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1.
Lancet ; 398(10303): 843-855, 2021 09 04.
Article in English | MEDLINE | ID: covidwho-2106189

ABSTRACT

BACKGROUND: A previous efficacy trial found benefit from inhaled budesonide for COVID-19 in patients not admitted to hospital, but effectiveness in high-risk individuals is unknown. We aimed to establish whether inhaled budesonide reduces time to recovery and COVID-19-related hospital admissions or deaths among people at high risk of complications in the community. METHODS: PRINCIPLE is a multicentre, open-label, multi-arm, randomised, controlled, adaptive platform trial done remotely from a central trial site and at primary care centres in the UK. Eligible participants were aged 65 years or older or 50 years or older with comorbidities, and unwell for up to 14 days with suspected COVID-19 but not admitted to hospital. Participants were randomly assigned to usual care, usual care plus inhaled budesonide (800 µg twice daily for 14 days), or usual care plus other interventions, and followed up for 28 days. Participants were aware of group assignment. The coprimary endpoints are time to first self-reported recovery and hospital admission or death related to COVID-19, within 28 days, analysed using Bayesian models. The primary analysis population included all eligible SARS-CoV-2-positive participants randomly assigned to budesonide, usual care, and other interventions, from the start of the platform trial until the budesonide group was closed. This trial is registered at the ISRCTN registry (ISRCTN86534580) and is ongoing. FINDINGS: The trial began enrolment on April 2, 2020, with randomisation to budesonide from Nov 27, 2020, until March 31, 2021, when the prespecified time to recovery superiority criterion was met. 4700 participants were randomly assigned to budesonide (n=1073), usual care alone (n=1988), or other treatments (n=1639). The primary analysis model includes 2530 SARS-CoV-2-positive participants, with 787 in the budesonide group, 1069 in the usual care group, and 974 receiving other treatments. There was a benefit in time to first self-reported recovery of an estimated 2·94 days (95% Bayesian credible interval [BCI] 1·19 to 5·12) in the budesonide group versus the usual care group (11·8 days [95% BCI 10·0 to 14·1] vs 14·7 days [12·3 to 18·0]; hazard ratio 1·21 [95% BCI 1·08 to 1·36]), with a probability of superiority greater than 0·999, meeting the prespecified superiority threshold of 0·99. For the hospital admission or death outcome, the estimated rate was 6·8% (95% BCI 4·1 to 10·2) in the budesonide group versus 8·8% (5·5 to 12·7) in the usual care group (estimated absolute difference 2·0% [95% BCI -0·2 to 4·5]; odds ratio 0·75 [95% BCI 0·55 to 1·03]), with a probability of superiority 0·963, below the prespecified superiority threshold of 0·975. Two participants in the budesonide group and four in the usual care group had serious adverse events (hospital admissions unrelated to COVID-19). INTERPRETATION: Inhaled budesonide improves time to recovery, with a chance of also reducing hospital admissions or deaths (although our results did not meet the superiority threshold), in people with COVID-19 in the community who are at higher risk of complications. FUNDING: National Institute of Health Research and United Kingdom Research Innovation.


Subject(s)
Budesonide/administration & dosage , COVID-19/drug therapy , Glucocorticoids/administration & dosage , Administration, Inhalation , Aged , Bayes Theorem , COVID-19/mortality , Female , Hospitalization , Humans , Male , Middle Aged , Prospective Studies , Risk Factors , SARS-CoV-2 , Treatment Outcome
3.
Psychopharmacol Bull ; 52(4): 8-30, 2022 Oct 27.
Article in English | MEDLINE | ID: covidwho-2101824

ABSTRACT

Objective: In a phase 2 study, pimavanserin demonstrated efficacy as adjunctive treatment for major depressive disorder (MDD). Subsequently, two phase 3 studies (NCT03968159 in the US; NCT03999918 in Europe) were initiated to examine the efficacy and safety of adjunctive pimavanserin in subjects with MDD and inadequate response to antidepressant treatment. Studies were combined with a prespecified statistical analysis plan owing to recruitment challenges related to the COVID-19 pandemic. Experimental design: The randomized, double-blind studies enrolled 298 patients with MDD and inadequate response to current antidepressants. Patients were randomly assigned 1:1 to pimavanserin or placebo added to current antidepressant for 6 weeks. Primary endpoint was change from baseline to week 5 in the Hamilton Rating Scale for Depression, 17-item version (HAM-D-17). Principal observations: There was no effect of pimavanserin in change from baseline to week 5 in the HAM-D-17 (pimavanserin [n = 138]: least-squares mean [LSM] [standard error {SE}], -9.0 [0.58]; placebo [n = 135]: -8.1 [0.58]; mixed-effects model for repeated measures LSM [SE] difference, -0.9 [0.82], P = 0.2956). Nominal improvement with pimavanserin was observed on 2 secondary endpoints: Clinical Global Impressions-Severity scale, Karolinska Sleepiness Scale. Treatment-emergent adverse events occurred in 58.1% of pimavanserin-treated and 54.7% of placebo-treated patients. Conclusions: Adjunctive pimavanserin did not significantly improve depressive symptoms, although pimavanserin was well tolerated.


