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1.
BMC Proceedings. Conference: 6th International Conference on Molecular Diagnostics and Biomarker Discovery, MDBD ; 16(Supplement 7), 2022.
Article in English | EMBASE | ID: covidwho-2196276

ABSTRACT

Background Coronaviruses are well-known to possess high mutation rate. The recent pandemic has demonstrated this fact that multiple SARS-CoV-2 variants have emerged since the first occurrence in 2019. Variants such as Beta, Delta and Omicron variant, even showed the ability of immune evasion in convalescent and vaccinated individuals [1], raising global concern about the efficacies of existing vaccines. Immunoinformatics approach is gaining traction in vaccine development due to significant time and cost reduction in immunogenicity studies and improved reliability [2]. Viral genome can be analysed for the mapping of potential T-cell and B-cell epitopes. Structural proteins, particularly spike protein (S) have been studied extensively as promising vaccine candidates. One rationale is that the RBD of SARS-CoV- 2 attaches to the ACE2 receptor on the host cells to initiate infection. Taken together, a vaccine that offers protection over a wide spectrum of coronaviruses is crucially demanded. Methodology The sequences of S proteins of the SARS-CoV-2 variants as well as SARS-CoV and MERS-CoV were retrieved from the NCBI database. Multiple sequence alignment (MSA) was performed to identify the conserved regions among S proteins from different human coronaviruses. All conserved regions were analysed for the antigenicity through VaxiJen. The conserved regions that passed the threshold value of 0.5 were then analysed for T-cell and B-cell epitope predictions using NetMHCpan EL4.1, IEDB recommended 2.22 and BepiPred 2.0, respectively. The antigenic conserved regions were also used to construct 3D model using SWISS-MODEL followed by structural refinement using GalaxyRefine2. All refined models were validated using ERRAT and PROCHECK. Lastly, the docking of 3D models against TLR-3 was performed via PatchDock and FireDock. Results and Discussion Based on the MSA result, S protein contains 12 conserved regions, which were then subjected to further analyses. Altogether 9 conserved regions were above the antigenicity threshold value and therefore selected. In terms of epitope prediction, the antigenic conserved regions were predicted to contain a total of 69 MHC Class-I epitopes, 45 MHC Class-II epitopes and 5 linear B-cell epitopes. Furthermore, all antigenic conserved regions were sent for 3D model building followed by structural refinement. The best refined model for each conserved region was chosen based on the Galaxy energy. These refined models were validated and the results showed that the models were of good quality. Following that, the refined model for each conserved region was docked against TLR-3. The global energies of complexes formed between the conserved regions and TLR-3 fell within the range of -11.74 to -7.36 kcal/mol. This implies that the conserved regions have good binding affinities with TLR-3. Conclusion The identified conserved regions of S protein were predicted to have a significant number of epitopes and showed promising docking results. This study provides some insights about the interaction of conserved S peptides with TLR-3, contributing to the vaccine design. Still, further analyses such as molecular dynamics and immune simulation are required to polish the results. In vitro and in vivo validation are also essential to evaluate the immunological roles of designed universal coronavirus vaccine.

2.
Vascular Medicine ; 27(6):NP20-NP21, 2022.
Article in English | EMBASE | ID: covidwho-2194547

ABSTRACT

Background: The Coronavirus Disease 2019 (COVID-19) has been shown to Increase incidence of venous thromboembolism (VTE). We describe a novel case of rivaroxaban treatment failure in a patient with COVID-19 infection who previously demonstrated efficacious treatment of prior pulmonary embolism (PE) with rivaroxaban Case presentation: A 75-year-old male patient originally presented for syncope and was found to have acute submissive PE on Computed tomography angiogram of his (CTA) chest. He was placed on heparin initially and he remained hemodynamically stable during his admission and was discharged home on rivaroxaban at standard induction dose. He presented again for shortness of breath 3 months later. CTA chest was repeated and demonstrated resolution of his prior PE. He was found to be positive for COVID-19 and admitted for further management, rivaroxaban was continued during his admission. Repeat CTA of his chest 2 weeks later demonstrated moderate right and small left PE without right heart strain. Vascular Medicine was consulted at that time. The patient reported taking his rivaroxaban as directed throughout the recommended course. He reported taking rivaroxaban with food. He said his son helped him with his medications and it was unlikely he missed any doses. He was able to get his medications from the Veterans Health Administration (VA) and had no issues with access to medications. Medication review revealed no drug interactions . that would decrease efficacy of rivaroxaban. The patient's weight of 116 kg was within the acceptable range for rivaroxaban use. Conclusion(s): This case is unique in that timing of CTA scans demonstrated complete resolution of patient's initial PE while taking rivaroxaban followed by new development of PE after COVID-19 infection despite continuation of rivaroxaban therapy.

