Early treatment with fluvoxamine, bromhexine, cyproheptadine, and niclosamide to prevent clinical deterioration in patients with symptomatic COVID-19: a randomized clinical trial.

Background: Repurposed drugs with host-directed antiviral and immunomodulatory properties have shown promise in the treatment of COVID-19, but few trials have studied combinations of these agents. The aim of this trial was to assess the effectiveness of affordable, widely available, repurposed drugs used in combination for treatment of COVID-19, which may be particularly relevant to low-resource countries. Methods: We conducted an open-label, randomized, outpatient, controlled trial in Thailand from October 1, 2021, to June 21, 2022, to assess whether early treatment within 48-h of symptoms onset with combinations of fluvoxamine, bromhexine, cyproheptadine, and niclosamide, given to adults with confirmed mild SARS-CoV-2 infection, can prevent 28-day clinical deterioration compared to standard care. Participants were randomly assigned to receive treatment with fluvoxamine alone, fluvoxamine + bromhexine, fluvoxamine + cyproheptadine, niclosamide + bromhexine, or standard care. The primary outcome measured was clinical deterioration within 9, 14, or 28 days using a 6-point ordinal scale. This trial is registered with ClinicalTrials.gov (NCT05087381). Findings: Among 1900 recruited, a total of 995 participants completed the trial. No participants had clinical deterioration by day 9, 14, or 28 days among those treated with fluvoxamine plus bromhexine (0%), fluvoxamine plus cyproheptadine (0%), or niclosamide plus bromhexine (0%). Nine participants (5.6%) in the fluvoxamine arm had clinical deterioration by day 28, requiring low-flow oxygen. In contrast, most standard care arm participants had clinical deterioration by 9, 14, and 28 days. By day 9, 32.7% (110) of patients in the standard care arm had been hospitalized without requiring supplemental oxygen but needing ongoing medical care. By day 28, this percentage increased to 37.5% (21). Additionally, 20.8% (70) of patients in the standard care arm required low-flow oxygen by day 9, and 12.5% (16) needed non-invasive or mechanical ventilation by day 28. All treated groups significantly differed from the standard care group by days 9, 14, and 28 (p < 0.0001). Also, by day 28, the three 2-drug treatments were significantly better than the fluvoxamine arm (p < 0.0001). No deaths occurred in any study group. Compared to standard care, participants treated with the combination agents had significantly decreased viral loads as early as day 3 of treatment (p < 0.0001), decreased levels of serum cytokines interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1ß) as early as day 5 of treatment, and interleukin-8 (IL-8) by day 7 of treatment (p < 0.0001) and lower incidence of post-acute sequelae of COVID-19 (PASC) symptoms (p < 0.0001). 23 serious adverse events occurred in the standard care arm, while only 1 serious adverse event was reported in the fluvoxamine arm, and zero serious adverse events occurred in the other arms. Interpretation: Early treatment with these combinations among outpatients diagnosed with COVID-19 was associated with lower likelihood of clinical deterioration, and with significant and rapid reduction in the viral load and serum cytokines, and with lower burden of PASC symptoms. When started very soon after symptom onset, these repurposed drugs have high potential to prevent clinical deterioration and death in vaccinated and unvaccinated COVID-19 patients. Funding: Ped Thai Su Phai (Thai Ducks Fighting Danger) social giver group.

Appropriateness of recommended chest compression depths for cardiopulmonary resuscitation based on chest computed tomography parameters among Thai population: A multicenter retrospective study.

Aim: We evaluated the appropriateness of various chest compression (CC) depths among Thai population by comparing the calculated heart compression fraction (HCF) using mathematical methods based on chest computed tomography (CT) measurements. Methods: This multicenter retrospective cross-sectional study was conducted from September 2014 to December 2020. Chest parameters included external anteroposterior diameter (EAPD), internal anteroposterior diameter (IAPD), heart anteroposterior diameter (HAPD), and non-cardiac soft tissue measured at the level of maximum left ventricular diameter (LVmax). We compared the HCFs as calculated from CT parameters using different CC depths at 5 cm, 6 cm, 1/4 of EAPD, and 1/3 of EAPD, with further subgroup analysis stratified by sex and BMI. Results: A total of 2927 eligible adult patients with contrast-enhanced chest CT were included. The study group had mean age of 60.1 ± 14.7 years, mean BMI of 22 ± 4.4 kg/m2, and were 57% males. The mean HCFs were 41.5%, 53.5%, 42.4%, and 62.6%, for CC depths of 50 mm, 60 mm, 1/4 of EAPD, and 1/3 of EAPD respectively. HCF was significantly lower in male patients for all CC depths. Advanced age and higher BMI showed significant correlation with lower HCF for CC depths of 50 mm and 60 mm. Conclusion: The CC depth measure of 50-60 mm demonstrated efficacy in maintaining HCF and coronary perfusion in the general population except for geriatric and obese individuals. Adjusting CC depth to 1/4-1/3 of the EAPD yielded better outcomes. Future research should prioritize determining individualized CC depths based on EAPD proportion.