Subject(s)
COVID-19 , Depressive Disorder, Major , Humans , Depressive Disorder, Major/drug therapy , Double-Blind Method , Pandemics , Antidepressive Agents/adverse effects , Treatment Outcome
4.
Am J Case Rep ; 23: e937739, 2022 Nov 01.
Article in English | MEDLINE | ID: covidwho-2100411

ABSTRACT

BACKGROUND We present the report of the first case, to the best of our knowledge, of central retinal vein occlusion (CRVO) that occurred 3 days after anticoagulation discontinuation in a patient with a history of pulmonary embolism in the course of COVID-19. CASE REPORT A previously healthy 38-year-old man was hospitalized in April 2021 with severe COVID-19 pneumonia, complicated by segmental and subsegmental pulmonary embolism. The patient was treated with a concurrent combination of remdesivir, dexamethasone, therapeutic enoxaparin, ceftriaxone, passive oxygen therapy, and convalescent plasma therapy, which led to pulmonary improvement. The treatment with therapeutic enoxaparin (80 mg/0.8 mL twice a day) was continued for 1 month after discharge, followed by 15 mg of rivaroxaban twice a day for 3 weeks and 20 mg of rivaroxaban once a day for 11 weeks. Within 3 days after rivaroxaban discontinuation, the patient experienced a decrease in visual acuity in his right eye, to the level of 5/25. Nonischemic CRVO with cystoid macular edema was diagnosed and an intravitreal injection of ranibizumab was performed. Common identifiable factors contributing to CRVO were excluded, and the treatment with prophylactic enoxaparin was initiated. Two weeks later, macular edema decreased significantly and visual acuity improved to 20/20. The treatment with enoxaparin was discontinued. CONCLUSIONS Rebound hypercoagulability after discontinuation of rivaroxaban therapy can manifest as CRVO in a young patient with a history of COVID-19 pulmonary embolism. It was successfully treated with an intravitreal injection of ranibizumab.


Subject(s)
COVID-19 , Macular Edema , Pulmonary Embolism , Retinal Vein Occlusion , Male , Humans , Adult , Retinal Vein Occlusion/complications , Retinal Vein Occlusion/drug therapy , Retinal Vein Occlusion/diagnosis , Rivaroxaban/therapeutic use , Ranibizumab/therapeutic use , Enoxaparin/therapeutic use , Glucocorticoids/therapeutic use , Macular Edema/drug therapy , Macular Edema/etiology , Intravitreal Injections , Pulmonary Embolism/drug therapy , Pulmonary Embolism/complications , Tomography, Optical Coherence , Angiogenesis Inhibitors/therapeutic use , Treatment Outcome
5.
Eur J Med Res ; 27(1): 223, 2022 Oct 29.
Article in English | MEDLINE | ID: covidwho-2098456

ABSTRACT

PURPOSE: Gamma knife radiosurgery (GK) is a commonly used approach for the treatment of intracranial lesions. Its radiation response is typically not immediate, but delayed. In this study, we analyzed cases from a prospectively collected database to assess the influence of COVID-19 pandemic on the decision making in patients treated by gamma knife radiosurgery. METHODS: From January 2019 to August 2021, 540 cases of intracranial lesions were treated by GK with 207 cases before COVID-19 pandemic as a control. During the COVID-19 pandemic, 333 cases were similarly treated on patients with or without the COVID-19 vaccination. All the GK treated parameters as well as time profile in the decision making were analyzed. The parameters included age, sex, characteristic of lesion, targeted volume, peripheral radiation dose, neurological status, Karnofsky Performance Status (KPS), time interval from MRI diagnosis to consultation, time interval from the approval to treatment, frequency of outpatient department (OPD) visit, and frequency of imaging follow-up. RESULTS: Longer time intervals from diagnosis to GK consultation and treatment were found in the pandemic group (36.8 ± 25.5/54.5 ± 27.6 days) compared with the pre-COVID control (17.1 ± 22.4/45.0 ± 28.0 days) or vaccination group (12.2 ± 7.1/29.6 ± 10.9 days) (p < 0.001, and p < 0.001, respectively). The fewer OPD visits and MRI examinations also showed the same trends. High proportion of neurological deficits were found in the pandemic group (65.4%) compared with the control (45.4%) or vaccination group (58.1%) (p < 0.001). The Charlson comorbidity in the pandemic group was 3.9 ± 3.3, the control group was 4.6 ± 3.2, and the vaccination group was 3.1 ± 3.1. There were similar inter-group difference (p < 0.001). In multiple variant analyses, longer time intervals from the diagnosis to consultation or treatment, OPD frequency and MRI examination were likely influenced by the status of the COVID-19 pandemic as they were alleviated by the vaccination. CONCLUSIONS: The decision making in patients requiring gamma knife treatment was most likely influenced by the status of the COVID-19 pandemic, while vaccination appeared to attenuate their hesitant behaviors. Patients with pre-treatment neurological deficits and high co-morbidity undergoing the gamma knife treatment were less affected by the COVID-19 pandemic.


Subject(s)
Brain Neoplasms , COVID-19 , Radiosurgery , Humans , Radiosurgery/adverse effects , Radiosurgery/methods , COVID-19/epidemiology , Pandemics , COVID-19 Vaccines , Retrospective Studies , Decision Making , Follow-Up Studies , Treatment Outcome
6.
Trials ; 23(1): 273, 2022 Apr 08.
Article in English | MEDLINE | ID: covidwho-2098437

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) has a heterogeneous outcome in individuals from remaining asymptomatic to death. In a majority of cases, mild symptoms are present that do not require hospitalization and can be successfully treated in the outpatient setting, though symptoms may persist for a long duration. We hypothesize that drugs suitable for decentralized study in outpatients will have efficacy among infected outpatients METHODS: The TREAT NOW platform is designed to accommodate testing multiple agents with the ability to incorporate new agents in the future. TREAT NOW is an adaptive, blinded, multi-center, placebo-controlled superiority randomized clinical trial which started with two active therapies (hydroxychloroquine and lopinavir/ritonavir) and placebo, with the hydroxychloroquine arm dropped shortly after enrollment began due to external evidence. Each arm has a target enrollment of 300 participants who will be randomly assigned in an equal allocation to receive either an active therapy or placebo twice daily for 14 days with daily electronic surveys collected over days 1 through 16 and on day 29 to evaluate symptoms and a modified COVID-19 ordinal outcome scale. Participants are enrolled remotely by telephone and consented with a digital interface, study drug is overnight mailed to study participants, and data collection occurs electronically without in-person interactions. DISCUSSION: If effective treatments for COVID-19 can be identified for individuals in the outpatient setting before they advance to severe disease, it will prevent progression to more severe disease, reduce the need for hospitalization, and shorten the duration of symptoms. The novel decentralized, "no touch" approach used by the TREAT NOW platform has distinction advantages over traditional in-person trials to reach broader populations and perform study procedures in a pragmatic yet rigorous manner. TRIAL REGISTRATION: ClinicalTrials.gov NCT04372628. Registered on April 30, 2020. First posted on May 4, 2020.