3.
Circulation Conference: American Heart Association's ; 146(Supplement 1), 2022.
Article in English | EMBASE | ID: covidwho-2194358

ABSTRACT

Introduction: Recent data shows that when adults are discharged after hospitalization for acute heart failure (HF), a clinic follow up with either cardiology or general medicine within 7 days results in significantly lower chances of 30 day readmissions. We sought to analyze the trends of clinic follow up after acute HF hospitalization and the associated barriers and facilitators at our safety net hospital. Method(s): Data was extracted from the electronic medical records using ICD 9,10 codes for acute HF admissions between Jan 2019 and Dec 2021. Quarterly trends of rates of clinic follow up were analyzed over the past 3 years;t-test was used to assess for statistical significance. Multivariable logistic regression models were constructed to test the association between patient level factors and clinic follow up after adjusting for sociodemographic factors. A p value < 0.05 was used to establish significance. Result(s): Of 1,037 patients admitted for acute HF between 2019-2021, 29.5% were 65 years or older, 64.7% were males, 48.7% were Black and 16.6% were uninsured. Only 8% and 23.1% had a 7 and 14 day clinic follow up respectively. Of those with scheduled follow up 65% and 56% showed up to their appointments at 7 and 14 days respectively. Overtime we noted an increase in the proportion of encounters with a 7 day follow up although the effective follow up (after accounting for no-shows) remained unchanged. Patients that had an inpatient cardiology consult had higher odds of getting a 7 day follow up (OR=1.42, p value = 0.001) after adjusting for age, gender, insurance status and race (black > white, OR = 1.34, p<0.001). Conclusion(s): Our study showed that the effective 7 day follow up did not improve from 2019 to 2021 likely due to COVID19 pandemic. However, a significantly higher proportion of patients obtained 7 day appointments in the last quarter with room for improvement. Steps to increase follow up rates include intervening on the highlighted modifiable factors to achieve better results. (Figure Presented).

4.
IEEE Journal of Biomedical and Health Informatics ; : 1-11, 2022.
Article in English | EMBASE | ID: covidwho-2191981

ABSTRACT

Early detection of COVID-19 is an ongoing area of research that can help with triage, monitoring and general health assessment of potential patients and may reduce operational strain on hospitals that cope with the coronavirus pandemic. Different machine learning techniques have been used in the literature to detect potential cases of coronavirus using routine clinical data (blood tests, and vital signs measurements). Data breaches and information leakage when using these models can bring reputational damage and cause legal issues for hospitals. In spite of this, protecting healthcare models against leakage of potentially sensitive information is an understudied research area. In this study, two machine learning techniques that aim to predict a patient's COVID-19 status are examined. Using adversarial training, robust deep learning architectures are explored with the aim to protect attributes related to demographic information about the patients. The two models examined in this work are intended to preserve sensitive information against adversarial attacks and information leakage. In a series of experiments using datasets from the Oxford University Hospitals (OUH), Bedfordshire Hospitals NHS Foundation Trust (BH), University Hospitals Birmingham NHS Foundation Trust (UHB), and Portsmouth Hospitals University NHS Trust (PUH), two neural networks are trained and evaluated. These networks predict PCR test results using information from basic laboratory blood tests, and vital signs collected from a patient upon arrival to the hospital. The level of privacy each one of the models can provide is assessed and the efficacy and robustness of the proposed architectures are compared with a relevant baseline. One of the main contributions in this work is the particular focus on the development of effective COVID-19 detection models with built-in mechanisms in order to selectively protect sensitive attributes against adversarial attacks. The results on hold-out test set and external validation confirmed that there was no impact on the generalisibility of the model using adversarial learning. Copyright Author

5.
Critical Care Medicine ; 51(1 Supplement):204, 2023.
Article in English | EMBASE | ID: covidwho-2190538

ABSTRACT

INTRODUCTION: Hydroxychloroquine (HCQ) was hoped to be repurposed for treating COVID-19, especially in regions where more expensive regimens were not available. Unfortunately, several randomized clinical trials (RCT) using HCQ to treat COVID-19, ranging from simple exposure to significant illness, have not improved outcomes. In five failed sepsis RCT's and one previous COVID-19 study the SMART statistical approach identified, from pre-randomization data, cohorts among whom study drugs reduced mortality significantly. Additionally, in one study the SMART statistical approach predicted futility. Whether such sub-groups exist in HCQ COVID-19 RCT's is unknown and is what this research aims to examine. OBJECTIVE(S): To determine from pre-randomization data if HCQ-responsive patients exist within the PETAL Clinical Trials Network ORCHID RCT in hospitalized COVID-19 patients. METHOD(S): With the approval of the BioLINCC data repository and the IRB of Inspira Health Network, HIPAAcompliant data on 452 ORCHID subjects (224 HCQ, 228 placebo) were analyzed. Pre-randomization stepwise logistic regression survival models were built separately for placebo and HCQ. Baseline data from all patients were then entered into both models. Interactions of placebo and HCQ survival models with 28-day mortality HCQ treatment effects determined optimum cutoffs, incrementally excluding from efficacy analysis patients predicted as HCQ non-responders. RESULT(S): Placebo model independent variables: age, VITHRH and potassium. HCQ model independent variables age, SOFA score SpO2, and D-BL-ICU. Overall, 28-day mortality was 10.71% placebo and 10.53% HCQ (p= 0.9483). Interactions of the mortality models with HCQ efficacy were optimized in a cohort of 49 patients (10.2% of total RCT), with placebo 28-day mortality 46% and HCQ mortality 24% (p=0.1085). In the non-SMART group (n=403, 89% of total), mortality was 6.5% placebo and 8.9% HCQ (p=0.3726) CONCLUSION(S): Even in a pre-randomization optimized SMART-identified cohort comprising only 10.2% of the ORCHID RCT, hydroxychloroquine did not reduce mortality significantly in hospitalized patients with COVID-19. These results predict futility for further RCTs of hydroxychloroquine in COVID-19. Hydroxychloroquine fails hospitalized COVID-19 patients.

