ethnically diverse population. Methods AFFINITY was a randomised, parallel-group, double-blind, placebo-controlled trial done in 43 hospital stroke units in Australia (n=29), New Zealand (four), and Vietnam (ten). Eligible patients were adults (aged ≥18 years) with a clinical diagnosis of acute stroke in the previous 2–15 days, brain imaging consistent with ischaemic or haemorrhagic stroke, and a persisting neurological deficit that produced a modified Rankin Scale (mRS) score of 1 or more. Patients were randomly assigned 1:1 via a web-based system using a minimisation algorithm to once daily, oral fluoxetine 20 mg capsules or matching placebo for 6 months. Patients, carers, investigators, and outcome assessors were masked to the treatment allocation. The primary outcome was functional status, measured by the mRS, at 6 months. The primary analysis was an ordinal logistic regression of the mRS at 6 months, adjusted for minimisation variables. Primary and safety analyses were done according to the patient's treatment allocation. The trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12611000774921. Findings Between Jan 11, 2013, and June 30, 2019, 1280 patients were recruited in Australia (n=532), New Zealand (n=42), and Vietnam (n=706), of whom 642 were randomly assigned to fluoxetine and 638 were randomly assigned to placebo. Mean duration of trial treatment was 167 days (SD 48·1). At 6 months, mRS data were available in 624 (97%) patients in the fluoxetine group and 632 (99%) in the placebo group. The distribution of mRS categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio 0·94, 95% CI 0·76–1·15; p=0·53). Compared with patients in the placebo group, patients in the fluoxetine group had more falls (20 [3%] vs seven [1%]; p=0·018), bone fractures (19 [3%] vs six [1%]; p=0·014), and epileptic seizures (ten [2%] vs two [<1%]; p=0·038) at 6 months. Interpretation Oral fluoxetine 20 mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and epileptic seizures. These results do not support the use of fluoxetine to improve functional outcome after stroke

Dynamics of Land Cover/Land Use Changes in the Mekong Delta, 1973–2011: A Remote Sensing Analysis of the Tran Van Thoi District, Ca Mau Province, Vietnam

The main objective of this study is to assess the spatio-temporal dynamics of land cover/land use changes in the lower Mekong Delta over the last 40 years with the coastal Tran Van Thoi District of Ca Mau Province, Vietnam as a case study. Land cover/land use change dynamics are derived from moderate to high spatial resolution (Landsat and SPOT) satellite imagery in six time intervals ranging from 1973 to 2011. Multi-temporal satellite images were collected, georeferenced, classified using per-pixel method, validated, and compared in post classification for the land use/land cover change detection in decades. Seven major land cover/land use classes were obtained, including cultivated lands, aquaculture ponds, mangrove forest, melaleuca forest, built up areas, bare lands, and natural water bodies. The accuracies of the land cover/land use maps for 1973, 1979, 1989, 1995, 2004, and 2011 were 81%, 82%, 86%, 87%, 89%, and 89%, respectively. The results show that the area of cultivated lands reduced over the period 1973–2011, however, it still represents the dominant land use in the case study. Aquaculture ponds were almost absent in 1973 but greatly increased from 1995 to 2004, to represent 20% of the land surface in 2011. Overall, from 1973 to 2011, bare lands, cultivated lands, mangrove forest, and melaleuca forest decreased by 104 km2, 77 km2, 61 km2, and 5 km2, respectively. In contrast, aquaculture lands and built up areas increased by 123 km2 and 120 km2, respectively. Temporal analysis highlights that these changes took place mostly between 1995 and 2004. This study is a first step to identify the main drivers of land use changes in this delta region, which include economical policies as well as demographic, socio-economic, and environmental changes

Convergent Synthesis of a Hexadecavalent Heterobifunctional ABO Blood Group Glycoconjugate

Naturally occurring glycans are often found in a multivalent presentation. Cell surface receptors that recognize these displays may form clusters, which can lead to signalling or endocytosis. One of the challenges in generating synthetic displays of multivalent carbohydrates is providing high valency as well as access to heterofunctional conjugates to allow attachment of multiple antigens or payloads. We designed a strategy based on a set of bifunctional linkers to generate a heterobifunctional multivalent display of two carbohydrate antigens to bind BCR and CD22 with four and twelve antigen copies, respectively. We confirmed that the conjugates were able to engage both CD22 and BCR on cells by observing receptor clustering. The strategy is modular and would allow for alternative carbohydrate antigens to be attached bearing amine and alkyne groups and should be of interest for the development of immunomodulators and vaccines

Mobilising Investment for Development: Role of ODA the 1993-2003 Experience in Vietnam

The Vietnamese economy was in the doldrums in the 1980s and until a certain progress had been made in the context of Doi Moi there was little incentive for businesses to invest. The following reasons are commonly given for the sluggish economic activity: a lack of appropriate infrastructure (causing market disconnectedness even within the country); weak links to the world market; a shortage of skilled labour and managerial capacity; and an inefficient or business unfriendly public administration. ODA to Vietnam was allocated in such a way as to remedy these obstacles and the donors’ well designed strategies are seen as a major factor behind the success of ODA. National ownership, an important feature of ODA programmes, has mostly been strong in ODA to Vietnam. Most of the activities of the past were closely aligned with the Vietnamese government’s development priorities. It should nevertheless be recognised that some ODA projects have aroused little enthusiasm among public ...

Additional file 1: of Association of apolipoprotein E polymorphism with plasma lipid disorders, independent of obesity-related traits in Vietnamese children

Table S1. Lipid profiles in cases and controls according to APOE haplotypes in Vietnamese children (mg/dL). TG, triglyceride; TC, total cholesterol; HDL-C, high-density lipoprotein-cholesterol; LDL-C, low-density lipoprotein-cholesterol. Data are median (interquatile range). P-values obtained by Kruskall-Wallis test. Bold values indicate a statistically significant difference among copy number of TC, TT, and CC haplotype after adjustment for multiple testing (P-values < 0.0125). (DOCX 19 kb