Subject(s)
COVID-19 , Antiviral Agents/adverse effects , COVID-19/drug therapy , Hospitalization , Humans , Hydroxychloroquine/adverse effects , Outpatients , Randomized Controlled Trials as Topic , SARS-CoV-2 , Treatment Outcome
7.
Georgian Med News ; (328-329): 75-80, 2022.
Article in English | MEDLINE | ID: covidwho-2092155

ABSTRACT

Fifty blood samples were collected from patients who were confirmed to have COVID-19 by conducting a diagnostic test using real-time RT-PCR for the direct qualitative detection of the Coronavirus when the patients attended the private clinics at Al Rabeea Private Hospital in Mosul for the period from the beginning of March to the end of May 2021. The patients' ages range from17-59 years, with 23 males (46%), and 27 females (54%). The blood samples were taken before giving any type of treatment for blood culture, biochemical, and immunological tests. Bacteremia is investigated to determine the types of bacteria that cause bacteremia, biochemical tests such as D-dimer, S. Ferritin, CRP, Protein S, Protein C, FBS, LDH, Blood Urea, Serum Creatinine, SGOT & SGPT, and immunological tests such as blood group, IgG & IgM, IL-1B, IL-6, TNF-α alpha, ASOT, ESR, C3, and C4. In this study, the relationship between bacteremia and the types of biomarkers used is determined in addition to the relationship of bacteremia to the patient's age, sex, SPO2, and body temperature. More accurate comparison is also accomplished in cases of bacteremia by adopting the types of bacteria isolated if they were gram-positive or gram-negative. The results of this study show an increase in the severity of COVID-19 disease caused by a secondary bacterial infection. This is determined by measuring several biomarkers used in this study and also by performing bacteriological tests to document bacteremia by blood culture. Also, these results can be adopted in future studies concentrating on the molecular level to determine the genetic changes associated with viral infection with or without secondary bacterial infection to develop an effective treatment protocol.


Subject(s)
Bacteremia , COVID-19 , Male , Female , Humans , Adolescent , Young Adult , Adult , Middle Aged , Bacteremia/microbiology , Biomarkers , Treatment Outcome
8.
Ter Arkh ; 94(5): 675-682, 2022 Jun 17.
Article in Russian | MEDLINE | ID: covidwho-2091501

ABSTRACT

BACKGROUND: The use of virus-neutralizing monoclonal antibodies is an effective method of etiotropic therapy for SARS-CoV-2 in patients of high-risk groups of severe COVID-19. Regdanvimab is a single-component monoclonal antibodies immunoglobulin G1, whose mechanism of action is aimed at binding SARS-CoV-2 virus at the RBD site of the spike protein S1 domain. In the Russian Federation, regdanvimab is approved for emergency administration in COVID-19 for adult patients not requiring respiratory therapy who are at high risk of developing a severe course of the disease. AIM: To evaluate the efficacy and safety of therapy with regdanvimab in patients with mild/moderate COVID-19 in a short-term hospital unit. MATERIALS AND METHODS: Virus-neutralizing therapy with regdanvimab was performed at the short-term hospital unit of the Moscow City Clinic. An open retrospective observational single-center study included 92 adult patients with mild/moderate coronavirus infection. All patients had comorbid chronic diseases and belonged to the high-risk group for the development of a severe COVID-19. INCLUSION CRITERIA: age 18 to 75 years; presence of a verified diagnosis of COVID-19 of mild/moderate COVID-19, polymerase chain reaction (PCR) confirmed; one or more chronic diseases; first 7 days from the onset of the first symptoms of COVID-19 (including day 7). EXCLUSION CRITERIA: need for oxygen support. Clinical efficacy was assessed according to the World Health Organization Сlinical Progression Scale and supplemented with laboratory markers at baseline and in dynamics, as well as with monitoring of virus elimination by PCR. STATISTICS: Calculations were performed using the statistical computing environment R 4.1.3 (R Foundation for Statistical Computing, Austria). For quantitative indices the median (1; 3 quartiles) was indicated. For binomial signs we calculated 95% confidence intervals according to Wilson's method. Time interval analysis was performed according to the KaplanMeier method. The significance level was determined at p0.05. RESULTS: A significant decrease in the severity of clinical manifestations according to the World Health Organization Clinical Progression Scale was noted by patients by day 4 after regdanvimab administration. All 92 patients in the cohort were discharged from the hospital l on average on day 5 after regdanvimab administration and on day 9 of the disease. On day 4 after drug administration 82% of patients was being PCR negative. No adverse events related to the administration of regdanvimab were reported during the study. CONCLUSION: In real clinical practice, the efficacy and safety of regdanvimab in patients at high risk of severe COVID-19 was confirmed once again, with a positive clinical result observed in a mixed cohort by the causative agent omicron and delta strain.