Exploring indoor and outdoor dust as a potential tool for detection and monitoring of COVID-19 transmission.

This study investigated the potential of using SARS-CoV-2 viral concentrations in dust as an additional surveillance tool for early detection and monitoring of COVID-19 transmission. Dust samples were collected from 8 public locations in 16 districts of Bangkok, Thailand, from June to August 2021. SARS-CoV-2 RNA concentrations in dust were quantified, and their correlation with community case incidence was assessed. Our findings revealed a positive correlation between viral concentrations detected in dust and the relative risk of COVID-19. The highest risk was observed with no delay (0-day lag), and this risk gradually decreased as the lag time increased. We observed an overall decline in viral concentrations in public places during lockdown, closely associated with reduced human mobility. The effective reproduction number for COVID-19 transmission remained above one throughout the study period, suggesting that transmission may persist in locations beyond public areas even after the lockdown measures were in place.

Care in emergencies and disasters: Can it be person-centered?

OBJECTIVES: While person-/patient-centered care aims to influence policymakers' rules and regulations to improve the care of individuals worldwide, exploration of the concept in the context of disaster and public health emergencies as an alternative ethical approach is lacking. This study aims to provide a nuanced understanding of the advantages and challenges of diverse ethical approaches in emergencies, to improve patient care. METHODS: A survey, created after several rounds of Delphi methodology, with 22 statements, was applied to 39 participants from nine different countries. The questionnaire's results, including participants' comments, were analyzed. RESULTS: The results show that practitioners chose to use a combination of diverse ethical approaches in managing victims of disasters and public health emergencies. CONCLUSION: The selection of an approach is context- and situation-dependent and seems to primarily respond to the nature of underlying etiology, creating a possibility to use diverse approaches to offer individualized care on a later occasion and when a flexible surge capacity is available. PRACTICE IMPLICATIONS: The outcomes of this study will enhance the future ethical discussion in person/patient-centered care during situations with limited resources and help to develop necessary ethical and educational guidelines.

Optimal chest compression position for cardiopulmonary resuscitation determined by computed tomography image: retrospective cross-sectional analysis.

The objective of this study was to determine the height of optimal hand position for chest compression during adult cardiopulmonary resuscitation (CPR) from the tip of the sternal xiphoid process (TOX) along with the relative heights of the left ventricular outflow tract (LVOT) and abdominal organs among the Thai population. The retrospective cross-sectional study was conducted through a review of medical records and contrast-enhanced chest computed tomography. The total of 204 Thai patients without obvious chest deformity at Ramathibodi Hospital from January to June 2018 was included as part of a multi-regional study. The heights of the level of maximal LV width (LVmax), LOVT, top of liver and stomach with respect to TOX were measured on midline sagittal image. Mean age and body mass index (BMI) were 59.5 years and 23.9 kg/m2, respectively. One hundred and one subjects (49.5%) had pulmonary diseases. Mean height of the LVmax from TOX was 37.7 mm, corresponding to 20% of the sternal length (SL) in the inspiration arm raised position (IAR). The adjusted height of LVmax from TOX in the expiration arm-down position (EAD) was 89.7 mm (48% of SL). The inter-nipple line was at 84.5 mm (45.1% of SL) from TOX on IAR. Among 178 and 109 subjects whose uppermost part of the liver and stomach were above TOX, 80.4% and 94.5% were located within the lower half of the sternum, respectively. The adjusted optimal hand position for chest compression during CPR was at approximately 89.7 mm from TOX in EAD (48% of SL). The hand position at the upper part of the lower half of the sternum is closest to the adjusted LVmax and has a better chance to avoid compression of intraabdominal organs.Trial registration This trial was retrospectively registered on 2 February 2023 in the Thai Clinical Trial Registry, identification number TCTR 20230202006.

The implication of a translational triage tool in mass casualty incidents: part three: a multinational study, using validated patient cards.