6.
Critical Care Medicine ; 51(1 Supplement):164, 2023.
Article in English | EMBASE | ID: covidwho-2190513

ABSTRACT

INTRODUCTION: The reduction of mortality in COVID-19 has been clinically established only for Dexamethasone and Tocilizumab to date, but the overall mortality in COVID-19 remains high. Baricitinib is a Janus Kinase 1/2 Inhibitor with known anti-inflammatory and anti-viral properties. The US FDA recently approved Baricitinib for the treatment of hospitalized adults with COVID-19 requiring either supplemental oxygen, non-invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO). We performed a meta-analysis of Randomized Controlled Trials (RCT) and observational studies assessing the effect of Baricitinib on mortality outcomes in hospitalized patients with COVID-19. METHOD(S): A systematic literature search was conducted on electronic databases including NIH LitCovid, WHO COVID-19 database, EMBASE, and Cochrane Central from inception until June 30th, 2022. Randomized Controlled Trials and observational studies evaluating the efficacy of Baricitinib in hospitalized patients with COVID-19 were screened for the assessment of all-cause mortality as the outcome. RESULT(S): Twenty-three studies (18 observational and 5 RCTs) were included in the mortality meta-analysis. Of the 16,390 patients (4,565 observational, 11,825 RCTs), 2,139 patients died (903 out of 7,610 in the Baricitinib arm and 1,236 out of 8,780 in the non-Baricitinib arm). Using the random-effects model, the odds of mortality in the therapeutic Baricitinib use showed a statistically significant reduction in all-cause mortality in hospitalized COVID-19 patients (OR 0.67, 95% CI 0.50-0.90;p=0.008, I2=79%). A similar trend of decreased mortality was observed in the subgroup analysis by study design (Observational OR 0.59, 95% CI 0.35-0.97, p=0.04, I2=83%;RCTs OR 0.72, 95% CI 0.56-0.93, p=0.01, I2=53%). CONCLUSION(S): Baricitinib used along with the standard of care treatments is associated with a reduction in mortality in hospitalized patients with COVID-19 disease.

7.
Open Forum Infectious Diseases ; 9(Supplement 2):S928, 2022.
Article in English | EMBASE | ID: covidwho-2190046

ABSTRACT

Background. The effectiveness of fluvoxamine to shorten symptom duration or prevent hospitalization among outpatients with mild-to-moderate coronavirus 2019 (COVID-19) is unclear. Tolerability has also been identified as a potential limiting factor for 100 mg twice daily of fluvoxamine. We evaluated the efficacy of low-dose fluvoxamine 50 mg twice daily for 10 days compared with placebo for the treatment of early mild-to-moderate COVID-19. Methods. ACTIV-6 is an ongoing, decentralized, double-blind, randomized, placebo-controlled platform trial testing repurposed medications in outpatients with confirmed SARS-CoV-2 infection. Non-hospitalized adults aged >= 30 years, experiencing >= 2 symptoms of acute infection for <= 7 days were randomized to fluvoxamine 50 mg twice daily for 10 days or placebo. The primary outcome was time to sustained recovery, defined as the third of 3 consecutive days without symptoms. Secondary outcomes included composites of hospitalization or death with or without urgent care or emergency department visit by day 28. Results. Of those eligible for the fluvoxamine arm, 675 were randomized to and received fluvoxamine;619 received concurrent placebo. Sixty-six percent of the study population reported at least 2 doses of a COVID-19 vaccine. There was no evidence of improvement in time to recovery with fluvoxamine compared with placebo (hazard ratio [HR] 0.96, 95% credible interval [CrI] 0.86-1.06;posterior probability for benefit [HR > 1]=0.2). Sixteen participants (2.4%) in the fluvoxamine arm had urgent care or emergency department visits or were hospitalized compared with 11 (1.8%) in the pooled, concurrent placebo arm (HR 1.5, 95% CrI 0.5-3.0;posterior probability for benefit [HR < 1]=0.1725). No participant in either arm was hospitalized, and no deaths occurred. Adverse events were uncommon in both arms. Conclusion. Treatment with low-dose fluvoxamine 50 mg dosed twice daily for 10 days did not result in improved time to recovery among outpatients with COVID-19 in the United States during the delta and omicron variant surges.