Subject(s)
COVID-19 , Adult , Humans , Adolescent , Young Adult , Middle Aged , Aged , COVID-19/drug therapy , COVID-19/epidemiology , SARS-CoV-2 , Retrospective Studies , Spike Glycoprotein, Coronavirus , Time Factors , Antibodies, Monoclonal, Humanized/adverse effects , Treatment Outcome , Oxygen
9.
Ter Arkh ; 94(5): 668-674, 2022 Jun 17.
Article in Russian | MEDLINE | ID: covidwho-2091500

ABSTRACT

AIM: To study the effect of levilimab or baricitinib in combination with standard therapy (ST) on the incidence of severe viral pneumonia associated with a new coronavirus infection COVID-19. MATERIALS AND METHODS: A multicenter, open-label observational study of the efficacy and safety of levilimab in combination with ST (group 1, n=100), baricitinib in combination with ST (group 2, n=139), or in comparison with ST (group 3, n=200) in outpatients with verified CT-1 pneumonia. RESULTS: According to the results of laboratory tests, patients treated with levilimab in combination with ST had the best dynamics of changes in CRP from reliably the highest level (mg/L) to the lowest in comparison with other groups. In the group of patients with ST, in contrast to the other groups, no dynamics of CRP was observed by day 5 of therapy. In group of hospitalized patients initially receiving levilimab in addition to ST, the rate of transfer to the intensive care unit (2 patients, 9.52%) and length of stay (4 days) was significantly lower compared to the values in patients in both the baricitinib group in combination with ST (7 patients, 15.56%; 5 days [interquartile range 36.5]) and in patients receiving ST alone (7 patients, 15.56%; 5 days [interquartile range 36.5]). Also in hospitalized patients we observed no statistically significant intergroup differences in the incidence of infectious complications and thromboembolic events, which confirms the safety of including levilimab or baricitinib in COVID-19 pathogenetic therapy regimens. Observational results support the hypothesis that the initial inclusion of levilimab or baricitinib in addition to ST is accompanied by a reduced risk of viral pneumonia progression. CONCLUSION: The addition of levilimab or baricitinib to the therapy regimen for coronavirus infection during the outpatient phase has demonstrated a preemptive anti-inflammatory effect and reduced the probability of lung tissue damage progression.


Subject(s)
COVID-19 , Pneumonia, Viral , Humans , COVID-19/drug therapy , Outpatients , SARS-CoV-2 , Pneumonia, Viral/complications , Pneumonia, Viral/drug therapy , Anti-Inflammatory Agents/therapeutic use , Treatment Outcome
10.
J Physiol Pharmacol ; 73(3)2022 Jun.
Article in English | MEDLINE | ID: covidwho-2091455

ABSTRACT

Systemic inflammation is a hallmark of severe coronavirus disease-19 (COVID-19). Anti-inflammatory therapy is considered crucial to modulate the hyperinflammatory response (cytokine storm) in hospitalized COVID-19 patients. There is currently no specific, conclusively proven, cost-efficient, and worldwide available anti-inflammatory therapy available to treat COVID-19 patients with cytokine storm. The present study aimed to investigate the treatment benefit of oral colchicine for hospitalized COVID-19 patients with suspected cytokine storm. Colchicine is an approved drug and possesses multiple anti-inflammatory mechanisms. This was a pilot, open-label randomized controlled clinical trial comparing standard of care (SOC) plus oral colchicine (colchicine arm) vs. SOC alone (control arm) in non-ICU hospitalized COVID-19 patients with suspected cytokine storm. Colchicine treatment was initiated within first 48 hours of admission delivered at 1.5 mg loading dose, followed by 0.5 mg b.i.d. for next 6 days and 0.5 mg q.d. for the second week. A total of 96 patients were randomly allocated to the colchicine (n=48) and control groups (n=48). Both colchicine and control group patients experienced similar clinical outcomes by day 14 of hospitalization. Treatment outcome by day 14 in colchicine vs control arm: recovered and discharged alive: 36 (75.0%) vs. 37 (77.1%), remain admitted after 14-days: 4 (8.3%) vs. 5 (10.4%), ICU transferred: 4 (8.3%) vs. 3 (6.3%), and mortality: 4 (8.3%) vs. 3 (6.3%). The speed of improvement of COVID-19 acute symptoms including shortness of breath, fever, cough, the need of supplementary oxygen, and oxygen saturation level, was almost identical in the two groups. Length of hospitalization was on average 1.5 day shorter in the colchicine group. There was no evidence for a difference between the two groups in the follow-up serum levels of inflammatory biomarkers including C-reactive protein (CRP), D-dimer, lactate dehydrogenase (LDH), ferritin, interleukin-6 (IL-6), high-sensitivity troponin T (hs-TnT) and N-terminal pro b-type natriuretic peptide (NT pro-BNP). According to the results of our study, oral colchicine does not appear to show clinical benefits in non-ICU hospitalized COVID-19 patients with suspected cytokine storm. It is possible that the anti-inflammatory pathways of colchicine are not crucially involved in the pathogenesis of COVID-19.


Subject(s)
COVID-19 , Humans , COVID-19/drug therapy , SARS-CoV-2 , Cytokine Release Syndrome/drug therapy , Colchicine/therapeutic use , Hospitalization , Anti-Inflammatory Agents/therapeutic use , Treatment Outcome
11.
Pan Afr Med J ; 42: 202, 2022.
Article in English | MEDLINE | ID: covidwho-2090887

ABSTRACT

The pandemic of coronavirus disease 2019 (COVID-19) still remains on an upsurge trend. The second and the waves of this disease have led to panic in many countries, and some parts of the world suffering from the fourth wave. In the midst of this pandemic, COVID-19 patients are acquiring secondary infections such as mucormycosis also known as "black fungus disease". Mucormycosis is a serious, but rare opportunistic fungal infection that spreads rapidly, and hence prompt diagnosis and treatment are necessary to avoid mortality and morbidity rate. We report in this paper, a case of a diabetic patient who presented with bilateral nasal obstruction, anosmia, and frontal headache diagnosed with rhinocerebral mucormycosis developing after COVID-19 infection with a favorable outcome after a medico-surgical treatment. Through this case, we aim to aware patricians of this possible association and the importance of early diagnosis to optimize treatment outcomes.


