INTEnsive care bundle with blood pressure reduction in acute cerebral hemorrhage trial (INTERACT3): study protocol for a pragmatic stepped-wedge cluster-randomized controlled trial

Background: Early intensive blood pressure (BP) lowering remains the most promising treatment for acute intracerebral hemorrhage (ICH), despite discordant results between clinical trials and potential variation in the treatment effects by approach to control BP. As the third in a series of clinical trials on this topic, the INTEnsive care bundle with blood pressure Reduction in Acute Cerebral hemorrhage Trial (INTERACT3) aims to determine the effectiveness of a goal-directed care bundle protocol of early physiological control (intensive BP lowering, glycemic control, and pyrexia treatment) and reversal of anticoagulation, in acute ICH. Methods: INTERACT3 is a pragmatic, international, multicenter, stepped-wedge (4 phases/3 steps), cluster-randomized controlled trial to determine the effectiveness of a multifaceted care package in adult (age ≥ 18 years) patients (target 8360) with acute ICH (< 6 h of onset) recruited from 110 hospitals (average of 19 consecutive patients per phase) in low- and middle-income countries. After a control phase, each hospital implements the intervention (intensive BP lowering, target systolic < 140 mmHg; glucose control, target 6.1–7.8 mmol/L and 7.8–10.0 mmol/L in those without and with diabetes mellitus, respectively; anti-pyrexia treatment to target body temperature ≤ 37.5 °C; and reversal of anticoagulation, target international normalized ratio < 1.5 within 1 h). Information will be obtained on demographic and baseline clinical characteristics, in-hospital management, and 7-day outcomes. Central trained blinded assessors will conduct telephone interviews to assess physical function and health-related quality of life at 6 months. The primary outcome is the modified Rankin scale (mRS) at 6 months analyzed using ordinal logistic regression. The sample size of 8360 subjects provides 90% power (α = 0.05) to detect a 5.6% absolute improvement (shift) in the primary outcome of the intervention versus control standard care, with various assumptions. Discussion: As the largest clinical trial in acute ICH, INTERACT3 is on schedule to provide an assessment of the effectiveness of a widely applicable goal-directed care bundle for a serious condition in which a clearly proven treatment has yet to be established. Trial registration: ClinicalTrials.gov NCT03209258. Registered on 1 July 2017. Chinese Trial Registry ChiCTR-IOC-17011787. Registered on 28 June 201

Associations of Early Systolic Blood Pressure Control and Outcome after Thrombolysis-Eligible Acute Ischemic Stroke: Results from the ENCHANTED Study

Background and Purpose: In thrombolysis-eligible patients with acute ischemic stroke, there is uncertainty over the most appropriate systolic blood pressure (SBP) lowering profile that provides an optimal balance of potential benefit (functional recovery) and harm (intracranial hemorrhage). We aimed to determine relationships of SBP parameters and outcomes in thrombolyzed acute ischemic stroke patients. Methods: Post hoc analyzes of the ENCHANTED (Enhanced Control of Hypertension and Thrombolysis Stroke Study), a partial-factorial trial of thrombolysis-eligible and treated acute ischemic stroke patients with high SBP (150-180 mm Hg) assigned to low-dose (0.6 mg/kg) or standard-dose (0.9 mg/kg) alteplase and intensive (target SBP, 130-140 mm Hg) or guideline-recommended (target SBP <180 mm Hg) treatment. All patients were followed up for functional status and serious adverse events to 90 days. Logistic regression models were used to analyze 3 SBP summary measures postrandomization: attained (mean), variability (SD) in 1-24 hours, and magnitude of reduction in 1 hour. The primary outcome was a favorable shift on the modified Rankin Scale. The key safety outcome was any intracranial hemorrhage. Results: Among 4511 included participants (mean age 67 years, 38% female, 65% Asian) lower attained SBP and smaller SBP variability were associated with favorable shift on the modified Rankin Scale (per 10 mm Hg increase: odds ratio, 0.76 [95% CI, 0.71-0.82]; P<0.001 and 0.86 [95% CI, 0.76-0.98]; P=0.025) respectively, but not for magnitude of SBP reduction (0.98, [0.93-1.04]; P=0.564). Odds of intracranial hemorrhage was associated with higher attained SBP and greater SBP variability (1.18 [1.06-1.31]; P=0.002 and 1.34 [1.11-1.62]; P=0.002) but not with magnitude of SBP reduction (1.05 [0.98-1.14]; P=0.184). Conclusions: Attaining early and consistent low levels in SBP <140 mm Hg, even as low as 110 to 120 mm Hg, over 24 hours is associated with better outcomes in thrombolyzed acute ischemic stroke patients. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01422616