8.
Open Forum Infectious Diseases ; 9(Supplement 2):S924-S925, 2022.
Article in English | EMBASE | ID: covidwho-2190039

ABSTRACT

Background. The effectiveness of fluvoxamine to shorten symptom duration or prevent hospitalization among outpatients with mild-to-moderate coronavirus 2019 (COVID-19) is unclear. Tolerability has also been identified as a potential limiting factor for 100 mg twice daily of fluvoxamine. We evaluated the efficacy of low-dose fluvoxamine 50 mg twice daily for 10 days compared with placebo for the treatment of early mild-to-moderate COVID-19. Methods. ACTIV-6 is an ongoing, decentralized, double-blind, randomized, placebo-controlled platform trial testing repurposed medications in outpatients with confirmed SARS-CoV-2 infection. Non-hospitalized adults aged >= 30 years, experiencing >= 2 symptoms of acute infection for <= 7 days were randomized to fluvoxamine 50 mg twice daily for 10 days or placebo. The primary outcome was time to sustained recovery, defined as the third of 3 consecutive days without symptoms. Secondary outcomes included composites of hospitalization or death with or without urgent care or emergency department visit by day 28. Results. Of those eligible for the fluvoxamine arm, 675 were randomized to and received fluvoxamine;619 received concurrent placebo. Sixty-six percent of the study population reported at least 2 doses of a COVID-19 vaccine. There was no evidence of improvement in time to recovery with fluvoxamine compared with placebo (hazard ratio [HR] 0.96, 95% credible interval [CrI] 0.86-1.06;posterior probability for benefit [HR > 1]=0.2). Sixteen participants (2.4%) in the fluvoxamine armhad urgent care or emergency department visits or were hospitalized compared with 11 (1.8%) in the pooled, concurrent placebo arm (HR 1.5, 95% CrI 0.5-3.0;posterior probability for benefit [HR < 1]=0.1725). No participant in either arm was hospitalized, and no deaths occurred. Adverse events were uncommon in both arms. Conclusion. Treatment with low-dose fluvoxamine 50 mg dosed twice daily for 10 days did not result in improved time to recovery among outpatients with COVID-19 in the United States during the delta and omicron variant surges.

9.
Open Forum Infectious Diseases ; 9(Supplement 2):S923, 2022.
Article in English | EMBASE | ID: covidwho-2190037

ABSTRACT

Background. Respiratory syncytial virus (RSV) is an important cause of disease in older adults and is associated with high morbidity and mortality, especially in those with high-risk conditions. Illness can vary from mild upper respiratory tract symptoms to more severe lower respiratory tract disease. After over 50 years of research, there is now hope for an RSV vaccine for any population, including older adults. An investigational bivalent RSV A and B, stabilized RSV prefusion F subunit vaccine (RSVpreF) was assessed successfully in a pivotal phase 3 efficacy study in older adults. (NCT05035212). Methods. The primary efficacy objective of this Phase 3, global, multicenter, randomized, double-blinded, placebo-controlled study was to evaluate the prevention of RSV associated lower respiratory tract illness (LRTI-RSV) in up to 40,000 adults >=60 years of age during the first winter season (September 2021-June 2022). Two primary endpoints were tested sequentially - LRTI-RSV with >=2 and >=3 symptoms. A pre-planned efficacy interim analysis (IA) was to be conducted by an external Data Monitoring Committee (DMC) upon accrual of at least 29 cases of LRTI-RSV with >=2 symptoms. With efficacy demonstrated for cases with >=2 symptoms and sufficient cases with >= 3 symptoms accrued, an efficacy analysis of cases with >= 3 symptoms was to be conducted. The ongoing study is collecting additional safety and descriptive efficacy data. Results. At the time of the IA, approximately 34,000 participants received either RSVpreF 120 mug (60 mug each of RSVpreF from RSV A and RSV B) or placebo (1:1 randomization). Forty-four LRTI-RSV cases with >=2 symptoms were accrued with 11 cases in the RSVpreF group and 33 cases in the placebo group corresponding to a VE of 66.7% (96.66% CI: 28.8%, 85.8%). Sixteen LRTI-RSV cases with >=3 symptoms were accrued with 2 cases in the RSVpreF group and 14 cases in the placebo group corresponding to a VE of 85.7% (96.66% CI: 32.0%, 98.7%). The investigational vaccine was well-tolerated with no safety concerns. Conclusion. Despite unpredictable RSV activity due to the COVID-19 pandemic, the primary objective of the study was met demonstrating that RSVpreF had a favorable safety profile and was highly efficacious in preventing LRTI-RSV with >=2 symptoms and >=3 symptoms in older adults 60 years and older.