Subject(s)
COVID-19 , Diabetes Mellitus , Mucormycosis , Opportunistic Infections , Humans , Mucormycosis/diagnosis , Mucormycosis/therapy , COVID-19/complications , COVID-19/diagnosis , Opportunistic Infections/diagnosis , Treatment Outcome
12.
Trials ; 23(1): 899, 2022 Oct 22.
Article in English | MEDLINE | ID: covidwho-2089229

ABSTRACT

BACKGROUND: The COVID-19 pandemic has had major impacts in many different spheres, including mental health. Children and adolescents are especially vulnerable because their central nervous system is still in development and they have fewer coping resources than do adults. Increases in the prevalence of depressive and anxiety symptomatology have been reported worldwide. However, access to mental health care is limited, especially for the paediatric population and in low- and middle-income countries. Therefore, we developed a brief internet-delivered cognitive-behavioural intervention for children and adolescents with symptoms of anxiety and depression. The aim of this proposed study is to test the efficacy of the intervention. METHODS: We will conduct a two-arm, parallel randomised controlled trial involving children and adolescents (8-11 and 12-17 years of age, respectively) with symptoms of anxiety, depression or both, according to the 25-item Revised Child Anxiety and Depression Scale (t-score > 70). A total of 280 participants will be randomised to the intervention group or the active control group, in a 1:1 ratio. Those in the intervention group will receive five weekly sessions of cognitive-behavioural therapy via teleconference. The sessions will focus on stress responses, family communication, diaphragmatic breathing, emotions, anger management, behavioural activation and cognitive restructuring. Participants in both groups will have access to 15 videos covering the same topics. Participant-guardian pairs will be expected to attend the sessions (intervention group), watch the videos (control group) or both (intervention group only). A blinded assessor will collect data on symptoms of anxiety, depression and irritability, at baseline, at the end of the intervention and 30 days thereafter. Adolescents with access to a smartphone will also be invited to participate in an ecological momentary assessment of emotional problems in the week before and the week after the intervention, as well as in passive data collection from existing smartphone sensors throughout the study. DISCUSSION: Internet-delivered interventions play a major role in increasing access to mental health care. A brief, manualised, internet-delivered intervention might help children and adolescents with anxiety or depressive symptomatology, even outside the context of the COVID-19 pandemic. TRIAL REGISTRATION: ClinicalTrials.gov NCT05139433. Registered prospectively in November 2021. Minor amendments made in July 2022.


Subject(s)
COVID-19 , Cognitive Behavioral Therapy , Internet-Based Intervention , Adolescent , Child , Humans , Anxiety/diagnosis , Anxiety/therapy , Cognition , Cognitive Behavioral Therapy/methods , Depression/diagnosis , Depression/therapy , Pandemics , Randomized Controlled Trials as Topic , Treatment Outcome
13.
Curr Opin Crit Care ; 28(6): 681-685, 2022 Dec 01.
Article in English | MEDLINE | ID: covidwho-2087889

ABSTRACT

PURPOSE OF REVIEW: In this article, we describe preoperative patient selection and outcomes of patients with lung disease secondary to infection from COVID-19 who receive lung transplantation. RECENT FINDINGS: Lung transplants for patients with lung disease secondary to infection from COVID-19 have been performed successfully in over 200 patients in the United States. The preoperative course of these patients is somewhat atypical in comparison with patients who have had lung transplants related to chronic lung diseases, where there are more traditional indications for lung transplants. COVID-19 patients have more severe pulmonary disease often requiring mechanical ventilation and extracorporeal mechanical ventilation (ECMO), frequent nosocomial infections, and renal and cardiac dysfunction. The intraoperative course of these COVID-19 patients is often longer and requires increased transfusions of blood products in comparison with non-COVID-19 patients. Additionally, in the postoperative period, COVID-19 patients more frequently require mechanical ventilation and ECMO support. However, the survival rate of such patients at 6 months is greater than 90%. SUMMARY: Patients with respiratory failure secondary to COVID-19 infection that require a lung transplant generally have a complicated preoperative course and the operations are more complex, but the long-term outcomes are excellent.


Subject(s)
COVID-19 , Extracorporeal Membrane Oxygenation , Lung Diseases , Lung Transplantation , Humans , COVID-19/therapy , Treatment Outcome , Lung Diseases/surgery , Retrospective Studies
14.
JAMA Netw Open ; 5(10): e2238507, 2022 10 03.
Article in English | MEDLINE | ID: covidwho-2084943

