Cryptococcal meningitis has high mortality. Flucytosine is a key treatment but is expensive and rarely available. The anticancer agent tamoxifen has synergistic anti-cryptococcal activity with ...amphotericin in vitro. It is off-patent, cheap, and widely available. We performed a trial to determine its therapeutic potential.
Open label randomized controlled trial. Participants received standard care - amphotericin combined with fluconazole for the first 2 weeks - or standard care plus tamoxifen 300 mg/day. The primary end point was Early Fungicidal Activity (EFA) - the rate of yeast clearance from cerebrospinal fluid (CSF). Trial registration https://clinicaltrials.gov/ct2/show/NCT03112031.
Fifty patients were enrolled (median age 34 years, 35 male). Tamoxifen had no effect on EFA (-0.48log10 colony-forming units/mL/CSF control arm versus -0.49 tamoxifen arm, difference -0.005log10CFU/ml/day, 95% CI: -0.16, 0.15, p=0.95). Tamoxifen caused QTc prolongation.
High-dose tamoxifen does not increase the clearance rate of
from CSF. Novel, affordable therapies are needed.
The trial was funded through the Wellcome Trust Asia Programme Vietnam Core Grant 106680 and a Wellcome Trust Intermediate Fellowship to JND grant number WT097147MA.
Abstract
Background
An endotracheal tube cuff pressure between 20 and 30 cmH2O is recommended to prevent ventilator-associated respiratory infection (VARI). We aimed to evaluate whether continuous ...cuff pressure control (CPC) was associated with reduced VARI incidence compared with intermittent CPC.
Methods
We conducted a multicenter open-label randomized controlled trial in intensive care unit (ICU) patients within 24 hours of intubation in Vietnam. Patients were randomly assigned 1:1 to receive either continuous CPC using an automated electronic device or intermittent CPC using a manually hand-held manometer. The primary endpoint was the occurrence of VARI, evaluated by an independent reviewer blinded to the CPC allocation.
Results
We randomized 600 patients; 597 received the intervention or control and were included in the intention to treat analysis. Compared with intermittent CPC, continuous CPC did not reduce the proportion of patients with at least one episode of VARI (74/296 25% vs 69/301 23%; odds ratio OR 1.13; 95% confidence interval CI .77–1.67. There were no significant differences between continuous and intermittent CPC concerning the proportion of microbiologically confirmed VARI (OR 1.40; 95% CI .94–2.10), the proportion of intubated days without antimicrobials (relative proportion RP 0.99; 95% CI .87–1.12), rate of ICU discharge (cause-specific hazard ratio HR 0.95; 95% CI .78–1.16), cost of ICU stay (difference in transformed mean DTM 0.02; 95% CI −.05 to .08, cost of ICU antimicrobials (DTM 0.02; 95% CI −.25 to .28), cost of hospital stay (DTM 0.02; 95% CI −.04 to .08), and ICU mortality risk (OR 0.96; 95% CI .67–1.38).
Conclusions
Maintaining CPC through an automated electronic device did not reduce VARI incidence.
Clinical Trial Registration
NCT02966392.
The results of this randomised controlled trial demonstrate that continuous endotracheal cuff pressure control using an electronic automated device does not reduce the occurrence of ventilator-associated respiratory infection (VARI) in intubated patients compared with intermittent control.
The emergence of drug resistant typhoid fever is a major public health problem, especially in Asia. An oral single dose typhoid vaccine would have major advantages. M01ZH09 is a live oral single dose ...candidate typhoid vaccine containing Salmonella enterica serovar Typhi (Ty2 aroC(-)ssaV(-)) ZH9 with two independently attenuating deletions. Studies in healthy adults demonstrated immunogenicity and an acceptable safety profile.
We conducted a randomised placebo controlled, single-blind trial to evaluate the safety and immunogenicity of M01ZH09 in healthy Vietnamese children aged 5 to 14 years.
Subjects were randomly assigned to receive either a nominal dose of 5x10(9) CFU of M01ZH09 or placebo and were followed up for 28 days. The primary safety outcome was the proportion of subjects with any adverse event attributed to M01ZH09. The primary immunogenicity endpoint was the proportion of subjects who showed a positive immune response to M01ZH09 in the Salmonella Typhi lipopolysaccharide (LPS) specific serum IgA and IgG ELISA.