10.
Open Forum Infectious Diseases ; 9(Supplement 2):S496-S497, 2022.
Article in English | EMBASE | ID: covidwho-2189808

ABSTRACT

Background. Nirmatrelvir with ritonavir (nirmatrelvir/r) is an oral antiviral COVID-19 treatment. We report its efficacy to shorten time to sustained alleviation and resolution of COVID-19 signs/symptoms in nonhospitalized adults with COVID-19 at high risk of severe disease as of primary completion data cut (11 Dec 2021). Methods. In this phase 2/3 double-blind study, eligible adults with confirmed SARS-CoV-2 and <= 5 days (d) of symptoms were randomized 1:1 to nirmatrelvir/r 300 mg/100 mg or placebo (PBO) every 12 hrs for 5 d. Pts logged presence and severity (on 3- or 4-point scales) of prespecified COVID-19 signs/symptoms daily Day 1 (predose) through 28. Times to sustained alleviation and resolution of all targeted signs/ symptoms were assessed, summarized with Kaplan-Meier curves, and compared by treatment by log-rank test. Individual signs/symptoms were compared with descriptive analyses. Results. From Jul-Dec 2021, 2246 pts enrolled;2085 pts (nirmatrelvir/r, n=1039;PBO, n=1046) met criteria for the mITT1 population (<= 5 d of symptom onset, did not/not expected to receive an mAb). More pts achieved sustained alleviation or sustained resolution with nirmatrelvir/r. Shorter median times to sustained alleviation/ resolution were observed with nirmatrelvir/r (13/16 d) vs PBO (15/19 d;Fig 1 & 2). Also, a shorter median time to sustained alleviation was seen in pts treated <= 3 d of symptoms with nirmatrelvir/r (12 d) vs PBO (15 d). The most common symptoms were cough, muscle/body aches, and headache in both groups. The median time to sustained alleviation of cough and headache was 2 d less with nirmatrelvir/r vs PBO. The median time to sustained resolution of muscle aches and shortness of breath was 3 d and 4 d less with nirmatrelvir/r. The proportion of pts with severe signs/symptoms in the nirmatrelvir/r vs PBO group was significantly higher at baseline, but significantly lower after treatment, showing nirmatrelvir/r significantly reduced symptom severity through Day 28 (Fig 3). Pts who were seronegative vs seropositive or had high vs low viral load at baseline achieved faster times to sustained alleviation with nirmatrelvir/r vs PBO. Conclusion. Nirmatrelvir/r treatment reduced duration and severity of COVID-19 symptoms vs PBO in pts at high risk of progressing to severe disease. NCT04960202.

11.
Open Forum Infectious Diseases ; 9(Supplement 2):S481, 2022.
Article in English | EMBASE | ID: covidwho-2189781

ABSTRACT

Background. Nelfinavir, an orally administered inhibitor of human immunodeficiency virus protease, inhibited the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro. To evaluate the efficacy and safety of nelfinavir, we conducted a randomized controlled trial. Methods. Adult patients testing positive for SARS-CoV-2 infection within 3 days were eligible for the study if they had no or mild symptoms of coronavirus disease 2019. Exclusion criteria included the followings: onset of symptoms >= 8 days before enrollment;oxygen saturation of 95% or less on room air;and vaccinated patients. Patients were randomly assigned (1:1) to receive oral nelfinavir 750 mg (x3 times daily) combined with standard-of-care or standard-of-care alone. The primary endpoint was the time to clearance of SARS-CoV-2. Saliva was collected every day and viral load was measured by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Nelfinavir was administered for 14 days. However, the treatment could be discontinued by the decision of investigator, if patients had 2 consecutive negative test results by qRT-PCR. Clinical course and safety information were collected through day 28. The study is registered with the Japan Registry of Clinical Trials (number, jRCT2071200023). Results. Between July 2020 and October 2021, 123 patients (63 in the nelfinavir group and 60 in the control group) were enrolled into the study and included in the analysis. The median time to viral clearance was 8.0 (95% confidence interval [CI] 7.0 to 12.0) days in the nelfinavir group and 8.0 (95% CI 7.0 to 10.0) days in the control group without statistically significant difference between the treatment group (hazard ratio 0.815, 95% CI 0.563 to 1.182;P = 0.1870). Adverse events were reported in 47 (74.6%) patients in the nelfinavir group and 20 (33.3%) in the control group. The most common adverse events in the nelfinavir group were diarrhea (49.2%) and nausea (6.3%). Conclusion. Nelfinavir did not reduce the time to viral clearance in this setting.