ABSTRACT

Importance: Patients from racially and ethnically minoritized populations, such as Black and Hispanic patients, may be less likely to receive evidence-based COVID-19 treatments than White patients, contributing to adverse clinical outcomes. Objective: To determine whether clinical treatments and outcomes among patients hospitalized with COVID-19 were associated with race. Design, Setting, and Participants: This retrospective cohort study was conducted in 130 Department of Veterans Affairs Medical Centers (VAMCs) between March 1, 2020, and February 28, 2022, with a 60-day follow-up period until May 1, 2022. Participants included veterans hospitalized with COVID-19. Data were analyzed from May 6 to June 2, 2022. Exposures: Self-reported race. Main Outcomes and Measures: Clinical care processes (eg, intensive care unit [ICU] admission; organ support measures, including invasive and noninvasive mechanical ventilation; prone position therapy, and COVID-19-specific medical treatments) were quantified. Clinical outcomes of interest included in-hospital mortality, 60-day mortality, and 30-day readmissions. Outcomes were assessed with multivariable random effects logistic regression models to estimate the association of race with outcomes not attributable to known mediators, such as socioeconomic status and age, while adjusting for potential confounding between outcomes and mediators. Results: A total of 43 222 veterans (12 135 Black veterans [28.1%]; 31 087 White veterans [71.9%]; 40 717 [94.2%] men) with a median (IQR) age of 71 (62-77) years who were hospitalized with SARS-CoV-2 infection were included. Controlling for site of treatment, Black patients were equally likely to be admitted to the ICU (4806 Black patients [39.6%] vs 13 427 White patients [43.2%]; within-center adjusted odds ratio [aOR], 0.95; 95% CI, 0.88-1.02; P = .17). Two-thirds of patients treated with supplemental oxygen or noninvasive or invasive mechanical ventilation also received systemic steroids, but Black veterans were less likely to receive steroids (within-center aOR, 0.88; 95% CI, 0.80-0.96; P = .004; between-center aOR, 0.67; 95% CI, 0.48-0.96; P = .03). Similarly, Black patients were less likely to receive remdesivir (within-center aOR, 0.89; 95% CI, 0.83-0.95; P < .001; between-center aOR, 0.68; 95% CI, 0.47-0.99; P = .02) or treatment with immunomodulatory drugs (within-center aOR, 0.77; 95% CI, 0.67-0.87; P < .001). After adjusting for patient demographic characteristics, chronic health conditions, severity of acute illness, and receipt of COVID-19-specific treatments, there was no association of Black race with hospital mortality (within-center aOR, 0.98; 95% CI, 0.86-1.10; P = .71) or 30-day readmission (within-center aOR, 0.95; 95% CI, 0.88-1.04; P = .28). Conclusions and Relevance: These findings suggest that Black veterans hospitalized with COVID-19 were less likely to be treated with evidence-based COVID-19 treatments, including systemic steroids, remdesivir, and immunomodulatory drugs.


Subject(s)
COVID-19 , Veterans , Male , Humans , Aged , Female , COVID-19/therapy , SARS-CoV-2 , Retrospective Studies , Treatment Outcome , Oxygen
15.
JAMA ; 328(16): 1595-1603, 2022 10 25.
Article in English | MEDLINE | ID: covidwho-2084929

ABSTRACT

Importance: The effectiveness of ivermectin to shorten symptom duration or prevent hospitalization among outpatients in the US with mild to moderate symptomatic COVID-19 is unknown. Objective: To evaluate the efficacy of ivermectin, 400 µg/kg, daily for 3 days compared with placebo for the treatment of early mild to moderate COVID-19. Design, Setting, and Participants: ACTIV-6, an ongoing, decentralized, double-blind, randomized, placebo-controlled platform trial, was designed to evaluate repurposed therapies in outpatients with mild to moderate COVID-19. A total of 1591 participants aged 30 years and older with confirmed COVID-19, experiencing 2 or more symptoms of acute infection for 7 days or less, were enrolled from June 23, 2021, through February 4, 2022, with follow-up data through May 31, 2022, at 93 sites in the US. Interventions: Participants were randomized to receive ivermectin, 400 µg/kg (n = 817), daily for 3 days or placebo (n = 774). Main Outcomes and Measures: Time to sustained recovery, defined as at least 3 consecutive days without symptoms. There were 7 secondary outcomes, including a composite of hospitalization or death by day 28. Results: Among 1800 participants who were randomized (mean [SD] age, 48 [12] years; 932 women [58.6%]; 753 [47.3%] reported receiving at least 2 doses of a SARS-CoV-2 vaccine), 1591 completed the trial. The hazard ratio (HR) for improvement in time to recovery was 1.07 (95% credible interval [CrI], 0.96-1.17; posterior P value [HR >1] = .91). The median time to recovery was 12 days (IQR, 11-13) in the ivermectin group and 13 days (IQR, 12-14) in the placebo group. There were 10 hospitalizations or deaths in the ivermectin group and 9 in the placebo group (1.2% vs 1.2%; HR, 1.1 [95% CrI, 0.4-2.6]). The most common serious adverse events were COVID-19 pneumonia (ivermectin [n = 5]; placebo [n = 7]) and venous thromboembolism (ivermectin [n = 1]; placebo [n = 5]). Conclusions and Relevance: Among outpatients with mild to moderate COVID-19, treatment with ivermectin, compared with placebo, did not significantly improve time to recovery. These findings do not support the use of ivermectin in patients with mild to moderate COVID-19. Trial Registration: ClinicalTrials.gov Identifier: NCT04885530.


Subject(s)
Anti-Infective Agents , COVID-19 , Hospitalization , Ivermectin , Female , Humans , Middle Aged , COVID-19/drug therapy , COVID-19/mortality , COVID-19/prevention & control , COVID-19 Vaccines/therapeutic use , Double-Blind Method , Ivermectin/adverse effects , Ivermectin/therapeutic use , SARS-CoV-2 , Treatment Outcome , Anti-Infective Agents/adverse effects , Anti-Infective Agents/therapeutic use , Ambulatory Care , Drug Repositioning , Time Factors , Recovery of Function , Male , Adult
16.
Am J Rhinol Allergy ; 36(6): 733-740, 2022 Nov.
Article in English | MEDLINE | ID: covidwho-2084686