One hundred and fifty-one children were enrolled, 101 subjects received M01ZH09 and 50 subjects received placebo. An intention to treat analysis was conducted. There were no serious adverse events and no bacteraemias. In the M01ZH09 group, 26 (26%; 95% CI, 18-5%) of 101 subjects experienced adverse events compared to 11 (22%; 95% CI, 12-36%) of 50 subjects in the placebo group (odds ratio (OR) 95%CI = 1.23 0.550-2.747; p = 0.691). Faecal shedding of S. Typhi (Ty2 aroC(-)ssaV(-)) ZH9 was detected in 51 (51%; 95% CI, 41-61%) of 100 M01ZH09 subjects. No shedding was detected beyond day 3. A positive immune response, defined as 70% increase (1.7 fold change) in LPS specific serum IgG (day 14 or 28) and/or 50% increase (1.5 fold change) in LPS specific serum IgA (day 7 or 14) from baseline was detected in 98 (97%; 95% CI, 92-99%) of 101 M01ZH09 recipients and 8 (16%; 95% CI, 7-29%) of 50 placebo recipients. Twenty-eight (100%; 95% CI, 88-100%) of 28 vaccine recipients who were evaluated in the LPS specific IgA ELISPOT assay showed a positive response compared to none of the 14 placebo recipients tested.
This was the first phase II trial of a novel oral candidate typhoid vaccine in children in an endemic country. M01ZH09 had an appropriate safety profile and was immunogenic in children.
Controlled-trials.com ISRCTN91111837.
ObjectivesTo investigate the impact of intracerebral haematoma (ICH) on the outcomes and the factors related to an ICH in patients with aneurysmal subarachnoid haemorrhage (aSAH) in a low- and ...middle-income country.DesignA multicentre prospective cohort study.SettingThree central hospitals in Hanoi, Vietnam.ParticipantsThis study included all patients (≥18 years) presenting with aSAH to the three central hospitals within 4 days of ictus, from August 2019 to June 2021, and excluded patients for whom the admission Glasgow Coma Scale was unable to be scored or patients who became lost at 90 days of follow-up during the study.Outcome measuresThe primary outcome was ICH after aneurysm rupture, defined as ICH detected on an admission head CT scan. The secondary outcomes were 90-day poor outcomes and 90-day death.ResultsOf 415 patients, 217 (52.3%) were females, and the median age was 57.0 years (IQR: 48.0–67.0). ICH was present in 20.5% (85/415) of patients with aSAH. There was a significant difference in the 90-day poor outcomes (43.5% (37/85) and 29.1% (96/330); p=0.011) and 90-day mortality (36.5% (31/85) and 20.0% (66/330); p=0.001) between patients who had ICH and patients who did not have ICH. The multivariable regression analysis showed that systolic blood pressure (SBP) ≥140 mm Hg (adjusted odds ratio (AOR): 2.674; 95% CI: 1.372 to 5.214; p=0.004), World Federation of Neurosurgical Societies (WFNS) grades II (AOR: 3.683; 95% CI: 1.250 to 10.858; p=0.018) to V (AOR: 6.912; 95% CI: 2.553 to 18.709; p<0.001) and a ruptured middle cerebral artery (MCA) aneurysm (AOR: 3.717; 95% CI: 1.848 to 7.477; p<0.001) were independently associated with ICH on admission.ConclusionsIn this study, ICH was present in a substantial proportion of patients with aSAH and contributed significantly to a high rate of poor outcomes and death. Higher SBP, worse WFNS grades and ruptured MCA aneurysms were independently associated with ICH on admission.
•MALDITOF MS provided more rapid identification of invasive bacterial and fungal pathogens than conventional microbiology.•MALDITOF MS did not increase the proportion of patients on optimal therapy ...at 24 or 48 hours after positive culture.•MALDITOF MS did not increase the proportion of patients receiving adequate therapy at 24 hours after positive culture.•The most common reason for therapy being sub-optimal was use of overly broad spectrum or unnecessary multiple antibiotics.
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.
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).
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).
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.