12.
Open Forum Infectious Diseases ; 9(Supplement 2):S380, 2022.
Article in English | EMBASE | ID: covidwho-2189675

ABSTRACT

Background. Antibiotic stewardship programs (ASP) are relatively new in Mexico. It was until May 2018 that it was established as a public health policy in the country. Few hospitals have acknowledged the mandate and started an ASP despite the efforts. Besides, little has been done to evaluate the efficacy of the program in terms of antibiotic expenditure and the incidence of associated infections. Therefore, the main objective was to evaluate antibiotic expenditure before and after the ASP in a third-level hospital in Mexico. As a secondary analysis, the relationship with Clostridioides difficile infections was explored. Methods. This is a retrospective and descriptive study from January 2017 to February 2020 (pre-COVID-19 pandemic). First, the mean antibiotic expenditure (adjusting for DDD/patient days-costs in USD) was evaluated before and after (June 2018 as the first month of implementation) the ASP. Statistical difference of the means was evaluated. It was also performed an exploratory analysis between the prescription of Clindamycin and Levofloxacin with the number of cases and deaths related to C. difficile infection. Results. The average antibiotic expenditure before ASP was US$13,468 +/- 3,267, and US$8,193 +/- 2,574 (p< 0.001) after. Graph 1 presents the changes in trend. Specifically, caspofungin, ciprofloxacin, clindamycin, fluconazole, levofloxacin, linezolid, piperacillin/tazobactam, and tigecycline showed statistically significant reduction after June 2018. Graph 2 displays the descriptive relationship between the prescription of levofloxacin and clindamycin, the cases of C. difficile infection, and the elimination of all associated mortality. Graph 1. Antibiotic expenditure. Before and after AMS Graph 2. Relationship between monthly consumption of clindamycin and levofloxacin and the number of cases/deaths secondary to Clostridioides difficile infections, before and after ASP. Conclusion. The ASP has significantly reduced the antibiotic expenditure in the hospital. Besides reducing the prescription of associated antibiotics, a possible reduction in C. difficile infections and associated deaths were observed.

13.
Open Forum Infectious Diseases ; 9(Supplement 2):S85, 2022.
Article in English | EMBASE | ID: covidwho-2189537

ABSTRACT

Background. Influenza viruses constantly change because of antigenic drift. Due to the time currently needed to develop and distribute flu shots, vaccines are often illmatched to circulating influenza strains. One silver lining of the COVID-19 pandemic was the acceleration of mRNA technology, which could significantly reduce the timeline between strain choice and deployment, potentially increasing vaccine efficacy. Significant private and public investments would be required to accommodate accelerated vaccine development and approval. Hence, it is important to understand the potential impact of mRNA technology on influenza hospitalizations and mortality. Methods. We developed a compartmental model stratified by age group to evaluate the potential effect of increased vaccine effectiveness (defined as a two-level measure of protection against infection and hospitalization) on influenza hospitalizations and mortality in the United States. We assume that mRNA technology can only shorten the time from strain choice to distribution but not distribution and administration. Thus, later decisions on vaccine composition would increase effectiveness but reduce availability. To assess this tradeoff, we evaluated two scenarios where strain choice was delayed until summer resulting in a more effective vaccine: (1) available to all age groups in the fall, or (2) available by August but only for adults 65 years and older. Results. Assuming current vaccine coverage rates, if not available until October, the vaccine would need a minimum of 80% effectiveness against infection to see a decrease in hospitalizations and deaths (Figures 1A and 1B). When delayed until November, even a 100% effective vaccine could not reduce hospitalizations or deaths (Figures 1C and 1D). For the elderly, a 50% effective vaccine against infection (Figures 1E and 1F) or a vaccine 40% effective against infection and 60% against hospitalization available in late summer was similar to an 80% effective vaccine available in October for all ages. Age-stratified weekly number of influenza-associated hospitalization per 100,000 population and total number of deaths in the United States for an mRNA vaccine that would be available in either October (A and B), November (C and D), or by late summer but only for the 65+ age group (E and F). The Baseline represents the 10-year average weekly hospitalization rate and mortality during the Flu Season (October to May). Conclusion. As the majority of influenza-associated hospitalizations and deaths are in adults 65 years and older, a combination policy targeting higher vaccine effectiveness for this age group in the short term would be the most efficacious. (Figure Presented).

14.
Journal of applied microbiology. ; 15, 2022.
Article in English | EMBASE | ID: covidwho-2189201

ABSTRACT

AIMS: This study aimed to provide operationally relevant SARS-CoV-2 surface disinfection efficacy information. METHODS AND RESULTS: Three EPA-registered disinfectants (Vital Oxide, Peroxide, Clorox Total 360 (C360)) and one antimicrobial formulation (CDC Bleach) were evaluated against SARS-CoV-2 on material coupons and were tested using Spray (no-touch with contact time) and Spray & Wipe (wipe immediately post-application) methods immediately and 2 hours post-contamination. Efficacy was evaluated for infectious virus, with a subset tested for vRNA recovery. Efficacy varied by method, disinfectant and material. CDC Bleach solution showed low efficacy against SARS-CoV-2 (Log Reduction < 1.7), unless applied via Spray & Wipe. Additionally, mechanical wiping increased the efficacy of treatments against SARS-CoV-2. Recovery of vRNA post-disinfection suggested vRNA may overestimate infectious virus remaining. CONCLUSION(S): Efficacy depends on surface material, chemical, and disinfection procedure, and suggests that mechanical wiping alone has some efficacy at removing SARS-CoV-2 from surfaces. We observed that disinfectant treatment biased recovery of vRNA over infectious virus. Copyright Published by Oxford University Press on behalf of Society for Applied Microbiology 2022.