ABSTRACT

BACKGROUND: The efficacy of topical corticosteroids is limited in chronic rhinosinusitis (CRS) due to rapid clearance from the nasal cavity and insufficient drug delivery to inflamed sinonasal passages. LYR-210 is an implantable corticosteroid matrix designed to provide up to 24 weeks of treatment to patients with CRS by locally delivering mometasone furoate (MF) to the sinonasal mucosa. In a randomized, controlled, dose-ranging LANTERN study, LYR-210 (7500 µg) achieved clinically relevant improvement in CRS cardinal symptom composite scores, the 22-item Sinonasal Outcome Test (SNOT-22), ethmoid opacification, and the need for rescue treatment at 24 weeks. OBJECTIVE: As the plasma MF concentrations of LYR-210 (2500 µg) and LYR-210 (7500 µg) were evaluated at weeks 4, 12, and 24 in the LANTERN study (data on file at Lyra Therapeutics, Inc.), this study aims to characterize the pharmacokinetic profiles of both doses of LYR-210 at earlier timepoints post-placement in patients with CRS. METHODS: Twenty-four surgically naïve adult patients with CRS were enrolled in an open-label, multicenter study and underwent in-office bilateral administration of LYR-210 (2500 µg) (n = 12 patients) or LYR-210 (7500 µg) (n = 12 patients) into the middle meatus. Plasma MF concentrations were determined pre-placement and 1-h post-placement (day 1), and on days 2, 3, 7, 14, 21, 28, 42, and 56 by liquid chromatography-tandem mass spectrometry. RESULTS: Both LYR-210 doses were well-tolerated with no serious adverse events. Systemic MF levels were dose-dependent and lower than reported values of other respiratory MF products. Plasma MF concentrations showed steady drug release from LYR-210 (2500 µg) and LYR-210 (7500 µg) that persisted through day 56. CONCLUSION: LYR-210 achieved dose-dependent, continuous local MF delivery at a steady rate with low systemic exposure for months.


Subject(s)
Pregnadienediols , Sinusitis , Adrenal Cortex Hormones/therapeutic use , Adult , Chronic Disease , Drug Liberation , Humans , Mometasone Furoate/therapeutic use , Pharmaceutical Preparations , Pregnadienediols/adverse effects , Pregnadienediols/pharmacokinetics , Sinusitis/drug therapy , Treatment Outcome
17.
Eur Rev Med Pharmacol Sci ; 26(19): 7297-7304, 2022 Oct.
Article in English | MEDLINE | ID: covidwho-2081434

ABSTRACT

OBJECTIVE: Pneumonia and hyperinflammatory state related to COVID-19 infection are fatal clinical conditions without definite treatment modalities. Interleukin-6 and Interleukin-1 targeted therapies have been proposed as treatment options. This study was conducted to investigate the efficacy of anakinra and tocilizumab added to corticosteroids in patients with COVID-19-associated pneumonia and hyper-inflammatory syndrome in our tertiary clinical center. PATIENTS AND METHODS: Patients with COVID-19-associated pneumonia and hyperinflammatory state who did not respond to initial treatments, including corticosteroids, were included in the study. The patients' electronic records were reviewed retrospectively and recorded according to a standardized data table. Univariate and multivariate regression analyses were used to identify risk factors associated with intubation. RESULTS: 388 patients were included in the study. 197 patients were intubated and most of them died (n=194/197, 98%). 67 patients received tocilizumab, and 97 patients received anakinra. Anakinra [OR: 0.440, 95% CI=0.244-0.794, p=0.006] and tocilizumab [OR: 0.491, 95% CI=0.256-0.943, p=0.033] were both associated with a decreased risk for intubation. However, having a neutrophil/lymphocyte ratio ≥ 10 [OR: 2.035, 95% CI=1.143-3.623, p=0.016], serum lactate dehydrogenase (LDH) level ≥ 400 [OR: 3.160, 95% CI=1.937-5.156, p<0.001] and age ≥ 50 [OR: 4.048, 95% CI=2.037-8.043, p < 0.001] was associated with an increased risk for intubation. CONCLUSIONS: Both anakinra and tocilizumab, added to initial standard COVID-19 treatments (including glucocorticoids) reduced the need for intubation in patients with COVID-19-associated severe pneumonia and hyperinflammatory syndrome. Given the high mortality rate of intubated patients with COVID-19, both treatments may have added benefits on mortality.


Subject(s)
COVID-19 , Humans , COVID-19/drug therapy , SARS-CoV-2 , Interleukin 1 Receptor Antagonist Protein/therapeutic use , Interleukin-6 , Retrospective Studies , Treatment Outcome , Adrenal Cortex Hormones/therapeutic use , Interleukin-1 , Lactate Dehydrogenases
18.
Exp Clin Transplant ; 20(Suppl 4): 74-79, 2022 08.
Article in English | MEDLINE | ID: covidwho-2080822

ABSTRACT

OBJECTIVES: The COVID-19 pandemic has hit the world in an almost unprecedented way. Patients with endstage chronic renal failure, who are on hemodialysis, with glomerulonephritis and complicated pyelonephritis and other nephrological diseases, were under constant close supervision of specialists, despite the existing difficulties for face-to-face contact between the patient and the doctor at our hospital in Tashkent, Uzbekistan, where primary detection and treatment of these patients were also actively conducted. Here, we report the features of the course of treatment for COVID-19 infection in patients who underwent kidney transplant living related donors during the global pandemic in Uzbekistan. MATERIALS AND METHODS: After a decree from the Cabinet of Ministers of the Republic of Uzbekistan in October 2017 for approval and regulations for related kidney and (or) liver lobe procedures, our center performed 609 kidney transplants from living related donors between 2017 and 2022, with 320 procedures during the pandemic. There were 228 transplant recipients with COVID-19 infections and COVID-19-associated pneumonia. RESULTS: Of total cases with COVID-19, 71% had moderate disease severity. Of patients who under went kidney transplant, 42% had pneumonia associated with COVID-19 infection. After lung damage was confirmed by multislice computed tomography of the lungs, patients were sent to the intensive care unit for appropriate treatment to ensure a quick recovery without possible complications to the graft. CONCLUSIONS: The Ministry of Health of the Republic of Uzbekistan indicated the possibility of treatment of patients with moderate and severe COVID-19 disease with monoclonal antibodies that block interleukin 6 receptors (tocilizumab and sarilumab). With timely detection of symptoms of COVID-19infection, treatment, and the use of prevention methods, kidney transplant recipients of living related donors had fewer complications of the disease than expected.