BACKGROUND: Mass casualty incidents (MCI) pose significant challenges to existing resources, entailing multiagency collaboration. Triage is a critical component in the management of MCIs, but the lack of a universally accepted triage system can hinder collaboration and lead to preventable loss of life. This multinational study uses validated patient cards (cases) based on real MCIs to evaluate the feasibility and effectiveness of a novel Translational Triage Tool (TTT) in primary triage assessment of mass casualty victims. METHODS: Using established triage systems versus TTT, 163 participants (1575 times) triaged five patient cases. The outcomes were statistically compared. RESULTS: TTT demonstrated similar sensitivity to the Sieve primary triage method and higher sensitivity than the START primary triage system. However, the TTT algorithm had a lower specificity compared to Sieve and higher over-triage rates. Nevertheless, the TTT algorithm demonstrated several advantages due to its straightforward design, such as rapid assessment, without the need for additional instrumental interventions, enabling the engagement of non-medical personnel. CONCLUSIONS: The TTT algorithm is a promising and feasible primary triage tool for MCIs. The high number of over-triages potentially impacts resource allocation, but the absence of under-triages eliminates preventable deaths and enables the use of other personal resources. Further research involving larger participant samples, time efficiency assessments, and real-world scenarios is needed to fully assess the TTT algorithm's practicality and effectiveness in diverse multiagency and multinational contexts.

The impact of the three-level collaboration exercise on collaboration and leadership during scenario-based hospital evacuation exercises using flexible surge capacity concept: a mixed method cross-sectional study.

BACKGROUND: Hospitals play a crucial role in responding to disasters and public health emergencies. However, they are also vulnerable to threats such as fire or flooding and can fail to respond or evacuate adequately due to unpreparedness and lack of evacuation measures. The United Nations Office for Disaster Risk Reduction has emphasised the importance of partnerships and capacity building in disaster response. One effective way to improve and develop disaster response is through exercises that focus on collaboration and leadership. This study aimed to examine the effectiveness of using the 3-level collaboration (3LC) exercise in developing collaboration and leadership in districts in Thailand, using the concept of flexible surge capacity (FSC) and its collaborative tool during a hospital evacuation simulation. METHODS: A mixed-method cross-sectional study was conducted with 40 participants recruited from disaster-response organisations and communities. The data from several scenario-based simulations were collected according to the collaborative elements (Command and control, Safety, Communication, Assessment, Triage, Treatment, Transport), in the disaster response education, "Major Incident Medical Management and Support" using self-evaluation survey pre- and post-exercises, and direct observation. RESULTS: The 3LC exercise effectively facilitated participants to gain a mutual understanding of collaboration, leadership, and individual and organisational flexibility. The exercise also identified gaps in communication and the utilisation of available resources. Additionally, the importance of early community engagement was highlighted to build up a flexible surge capacity during hospital evacuation preparedness. CONCLUSIONS: the 3LC exercise is valuable for improving leadership skills and multiagency collaboration by incorporating the collaborative factors of Flexible Surge Capacity concept in hospital evacuation preparedness.

Tracing the transmission of mpox through wastewater surveillance in Southeast Asia.

High population density and tourism in Southeast Asia increase the risk of mpox due to frequent interpersonal contacts. Our wastewater surveillance in six Southeast Asian countries revealed positive signals for Monkeypox virus (MPXV) DNA, indicating local transmission. This alerts clinicians and helps allocate resources like testing, vaccines and therapeutics in resource-limited countries.

Ca-EDTA restores the activity of ceftazidime-avibactam or aztreonam against carbapenemase-producing Klebsiellapneumoniae infections.

Developing an effective therapy to overcome carbapenemase-positive Klebsiella pneumoniae (CPKp) is an important therapeutic challenge that must be addressed urgently. Here, we explored a Ca-EDTA combination with aztreonam or ceftazidime-avibactam in vitro and in vivo against diverse CPKp clinical isolates. The synergy testing of this study demonstrated that novel aztreonam-Ca-EDTA or ceftazidime-avibactam-Ca-EDTA combination was significantly effective in eliminating planktonic and mature biofilms in vitro, as well as eradicating CPKp infections in vivo. Both combinations revealed significant therapeutic efficacies in reducing bacterial load in internal organs and protecting treated mice from mortality. Conclusively, this is the first in vitro and in vivo study to demonstrate that novel aztreonam-Ca-EDTA or ceftazidime-avibactam-Ca-EDTA combinations provide favorable efficacy and safety for successful eradication of carbapenemase-producing Klebsiella pneumoniae planktonic and biofilm infections.

COVID-19 monitoring with sparse sampling of sewered and non-sewered wastewater in urban and rural communities.

