Establishing and validating noninvasive prenatal testing procedure for fetal aneuploidies in Vietnam

Noninvasive prenatal testing (NIPT) for fetal aneuploidies has been widely adopted in developed countries. Despite the sharp decrease in the cost of massively parallel sequencing, the technical know-how and skilled personnel are still one of the major limiting factors for applying this technology to NIPT in low-income settings. Here, we present the establishment and validation of our NIPT procedure called triSure for detection of fetal aneuploidies.We established the triSure algorithm based on the difference in proportion of fetal and maternal fragments from the target chromosome to all chromosomes. Our algorithm was validated using a published data set and an in-house data set obtained from high-risk pregnant women in Vietnam who have undergone amniotic testing. Several other aneuploidy calling methods were also applied to the same data set to benchmark triSure performance.The triSure algorithm showed similar accuracy to size-based method when comparing them using published data set. Using our in-house data set from 130 consecutive samples, we showed that triSure correctly identified the most samples (overall sensitivity and specificity of 0.983 and 0.986, respectively) compared to other methods tested including count-based, sized-based, RAPIDR and NIPTeR.We have demonstrated that our triSure NIPT procedure can be applied to pregnant women in low-income settings such as Vietnam, providing low-risk screening option to reduce the need for invasive diagnostic tests

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

Physical activity and nutrition behaviour outcomes of a cluster-randomized controlled trial for adults with metabolic syndrome in Vietnam

Background: Metabolic syndrome is prevalent among Vietnamese adults, especially those aged 50-65 years. This study evaluated the effectiveness of a 6 month community-based lifestyle intervention to increase physical activity levels and improve dietary behaviours for adults with metabolic syndrome in Vietnam. Methods: Ten communes, involving participants aged 50-65 years with metabolic syndrome, were recruited from Hanam province in northern Vietnam. The communes were randomly allocated to either the intervention (five communes, n = 214) or the control group (five communes, n = 203). Intervention group participants received a health promotion package, consisting of an information booklet, education sessions, a walking group, and a resistance band. Control group participants received one session of standard advice during the 6 month period. Data were collected at baseline and after the intervention to evaluate programme effectiveness. The International Physical Activity Questionnaire - Short Form and a modified STEPS questionnaire were used to assess physical activity and dietary behaviours, respectively, in both groups. Pedometers were worn by the intervention participants only for 7 consecutive days at baseline and post-intervention testing. To accommodate the repeated measures and the clustering of individuals within communes, multilevel mixed regression models with random effects were fitted to determine the impacts of intervention on changes in outcome variables over time and between groups. Results: With a retention rate of 80.8%, the final sample comprised 175 intervention and 162 control participants. After controlling for demographic and other confounding factors, the intervention participants showed significant increases in moderate intensity activity (P = 0.018), walking (P < 0.001) and total physical activity (P = 0.001), as well as a decrease in mean sitting time (P < 0.001), relative to their control counterparts. Significant improvements in dietary behaviours were also observed, particularly reductions in intake of animal internal organs (P = 0.001) and in using cooking oil for daily meal preparation (P = 0.001). Conclusions: The prescribed community-based physical activity and nutrition intervention programme successfully improved physical activity and dietary behaviours for adults with metabolic syndrome in Vietnam. Trial registration: Australian New Zealand Clinical Trials Registry, ACTRN12614000811606. Registered on 31 July 201

Associations of Underlying Health Conditions With Anxiety and Depression Among Outpatients: Modification Effects of Suspected COVID-19 Symptoms, Health-Related and Preventive Behaviors

Objectives: We explored the association of underlying health conditions (UHC) with depression and anxiety, and examined the modification effects of suspected COVID-19 symptoms (S-COVID-19-S), health-related behaviors (HB), and preventive behaviors (PB).Methods: A cross-sectional study was conducted on 8,291 outpatients aged 18–85 years, in 18 hospitals and health centers across Vietnam from 14th February to May 31, 2020. We collected the data regarding participant's characteristics, UHC, HB, PB, depression, and anxiety.Results: People with UHC had higher odds of depression (OR = 2.11; p < 0.001) and anxiety (OR = 2.86; p < 0.001) than those without UHC. The odds of depression and anxiety were significantly higher for those with UHC and S-COVID-19-S (p < 0.001); and were significantly lower for those had UHC and interacted with “unchanged/more” physical activity (p < 0.001), or “unchanged/more” drinking (p < 0.001 for only anxiety), or “unchanged/healthier” eating (p < 0.001), and high PB score (p < 0.001), as compared to those without UHC and without S-COVID-19-S, “never/stopped/less” physical activity, drinking, “less healthy” eating, and low PB score, respectively.Conclusion: S-COVID-19-S worsen psychological health in patients with UHC. Physical activity, drinking, healthier eating, and high PB score were protective factors

Intercostal Nerve Cryoanalgesia Versus Thoracic Epidural Analgesia in Lung Transplantation: A Retrospective Single-Center Study.

IntroductionThe optimal pain management strategy after lung transplantation is unknown. This study compared analgesic outcomes of intercostal nerve blockade by cryoanalgesia (Cryo) versus thoracic epidural analgesia (TEA).MethodsSeventy-two patients who underwent bilateral lung transplantation via clamshell incision at our center from 2016 to 2018 were managed with TEA (N = 43) or Cryo (N = 29). We evaluated analgesic-specific complications, opioid use in oral morphine equivalents (OME), and pain scores (0-10) through postoperative day 7. Adjusted linear regression was used to assess for non-inferiority of Cryo to TEA.ResultsThe overall mean pain scores (Cryo 3.2 vs TEA 3.8, P = 0.21), maximum mean pain scores (Cryo 4.7 vs TEA 5.5, P = 0.16), and the total opioid use (Cryo 484 vs TEA 705 OME, P = 0.12) were similar in both groups, while the utilization of postoperative opioid-sparing analgesia, measured as use of lidocaine patches, was lower in the Cryo group (Cryo 21% vs TEA 84%, P < 0.001). Analgesic outcomes remained similar between the cohorts after adjustment for pertinent patient and analgesic characteristics (P = 0.26), as well as after exclusion of Cryo patients requiring rescue TEA (P = 0.32). There were no Cryo complications, with four patients requiring subsequent TEA for pain control. Two TEA patients experienced hemodynamic instability following a test TEA bolus requiring code measures. Additionally, TEA placement was delayed beyond postoperative day 1 in 33% owing to need for anticoagulation or clinical instability.ConclusionsIn lung transplantation, Cryo was found to be safe with analgesic effectiveness similar to TEA. Cryo may be advantageous in this complex patient population, as it can be used in all clinical scenarios and eliminates risks and delays associated with TEA

Effectiveness of continuous endotracheal cuff pressure control for the prevention of ventilator associated respiratory infections: an open-label randomised, controlled trial

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

Ventilator-associated respiratory infection in a resource-restricted setting: impact and etiology

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.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.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).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