Subject(s)
COVID-19 , Kidney Transplantation , Humans , Incidence , Pandemics , SARS-CoV-2 , Transplant Recipients , Treatment Outcome , Uzbekistan
19.
PLoS Med ; 19(10): e1004120, 2022 10.
Article in English | MEDLINE | ID: covidwho-2079651

ABSTRACT

BACKGROUND: Early antiviral treatment is effective for Coronavirus Disease 2019 (COVID-19) but currently available agents are expensive. Favipiravir is routinely used in many countries, but efficacy is unproven. Antiviral combinations have not been systematically studied. We aimed to evaluate the effect of favipiravir, lopinavir-ritonavir or the combination of both agents on Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) viral load trajectory when administered early. METHODS AND FINDINGS: We conducted a Phase 2, proof of principle, randomised, placebo-controlled, 2 × 2 factorial, double-blind trial of ambulatory outpatients with early COVID-19 (within 7 days of symptom onset) at 2 sites in the United Kingdom. Participants were randomised using a centralised online process to receive: favipiravir (1,800 mg twice daily on Day 1 followed by 400 mg 4 times daily on Days 2 to 7) plus lopinavir-ritonavir (400 mg/100 mg twice daily on Day 1, followed by 200 mg/50 mg 4 times daily on Days 2 to 7), favipiravir plus lopinavir-ritonavir placebo, lopinavir-ritonavir plus favipiravir placebo, or both placebos. The primary outcome was SARS-CoV-2 viral load at Day 5, accounting for baseline viral load. Between 6 October 2020 and 4 November 2021, we recruited 240 participants. For the favipiravir+lopinavir-ritonavir, favipiravir+placebo, lopinavir-ritonavir+placebo, and placebo-only arms, we recruited 61, 59, 60, and 60 participants and analysed 55, 56, 55, and 58 participants, respectively, who provided viral load measures at Day 1 and Day 5. In the primary analysis, the mean viral load in the favipiravir+placebo arm had changed by -0.57 log10 (95% CI -1.21 to 0.07, p = 0.08) and in the lopinavir-ritonavir+placebo arm by -0.18 log10 (95% CI -0.82 to 0.46, p = 0.58) compared to the placebo arm at Day 5. There was no significant interaction between favipiravir and lopinavir-ritonavir (interaction coefficient term: 0.59 log10, 95% CI -0.32 to 1.50, p = 0.20). More participants had undetectable virus at Day 5 in the favipiravir+placebo arm compared to placebo only (46.3% versus 26.9%, odds ratio (OR): 2.47, 95% CI 1.08 to 5.65; p = 0.03). Adverse events were observed more frequently with lopinavir-ritonavir, mainly gastrointestinal disturbance. Favipiravir drug levels were lower in the combination arm than the favipiravir monotherapy arm, possibly due to poor absorption. The major limitation was that the study population was relatively young and healthy compared to those most affected by the COVID-19 pandemic. CONCLUSIONS: At the current doses, no treatment significantly reduced viral load in the primary analysis. Favipiravir requires further evaluation with consideration of dose escalation. Lopinavir-ritonavir administration was associated with lower plasma favipiravir concentrations. TRIAL REGISTRATION: Clinicaltrials.gov NCT04499677 EudraCT: 2020-002106-68.


Subject(s)
COVID-19 , Humans , COVID-19/drug therapy , Lopinavir/therapeutic use , Pandemics , Ritonavir/therapeutic use , Antiviral Agents/adverse effects , SARS-CoV-2 , Treatment Outcome
20.
Curr Opin Rheumatol ; 32(6): 572-582, 2020 11.
Article in English | MEDLINE | ID: covidwho-2077899

ABSTRACT

PURPOSE OF REVIEW: The purpose of this review is highlighting the most recent evidence on the clinical efficacy and toxicity of antimalarials in systemic lupus erythematosus (SLE). RECENT FINDINGS: New data confirm the effects of antimalarials in preventing SLE activity, damage and infections and in decreasing mortality. An important reduction in use of health resources is related to continued antimalarial use. Hydroxychloroquine (HCQ) may prevent preeclampsia in pregnant women with SLE. HCQ ocular toxicity is infrequent and could be associated with blood levels. Gastrointestinal and skin toxicity are underrecognized and could influence adherence. Prolongation of QT interval is extremely unusual with HCQ. Doses of HCQ of 200 mg/day seem to offer a good efficacy/toxicity balance. HCQ protection against herpes zoster and Pneumocystis jirovecii infection has been shown. On the contrary, HCQ prescription by doctors and adherence by patients are both under recommended standards. The recent coronavirus disease 2019 pandemic has resulted in a significant shortage of HCQ in many countries with possible consequences in the correct treatment of lupus patients. SUMMARY: Recent evidence reinforces the central role of HCQ in SLE therapy. The reduction in activity, damage accrual and mortality is consistent across studies, countries and ethnical groups. On the contrary, and despite the well established beneficial effects of prolonged regular HCQ therapy, many SLE patients do never take this drug or it is eventually stopped in the setting of severe flares, pregnancy or presumed toxicity. Every effort must be made to assure the correct prescription of HCQ and not to withdraw the drug unless unequivocal signs of toxicity are present.


Subject(s)
Antimalarials/therapeutic use , Betacoronavirus , Coronavirus Infections/epidemiology , Lupus Erythematosus, Systemic/drug therapy , Pandemics , Pneumonia, Viral/epidemiology , COVID-19 , Comorbidity , Coronavirus Infections/drug therapy , Female , Humans , Lupus Erythematosus, Systemic/epidemiology , Pneumonia, Viral/drug therapy , SARS-CoV-2 , Treatment Outcome
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