15.
European Heart Journal, Supplement ; 24(Supplement K):K253, 2022.
Article in English | EMBASE | ID: covidwho-2188694

ABSTRACT

Background: The implementation of guidelines on LDL cholesterol levels after acute coronary syndrome (ACS) is very poor according to registries and surveys. Telemedicine could improve adherence to guidelines and facilitate clinical followup of patients with ACS, even with the limitations of Covid-19 pandemic. Aim of the study: To evaluate the efficacy of telemedicine follow-up in improving adherence to LDL guidelines and improving rates of prescription of PCSK9-inhibitors. Design and Methods: 650 consecutive patients discharged with diagnosis of ACS or Chronic CS were enrolled in the study and followed after 2 and 4 months. LDL levels and lipid lowering drug prescription were recorded. Data from 300 patients with ACS patients and <80 years were analyzed and LDL values of telemedicine followedup patients (telephone/smartphone app/pc teleconsultation) were compared with controls. Result(s): Baseline mean LDL levels were 120 mg/dl, 55% of patients were naive of lipid lowering therapy. At second follow-up mean LDL levels were 55 mg/dl (p<0.05 vs baseline) and rates of prescription of statins, ezetimibe and PCSK9-inhibitors were 98%, 79%, and 18% respectively. Rates of subjects with LDL levels below recommended threshold were 4% at baseline, 39% at first follow-up, 53% at second follow-up (p<0.05). Patients followed up with telemedicine showed lower LDL levels at second follow-up (55vs72 mg/dl, p=0.08) and higher rates of subjects below recommended LDL levels (63%vs30%, p=0.05). Conclusion(s): Telemedicine follow-up may improve the implementation of guideline recommended LDL levels after ACS..

16.
Accounts of chemical research ; 09, 2023.
Article in English | EMBASE | ID: covidwho-2185418

ABSTRACT

ConspectusThe outbreak of the coronavirus disease 2019 (COVID-19) pandemic and swift approval of two mRNA vaccines have put nucleic acid therapeutics in the spotlight of both the scientific community and the general public. Actually, in addition to mRNAs, multiple nucleic acid therapeutics have been successively commercialized over the past few years. The rapid development of nucleic acid drugs not only demonstrates their superior potency but also marks a new era of the field. Compared with conventional treatments targeting proteins rather than the root causes of diseases at the genetic level, nucleic acids are capable of achieving long-standing or even curative effects against undruggable disorders by modulating gene expression via inhibition, editing, addition, or replacement. This offers a terrific arsenal for expanding therapeutic access to diseases lacking current treatment options and developing vaccines to provide swift responses to emerging global health threats.Despite the stunning success and recent resurgence of interest in the field, the unfavorable physicochemical characteristics (i.e., the negative charge, large molecular weight, and hydrophilicity), susceptibility to nuclease degradation, off-target toxicity, and immunogenicity are a brake for moving nucleic acid therapeutics from bench to bedside. Currently, developing technologies to improve the circulation stability, targeting affinity, cellular entry, endolysosomal escape, efficacy, and safety of nucleic acid drugs still remains a major pharmaceutical bottleneck.In this Account, we outline the research efforts from our group on the development of technology platforms to overcome the pharmaceutical bottlenecks for nucleic acid therapeutics. We have engineered a variety of intelligent delivery platforms such as synthetic nanomaterials (i.e., lipid nanoparticles, polymers, and inorganic nanoparticles), physical delivery methods (i.e., electroporation), and naturally derived vehicles (i.e., extracellular vesicles), aiming at endowing nucleic acids with improved circulation stability, targeting affinity, and cellular internalization (Get in) and stimuli responsive endolysosomal escape capability (Get out). Moreover, we will discuss our progress in developing a series of modification strategies for sequence engineering of nucleic acids to endow them with enhanced nuclease resistance, translation efficiency, and potency while alleviating their off-target toxicity and immunogenicity (Sequence engineering). Integrating these technologies may promote the development of nucleic acid therapeutics with potent efficacy and improved safety (Efficacy & safety). With this Account, we hope to offer insights into rational design of cutting-edge nucleic acid therapeutic platforms. We believe that the continuing advances in nucleic acid technologies together with academic-industry collaborations in the clinic, will promise to usher in more clinically translatable nucleic acid therapeutics in the foreseeable future.

17.
Journal of the American Academy of Child and Adolescent Psychiatry ; 61(10 Supplement):S150, 2022.
Article in English | EMBASE | ID: covidwho-2179857