On an inverse boundary value problem of a nonlinear elliptic equation in three dimensions

This work considers an inverse boundary value problem for a 3D nonlinear elliptic partial differential equation in a bounded domain. In general, the problem is severely ill-posed. The formal solution can be written as a hyperbolic cosine function in terms of the 2D elliptic operator via its eigenfunction expansion, and it is shown that the solution is stabilized or regularized if the large eigenvalues are cut off. In a theoretical framework, a truncation approach is developed to approximate the solution of the ill-posed problem in a regularization manner. Under some assumptions on regularity of the exact solution, we obtain several explicit error estimates including an error estimate of Hölder type. A local Lipschitz case of source term for this nonlinear problem is obtained. For numerical illustration, two examples on the elliptic sine-Gordon and elliptic Allen-Cahn equations are constructed to demonstrate the feasibility and efficiency of the proposed methods

Measuring serum beta2-microglobulin to predict long-term mortality in hemodialysis patients using low-flux dialyzer reuse

Nguyen Huu Dung,1 Nguyen Trung Kien,2 Nguyen Thi Thu Hai,1 Phan The Cuong,1 Nguyen Thi Thu Huong,3 Dao Bui Quy Quyen,4 Nguyen Minh Tuan,4 Do Manh Ha,2 Truong Quy Kien,2 Nguyen Thi Thuy Dung,2 Pham Quoc Toan,2 Hoang Trung Vinh,2 Tomoko Usui,5 Le Viet Thang21Bach Mai Hospital, Ha Noi, Vietnam; 2Military Hospital 103, Ha Noi, Vietnam; 3Ha Noi Kidney Hospital, Ha Noi, Vietnam; 4Cho Ray Hospital, Ho Chi Minh, Vietnam; 5University of Tokyo Hospital, Tokyo, JapanPurpose: Beta2-microglobulin (&beta;2-M) is recognized as a surrogate marker relating to the mechanisms of dialysis-associated amyloidosis. Few studies have evaluated the association of serum &beta;2-M with clinical outcome in hemodialysis patients using high-flux type. However, study on patients using low-flux dialyzer reuse has not been done yet.Patients and methods: Using serum &beta;2-M level on predicting long-term mortality of hemodialysis patients was examined in 326 prevalent hemodialysis patients (45.59&plusmn;14.46 years, hemodialysis duration of 47.5 (26&ndash;79) months, 186 males and 140 females). The patients were divided into 3 groups with equal number of patients, according to their serum &beta;2-M levels: group A (n=109, serum &beta;2-M concentration &le;55.7 mg/L), group B (n=109, serum &beta;2-M level from 55.8 mg/L to 75.4 mg/L) and group C (n=108, serum &beta;2-M concentration &gt;75.4 mg/L).Results: During the follow-up period of 5 years, there were 75 all-cause deaths (23.0%). Kaplan&ndash;Meier analysis revealed that all-cause mortality in the higher &beta;2-M group was significantly higher compared to that in the lower &beta;2-M groups (p&lt;0.001). Serum &beta;2-M level was a significant predictor for all-cause mortality (AUC =0.898; p&lt;0.001; Cut-off value: 74.9 mg/L, Se=93.3%, Sp=92.9%).Conclusion: Serum &beta;2-M levels were a significant predictor of long-term mortality in hemodialysis patients, who use only low-flux dialyzers and reuse 6 times.Keywords: Beta2-microglobulin, mortality, hemodialysi

Antimicrobial Resistance Patterns of Staphylococcus Aureus Isolated at a General Hospital in Vietnam Between 2014 and 2021