A second cluster of COVID-19 cases imported from Europe occured in Vietnam from early March 2020. We describe 44 SARS-CoV-2 RT-PCR positive patients (cycle threshold value <30) admitted to the ...National Hospital for Tropical Diseases in Hanoi between March 6 and April 15 2020. Whole SARS-CoV-2 genomes from these patients were sequenced using Illumina Miseq and analysed for common genetic variants and relationships to local and globally circulating strains. Results showed that 32 cases were Vietnamese with a median age of 37 years (range 15-74 years), and 23 were male. Most cases were acquired outside Vietnam, mainly from the UK (n = 15), other European countries (n = 14), Russia (n = 6) and countries in Asia (n = 3). No cases had travelled from China. Forty-one cases had symptoms at admission, typically dry cough (n = 36), fever (n = 20), sore throat (n = 14) and diarrhoea (n = 12). Hospitalisation was long with a median of 25 days, most commonly from 20-29 days. All SARS-CoV-2 genomes were similar (92-100% sequence homology) to the reference sequence Wuhan_1 (NC_045512), and 32 strains belonged to the B.1.1 lineage. The three most common variants were linked, and included C3037T, C14408T (nsp12: P323L) and A23403G (S: D614G) mutations. This group of mutations often accompanied variant C241T (39/44 genomes) or GGG 28881..28883 AAC (33/44 genomes). The prevalence of the former reflected probable European origin of viruses, and the transition D614G was dominant in Vietnam. New variants were identified; however, none could be associated with disease severity.
Dengue is a disease of major global importance. While most symptomatic infections are mild, a small proportion of patients progress to severe disease with risk of hypovolaemic shock, organ ...dysfunction and death. In the absence of effective antiviral or disease modifying drugs, clinical management is solely reliant on supportive measures. Obesity is a growing problem among young people in Vietnam and is increasingly recognised as an important risk factor for severe dengue, likely due to alterations in host immune and inflammatory pathways. Metformin, a widely used anti-hyperglycaemic agent with excellent safety profile, has demonstrated potential as a dengue therapeutic
and in a retrospective observational study of adult dengue patients with type 2 diabetes. This study aims to assess the safety and tolerability of metformin treatment in overweight and obese dengue patients, and investigate its effects on several clinical, immunological and virological markers of disease severity.
This open label trial of 120 obese/overweight dengue patients will be performed in two phases, with a metformin dose escalation if no safety concerns arise in phase one. The primary endpoint is identification of clinical and laboratory adverse events. Sixty overweight and obese dengue patients aged 10-30 years will be enrolled at the Hospital for Tropical Diseases in Ho Chi Minh City, Vietnam. Participants will complete a 5-day course of metformin therapy and be compared to a non-treated group of 60 age-matched overweight and obese dengue patients.
Previously observed antiviral and immunomodulatory effects of metformin make it a promising dengue therapeutic candidate in appropriately selected patients. This study will assess the safety and tolerability of adjunctive metformin in the management of overweight and obese young dengue patients, as well as its effects on markers of viral replication, endothelial dysfunction and host immune responses.
ClinicalTrials.gov: NCT04377451 (May 6
2020).
Background:
Dengue is a disease of major global importance. While most symptomatic infections are mild, a small proportion of patients progress to severe disease with risk of hypovolaemic shock, ...organ dysfunction and death. In the absence of effective antiviral or disease modifying drugs, clinical management is solely reliant on supportive measures. Obesity is a growing problem among young people in Vietnam and is increasingly recognised as an important risk factor for severe dengue, likely due to alterations in host immune and inflammatory pathways. Metformin, a widely used anti-hyperglycaemic agent with excellent safety profile, has demonstrated potential as a dengue therapeutic
in vitro
and in a retrospective observational study of adult dengue patients with type 2 diabetes. This study aims to assess the safety and tolerability of metformin treatment in overweight and obese dengue patients, and investigate its effects on several clinical, immunological and virological markers of disease severity.
Methods:
This open label trial of 120 obese/overweight dengue patients will be performed in two phases, with a metformin dose escalation if no safety concerns arise in phase one. The primary endpoint is identification of clinical and laboratory adverse events. Sixty overweight and obese dengue patients aged 10-30 years will be enrolled at the Hospital for Tropical Diseases in Ho Chi Minh City, Vietnam. Participants will complete a 5-day course of metformin therapy and be compared to a non-treated group of 60 age-matched overweight and obese dengue patients.