ABSTRACT

Objectives: Adolescent depression's impact is far-reaching, such as an elevated risk of suicide, comorbidities, and functioning impairments. Engaging mobile technology can enhance treatment adherence, and reduce costs and wait times for mental health care. SparkRx is a 5-week, self-guided, CBT-based digital therapeutic app designed to treat adolescents' depressive symptoms. An RCT (NCT04524598) evaluated SparkRx's clinical effectiveness by comparing SparkRx to a psychoeducation control app (Ctrl). Method(s): A total of 160 eligible adolescents (101 female, aged 13-21 years) with self-reported depressive symptoms were recruited nationwide. They were randomized to use SparkRx or Ctrl for 5 weeks and completed a Patient Health Questionnaire-8 (PHQ-8) weekly. Participants (and caregivers if <18) completed pre- and postintervention assessments. Intention-to-treat analyses (ITT) of all participants with moderate to severe baseline symptom severity (PHQ-8 >=10;N = 121) and per protocol (PP) analyses of only those completing all weekly assessments (N = 83) assessed intervention related depressive symptom changes. We examined engagement with SparkRx (daily active users [DAUs], modules completed and number of mood logs and behavioral activations (BAs) scheduled/completed) and symptom change moderators (gender, baseline severity, concurrent treatment, concurrent treatment changes, age, and ADHD diagnosis). Result(s): SparkRx users had clinically meaningful reductions in depressive symptoms (mu = 5.18 in ITT;mu = 5.98 in PP). ITT (SparkRx vs Ctrl) did not reach statistical significance. PP showed that SparkRx significantly reduced depressive symptoms vs Ctrl (p =.023). SparkRx's median DAUs was 41.95%. On average, SparkRx users completed 63.49% of modules, 19.73 (8.32) mood logs, and 8.71 (5.04) BAs (scheduled 9.86 [5.74]). Mixed linear effects models showed no moderating effects. Conclusion(s): SparkRx was shown to reduce adolescent depressive symptoms and was engaging. Limitations included a sample size that was not fully powered. These claims have not been reviewed by the US FDA with regard to SparkRx's safety or efficacy. In October 2021, Limbix released the initial version of SparkRx under FDA's "Enforcement Policy for Digital Health Devices For Treating Psychiatric Disorders During the Coronavirus Disease 2019 (COVID-19) Public Health Emergency." DDD, ADOL, CBT Copyright © 2022

18.
Journal of the American Academy of Child and Adolescent Psychiatry ; 61(10 Supplement):S149, 2022.
Article in English | EMBASE | ID: covidwho-2179855

ABSTRACT

Objectives: Mental health problems, including depression, often start in childhood or adolescence. The COVID-19 pandemic has contributed to alarming rates of child and adolescent depression. An emerging potential treatment in adults is omega-3 polyunsaturated fatty acids (PUFAs), which are naturally found in fatty fish, marine sources, and some nuts and seeds. We will determine the efficacy of omega-3 PUFAs for children and adolescents with clinical depression. Method(s): Electronic searches were conducted in several databases. Reference lists of relevant studies and grey literature were also searched for additional references. Randomized controlled trials involving supplementary omega-3 fatty acid treatment of any dose as monotherapy or adjunctive therapy among males and females who were 6 to 19 years of age with depression qualified for inclusion. All screening of citations was conducted in duplicate. Full-text citations were assessed for inclusion criteria and methodological quality from potentially relevant s. The standardized mean difference with 95% CI was determined. Result(s): This review included 6 trials involving 253 participants. Five studies involving 202 participants included in the primary outcome analysis demonstrated a moderate effect size when compared to placebo with a standardized mean difference (SMD) of -0.47 (95% CI, -1.07 to 0.13). Attrition rates were highly variable and not significant, with an OR of 0.63 (95% CI, 0.34-1.20). Conclusion(s): To date, there is insufficient evidence to determine the efficacy of omega-3 PUFAs on depressive symptoms in children and adolescents. However, this review suggests a moderate beneficial effect of omega-3 PUFAs on depressive symptoms compared to placebo, although the effect estimate is imprecise and not significant. Further research that addresses limitations in the current body of research on this topic in children and adolescents, including small sample sizes, remission, adverse events, dosage, and delivery modes, will help increase the precision in the effect estimates. DDD, TREAT Copyright © 2022

19.
Health Policy and Technology ; (no pagination), 2023.
Article in English | EMBASE | ID: covidwho-2179078

ABSTRACT

Objectives: In the face of pandemics, a viable global strategy, beyond relying on the fast discovery of a vaccine or a cure, is needed. We study quantitatively the feasibility and effectiveness of mass testing to contain an epidemic. We also explore the implications of various smart testing strategies to decrease the needed testing rates. Method(s): We use a modified SIR model with testing and extend the model to incorporate mobility patterns in a densely populated area. Result(s): For a pandemic like COVID-19, model simulations show that the rate of testing needed to squash the curve within a month varies between 20-30 percent of the population randomly tested daily to less than 5 percent, combining periodic and group testing. We also show that mobility restrictions can enhance the efficacy of testing. Scale could be as important as accuracy in testing, implying that an epidemiological rather than clinical approach for the approval of tests is needed. The estimated cost of testing is dwarfed by its return, mitigating the economic fallout of the pandemic. Conclusion(s): Without a vaccine or a cure, mass testing is the only viable and less costly strategy to indefinitely "squash the curve" while allowing for major economic activities to resume. Planning and executing a testing strategy is necessary and urgent as an insurance policy against future pandemics. It should be considered as an investment to build a testing and isolation infrastructure, which should be maintained as part of the pandemic preparedness. Copyright © 2022

20.
Indian Pediatrics ; 59(11):894, 2022.
Article in English | EMBASE | ID: covidwho-2175229
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