Nguyen Van An,1,&ast; Le Ha long Hai,2,3,&ast; Vu Huy Luong,4,5 Nguyen Thi Ha Vinh,5,6 Pham Quynh Hoa,7 Le Van Hung,5,7 Nguyen Thai Son,1 Le Thu Hong,1 Dinh Viet Hung,8 Hoang Trung Kien,9 Minh Nhat Le,10,11 Nguyen Hoang Viet,12 Duc Hoang Nguyen,13 Ngai Van Pham,14 Ta Ba Thang,15 Tran Viet Tien,16 Le Huy Hoang17 1Department of Microbiology, Military Hospital 103, Vietnam Military Medical University, Hanoi, Vietnam; 2Department of Clinical Microbiology and Parasitology, Faculty of Medical Technology, Hanoi Medical University, Hanoi, Vietnam; 3Department of Biochemistry, Hematology and Immunology, National Hospital of Dermatology and Venereology, Hanoi, Vietnam; 4Department of Laser and Skin Care, National hospital of Dermatology and Venereology, Hanoi, Vietnam; 5Department of Dermatology and Venereology, Hanoi Medical University, Hanoi, Vietnam; 6Department of General Planning, National hospital of Dermatology and Venereology, Hanoi, Vietnam; 7Department of Microbiology, Mycology and Parasitology, National hospital of Dermatology and Venereology, Hanoi, Vietnam; 8Department of Psychiatry, Military Medical 103, Vietnam Military Medical University, Hanoi, Vietnam; 9Department of Immunology, Vietnam Military Medical University, Hanoi, Vietnam; 10Tay Nguyen Institute of Science Research, Vietnam Academy of Science and Technology, VAST, Hanoi, Vietnam; 11Antimicrobial Resistance Research Center, National Institute of Infectious Disease, Tokyo, Japan; 12Molecular Pathology Department, Faculty of Medical Technology, Hanoi Medical University, Hanoi, Vietnam; 13Cardiovascular Laboratories, Methodist Hospital, Merrillville, Indiana, USA; 14Medical Testing Center, Medlatec Group, Hanoi, Vietnam; 15Respiratory Center, Military Hospital 103, Vietnam Military Medical University, Hanoi, Vietnam; 16Department of Infectious diseases, Military Hospital 103, Vietnam Medical Military University, Hanoi, Vietnam; 17Department of Bacteriology, National of Hygiene and Epidemiology, Hanoi, Vietnam&ast;These authors contributed equally to this workCorrespondence: Le Huy Hoang, Department of Bacteriology, National of Hygiene and Epidemiology, Hanoi, 100000, Vietnam, Tel + 84 977 803 986, Email [email protected]: Staphylococcus aureus is a commensal bacteria species that can cause various illnesses, from mild skin infections to severe diseases, such as bacteremia. The distribution and antimicrobial resistance (AMR) pattern of S. aureus varies by population, time, geographic location, and hospital wards. In this study, we elucidated the epidemiology and AMR patterns of S. aureus isolated from a general hospital in Vietnam.Methods: This was a cross-sectional study. Data on all S. aureus infections from 2014 to 2021 were collected from the Microbiology department of Military Hospital 103, Vietnam. Only the first isolation from each kind of specimen from a particular patient was analyzed using the Cochran–Armitage and chi-square tests.Results: A total of 1130 individuals were diagnosed as S. aureus infection. Among them, 1087 strains were tested for AMR features. Most patients with S. aureus infection were in the age group of 41– 65 years (39.82%). S. aureus isolates were predominant in the surgery wards, and pus specimens were the most common source of isolates (50.62%). S. aureus was most resistant to azithromycin (82.28%), erythromycin (82.82%), and clindamycin (82.32%) and least resistant to teicoplanin (0.0%), tigecycline (0.16%), quinupristin-dalfopristin (0.43%), linezolid (0.62%), and vancomycin (2.92%). Methicillin-resistant S. aureus (MRSA) and multidrug-resistant (MDR) S. aureus were prevalent, accounting for 73.02% and 60.90% of the total strains respectively, and the strains isolated from the intensive care unit (ICU) had the highest percentage of multidrug resistance (77.78%) among the wards.Conclusion: These findings highlight the urgent need for continuous AMR surveillance and updated treatment guidelines, particularly considering high resistance in MRSA, MDR strains, and ICU isolates. Future research focusing on specific resistant populations and potential intervention strategies is crucial to combat this rising threat.Keywords: Staphylococcus aureus, antimicrobial resistance, methicillin-resistant S. aureus, multidrug resistance, Hanoi, Vietna