Equitable SARS-CoV-2 surveillance in low-resource communities lacking centralized sewers is critical as wastewater-based epidemiology (WBE) progresses. However, large-scale studies on SARS-CoV-2 detection in wastewater from low-and middle-income countries is limited because of economic and technical reasons. In this study, wastewater samples were collected twice a month from 186 urban and rural subdistricts in nine provinces of Thailand mostly having decentralized and non-sewered sanitation infrastructure and analyzed for SARS-CoV-2 RNA variants using allele-specific RT-qPCR. Wastewater SARS-CoV-2 RNA concentration was used to estimate the real-time incidence and time-varying effective reproduction number (Re). Results showed an increase in SARS-CoV-2 RNA concentrations in wastewater from urban and rural areas 14-20 days earlier than infected individuals were officially reported. It also showed that community/food markets were "hot spots" for infected people. This approach offers an opportunity for early detection of transmission surges, allowing preparedness and potentially mitigating significant outbreaks at both spatial and temporal scales.

Using computed tomography to evaluate proper chest compression depth for cardiopulmonary resuscitation in Thai population: A retrospective cross-sectional study.

INTRODUCTION: The effectiveness of cardiopulmonary resuscitation is determined by appropriate chest compression depth and rate. The American Heart Association recommended CC depth at 5-6 cm to indicate proper cardiac output during cardiac arrest. However, many studies showed the differences in the body builds between Caucasians and Asians. Therefore, this study aimed to determine heart compression fraction (HCF) in the Thai population by using contrast-enhanced computed tomography (CT) scan of the chest and a mathematical model. MATERIALS AND METHODS: Consecutive contrast-enhanced CT scans of the chest performed at Ramathibodi Hospital were retrospectively reviewed from January to March 2018 by two independent radiologists. Patients' characteristics, including gender, age, weight, height, and pre-existing diseases, were recorded, and the chest parameters were measured from a CT scan. The heart compression fraction (HCF) was subsequently calculated. RESULTS: Of 306 subjects, there were 139 (45.4%) males, 148 (47.4%) lung diseases and 10 (3.3%) heart diseases. Mean age and BMI were 60.4 years old and 23.8 kg/m2, respectively. Chest diameter, heart diameter, and non-cardiac soft tissue were significantly smaller in females compared to males. Mean (SD) HCF proportional with 50 mm and 60 mm depth were 38.3% (13.3%) and 50% (14.3%), respectively. There were significant differences of HCF proportional by 50 mm and 60 mm depth between men and women (33.2% vs 42.6% and 44% vs 54.9%, respectively (P<0.001)). In addition, a decrease in HCF was significantly observed among higher BMI groups. CONCLUSION: The CT scan and mathematical model showed that 38% and 50% HCF proportions were generated by 50 mm and 60 mm CC depth. HCF proportions were significantly different between genders and among BMI groups. The recommended depth of 5-6 cm is likely to provide sufficient CC depth in the population of Thailand.

Association between Mode of Transport and Patient Outcomes in the Emergency Department following Out-of-Hospital Cardiac Arrest: A Single-Center Retrospective Study.

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) remains a health problem worldwide, carrying a high mortality rate. Comparison of emergency department (ED) return of spontaneous circulation (ROSC) after OHCA in relation to emergency medical services (EMS) and non-EMS modes of transportation to the hospital was conducted to assess the impact points of the EMS system in Thailand. METHODS: This retrospective observational study enrolled all OHCA patients who visited the ED of Ramathibodi Hospital, a tertiary university hospital in Bangkok, between January 1, 2008, and May 31, 2020. Patients were differentiated into EMS and non-EMS groups according to mode of transportation to the ED. Patients' characteristics and comorbidities, witnessed arrests, bystander chest compression, initial rhythm, and resuscitation treatment were documented. ED-sustained ROSC, ED survival, 30-day survival, and 30-day survival with good cerebral performance category (CPC) scores were monitored and recorded. Multivariate logistic analyses were performed to assess factors influencing clinical outcomes. RESULTS: A total of 339 patients were enrolled, 117 (34.51%) of whom were in the EMS transport group. There were no differences between the EMS and non-EMS groups in ED-sustained ROSC (adjusted odds ratio [aOR], 0.99; 95% confidence interval [CI], 0.58-1.70; P = 0.98), or ED survival (aOR, 0.99; 95% CI, 0.57-1.71; P = 0.97). There were also no differences in 30-day survival or 30-day survival with good CPC score between the two groups. CONCLUSIONS: In our cohort data of OHCA, ED-sustained ROSC and ED survival outcomes were not superior in the EMS transportation group. Evidence to show that EMS transportation affected 30-day survival and 30-day good CPC score was also lacking. Thus, public promotion of Thailand's EMS system is advocated with a simultaneous improvement of EMS response to enhance OHCA outcomes.