Discussion:
Previously observed antiviral and immunomodulatory effects of metformin make it a promising dengue therapeutic candidate in appropriately selected patients. This study will assess the safety and tolerability of adjunctive metformin in the management of overweight and obese young dengue patients, as well as its effects on markers of viral replication, endothelial dysfunction and host immune responses.
Trial registration:
ClinicalTrials.gov:
NCT04377451
(May 6
th
2020).
: COVID-19 is a respiratory disease caused by a novel coronavirus (SARS-CoV-2) and causes substantial morbidity and mortality. There is currently no vaccine to prevent COVID-19 or therapeutic agent ...to treat COVID-19. This clinical trial is designed to evaluate chloroquine as a potential therapeutic for the treatment of hospitalised people with COVID-19. We hypothesise that chloroquine slows viral replication in patients with COVID-19, attenuating the infection, and resulting in more rapid decline of viral load in throat/nose swabs. This viral attenuation should be associated with improved patient outcomes.
: The study will start with a 10-patient prospective observational pilot study following the same entry and exclusion criteria as for the randomized trial and undergoing the same procedures. The main study is an open label, randomised, controlled trial with two parallel arms of standard of care (control arm) versus standard of care with 10 days of chloroquine (intervention arm) with a loading dose over the first 24 hours, followed by 300mg base orally once daily for nine days. The study will recruit patients in three sites in Ho Chi Minh City, Vietnam: the Hospital for Tropical Diseases, the Cu Chi Field Hospital, and the Can Gio COVID hospital. The primary endpoint is the time to viral clearance from throat/nose swab, defined as the time following randomization until the midpoint between the last positive and the first of the negative throat/nose swabs. Viral presence will be determined using RT-PCR to detect SARS-CoV-2 RNA.
The results of the study will add to the evidence-based guidelines for management of COVID-19. Given the enormous experience of its use in malaria chemoprophylaxis, excellent safety and tolerability profile, and its very low cost, if proved effective then chloroquine would be a readily deployable and affordable treatment for patients with COVID-19.
Clinicaltrials.gov NCT04328493 31/03/2020.
There are a host of emergent technologies with the potential to improve hospital care in low- and middle-income countries such as Vietnam. Wearable monitors and artificial intelligence-based decision ...support systems could be integrated with hospital-based digital health systems such as electronic health records (EHRs) to provide higher level care at a relatively low cost. However, the appropriate and sustainable application of these innovations in low- and middle-income countries requires an understanding of the local government's requirements and regulations such as technology specifications, cybersecurity, data-sharing protocols, and interoperability.
This scoping review aims to explore the current state of digital health research and the policies that govern the adoption of digital health systems in Vietnamese hospitals.
We conducted a scoping review using a modification of the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) guidelines. PubMed and Web of Science were searched for academic publications, and Thư Viện Pháp Luật, a proprietary database of Vietnamese government documents, and the Vietnam Electronic Health Administration website were searched for government documents. Google Scholar and Google Search were used for snowballing searches. The sources were assessed against predefined eligibility criteria through title, abstract, and full-text screening. Relevant information from the included sources was charted and summarized. The review process was primarily undertaken by one researcher and reviewed by another researcher during each step.
In total, 11 academic publications and 20 government documents were included in this review. Among the academic studies, 5 reported engineering solutions for information systems in hospitals, 2 assessed readiness for EHR implementation, 1 tested physicians' performance before and after using clinical decision support software, 1 reported a national laboratory information management system, and 2 reviewed the health system's capability to implement eHealth and artificial intelligence. Of the 20 government documents, 19 were promulgated from 2013 to 2020. These regulations and guidance cover a wide range of digital health domains, including hospital information management systems, general and interoperability standards, cybersecurity in health organizations, conditions for the provision of health information technology (HIT), electronic health insurance claims, laboratory information systems, HIT maturity, digital health strategies, electronic medical records, EHRs, and eHealth architectural frameworks.
Research about hospital-based digital health systems in Vietnam is very limited, particularly implementation studies. Government regulations and guidance for HIT in health care organizations have been released with increasing frequency since 2013, targeting a variety of information systems such as electronic medical records, EHRs, and laboratory information systems. In general, these policies were focused on the basic specifications and standards that digital health systems need to meet. More research is needed in the future to guide the implementation of digital health care systems in the Vietnam hospital setting.
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