The application of sample pooling for mass screening of SARS-CoV-2 in an outbreak of COVID-19 in Vietnam

We sampled nasal–pharyngeal throat swabs from 96,123 asymptomatic individuals at risk of SARS-CoV-2 infection, and generated 22,290 pools at collection, each containing samples from two to seven individuals. We detected SARS-CoV-2 in 24 pools, and confirmed the infection in 32 individuals after resampling and testing of 104 samples from positive pools. We completed the testing within 14 days. We would have required 64 days to complete the screening for the same number of individuals if we had based our testing strategy on individual testing. There was no difference in cycle threshold (Ct) values of pooled and individual samples. Thus, compared with individual sample testing, our approach did not compromise PCR sensitivity, but saved 77% of the resources. The present strategy might be applicable in settings, where there are shortages of reagents and the disease prevalence is low, but the demand for testing is high

Low-dose vs standard-dose alteplase for patients with acute ischemic stroke: Secondary analysis of the ENCHANTED randomized clinical trial

IMPORTANCE: A lower dose of intravenous alteplase appears to be a safer treatment option than the standard dose, reducing the risk of symptomatic intracerebral hemorrhage. There is uncertainty, however, over how this effect translates into an overall clinical benefit for patients with acute ischemic stroke (AIS). OBJECTIVE: To assess whether older, Asian, or severely affected patients with AIS who are considered at high risk of thrombolysis may benefit more from low-dose rather than standard-dose alteplase treatment. DESIGN, SETTING, AND PARTICIPANTS: This study is a prespecified secondary analysis of the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED), an international, randomized, open-label, blinded, end-point clinical trial of low-dose vs standard-dose intravenous alteplase for patients with AIS. From March 1, 2012, to August 31, 2015, a total of 3310 patients who had a clinical diagnosis of AIS as confirmed by brain imaging and who fulfilled the local criteria for thrombolysis treatment were included in the alteplase-dose arms. Patients were randomly assigned to receive low-dose (0.6 mg/kg; 15% as bolus and 85% as infusion over 1 hour) or standard-dose (0.9 mg/kg; 10% as bolus and 90% as infusion over 1 hour) alteplase. Of the 3310 randomized patients, 13 patients were excluded for missing consent, mistaken randomization, and duplicate randomization numbers. This secondary analysis was conducted between May 1, 2016, and April 28, 2017. MAIN OUTCOMES AND MEASURES: The primary end point was a poor outcome defined by the combination of death and any disability as scored by the modified Rankin Scale (scores range from 2 to 6, with the highest score indicating death) at 90 days. RESULTS: Of the 3297 patients included in the analysis, 1248 (37.9%) were women, and the mean (SD) age was 67 (13) years. No significant differences in the treatment effects were observed between low- and standard-dose alteplase for poor outcomes (death or disability) by age, ethnicity, or severity (all P > .37 for interaction). Similarly, the treatment effects of low- vs standard-dose alteplase on function outcome (ordinal shift of the modified Rankin Scale) in Asians (odds ratio, 1.05; 95% CI, 0.90-1.22) was consistent with non-Asians (odds ratio, 0.93; 95% CI, 0.76-1.14) (P = .32 for interaction). There were generally consistent reductions in rates of symptomatic intracerebral hemorrhage with low-dose alteplase, although this reduction was not statistically significant by age, ethnicity, or severity. CONCLUSIONS AND RELEVANCE: This analysis found that the effects of low-dose alteplase were not clearly superior to the effects of standard-dose alteplase on death or disability in key demographic subgroups of patients with AIS. Further investigation is required to identify patients with AIS who may benefit from low-dose alteplase. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01422616