Multiple traces of monkeypox detected in non-sewered wastewater with sparse sampling from a densely populated metropolitan area in Asia.

The monkeypox virus is excreted in the feces of infected individuals. Therefore, there is an interest in using viral load detection in wastewater for sentinel early surveillance at a community level and as a complementary approach to syndromic surveillance. We collected wastewater from 63 sewered and non-sewered locations in Bangkok city center between May and August 2022. Monkeypox viral DNA copy numbers were quantified using real-time polymerase chain reaction (PCR) and confirmed positive by Sanger sequencing. Monkeypox viral DNA was first detected in wastewater from the second week of June 2022, with a mean copy number of 16.4 copies/ml (n = 3). From the first week of July, the number of viral DNA copies increased to a mean copy number of 45.92 copies/ml. Positive samples were Sanger sequenced and confirmed the presence of the monkeypox virus. Our study is the first to detect monkeypox viral DNA in wastewater from various locations within Thailand. Results suggest that this could be a complementary source for detecting viral DNA and predicting upcoming outbreaks.

Characteristics and outcomes of out-of-hospital cardiac arrest patients before and during the COVID-19 pandemic in Thailand.

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) remains one of the leading causes of death worldwide, and bystander CPR with public-access defibrillation improves OHCA survival outcomes. The COVID-19 pandemic has posed many challenges for emergency medical services (EMS), including the suggestion of compression-only resuscitation and recommendations for complete personal protective equipment, which have created operational difficulties and prolonged response time. However, the risk factors affecting OHCA outcomes during the pandemic are poorly defined. This study aimed to assess the characteristics and outcomes of OHCA patients before and during the COVID-19 pandemic in Thailand. METHODS: This single-center, retrospective cohort study used data from electronic medical records and EMS paper records. All OHCA patients who visited Ramathibodi Hospital's emergency department before COVID-19 (March 2018 to December 2019) and during COVID-19 (March 2020-December 2021) were identified, and the number of emergency department returns of spontaneous circulation (ED-ROSC) and characteristics in OHCA patients before and during the COVID-19 pandemic in Thailand were collected. RESULTS: A total of 136 patients were included (78 men [59.1%]; mean [SD] age, 67.9 [18] years); 60 of these were during the COVID-19 period (beginning March 2020), and 76 were before the COVID-19 period. The overall baseline characteristics that differed significantly between the two groups were bystander witness and mode of chest compression (p-values < 0.001 and < 0.001, respectively). The ED ROSC during the COVID-19 period was significantly lower than before the COVID-19 period (26.67% vs. 46.05%, adjusted OR 0.21, p-value < 0.001). There were significant differences in survival to admission between the COVID-19 period and before (25.00% and 40.79%, adjusted OR 0.26, p-value 0.005). However, 30-day survivals were not significantly different (3.3% during the COVID-19 period and 10.53% before the COVID-19 period). CONCLUSIONS: During the COVID-19 pandemic in Thailand, ED ROSC and survival to admission in out-of-hospital cardiac arrest patients were significantly reduced. Additionally, the witness responses and mode of chest compression were very different between the two groups. TRIAL REGISTRATION: This trial was retrospectively registered on 7 December 2021 in the Thai Clinical Trial Registry, identification number TCTR20211207006.

Overcoming addition of phosphoethanolamine to lipid A mediated colistin resistance in Acinetobacter baumannii clinical isolates with colistin-sulbactam combination therapy.

Overcoming colistin-resistant Acinetobacter baumannii (CoR-AB) has become a major concern due to the lack of effective antibiotics. This study aimed to explore the prevalence of CoR-AB clinical isolates in Thailand, their mechanisms of resistance, and test the efficacy of colistin plus sulbactam against CoR-AB isolates. The colistin resistance rate among carbapenem-resistant A. baumannii was 15.14%. The mcr gene or its variants were not detected in CoR-AB isolates by PCR screening. The lipid A mass spectra of CoR-AB isolates showed the additional [M-H]- ion peak at m/z = 2034 that correlated to the phosphoethanolamine (pEtN) addition to lipid A (N = 27/30). The important amino acid substitutions were found at position S14P, A138T, A227V in PmrB that are associated with overexpression of the pEtN transferase (PmrC) and contributed the pEtN addition. The lipopolysacccharide production genes (lpxACD) were not related to lipid A mass spectra. A colistin plus sulbactam combination exhibited the synergy rate at 86.7% against CoR-AB isolates compare to sulbactam (85.89% resistance) or colistin (15.14% resistance) alone. The excellent synergistic activity of colistin plus sulbactam combination has the potential for the treatment of CoR-AB infections.